Discovery of potent and novel smoothened antagonists via structure-based virtual screening and biological assays.

PubMed

Lu, Wenfeng; Zhang, Dihua; Ma, Haikuo; Tian, Sheng; Zheng, Jiyue; Wang, Qin; Luo, Lusong; Zhang, Xiaohu

2018-05-23

The Hedgehog (Hh) signaling pathway plays a critical role in controlling patterning, growth and cell migration during embryonic development. Aberrant activation of Hh signaling has been linked to tumorigenesis in various cancers, such as basal cell carcinoma (BCC) and medulloblastoma. As a key member of the Hh pathway, the Smoothened (Smo) receptor, a member of the G protein-coupled receptor (GPCR) family, has emerged as an attractive therapeutic target for the treatment and prevention of human cancers. The recent determination of several crystal structures of Smo in complex with different antagonists offers the possibility to perform structure-based virtual screening for discovering potent Smo antagonists with distinct chemical scaffolds. In this study, based on the two Smo crystal complexes with the best capacity to distinguish the known Smo antagonists from decoys, the molecular docking-based virtual screening was conducted to identify promising Smo antagonists from ChemDiv library. A total of 21 structurally novel and diverse compounds were selected for experimental testing, and six of them exhibited significant inhibitory activity against the Hh pathway activation (IC 50  < 10 μM) in a GRE (Gli-responsive element) reporter gene assay. Specifically, the most potent compound (compound 20: 47 nM) showed comparable Hh signaling inhibition to vismodegib (46 nM). Compound 20 was further confirmed to be a potent Smo antagonist in a fluorescence based competitive binding assay. Optimization using substructure searching method led to the discovery of 12 analogues of compound 20 with decent Hh pathway inhibition activity, including four compounds with IC 50 lower than 1 μM. The important residues uncovered by binding free energy calculation (MM/GBSA) and binding free energy decomposition were highlighted and discussed. These findings suggest that the novel scaffold afforded by compound 20 can be used as a good starting point for further modification/optimization and the clarified interaction patterns may also guide us to find more potent Smo antagonists. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Spectral Estimation Model Construction of Heavy Metals in Mining Reclamation Areas

PubMed Central

Dong, Jihong; Dai, Wenting; Xu, Jiren; Li, Songnian

2016-01-01

The study reported here examined, as the research subject, surface soils in the Liuxin mining area of Xuzhou, and explored the heavy metal content and spectral data by establishing quantitative models with Multivariable Linear Regression (MLR), Generalized Regression Neural Network (GRNN) and Sequential Minimal Optimization for Support Vector Machine (SMO-SVM) methods. The study results are as follows: (1) the estimations of the spectral inversion models established based on MLR, GRNN and SMO-SVM are satisfactory, and the MLR model provides the worst estimation, with R2 of more than 0.46. This result suggests that the stress sensitive bands of heavy metal pollution contain enough effective spectral information; (2) the GRNN model can simulate the data from small samples more effectively than the MLR model, and the R2 between the contents of the five heavy metals estimated by the GRNN model and the measured values are approximately 0.7; (3) the stability and accuracy of the spectral estimation using the SMO-SVM model are obviously better than that of the GRNN and MLR models. Among all five types of heavy metals, the estimation for cadmium (Cd) is the best when using the SMO-SVM model, and its R2 value reaches 0.8628; (4) using the optimal model to invert the Cd content in wheat that are planted on mine reclamation soil, the R2 and RMSE between the measured and the estimated values are 0.6683 and 0.0489, respectively. This result suggests that the method using the SMO-SVM model to estimate the contents of heavy metals in wheat samples is feasible. PMID:27367708

Spectral Estimation Model Construction of Heavy Metals in Mining Reclamation Areas.

PubMed

Dong, Jihong; Dai, Wenting; Xu, Jiren; Li, Songnian

2016-06-28

The study reported here examined, as the research subject, surface soils in the Liuxin mining area of Xuzhou, and explored the heavy metal content and spectral data by establishing quantitative models with Multivariable Linear Regression (MLR), Generalized Regression Neural Network (GRNN) and Sequential Minimal Optimization for Support Vector Machine (SMO-SVM) methods. The study results are as follows: (1) the estimations of the spectral inversion models established based on MLR, GRNN and SMO-SVM are satisfactory, and the MLR model provides the worst estimation, with R² of more than 0.46. This result suggests that the stress sensitive bands of heavy metal pollution contain enough effective spectral information; (2) the GRNN model can simulate the data from small samples more effectively than the MLR model, and the R² between the contents of the five heavy metals estimated by the GRNN model and the measured values are approximately 0.7; (3) the stability and accuracy of the spectral estimation using the SMO-SVM model are obviously better than that of the GRNN and MLR models. Among all five types of heavy metals, the estimation for cadmium (Cd) is the best when using the SMO-SVM model, and its R² value reaches 0.8628; (4) using the optimal model to invert the Cd content in wheat that are planted on mine reclamation soil, the R² and RMSE between the measured and the estimated values are 0.6683 and 0.0489, respectively. This result suggests that the method using the SMO-SVM model to estimate the contents of heavy metals in wheat samples is feasible.

Design and pitch scaling for affordable node transition and EUV insertion scenario

NASA Astrophysics Data System (ADS)

Kim, Ryoung-han; Ryckaert, Julien; Raghavan, Praveen; Sherazi, Yasser; Debacker, Peter; Trivkovic, Darko; Gillijns, Werner; Tan, Ling Ee; Drissi, Youssef; Blanco, Victor; Bekaert, Joost; Mao, Ming; Larivière, Stephane; McIntyre, Greg

2017-04-01

imec's DTCO and EUV achievement toward imec 7nm (iN7) technology node which is industry 5nm node equivalent is reported with a focus on cost and scaling. Patterning-aware design methodology supports both iArF multiple patterning and EUV under one compliant design rule. FinFET device with contacted poly pitch of 42nm and metal pitch of 32nm with 7.5-track, 6.5-track, and 6-track standard cell library are explored. Scaling boosters are used to provide additional scaling and die cost benefit while lessening pitch shrink burden, and it makes EUV insertion more affordable. EUV pattern fidelity is optimized through OPC, SMO, M3D, mask sizing and SRAF. Processed wafers were characterized and edge-placement-error (EPE) variability is validated for EUV insertion. Scale-ability and cost of ownership of EUV patterning in aligned with iN7 standard cell design, integration and patterning specification are discussed.

Working set selection using functional gain for LS-SVM.

PubMed

Bo, Liefeng; Jiao, Licheng; Wang, Ling

2007-09-01

The efficiency of sequential minimal optimization (SMO) depends strongly on the working set selection. This letter shows how the improvement of SMO in each iteration, named the functional gain (FG), is used to select the working set for least squares support vector machine (LS-SVM). We prove the convergence of the proposed method and give some theoretical support for its performance. Empirical comparisons demonstrate that our method is superior to the maximum violating pair (MVP) working set selection.

Power law-based local search in spider monkey optimisation for lower order system modelling

NASA Astrophysics Data System (ADS)

Sharma, Ajay; Sharma, Harish; Bhargava, Annapurna; Sharma, Nirmala

2017-01-01

The nature-inspired algorithms (NIAs) have shown efficiency to solve many complex real-world optimisation problems. The efficiency of NIAs is measured by their ability to find adequate results within a reasonable amount of time, rather than an ability to guarantee the optimal solution. This paper presents a solution for lower order system modelling using spider monkey optimisation (SMO) algorithm to obtain a better approximation for lower order systems and reflects almost original higher order system's characteristics. Further, a local search strategy, namely, power law-based local search is incorporated with SMO. The proposed strategy is named as power law-based local search in SMO (PLSMO). The efficiency, accuracy and reliability of the proposed algorithm is tested over 20 well-known benchmark functions. Then, the PLSMO algorithm is applied to solve the lower order system modelling problem.

Sterol Methyl Oxidases Affect Embryo Development via Auxin-Associated Mechanisms.

PubMed

Zhang, Xia; Sun, Shuangli; Nie, Xiang; Boutté, Yohann; Grison, Magali; Li, Panpan; Kuang, Susu; Men, Shuzhen

2016-05-01

Sterols are essential molecules for multiple biological processes, including embryogenesis, cell elongation, and endocytosis. The plant sterol biosynthetic pathway is unique in the involvement of two distinct sterol 4α-methyl oxidase (SMO) families, SMO1 and SMO2, which contain three and two isoforms, respectively, and are involved in sequential removal of the two methyl groups at C-4. In this study, we characterized the biological functions of members of the SMO2 gene family. SMO2-1 was strongly expressed in most tissues during Arabidopsis (Arabidopsis thaliana) development, whereas SMO2-2 showed a more specific expression pattern. Although single smo2 mutants displayed no obvious phenotype, the smo2-1 smo2-2 double mutant was embryonic lethal, and the smo2-1 smo2-2/+ mutant was dwarf, whereas the smo2-1/+ smo2-2 mutant exhibited a moderate phenotype. The phenotypes of the smo2 mutants resembled those of auxin-defective mutants. Indeed, the expression of DR5rev:GFP, an auxin-responsive reporter, was reduced and abnormal in smo2-1 smo2-2 embryos. Furthermore, the expression and subcellular localization of the PIN1 auxin efflux facilitator also were altered. Consistent with these observations, either the exogenous application of auxin or endogenous auxin overproduction (YUCCA9 overexpression) partially rescued the smo2-1 smo2-2 embryonic lethality. Surprisingly, the dwarf phenotype of smo2-1 smo2-2/+ was completely rescued by YUCCA9 overexpression. Gas chromatography-mass spectrometry analysis revealed a substantial accumulation of 4α-methylsterols, substrates of SMO2, in smo2 heterozygous double mutants. Together, our data suggest that SMO2s are important for correct sterol composition and function partially through effects on auxin accumulation, auxin response, and PIN1 expression to regulate Arabidopsis embryogenesis and postembryonic development. © 2016 American Society of Plant Biologists. All Rights Reserved.

Sterol Methyl Oxidases Affect Embryo Development via Auxin-Associated Mechanisms1

PubMed Central

Zhang, Xia; Sun, Shuangli; Nie, Xiang; Boutté, Yohann; Grison, Magali; Li, Panpan; Kuang, Susu

2016-01-01

Sterols are essential molecules for multiple biological processes, including embryogenesis, cell elongation, and endocytosis. The plant sterol biosynthetic pathway is unique in the involvement of two distinct sterol 4α-methyl oxidase (SMO) families, SMO1 and SMO2, which contain three and two isoforms, respectively, and are involved in sequential removal of the two methyl groups at C-4. In this study, we characterized the biological functions of members of the SMO2 gene family. SMO2-1 was strongly expressed in most tissues during Arabidopsis (Arabidopsis thaliana) development, whereas SMO2-2 showed a more specific expression pattern. Although single smo2 mutants displayed no obvious phenotype, the smo2-1 smo2-2 double mutant was embryonic lethal, and the smo2-1 smo2-2/+ mutant was dwarf, whereas the smo2-1/+ smo2-2 mutant exhibited a moderate phenotype. The phenotypes of the smo2 mutants resembled those of auxin-defective mutants. Indeed, the expression of DR5rev:GFP, an auxin-responsive reporter, was reduced and abnormal in smo2-1 smo2-2 embryos. Furthermore, the expression and subcellular localization of the PIN1 auxin efflux facilitator also were altered. Consistent with these observations, either the exogenous application of auxin or endogenous auxin overproduction (YUCCA9 overexpression) partially rescued the smo2-1 smo2-2 embryonic lethality. Surprisingly, the dwarf phenotype of smo2-1 smo2-2/+ was completely rescued by YUCCA9 overexpression. Gas chromatography-mass spectrometry analysis revealed a substantial accumulation of 4α-methylsterols, substrates of SMO2, in smo2 heterozygous double mutants. Together, our data suggest that SMO2s are important for correct sterol composition and function partially through effects on auxin accumulation, auxin response, and PIN1 expression to regulate Arabidopsis embryogenesis and postembryonic development. PMID:27006488

The Smo/Smo model: hedgehog-induced medulloblastoma with 90% incidence and leptomeningeal spread.

PubMed

Hatton, Beryl A; Villavicencio, Elisabeth H; Tsuchiya, Karen D; Pritchard, Joel I; Ditzler, Sally; Pullar, Barbara; Hansen, Stacey; Knoblaugh, Sue E; Lee, Donghoon; Eberhart, Charles G; Hallahan, Andrew R; Olson, James M

2008-03-15

Toward the goal of generating a mouse medulloblastoma model with increased tumor incidence, we developed a homozygous version of our ND2:SmoA1 model. Medulloblastomas form in 94% of homozygous Smo/Smo mice by 2 months of age. Tumor formation is, thus, predictable by age, before the symptomatic appearance of larger lesions. This high incidence and early onset of tumors is ideal for preclinical studies because mice can be enrolled before symptom onset and with a greater latency period before late-stage disease. Smo/Smo tumors also display leptomeningeal dissemination of neoplastic cells to the brain and spine, which occurs in many human cases. Despite an extended proliferation of granule neuron precursors (GNP) in the postnatal external granular layer (EGL), the internal granular layer formed normally in Smo/Smo mice and tumor formation occurred only in localized foci on the superficial surface of the molecular layer. Thus, tumor formation is not simply the result of over proliferation of GNPs within the EGL. Moreover, Smo/Smo medulloblastomas were transplantable and serially passaged in vivo, demonstrating the aggressiveness of tumor cells and their transformation beyond a hyperplastic state. The Smo/Smo model is the first mouse medulloblastoma model to show leptomeningeal spread. The adherence to human pathology, high incidence, and early onset of tumors thus make Smo/Smo mice an efficient model for preclinical studies.

Reticle decision center: a novel applications platform for enhancing reticle yield and productivity at 10nm technology and beyond

NASA Astrophysics Data System (ADS)

Hwa, George; Bugata, Raj; Chiang, Kaiming; Lakkapragada, Suresh; Tolani, Vikram; Gopalakrishnan, Sandhya; Chen, Chun-Jen; Yang, Chin-Ting; Hsu, Sheng-Chang; Tuo, Laurent

2016-10-01

In the semiconductor IC manufacturing industry, challenges associated with producing defect-free photomasks have been dramatically increasing. At the 10nm technology node, since the 193nm immersion scanner numerical aperture has remained the same 1.35 as in previous nodes, more multi-patterning and aggressive SMO illumination sources are being used to effectively print smaller feature CDs and pitches. To accommodate such specialized sources, more model-based mask OPC and ILT have been used making mask designs very complicated. This in turn makes mask manufacturing very challenging especially for the defect inspection, repair, and metrology processes that need to guarantee defect-free masks. Over the past few years, considerable innovation have been made in the areas of defect inspection and disposition that has ensured continued predictability of mask quality to wafer and final chip yields. The accurate disposition of each mask defect before and after repair has been facilitated by a suite of automated applications such as ADC, LPR, RPG, AIA, etc. that work together with the inspection, repair, and metrology tools and effectively also provide the best possible utilization of the tool capability, capacity and operator resources. In this paper we introduce a new consolidated applications platform called the Reticle Decision Center (RDC) which hosts all these supporting software applications on a centralized server with direct connectivity to mask inspection, repair, metrology tools and more. The paper details how the RDC server is architected to host any application in its native operating system environment and provides for high availability with automatic failover and redundancy. The server along with its host of applications has been tightly integrated with KLA-Tencor's Teron mask inspectors. The paper concludes with showing benefits realized in mask cycle-time and yield as a result of implementing RDC into a high-volume 10nm mask-shop production line.

Heterologous expression and characterization of mouse spermine oxidase.

PubMed

Cervelli, Manuela; Polticelli, Fabio; Federico, Rodolfo; Mariottini, Paolo

2003-02-14

Polyamine oxidases are key enzymes responsible of the polyamine interconversion metabolism in animal cells. Recently, a novel enzyme belonging to this class of enzymes has been characterized for its capability to oxidize preferentially spermine and designated as spermine oxidase. This is a flavin adenine dinucleotide-containing enzyme, and it has been expressed both in vitro and in vivo systems. The primary structure of mouse spermine oxidase (mSMO) was deduced from a cDNA clone (Image Clone 264769) recovered by a data base search utilizing the human counterpart of polyamine oxidases, PAOh1. The open reading frame predicts a 555-amino acid protein with a calculated M(r) of 61,852.30, which shows a 95.1% identity with PAOh1. To understand the biochemical properties of mSMO and its structure/function relationship, the mSMO cDNA has been subcloned and expressed in secreted and secreted-tagged forms into Escherichia coli BL21 DE3 cells. The recombinant enzyme shows an optimal pH value of 8.0 and is able to oxidize rapidly spermine to spermidine and 3-aminopropanal and fails to act upon spermidine and N(1)-acetylpolyamines. The purified recombinant-tagged form enzyme (M(r) approximately 68,000) has K(m) and k(cat) values of 90 microm and 4.5 s(-1), respectively, using spermine as substrate at pH 8.0. Molecular modeling of mSMO protein based on maize polyamine oxidase three-dimensional structure suggests that the general features of maize polyamine oxidase active site are conserved in mSMO.

ℓ0 -based sparse hyperspectral unmixing using spectral information and a multi-objectives formulation

NASA Astrophysics Data System (ADS)

Xu, Xia; Shi, Zhenwei; Pan, Bin

2018-07-01

Sparse unmixing aims at recovering pure materials from hyperpspectral images and estimating their abundance fractions. Sparse unmixing is actually ℓ0 problem which is NP-h ard, and a relaxation is often used. In this paper, we attempt to deal with ℓ0 problem directly via a multi-objective based method, which is a non-convex manner. The characteristics of hyperspectral images are integrated into the proposed method, which leads to a new spectra and multi-objective based sparse unmixing method (SMoSU). In order to solve the ℓ0 norm optimization problem, the spectral library is encoded in a binary vector, and a bit-wise flipping strategy is used to generate new individuals in the evolution process. However, a multi-objective method usually produces a number of non-dominated solutions, while sparse unmixing requires a single solution. How to make the final decision for sparse unmixing is challenging. To handle this problem, we integrate the spectral characteristic of hyperspectral images into SMoSU. By considering the spectral correlation in hyperspectral data, we improve the Tchebycheff decomposition function in SMoSU via a new regularization item. This regularization item is able to enforce the individual divergence in the evolution process of SMoSU. In this way, the diversity and convergence of population is further balanced, which is beneficial to the concentration of individuals. In the experiments part, three synthetic datasets and one real-world data are used to analyse the effectiveness of SMoSU, and several state-of-art sparse unmixing algorithms are compared.

ILT based defect simulation of inspection images accurately predicts mask defect printability on wafer

NASA Astrophysics Data System (ADS)

Deep, Prakash; Paninjath, Sankaranarayanan; Pereira, Mark; Buck, Peter

2016-05-01

At advanced technology nodes mask complexity has been increased because of large-scale use of resolution enhancement technologies (RET) which includes Optical Proximity Correction (OPC), Inverse Lithography Technology (ILT) and Source Mask Optimization (SMO). The number of defects detected during inspection of such mask increased drastically and differentiation of critical and non-critical defects are more challenging, complex and time consuming. Because of significant defectivity of EUVL masks and non-availability of actinic inspection, it is important and also challenging to predict the criticality of defects for printability on wafer. This is one of the significant barriers for the adoption of EUVL for semiconductor manufacturing. Techniques to decide criticality of defects from images captured using non actinic inspection images is desired till actinic inspection is not available. High resolution inspection of photomask images detects many defects which are used for process and mask qualification. Repairing all defects is not practical and probably not required, however it's imperative to know which defects are severe enough to impact wafer before repair. Additionally, wafer printability check is always desired after repairing a defect. AIMSTM review is the industry standard for this, however doing AIMSTM review for all defects is expensive and very time consuming. Fast, accurate and an economical mechanism is desired which can predict defect printability on wafer accurately and quickly from images captured using high resolution inspection machine. Predicting defect printability from such images is challenging due to the fact that the high resolution images do not correlate with actual mask contours. The challenge is increased due to use of different optical condition during inspection other than actual scanner condition, and defects found in such images do not have correlation with actual impact on wafer. Our automated defect simulation tool predicts printability of defects at wafer level and automates the process of defect dispositioning from images captured using high resolution inspection machine. It first eliminates false defects due to registration, focus errors, image capture errors and random noise caused during inspection. For the remaining real defects, actual mask-like contours are generated using the Calibre® ILT solution [1][2], which is enhanced to predict the actual mask contours from high resolution defect images. It enables accurate prediction of defect contours, which is not possible from images captured using inspection machine because some information is already lost due to optical effects. Calibre's simulation engine is used to generate images at wafer level using scanner optical conditions and mask-like contours as input. The tool then analyses simulated images and predicts defect printability. It automatically calculates maximum CD variation and decides which defects are severe to affect patterns on wafer. In this paper, we assess the printability of defects for the mask of advanced technology nodes. In particular, we will compare the recovered mask contours with contours extracted from SEM image of the mask and compare simulation results with AIMSTM for a variety of defects and patterns. The results of printability assessment and the accuracy of comparison are presented in this paper. We also suggest how this method can be extended to predict printability of defects identified on EUV photomasks.

Hazardous Traffic Event Detection Using Markov Blanket and Sequential Minimal Optimization (MB-SMO)

PubMed Central

Yan, Lixin; Zhang, Yishi; He, Yi; Gao, Song; Zhu, Dunyao; Ran, Bin; Wu, Qing

2016-01-01

The ability to identify hazardous traffic events is already considered as one of the most effective solutions for reducing the occurrence of crashes. Only certain particular hazardous traffic events have been studied in previous studies, which were mainly based on dedicated video stream data and GPS data. The objective of this study is twofold: (1) the Markov blanket (MB) algorithm is employed to extract the main factors associated with hazardous traffic events; (2) a model is developed to identify hazardous traffic event using driving characteristics, vehicle trajectory, and vehicle position data. Twenty-two licensed drivers were recruited to carry out a natural driving experiment in Wuhan, China, and multi-sensor information data were collected for different types of traffic events. The results indicated that a vehicle’s speed, the standard deviation of speed, the standard deviation of skin conductance, the standard deviation of brake pressure, turn signal, the acceleration of steering, the standard deviation of acceleration, and the acceleration in Z (G) have significant influences on hazardous traffic events. The sequential minimal optimization (SMO) algorithm was adopted to build the identification model, and the accuracy of prediction was higher than 86%. Moreover, compared with other detection algorithms, the MB-SMO algorithm was ranked best in terms of the prediction accuracy. The conclusions can provide reference evidence for the development of dangerous situation warning products and the design of intelligent vehicles. PMID:27420073

Hazardous Traffic Event Detection Using Markov Blanket and Sequential Minimal Optimization (MB-SMO).

PubMed

Yan, Lixin; Zhang, Yishi; He, Yi; Gao, Song; Zhu, Dunyao; Ran, Bin; Wu, Qing

2016-07-13

The ability to identify hazardous traffic events is already considered as one of the most effective solutions for reducing the occurrence of crashes. Only certain particular hazardous traffic events have been studied in previous studies, which were mainly based on dedicated video stream data and GPS data. The objective of this study is twofold: (1) the Markov blanket (MB) algorithm is employed to extract the main factors associated with hazardous traffic events; (2) a model is developed to identify hazardous traffic event using driving characteristics, vehicle trajectory, and vehicle position data. Twenty-two licensed drivers were recruited to carry out a natural driving experiment in Wuhan, China, and multi-sensor information data were collected for different types of traffic events. The results indicated that a vehicle's speed, the standard deviation of speed, the standard deviation of skin conductance, the standard deviation of brake pressure, turn signal, the acceleration of steering, the standard deviation of acceleration, and the acceleration in Z (G) have significant influences on hazardous traffic events. The sequential minimal optimization (SMO) algorithm was adopted to build the identification model, and the accuracy of prediction was higher than 86%. Moreover, compared with other detection algorithms, the MB-SMO algorithm was ranked best in terms of the prediction accuracy. The conclusions can provide reference evidence for the development of dangerous situation warning products and the design of intelligent vehicles.

Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm.

PubMed

Cervelli, Manuela; Bellavia, Gabriella; Fratini, Emiliano; Amendola, Roberto; Polticelli, Fabio; Barba, Marco; Federico, Rodolfo; Signore, Fabrizio; Gucciardo, Giacomo; Grillo, Rosalba; Woster, Patrick M; Casero, Robert A; Mariottini, Paolo

2010-10-14

Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO enzyme. BC tissue samples were analyzed for SMO transcript level and SMO activity. Student's t test was applied to evaluate the significance of the differences in value observed in T and NT samples. The structure modeling analysis of BENSpm and CPENSpm complexes formed with the SMO enzyme and their inhibitory activity, assayed by in vitro experiments, were examined. Both the expression level of SMO mRNA and SMO enzyme activity were significantly lower in BC samples compared to NT samples. The modeling of BENSpm and CPENSpm complexes formed with SMO and their inhibition properties showed that both were good inhibitors. This study shows that underexpression of SMO is a negative marker in BC. The SMO induction is a remarkable chemotherapeutical target. The BENSpm and CPENSpm are efficient SMO inhibitors. The inhibition properties shown by these analogues could explain their poor positive outcomes in Phases I and II of clinical trials.

Spermine oxidase (SMO) activity in breast tumor tissues and biochemical analysis of the anticancer spermine analogues BENSpm and CPENSpm

PubMed Central

2010-01-01

Background Polyamine metabolism has a critical role in cell death and proliferation representing a potential target for intervention in breast cancer (BC). This study investigates the expression of spermine oxidase (SMO) and its prognostic significance in BC. Biochemical analysis of Spm analogues BENSpm and CPENSpm, utilized in anticancer therapy, was also carried out to test their property in silico and in vitro on the recombinant SMO enzyme. Methods BC tissue samples were analyzed for SMO transcript level and SMO activity. Student's t test was applied to evaluate the significance of the differences in value observed in T and NT samples. The structure modeling analysis of BENSpm and CPENSpm complexes formed with the SMO enzyme and their inhibitory activity, assayed by in vitro experiments, were examined. Results Both the expression level of SMO mRNA and SMO enzyme activity were significantly lower in BC samples compared to NT samples. The modeling of BENSpm and CPENSpm complexes formed with SMO and their inhibition properties showed that both were good inhibitors. Conclusions This study shows that underexpression of SMO is a negative marker in BC. The SMO induction is a remarkable chemotherapeutical target. The BENSpm and CPENSpm are efficient SMO inhibitors. The inhibition properties shown by these analogues could explain their poor positive outcomes in Phases I and II of clinical trials. PMID:20946629

CFS-SMO based classification of breast density using multiple texture models.

PubMed

Sharma, Vipul; Singh, Sukhwinder

2014-06-01

It is highly acknowledged in the medical profession that density of breast tissue is a major cause for the growth of breast cancer. Increased breast density was found to be linked with an increased risk of breast cancer growth, as high density makes it difficult for radiologists to see an abnormality which leads to false negative results. Therefore, there is need for the development of highly efficient techniques for breast tissue classification based on density. This paper presents a hybrid scheme for classification of fatty and dense mammograms using correlation-based feature selection (CFS) and sequential minimal optimization (SMO). In this work, texture analysis is done on a region of interest selected from the mammogram. Various texture models have been used to quantify the texture of parenchymal patterns of breast. To reduce the dimensionality and to identify the features which differentiate between breast tissue densities, CFS is used. Finally, classification is performed using SMO. The performance is evaluated using 322 images of mini-MIAS database. Highest accuracy of 96.46% is obtained for two-class problem (fatty and dense) using proposed approach. Performance of selected features by CFS is also evaluated by Naïve Bayes, Multilayer Perceptron, RBF Network, J48 and kNN classifier. The proposed CFS-SMO method outperforms all other classifiers giving a sensitivity of 100%. This makes it suitable to be taken as a second opinion in classifying breast tissue density.

METABOLISM OF N-ALKYLATED SPERMINE ANALOGUES BY POLYAMINE AND SPERMINE OXIDASES

PubMed Central

Häkkinen, Merja R.; Hyvönen, Mervi T.; Auriola, Seppo; Casero, Robert A.; Vepsäläinen, Jouko; Khomutov, Alex R.; Alhonen, Leena; Keinänen, Tuomo A.

2010-01-01

SUMMARY N-alkylated polyamine analogues have potential as anticancer and antiparasitic drugs. However, their metabolism in the host has remained incompletely defined thus potentially limiting their utility. Here, we have studied the degradation of three different spermine analogues N,N′-bis-(3-ethylaminopropyl)butane-1,4-diamine (DESPM), N-(3-benzyl-aminopropyl)-N'-(3-ethylaminopropyl)butane-1,4-diamine (BnEtSPM) and N,N′-bis-(3-benzylaminopropyl)butane-1,4-diamine (DBSPM) and related mono-alkylated derivatives as substrates of recombinant human polyamine oxidase (APAO) and spermine oxidase (SMO). APAO and SMO metabolized DESPM to EtSPD (Km(APAO)=10μM, kcat(APAO)=1.1s−1 and Km(SMO)=28μM, kcat(SMO)=0.8s−1, respectively), metabolized BnEtSPM to EtSPD (Km(APAO)=0.9 μM, kcat(APAO)=1.1s−1 and Km(SMO)=51μM, kcat(SMO)=0.4s−1, respectively), and metabolized DBSPM to BnSPD (Km(APAO)=5.4μM, kcat(APAO)= 2.0s−1 and Km(SMO)=33μM, kcat(SMO)=0.3s−1, respectively). Interestingly, mono-alkylated spermine derivatives were metabolized by APAO and SMO to SPD (EtSPM Km(APAO)=16μM, kcat(APAO)=1.5s−1; Km(SMO)=25μM, kcat(SMO) =8.2s−1; BnSPM Km(APAO)=6.0μM, kcat(APAO)=2.8s−1; Km(SMO)=19μM, kcat(SMO)=0.8s−1, respectively). Surprisingly, E t S P D ( Km(APAO)=37μM, kcat(APAO)=0.1s−1; Km(SMO)=48μM, kcat(SMO)=0.05s−1) and BnSPD (Km(APAO)=2.5μM, kcat(APAO)=3.5s−1; Km(SMO)=60μM, kcat(SMO)=0.54s−1) were metabolized to SPD by both the oxidases. Furthermore, we studied the degradation of DESPM, BnEtSPM or DBSPM in the DU145 prostate carcinoma cell line. The same major metabolites EtSPD and/or BnSPD were detected both in the culture medium and intracellularly after 48 hours of culture. Moreover, EtSPM and BnSPM were detected from cell samples. Present data shows that inducible SMO parallel with APAO could play an important role in polyamine based drug action, i.e. degradation of parent drug and its metabolites, having significant impact on efficiency of these drugs, and hence for the development of novel N-alkylated polyamine analogues. PMID:20012116

Electronic structure of SmO and SmO- via slow photoelectron velocity-map imaging spectroscopy and spin-orbit CASPT2 calculations

NASA Astrophysics Data System (ADS)

Weichman, Marissa L.; Vlaisavljevich, Bess; DeVine, Jessalyn A.; Shuman, Nicholas S.; Ard, Shaun G.; Shiozaki, Toru; Neumark, Daniel M.; Viggiano, Albert A.

2017-12-01

The chemi-ionization reaction of atomic samarium, Sm + O → SmO+ + e-, has been investigated by the Air Force Research Laboratory as a means to modify local electron density in the ionosphere for reduction of scintillation of high-frequency radio waves. Neutral SmO is a likely unwanted byproduct. The spectroscopy of SmO is of great interest to aid in interpretation of optical emission spectra recorded following atmospheric releases of Sm as part of the Metal Oxide Space Cloud (MOSC) observations. Here, we report a joint experimental and theoretical study of SmO using slow photoelectron velocity-map imaging spectroscopy of cryogenically cooled SmO- anions (cryo-SEVI) and high-level spin-orbit complete active space calculations with corrections from second order perturbation theory (CASPT2). With cryo-SEVI, we measure the electron affinity of SmO to be 1.0581(11) eV and report electronic and vibrational structure of low-lying electronic states of SmO in good agreement with theory and prior experimental work. We also obtain spectra of higher-lying excited states of SmO for direct comparison to the MOSC results.

SmoXYB1C1Z of Mycobacterium sp. Strain NBB4: a Soluble Methane Monooxygenase (sMMO)-Like Enzyme, Active on C2 to C4 Alkanes and Alkenes

PubMed Central

Martin, Kiri E.; Ozsvar, Jazmin

2014-01-01

Monooxygenase (MO) enzymes initiate the aerobic oxidation of alkanes and alkenes in bacteria. A cluster of MO genes (smoXYB1C1Z) of thus-far-unknown function was found previously in the genomes of two Mycobacterium strains (NBB3 and NBB4) which grow on hydrocarbons. The predicted Smo enzymes have only moderate amino acid identity (30 to 60%) to their closest homologs, the soluble methane and butane MOs (sMMO and sBMO), and the smo gene cluster has a different organization from those of sMMO and sBMO. The smoXYB1C1Z genes of NBB4 were cloned into pMycoFos to make pSmo, which was transformed into Mycobacterium smegmatis mc2-155. Cells of mc2-155(pSmo) metabolized C2 to C4 alkanes, alkenes, and chlorinated hydrocarbons. The activities of mc2-155(pSmo) cells were 0.94, 0.57, 0.12, and 0.04 nmol/min/mg of protein with ethene, ethane, propane, and butane as substrates, respectively. The mc2-155(pSmo) cells made epoxides from ethene, propene, and 1-butene, confirming that Smo was an oxygenase. Epoxides were not produced from larger alkenes (1-octene and styrene). Vinyl chloride and 1,2-dichloroethane were biodegraded by cells expressing Smo, with production of inorganic chloride. This study shows that Smo is a functional oxygenase which is active against small hydrocarbons. M. smegmatis mc2-155(pSmo) provides a new model for studying sMMO-like monooxygenases. PMID:25015887

Evaluation of Semi-supervised Learning for Classification of Protein Crystallization Imagery.

PubMed

Sigdel, Madhav; Dinç, İmren; Dinç, Semih; Sigdel, Madhu S; Pusey, Marc L; Aygün, Ramazan S

2014-03-01

In this paper, we investigate the performance of two wrapper methods for semi-supervised learning algorithms for classification of protein crystallization images with limited labeled images. Firstly, we evaluate the performance of semi-supervised approach using self-training with naïve Bayesian (NB) and sequential minimum optimization (SMO) as the base classifiers. The confidence values returned by these classifiers are used to select high confident predictions to be used for self-training. Secondly, we analyze the performance of Yet Another Two Stage Idea (YATSI) semi-supervised learning using NB, SMO, multilayer perceptron (MLP), J48 and random forest (RF) classifiers. These results are compared with the basic supervised learning using the same training sets. We perform our experiments on a dataset consisting of 2250 protein crystallization images for different proportions of training and test data. Our results indicate that NB and SMO using both self-training and YATSI semi-supervised approaches improve accuracies with respect to supervised learning. On the other hand, MLP, J48 and RF perform better using basic supervised learning. Overall, random forest classifier yields the best accuracy with supervised learning for our dataset.

Plant sterol biosynthesis: identification of two distinct families of sterol 4alpha-methyl oxidases.

PubMed Central

Darnet, Sylvain; Rahier, Alain

2004-01-01

In plants, the conversion of cycloartenol into functional phytosterols requires the removal of the two methyl groups at C-4 by an enzymic complex including a sterol 4alpha-methyl oxidase (SMO). We report the cloning of candidate genes for SMOs in Arabidopsis thaliana, belonging to two distinct families termed SMO1 and SMO2 and containing three and two isoforms respectively. SMO1 and SMO2 shared low sequence identity with each other and were orthologous to the ERG25 gene from Saccharomyces cerevisiae which encodes the SMO. The plant SMO amino acid sequences possess all the three histidine-rich motifs (HX3H, HX2HH and HX2HH), characteristic of the small family of membrane-bound non-haem iron oxygenases that are involved in lipid oxidation. To elucidate the precise functions of SMO1 and SMO2 gene families, we have reduced their expression by using a VIGS (virus-induced gene silencing) approach in Nicotiana benthamiana. SMO1 and SMO2 cDNA fragments were inserted into a viral vector and N. benthamiana inoculated with the viral transcripts. After silencing with SMO1, a substantial accumulation of 4,4-dimethyl-9beta,19-cyclopropylsterols (i.e. 24-methylenecycloartanol) was obtained, whereas qualitative and quantitative levels of 4alpha-methylsterols were not affected. In the case of silencing with SMO2, a large accumulation of 4alpha-methyl-Delta7-sterols (i.e. 24-ethylidenelophenol and 24-ethyllophenol) was found, with no change in the levels of 4,4-dimethylsterols. These clear and distinct biochemical phenotypes demonstrate that, in contrast with animals and fungi, in photosynthetic eukaryotes, these two novel families of cDNAs are coding two distinct types of C-4-methylsterol oxidases controlling the level of 4,4-dimethylsterol and 4alpha-methylsterol precursors respectively. PMID:14653780

Structural basis for Smoothened receptor modulation and chemoresistance to anti-cancer drugs

PubMed Central

Wang, Chong; Wu, Huixian; Evron, Tama; Vardy, Eyal; Han, Gye Won; Huang, Xi-Ping; Hufeisen, Sandy J.; Mangano, Thomas J.; Urban, Dan J.; Katritch, Vsevolod; Cherezov, Vadim; Caron, Marc G.; Roth, Bryan L.; Stevens, Raymond C.

2014-01-01

The Smoothened receptor (SMO) mediates signal transduction in the hedgehog pathway, which is implicated in normal development and carcinogenesis. SMO antagonists can suppress the growth of some tumors; however, mutations at SMO have been found to abolish their anti-tumor effects, a phenomenon known as chemoresistance. Here we report three crystal structures of human SMO bound to the antagonists SANT1 and Anta XV, and the agonist, SAG1.5, at 2.6–2.8Å resolution. The long and narrow cavity in the transmembrane domain of SMO harbors multiple ligand binding sites, where SANT1 binds at a deeper site as compared with other ligands. Distinct interactions at D4736.55 elucidated the structural basis for the differential effects of chemoresistance mutations on SMO antagonists. The agonist SAG1.5 induces a conformational rearrangement of the binding pocket residues, which could contribute to SMO activation. Collectively, these studies reveal the structural basis for the modulation of SMO by small molecules. PMID:25008467

PI(4)P Promotes Phosphorylation and Conformational Change of Smoothened through Interaction with Its C-terminal Tail

PubMed Central

Zhang, Jie; Li, Xiang-An; Evers, B. Mark; Zhu, Haining; Jia, Jianhang

2016-01-01

In Hedgehog (Hh) signaling, binding of Hh to the Patched-Interference Hh (Ptc-Ihog) receptor complex relieves Ptc inhibition on Smoothened (Smo). A longstanding question is how Ptc inhibits Smo and how such inhibition is relieved by Hh stimulation. In this study, we found that Hh elevates production of phosphatidylinositol 4-phosphate (PI(4)P). Increased levels of PI(4)P promote, whereas decreased levels of PI(4)P inhibit, Hh signaling activity. We further found that PI(4)P directly binds Smo through an arginine motif, which then triggers Smo phosphorylation and activation. Moreover, we identified the pleckstrin homology (PH) domain of G protein-coupled receptor kinase 2 (Gprk2) as an essential component for enriching PI(4)P and facilitating Smo activation. PI(4)P also binds mouse Smo (mSmo) and promotes its phosphorylation and ciliary accumulation. Finally, Hh treatment increases the interaction between Smo and PI(4)P but decreases the interaction between Ptc and PI(4)P, indicating that, in addition to promoting PI(4)P production, Hh regulates the pool of PI(4)P associated with Ptc and Smo. PMID:26863604

Antineoplastic Efficacy of Novel Polyamine Analogues in Human Breast Cancer

DTIC Science & Technology

2006-06-01

Davidson, N.E., and Casero, R.A.. Spermine oxidase SMO(PAOh1), not N1-acetylpolyamine oxidase (PAO) is the primary source of cytotoxic H2O2 in...human spermine oxidase SMO(PAOh1). SMO(PAOh1) uses unacetylated spermine as substrate and is inducible by specific polyamine analogs [15,16]. These...technique to find the identical clone termed spermine oxidase (SMO) [16]. The function of SMO(PAOh1) as a spermine oxidase has been confirmed [15,67,68

Pharmacodynamic interactions of a solid formulation of sodium oxybate and ethanol in healthy volunteers

PubMed Central

Pross, Nathalie; Patat, Alain; Vivet, Philippe; Bidaut, Michelle; Fauchoux, Nicolas

2015-01-01

Aim The pharmacologic effects of sodium oxybate (SO) have a number of similarities with those of alcohol. This study evaluated the pharmacodynamic interaction of SMO.IR (a solid immediate release formulation of SO) and alcohol (0.7 (males) or 0.57 (females) g kg–1 alcohol using 40% vodka). Methods In a randomized, double-blind, double-dummy, crossover trial, 24 healthy volunteers received randomly a) 2.25 g SMO.IR and placebo alcohol preparation, b) 2.25 g f SMO.IR and alcohol, c) 2.25 g SMO.IR matching placebo and alcohol and d) 2.25 g of SMO.IR matching placebo and placebo alcohol preparation. Objective and subjective cognitive parameters, adverse events and vital signs were assessed before, 15 and 165 min after treatment administration. Results Alcohol produced the expected cognitive impairment and the expected subjective sedation rapidly after intake (from 15 min). The objective effects of SMO.IR were much less pronounced than those of alcohol. The reverse was observed for subjective complaints, which were related to lesser stimulation and greater sedation. Nevertheless, 165 min after administration this sedation feeling was less with SMO.IR than with alcohol. There was a significant interaction between SMO.IR and alcohol at 15 min (i.e. increase in alertness and stimulation and decrease in sedation). In addition, an isolated mild decrease in digit vigilance accuracy occurred at 165 min post-dose after the combination. The co-administration of SMO.IR and alcohol was safe and well-tolerated. Conclusion SMO.IR and alcohol have distinct adverse effect profiles. The objective effects of SMO.IR are much less marked than those of alcohol. No deleterious interaction was observed. PMID:25782469

Evaluation of Semi-supervised Learning for Classification of Protein Crystallization Imagery

PubMed Central

Sigdel, Madhav; Dinç, İmren; Dinç, Semih; Sigdel, Madhu S.; Pusey, Marc L.; Aygün, Ramazan S.

2015-01-01

In this paper, we investigate the performance of two wrapper methods for semi-supervised learning algorithms for classification of protein crystallization images with limited labeled images. Firstly, we evaluate the performance of semi-supervised approach using self-training with naïve Bayesian (NB) and sequential minimum optimization (SMO) as the base classifiers. The confidence values returned by these classifiers are used to select high confident predictions to be used for self-training. Secondly, we analyze the performance of Yet Another Two Stage Idea (YATSI) semi-supervised learning using NB, SMO, multilayer perceptron (MLP), J48 and random forest (RF) classifiers. These results are compared with the basic supervised learning using the same training sets. We perform our experiments on a dataset consisting of 2250 protein crystallization images for different proportions of training and test data. Our results indicate that NB and SMO using both self-training and YATSI semi-supervised approaches improve accuracies with respect to supervised learning. On the other hand, MLP, J48 and RF perform better using basic supervised learning. Overall, random forest classifier yields the best accuracy with supervised learning for our dataset. PMID:25914518

Discovery of novel hedgehog antagonists from cell-based screening: Isosteric modification of p38 bisamides as potent inhibitors of SMO.

PubMed

Yang, Bin; Hird, Alexander W; Russell, Daniel John; Fauber, Benjamin P; Dakin, Les A; Zheng, Xiaolan; Su, Qibin; Godin, Robert; Brassil, Patrick; Devereaux, Erik; Janetka, James W

2012-07-15

Cell-based subset screening of compounds using a Gli transcription factor reporter cell assay and shh stimulated cell differentiation assay identified a series of bisamide compounds as hedgehog pathway inhibitors with good potency. Using a ligand-based optimization strategy, heteroaryl groups were utilized as conformationally restricted amide isosteres replacing one of the amides which significantly increased their potency against SMO and the hedgehog pathway while decreasing activity against p38α kinase. We report herein the identification of advanced lead compounds such as imidazole 11c and 11f encompassing good p38α selectivity, low nanomolar potency in both cell assays, excellent physiochemical properties and in vivo pharmacokinetics. Copyright © 2012 Elsevier Ltd. All rights reserved.

Electrical comparison of iN7 EUV hybrid and EUV single patterning BEOL metal layers

NASA Astrophysics Data System (ADS)

Larivière, Stéphane; Wilson, Christopher J.; Kutrzeba Kotowska, Bogumila; Versluijs, Janko; Decoster, Stefan; Mao, Ming; van der Veen, Marleen H.; Jourdan, Nicolas; El-Mekki, Zaid; Heylen, Nancy; Kesters, Els; Verdonck, Patrick; Béral, Christophe; Van den Heuvel, Dieter; De Bisschop, Peter; Bekaert, Joost; Blanco, Victor; Ciofi, Ivan; Wan, Danny; Briggs, Basoene; Mallik, Arindam; Hendrickx, Eric; Kim, Ryoung-han; McIntyre, Greg; Ronse, Kurt; Bömmels, Jürgen; Tőkei, Zsolt; Mocuta, Dan

2018-03-01

The semiconductor scaling roadmap shows the continuous node to node scaling to push Moore's law down to the next generations. In that context, the foundry N5 node requires 32nm metal pitch interconnects for the advanced logic Back- End of Line (BEoL). 193immersion usage now requires self-aligned and/or multiple patterning technique combinations to enable such critical dimension. On the other hand, EUV insertion investigation shows that 32nm metal pitch is still a challenge but, related to process flow complexity, presents some clear motivations. Imec has already evaluated on test chip vehicles with different patterning approaches: 193i SAQP (Self-Aligned Quadruple Patterning), LE3 (triple patterning Litho Etch), tone inversion, EUV SE (Single Exposure) with SMO (Source-mask optimization). Following the run path in the technology development for EUV insertion, imec N7 platform (iN7, corresponding node to the foundry N5) is developed for those BEoL layers. In this paper, following technical motivation and development learning, a comparison between the iArF SAQP/EUV block hybrid integration scheme and a single patterning EUV flow is proposed. These two integration patterning options will be finally compared from current morphological and electrical criteria.

Dielectric tunability of vertically aligned ferroelectric-metal oxide nanocomposite films controlled by out-of-plane misfit strain

NASA Astrophysics Data System (ADS)

Wu, Huaping; Ma, Xuefu; Zhang, Zheng; Zhu, Jun; Wang, Jie; Chai, Guozhong

2016-04-01

A nonlinear thermodynamic model based on the vertically aligned nanocomposite (VAN) thin films of ferroelectric-metal oxide system has been developed to investigate the physical properties of the epitaxial Ba0.6Sr0.4TiO3 (BST) films containing vertical Sm2O3 (SmO) nanopillar arrays on the SrTiO3 substrate. The phase diagrams of out-of-plane lattice mismatch vs. volume fraction of SmO are calculated by minimizing the total free energy. It is found that the phase transformation and dielectric response of BST-SmO VAN systems are extremely dependent on the in-plane misfit strain, the out-of-plane lattice mismatch, the volume fraction of SmO phase, and the external electric field applied to the nanocomposite films at room temperature. In particular, the BST-SmO VAN systems exhibit higher dielectric properties than pure BST films. Giant dielectric response and maximum tunability are obtained near the lattice mismatch where the phase transition occurs. Under the in-plane misfit strain of umf=0.3 % and the out-of-plane lattice mismatch of u3=0.002 , the dielectric tunability can be dramatically enhanced to 90% with the increase of SmO volume fraction, which is well consistent with previous experimental results. This work represents an approach to further understand the dependence of physical properties on the lattice mismatch (in-plane and out-of-plane) and volume fraction, and to manipulate or optimize functionalities in the nanocomposite oxide thin films.

Hydrogen Gas Sensors Based on Semiconductor Oxide Nanostructures

PubMed Central

Gu, Haoshuang; Wang, Zhao; Hu, Yongming

2012-01-01

Recently, the hydrogen gas sensing properties of semiconductor oxide (SMO) nanostructures have been widely investigated. In this article, we provide a comprehensive review of the research progress in the last five years concerning hydrogen gas sensors based on SMO thin film and one-dimensional (1D) nanostructures. The hydrogen sensing mechanism of SMO nanostructures and some critical issues are discussed. Doping, noble metal-decoration, heterojunctions and size reduction have been investigated and proved to be effective methods for improving the sensing performance of SMO thin films and 1D nanostructures. The effect on the hydrogen response of SMO thin films and 1D nanostructures of grain boundary and crystal orientation, as well as the sensor architecture, including electrode size and nanojunctions have also been studied. Finally, we also discuss some challenges for the future applications of SMO nanostructured hydrogen sensors. PMID:22778599

Constitutive Activation of Smoothened in the Renal Collecting Ducts Leads to Renal Hypoplasia, Hydronephrosis, and Hydroureter.

PubMed

Gupta, Deepak Prasad; Hwang, Jae-Won; Cho, Eui-Sic; Kim, Won; Song, Chang Ho; Chai, Ok Hee

2017-01-01

Sonic Hedgehog (Shh) signaling plays a major role in and is essential for regulation, patterning, and proliferation during renal development. Smoothened (Smo) plays a pivot role in transducing the Shh-glioma-associated oncogene Kruppel family member. However, the cellular and molecular mechanism underlying the role of sustained Smo activation in postnatal kidney development is still not clearly understood. Using a conditional knockin mouse model that expresses a constitutively activated form of Smo (SmoM2) upon Homeobox-B7-mediated recombination (Hoxb7-Cre), the effects of Shh signaling were determined in postnatal kidney development. SmoM2;Hoxb7-Cre mutant mice showed growth retardation with a reduction of body weight. Constitutive activation of Smo in the renal collecting ducts caused renal hypoplasia, hydronephrosis, and hydroureter. The parenchymal area and glomerular numbers were reduced, but the glomerular density was increased in SmoM2;Hoxb7-Cre mutant mice. The expression of Patched 1, the receptor of Shh and a downstream target gene of the Shh signaling pathway, was highly restricted and it was upregulated in the inner medullary collecting ducts of the kidney. The proliferative cells in the mesenchyme and collecting ducts were decreased in SmoM2;Hoxb7-Cre mutant mice. This study showed for the first time that sustained Smo inhibits postnatal kidney development by suppressing the proliferation of the mesenchyme and medullary collecting ducts in mice. © 2017 S. Karger AG, Basel.

DYRK1B as therapeutic target in Hedgehog/GLI-dependent cancer cells with Smoothened inhibitor resistance

PubMed Central

Gruber, Wolfgang; Hutzinger, Martin; Elmer, Dominik Patrick; Parigger, Thomas; Sternberg, Christina; Cegielkowski, Lukasz; Zaja, Mirko; Leban, Johann; Michel, Susanne; Hamm, Svetlana; Vitt, Daniel; Aberger, Fritz

2016-01-01

A wide range of human malignancies displays aberrant activation of Hedgehog (HH)/GLI signaling, including cancers of the skin, brain, gastrointestinal tract and hematopoietic system. Targeting oncogenic HH/GLI signaling with small molecule inhibitors of the essential pathway effector Smoothened (SMO) has shown remarkable therapeutic effects in patients with advanced and metastatic basal cell carcinoma. However, acquired and de novo resistance to SMO inhibitors poses severe limitations to the use of SMO antagonists and urgently calls for the identification of novel targets and compounds. Here we report on the identification of the Dual-Specificity-Tyrosine-Phosphorylation-Regulated Kinase 1B (DYRK1B) as critical positive regulator of HH/GLI signaling downstream of SMO. Genetic and chemical inhibition of DYRK1B in human and mouse cancer cells resulted in marked repression of HH signaling and GLI1 expression, respectively. Importantly, DYRK1B inhibition profoundly impaired GLI1 expression in both SMO-inhibitor sensitive and resistant settings. We further introduce a novel small molecule DYRK1B inhibitor, DYRKi, with suitable pharmacologic properties to impair SMO-dependent and SMO-independent oncogenic GLI activity. The results support the use of DYRK1B antagonists for the treatment of HH/GLI-associated cancers where SMO inhibitors fail to demonstrate therapeutic efficacy. PMID:26784250

Design intent optimization at the beyond 7nm node: the intersection of DTCO and EUVL stochastic mitigation techniques

NASA Astrophysics Data System (ADS)

Crouse, Michael; Liebmann, Lars; Plachecki, Vince; Salama, Mohamed; Chen, Yulu; Saulnier, Nicole; Dunn, Derren; Matthew, Itty; Hsu, Stephen; Gronlund, Keith; Goodwin, Francis

2017-03-01

The initial readiness of EUV patterning was demonstrated in 2016 with IBM Alliance's 7nm device technology. The focus has now shifted to driving the 'effective' k1 factor and enabling the second generation of EUV patterning. Thus, Design Technology Co-optimization (DTCO) has become a critical part of technology enablement as scaling has become more challenging and the industry pushes the limits of EUV lithography. The working partnership between the design teams and the process development teams typically involves an iterative approach to evaluate the manufacturability of proposed designs, subsequent modifications to those designs and finally a design manual for the technology. While this approach has served the industry well for many generations, the challenges at the Beyond 7nm node require a more efficient approach. In this work, we describe the use of "Design Intent" lithographic layout optimization where we remove the iterative component of DTCO and replace it with an optimization that achieves both a "patterning friendly" design and minimizes the well-known EUV stochastic effects. Solved together, this "design intent" approach can more quickly achieve superior lithographic results while still meeting the original device's functional specifications. Specifically, in this work we will demonstrate "design intent" optimization for critical BEOL layers using design tolerance bands to guide the source mask co-optimization. The design tolerance bands can be either supplied as part of the original design or derived from some basic rules. Additionally, the EUV stochastic behavior is mitigated by enhancing the image log slope (ILS) for specific key features as part of the overall optimization. We will show the benefit of the "design intent approach" on both bidirectional and unidirectional 28nm min pitch standard logic layouts and compare the more typical iterative SMO approach. Thus demonstrating the benefit of allowing the design to float within the specified range. Lastly, we discuss how the evolution of this approach could lead to layout optimization based entirely on some minimal set of functional requirements and process constraints.

Inhibition of polyamine and spermine oxidases by polyamine analogues.

PubMed

Bianchi, Marzia; Polticelli, Fabio; Ascenzi, Paolo; Botta, Maurizio; Federico, Rodolfo; Mariottini, Paolo; Cona, Alessandra

2006-03-01

Polyamine oxidase (PAO) and spermine oxidase (SMO) are involved in the catabolism of polyamines--basic regulators of cell growth and proliferation. The discovery of selective inhibitors of PAO and SMO represents an important tool in studying the involvement of these enzymes in polyamine homeostasis and a starting point for the development of novel antineoplastic drugs. Here, a comparative study on murine PAO (mPAO) and SMO (mSMO) inhibition by the polyamine analogues 1,8-diaminooctane, 1,12-diaminododecane, N-prenylagmatine (G3), guazatine and N,N1-bis(2,3-butadienyl)-1,4-butanediamine (MDL72527) is reported. Interestingly, 1,12-Diaminododecane and G3 behave as specific inhibitors of mPAO, values of K(i) for mPAO inhibition being lower than those for mSMO inactivation by several orders of magnitude. The analysis of molecular models of mPAO and mSMO indicates a significant reduction of the hydrophobic pocket located in maize PAO (MPAO) at the wider catalytic tunnel opening. This observation provides a rationale to explain the lower affinity displayed by G3, guazatine and MDL72527 for mPAO and mSMO as compared to MPAO. The different behaviour displayed by 1,12-diaminododecane towards mPAO and mSMO reveals the occurrence of basic differences in the ligand binding mode of the two enzymes, the first enzyme interacting mainly with substrate secondary amino groups and the second one with substrate primary amino groups. Thus, the data reported here provide the basis for the development of novel and selective inhibitors able to discriminate between mammalian SMO and PAO activities.

The intrahepatic signalling niche of hedgehog is defined by primary cilia positive cells during chronic liver injury.

PubMed

Grzelak, Candice Alexandra; Martelotto, Luciano Gastón; Sigglekow, Nicholas David; Patkunanathan, Bramilla; Ajami, Katerina; Calabro, Sarah Ruth; Dwyer, Benjamin James; Tirnitz-Parker, Janina Elke Eleonore; Watkins, D Neil; Warner, Fiona Jane; Shackel, Nicholas Adam; McCaughan, Geoffrey William

2014-01-01

In vertebrates, canonical Hedgehog (Hh) pathway activation requires Smoothened (SMO) translocation to the primary cilium (Pc), followed by a GLI-mediated transcriptional response. In addition, a similar gene regulation occurs in response to growth factors/cytokines, although independently of SMO signalling. The Hh pathway plays a critical role in liver fibrosis/regeneration, however, the mechanism of activation in chronic liver injury is poorly understood. This study aimed to characterise Hh pathway activation upon thioacetamide (TAA)-induced chronic liver injury in vivo by defining Hh-responsive cells, namely cells harbouring Pc and Pc-localised SMO. C57BL/6 mice (wild-type or Ptc1(+/-)) were TAA-treated. Liver injury and Hh ligand/pathway mRNA and protein expression were assessed in vivo. SMO/GLI manipulation and SMO-dependent/independent activation of GLI-mediated transcriptional response in Pc-positive (Pc(+)) cells were studied in vitro. In vivo, Hh activation was progressively induced following TAA. At the epithelial-mesenchymal interface, injured hepatocytes produced Hh ligands. Progenitors, myofibroblasts, leukocytes and hepatocytes were GLI2(+). Pc(+) cells increased following TAA, but only EpCAM(+)/GLI2(+) progenitors were Pc(+)/SMO(+). In vitro, SMO knockdown/hGli3-R overexpression reduced proliferation/viability in Pc(+) progenitors, whilst increased proliferation occurred with hGli1 overexpression. HGF induced GLI transcriptional activity independently of Pc/SMO. Ptc1(+/-) mice exhibited increased progenitor, myofibroblast and fibrosis responses. In chronic liver injury, Pc(+) progenitors receive Hh ligand signals and process it through Pc/SMO-dependent activation of GLI-mediated transcriptional response. Pc/SMO-independent GLI activation likely occurs in Pc(-)/GLI2(+) cells. Increased fibrosis in Hh gain-of-function mice likely occurs by primary progenitor expansion/proliferation and secondary fibrotic myofibroblast expansion, in close contact with progenitors. Copyright © 2013 European Association for the Study of the Liver. All rights reserved.

Best Matching Protein Conformations and Docking Programs for a Virtual Screening Campaign Against SMO Receptor.

PubMed

Amendola, Giorgio; Di Maio, Danilo; La Pietra, Valeria; Cosconati, Sandro

2016-09-01

SMO receptor is one of the main components of the Hedgehog biochemical pathway. In the last decades compelling body of evidence demonstrated that this receptor is a pertinent target for the treatment of various types of solid tumors. Recently, the X-ray determination of the three-dimensional structure of SMO in complex with different antagonists opened up the way for the structure-based design of new antagonists for this receptor that could possibly overcome the limitations connected with the induction of acquired tumor resistance. Herein, taking advantage of three different docking software (namely Glide, PLANTS, and Vina) and of the available SMO structures we set up a retrospective virtual screening (VS) protocol. A database, made up by known SMO antagonists and compounds with no alleged activity against the receptor was created and screened against the different SMO structures. To evaluate the performance of the ranking in VS calculations different statistical metrics (EF, AUAC and BEDROC) were employed allowing to identify the best performing VS docking protocol. Results of these studies will serve as a platform for the application of structure-based VS against the pharmaceutically relevant SMO receptor. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Induction of human spermine oxidase SMO(PAOh1) is regulated at the levels of new mRNA synthesis, mRNA stabilization and newly synthesized protein

PubMed Central

2004-01-01

The oxidation of polyamines induced by antitumour polyamine analogues has been associated with tumour response to specific agents. The human spermine oxidase, SMO(PAOh1), is one enzyme that may play a direct role in the cellular response to the antitumour polyamine analogues. In the present study, the induction of SMO(PAOh1) enzyme activity by CPENSpm [N1-ethyl-N11-(cyclopropyl)methyl-4,8,diazaundecane] is demonstrated to be a result of newly synthesized mRNA and protein. Inhibition of new RNA synthesis by actinomycin D inhibits both the appearance of SMO(PAOh1) mRNA and enzyme activity. Similarly, inhibition of newly synthesized protein with cycloheximide prevents analogue-induced enzyme activity. Half-life determinations indicate that stabilization of SMO(PAOh1) protein does not play a significant role in analogue-induced activity. However, half-life experiments using actinomycin D indicate that CPENSpm treatment not only increases mRNA expression, but also leads to a significant increase in mRNA half-life (17.1 and 8.8 h for CPENSpm-treated cells and control respectively). Using reporter constructs encompassing the SMO(PAOh1) promoter region, a 30–90% increase in transcription is observed after exposure to CPENSpm. The present results are consistent with the hypothesis that analogue-induced expression of SMO(PAOh1) is a result of increased transcription and stabilization of SMO(PAOh1) mRNA, leading to increased protein production and enzyme activity. These data indicate that the major level of control of SMO(PAOh1) expression in response to polyamine analogues exposure is at the level of mRNA. PMID:15496143

Spermine oxidase, a polyamine catabolic enzyme that links Helicobacter pylori CagA and gastric cancer risk

PubMed Central

Chaturvedi, Rupesh; de Sablet, Thibaut; Peek, Richard M.; Wilson, Keith T.

2012-01-01

We have recently reported that Helicobacter pylori strains expressing the virulence factor cytotoxin-associated gene A (CagA) stimulate increased levels of spermine oxidase (SMO) in gastric epithelial cells, while cagA– strains did not. SMO catabolizes the polyamine spermine and produces H2O2 that results in both apoptosis and DNA damage. Exogenous overexpression of CagA confirmed these findings, and knockdown or inhibition of SMO blocked CagA-mediated apoptosis and DNA damage. The strong association of SMO, apoptosis, and DNA damage was also demonstrated in humans infected with cagA+, but not cagA– strains. In infected gerbils and mice, DNA damage was CagA-dependent and only present in epithelial cells that expressed SMO. We also discovered SMOhigh gastric epithelial cells from infected animals with dysplasia that are resistant to apoptosis despite high levels of DNA damage. Inhibition of polyamine synthesis or SMO could abrogate the development of this cell population that may represent precursors for neoplastic transformation. PMID:22555547

Subcellular Localization of Patched and Smoothened, the Receptors for Sonic Hedgehog Signaling, in the Hippocampal Neuron

PubMed Central

Petralia, Ronald S.; Schwartz, Catherine M.; Wang, Ya-Xian; Mattson, Mark P.; Yao, Pamela J.

2011-01-01

Cumulative evidence suggests that, aside from patterning the embryonic neural tube, Sonic hedgehog (Shh) signaling plays important roles in the mature nervous system. In this study, we investigate the expression and localization of the Shh signaling receptors, Patched (Ptch) and Smoothened (Smo), in the hippocampal neurons of young and mature rats. Reverse transcriptase-polymerase chain reaction and immunoblotting analyses show that the expression of Ptch and Smo remains at a moderate level in young postnatal and adult brains. By using immunofluorescence light microscopy and immunoelectron microscopy, we examine the spatial distribution of Ptch and Smo within the hippocampal neurons. In young developing neurons, Ptch and Smo are present in the processes and are clustered at their growth cones. In mature neurons, Ptch and Smo are concentrated in dendrites, spines, and postsynaptic sites. Synaptic Ptch and Smo often co-exist with unusual structures—synaptic spinules and autophagosomes. Our results reveal the anatomical organization of the Shh receptors within both the young and the mature hippocampal neurons. PMID:21618238

CoSMoS Unravels Mysteries of Transcription Initiation

PubMed Central

Gourse, Richard L.; Landick, Robert

2013-01-01

Using a fluorescence method called colocalization single-molecule spectroscopy (CoSMoS), Friedman and Gelles dissect the kinetics of transcription initiation at a bacterial promoter. Ultimately, CoSMoS could greatly aid the study of the effects of DNA sequence and transcription factors on both prokaryotic and eukaryotic promoters. PMID:22341438

Pixel-based OPC optimization based on conjugate gradients.

PubMed

Ma, Xu; Arce, Gonzalo R

2011-01-31

Optical proximity correction (OPC) methods are resolution enhancement techniques (RET) used extensively in the semiconductor industry to improve the resolution and pattern fidelity of optical lithography. In pixel-based OPC (PBOPC), the mask is divided into small pixels, each of which is modified during the optimization process. Two critical issues in PBOPC are the required computational complexity of the optimization process, and the manufacturability of the optimized mask. Most current OPC optimization methods apply the steepest descent (SD) algorithm to improve image fidelity augmented by regularization penalties to reduce the complexity of the mask. Although simple to implement, the SD algorithm converges slowly. The existing regularization penalties, however, fall short in meeting the mask rule check (MRC) requirements often used in semiconductor manufacturing. This paper focuses on developing OPC optimization algorithms based on the conjugate gradient (CG) method which exhibits much faster convergence than the SD algorithm. The imaging formation process is represented by the Fourier series expansion model which approximates the partially coherent system as a sum of coherent systems. In order to obtain more desirable manufacturability properties of the mask pattern, a MRC penalty is proposed to enlarge the linear size of the sub-resolution assistant features (SRAFs), as well as the distances between the SRAFs and the main body of the mask. Finally, a projection method is developed to further reduce the complexity of the optimized mask pattern.

Modeling OPC complexity for design for manufacturability

NASA Astrophysics Data System (ADS)

Gupta, Puneet; Kahng, Andrew B.; Muddu, Swamy; Nakagawa, Sam; Park, Chul-Hong

2005-11-01

Increasing design complexity in sub-90nm designs results in increased mask complexity and cost. Resolution enhancement techniques (RET) such as assist feature addition, phase shifting (attenuated PSM) and aggressive optical proximity correction (OPC) help in preserving feature fidelity in silicon but increase mask complexity and cost. Data volume increase with rise in mask complexity is becoming prohibitive for manufacturing. Mask cost is determined by mask write time and mask inspection time, which are directly related to the complexity of features printed on the mask. Aggressive RET increase complexity by adding assist features and by modifying existing features. Passing design intent to OPC has been identified as a solution for reducing mask complexity and cost in several recent works. The goal of design-aware OPC is to relax OPC tolerances of layout features to minimize mask cost, without sacrificing parametric yield. To convey optimal OPC tolerances for manufacturing, design optimization should drive OPC tolerance optimization using models of mask cost for devices and wires. Design optimization should be aware of impact of OPC correction levels on mask cost and performance of the design. This work introduces mask cost characterization (MCC) that quantifies OPC complexity, measured in terms of fracture count of the mask, for different OPC tolerances. MCC with different OPC tolerances is a critical step in linking design and manufacturing. In this paper, we present a MCC methodology that provides models of fracture count of standard cells and wire patterns for use in design optimization. MCC cannot be performed by designers as they do not have access to foundry OPC recipes and RET tools. To build a fracture count model, we perform OPC and fracturing on a limited set of standard cells and wire configurations with all tolerance combinations. Separately, we identify the characteristics of the layout that impact fracture count. Based on the fracture count (FC) data from OPC and mask data preparation runs, we build models of FC as function of OPC tolerances and layout parameters.

Changes in ankle joint motion after Supramalleolar osteotomy: a cadaveric model.

PubMed

Kim, Hak Jun; Yeo, Eui Dong; Rhyu, Im Joo; Lee, Soon-Hyuck; Lee, Yeon Soo; Lee, Young Koo

2017-09-09

Malalignment of the ankle joint has been found after trauma, by neurological disorders, genetic predisposition and other unidentified factors, and results in asymmetrical joint loading. For a medial open wedge supramalleolar osteotomy(SMO), there are some debates as to whether concurrent fibular osteotomy should be performed. We assessed the changes in motion of ankle joint and plantar pressure after supramalleolar osteotomy without fibular osteotomy. Ten lower leg specimens below the knee were prepared from fresh-frozen human cadavers. They were harvested from five males (10 ankles)whose average age was 70 years. We assessed the motion of ankle joint as well as plantar pressure for SS(supra-syndesmotic) SMO and IS(intra-syndesmotic) SMO. After the osteotomy, each specimen was subjected to axial compression from 20 N preload to 350 N representing half-body weight. For the measurement of the motion of ankle joint, the changes in gap and point, angles in ankle joint were measured. The plantar pressure were also recorded using TekScan sensors. The changes in the various gap, point, and angles movements on SS-SMO and IS-SMO showed no statistically significant differences between the two groups. Regarding the shift of plantar center of force (COF) were noted in the anterolateral direction, but not statistically significant. SS-SMO and IS-SMO with intact fibula showed similar biomechanical effect on the ankle joint. We propose that IS-SMO should be considered carefully for the treatment of osteoarthrosis when fibular osteotomy is not performed because lateral cortex fracture was less likely using the intrasyndesmosis plane because of soft tissue support.

Subcellular localization of Patched and Smoothened, the receptors for Sonic hedgehog signaling, in the hippocampal neuron.

PubMed

Petralia, Ronald S; Schwartz, Catherine M; Wang, Ya-Xian; Mattson, Mark P; Yao, Pamela J

2011-12-15

Cumulative evidence suggests that, aside from patterning the embryonic neural tube, Sonic hedgehog (Shh) signaling plays important roles in the mature nervous system. In this study, we investigate the expression and localization of the Shh signaling receptors, Patched (Ptch) and Smoothened (Smo), in the hippocampal neurons of young and mature rats. Reverse transcriptase-polymerase chain reaction and immunoblotting analyses show that the expression of Ptch and Smo remains at a moderate level in young postnatal and adult brains. By using immunofluorescence light microscopy and immunoelectron microscopy, we examine the spatial distribution of Ptch and Smo within the hippocampal neurons. In young developing neurons, Ptch and Smo are present in the processes and are clustered at their growth cones. In mature neurons, Ptch and Smo are concentrated in dendrites, spines, and postsynaptic sites. Synaptic Ptch and Smo often co-exist with unusual structures-synaptic spinules and autophagosomes. Our results reveal the anatomical organization of the Shh receptors within both the young and the mature hippocampal neurons. Copyright © 2011 Wiley-Liss, Inc.

Silybum marianum oil attenuates oxidative stress and ameliorates mitochondrial dysfunction in mice treated with D-galactose

PubMed Central

Zhu, Shu Yun; Dong, Ying; Tu, Jie; Zhou, Yue; Zhou, Xing Hua; Xu, Bin

2014-01-01

Background: Silybum marianum has been used as herbal medicine for the treatment of liver disease, liver cirrhosis, and to prevent liver cancer in Europe and Asia since ancient times. Silybum marianum oil (SMO), a by-product of silymarin production, is rich in essential fatty acids, phospholipids, sterols, and vitamin E. However, it has not been very good development and use. Objective: In the present study, we used olive oil as a control to investigate the antioxidant and anti-aging effect of SMO in D-galactose (D-gal)-induced aging mice. Materials and Methods: D-gal was injected intraperitoneally (500 mg/kg body weight daily) for 7 weeks while SMO was simultaneously administered orally. The triglycerides (TRIG) and cholesterol (CHOL) levels were estimated in the serum. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), monoamine oxidase (MAO), malondialdehyde (MDA), caspase-3, and Bcl-2 were determined in the liver and brain. The activities of Na+-K+-adenosine triphosphatase (ATPase), Ca2+-Mg2+-ATPase, membrane potential (ΔΨm), and membrane fluidity of the liver mitochondrial were estimated. Results: SMO decreased levels of TRIG and CHOL in aging mice. SMO administration elevated the activities of SOD, GSH-Px, and T-AOC, which are suppressed by aging. The levels of MAO and MDA in the liver and brain were reduced by SMO administration in aging mice. Enzyme linked immunosorbent assay showed that SMO significantly decreased the concentration of caspase-3 and improved the activity of Bcl-2 in the liver and brain of aging mice. Furthermore, SMO significantly attenuated the D-gal induced liver mitochondrial dysfunction by improving the activities of Na+-K+-ATPase, Ca2+-Mg2+-ATPase, membrane potential (ΔΨm), and membrane fluidity. Conclusion: These results indicate that SMO effectively attenuated oxidative damage and improved apoptosis related factors as well as liver mitochondrial dysfunction in aging mice. PMID:24914315

A tool for urban soundscape evaluation applying Support Vector Machines for developing a soundscape classification model.

PubMed

Torija, Antonio J; Ruiz, Diego P; Ramos-Ridao, Angel F

2014-06-01

To ensure appropriate soundscape management in urban environments, the urban-planning authorities need a range of tools that enable such a task to be performed. An essential step during the management of urban areas from a sound standpoint should be the evaluation of the soundscape in such an area. In this sense, it has been widely acknowledged that a subjective and acoustical categorization of a soundscape is the first step to evaluate it, providing a basis for designing or adapting it to match people's expectations as well. In this sense, this work proposes a model for automatic classification of urban soundscapes. This model is intended for the automatic classification of urban soundscapes based on underlying acoustical and perceptual criteria. Thus, this classification model is proposed to be used as a tool for a comprehensive urban soundscape evaluation. Because of the great complexity associated with the problem, two machine learning techniques, Support Vector Machines (SVM) and Support Vector Machines trained with Sequential Minimal Optimization (SMO), are implemented in developing model classification. The results indicate that the SMO model outperforms the SVM model in the specific task of soundscape classification. With the implementation of the SMO algorithm, the classification model achieves an outstanding performance (91.3% of instances correctly classified). © 2013 Elsevier B.V. All rights reserved.

Probing mammalian spermine oxidase enzyme-substrate complex through molecular modeling, site-directed mutagenesis and biochemical characterization.

PubMed

Tavladoraki, Paraskevi; Cervelli, Manuela; Antonangeli, Fabrizio; Minervini, Giovanni; Stano, Pasquale; Federico, Rodolfo; Mariottini, Paolo; Polticelli, Fabio

2011-04-01

Spermine oxidase (SMO) and acetylpolyamine oxidase (APAO) are FAD-dependent enzymes that are involved in the highly regulated pathways of polyamine biosynthesis and degradation. Polyamine content is strictly related to cell growth, and dysfunctions in polyamine metabolism have been linked with cancer. Specific inhibitors of SMO and APAO would allow analyzing the precise role of these enzymes in polyamine metabolism and related pathologies. However, none of the available polyamine oxidase inhibitors displays the desired characteristics of selective affinity and specificity. In addition, repeated efforts to obtain structural details at the atomic level on these two enzymes have all failed. In the present study, in an effort to better understand structure-function relationships, SMO enzyme-substrate complex has been probed through a combination of molecular modeling, site-directed mutagenesis and biochemical studies. Results obtained indicate that SMO binds spermine in a similar conformation as that observed in the yeast polyamine oxidase FMS1-spermine complex and demonstrate a major role for residues His82 and Lys367 in substrate binding and catalysis. In addition, the SMO enzyme-substrate complex highlights the presence of an active site pocket with highly polar characteristics, which may explain the different substrate specificity of SMO with respect to APAO and provide the basis for the design of specific inhibitors for SMO and APAO.

Optimization technique of wavefront coding system based on ZEMAX externally compiled programs

NASA Astrophysics Data System (ADS)

Han, Libo; Dong, Liquan; Liu, Ming; Zhao, Yuejin; Liu, Xiaohua

2016-10-01

Wavefront coding technique as a means of athermalization applied to infrared imaging system, the design of phase plate is the key to system performance. This paper apply the externally compiled programs of ZEMAX to the optimization of phase mask in the normal optical design process, namely defining the evaluation function of wavefront coding system based on the consistency of modulation transfer function (MTF) and improving the speed of optimization by means of the introduction of the mathematical software. User write an external program which computes the evaluation function on account of the powerful computing feature of the mathematical software in order to find the optimal parameters of phase mask, and accelerate convergence through generic algorithm (GA), then use dynamic data exchange (DDE) interface between ZEMAX and mathematical software to realize high-speed data exchanging. The optimization of the rotational symmetric phase mask and the cubic phase mask have been completed by this method, the depth of focus increases nearly 3 times by inserting the rotational symmetric phase mask, while the other system with cubic phase mask can be increased to 10 times, the consistency of MTF decrease obviously, the maximum operating temperature of optimized system range between -40°-60°. Results show that this optimization method can be more convenient to define some unconventional optimization goals and fleetly to optimize optical system with special properties due to its externally compiled function and DDE, there will be greater significance for the optimization of unconventional optical system.

CoSMoS unravels mysteries of transcription initiation.

PubMed

Gourse, Richard L; Landick, Robert

2012-02-17

Using a fluorescence method called colocalization single-molecule spectroscopy (CoSMoS), Friedman and Gelles dissect the kinetics of transcription initiation at a bacterial promoter. Ultimately, CoSMoS could greatly aid the study of the effects of DNA sequence and transcription factors on both prokaryotic and eukaryotic promoters. Copyright © 2012 Elsevier Inc. All rights reserved.

Challenges of anamorphic high-NA lithography and mask making

NASA Astrophysics Data System (ADS)

Hsu, Stephen D.; Liu, Jingjing

2017-06-01

Chip makers are actively working on the adoption of 0.33 numerical aperture (NA) EUV scanners for the 7-nm and 5-nm nodes (B. Turko, S. L. Carson, A. Lio, T. Liang, M. Phillips, et al., in `Proc. SPIE9776, Extreme Ultraviolet (EUV) Lithography VII', vol. 977602 (2016) doi: 10.1117/12.2225014; A. Lio, in `Proc. SPIE9776, Extreme Ultraviolet (EUV) Lithography VII', vol. 97760V (2016) doi: 10.1117/12.2225017). In the meantime, leading foundries and integrated device manufacturers are starting to investigate patterning options beyond the 5-nm node (O. Wood, S. Raghunathan, P. Mangat, V. Philipsen, V. Luong, et al., in `Proc. SPIE. 9422, Extreme Ultraviolet (EUV) Lithography VI', vol. 94220I (2015) doi: 10.1117/12.2085022). To minimize the cost and process complexity of multiple patterning beyond the 5-nm node, EUV high-NA single-exposure patterning is a preferred method over EUV double patterning (O. Wood, S. Raghunathan, P. Mangat, V. Philipsen, V. Luong, et al., in `Proc. SPIE. 9422, Extreme Ultraviolet (EUV) Lithography VI', vol. 94220I (2015) doi: 10.1117/12.2085022; J. van Schoot, K. van Ingen Schenau, G. Bottiglieri, K. Troost, J. Zimmerman, et al., `Proc. SPIE. 9776, Extreme Ultraviolet (EUV) Lithography VII', vol. 97761I (2016) doi: 10.1117/12.2220150). The EUV high-NA scanner equipped with a projection lens of 0.55 NA is designed to support resolutions below 10 nm. The high-NA system is beneficial for enhancing resolution, minimizing mask proximity correction bias, improving normalized image log slope (NILS), and controlling CD uniformity (CDU). However, increasing NA from 0.33 to 0.55 reduces the depth of focus (DOF) significantly. Therefore, the source mask optimization (SMO) with sub-resolution assist features (SRAFs) are needed to increase DOF to meet the demanding full chip process control requirements (S. Hsu, R. Howell, J. Jia, H.-Y. Liu, K. Gronlund, et al., EUV `Proc. SPIE9048, Extreme Ultraviolet (EUV) Lithography VI', (2015) doi: 10.1117/12.2086074). To ensure no assist feature printing, the assist feature sizes need to be scaled with λ/NA. The extremely small SRAF width (below 25 nm on the reticle) is difficult to fabricate across the full reticle. In this paper, we introduce an innovative `attenuated SRAF' to improve SRAF manufacturability and still maintain the process window benefit. A new mask fabrication process is proposed to use existing mask-making capability to manufacture the attenuated SRAFs. The high-NA EUV system utilizes anamorphic reduction; 4× in the horizontal (slit) direction and 8× in the vertical (scanning) direction (J. van Schoot, K. van Ingen Schenau, G. Bottiglieri, K. Troost, J. Zimmerman, et al., `Proc. SPIE. 9776, Extreme Ultraviolet (EUV) Lithography VII', vol. 97761I (2016) doi: 10.1117/12.2220150; B. Kneer, S. Migura, W. Kaiser, J. T. Neumann, J. van Schoot, in `Proc. SPIE9422, Extreme Ultraviolet (EUV) Lithography VI', vol. 94221G (2015) doi: 10.1117/12.2175488). For an anamorphic system, the magnification has an angular dependency, and thus, familiar mask specifications such as mask error factor (MEF) need to be redefined. Similarly, mask-manufacturing rule check (MRC) needs to consider feature orientation.

Spermine oxidase is a regulator of macrophage host response to Helicobacter pylori: enhancement of antimicrobial nitric oxide generation by depletion of spermine.

PubMed

Chaturvedi, Rupesh; Asim, Mohammad; Barry, Daniel P; Frye, Jeanetta W; Casero, Robert A; Wilson, Keith T

2014-03-01

The gastric pathogen Helicobacter pylori causes peptic ulcer disease and gastric cancer. We have reported that in H. pylori-activated macrophages, nitric oxide (NO) derived from inducible NO synthase (iNOS) can kill the bacterium, iNOS protein expression is dependent on uptake of its substrate L-arginine (L-Arg), the polyamine spermine can inhibit iNOS translation by inhibiting L-Arg uptake, and inhibition of polyamine synthesis enhances NO-mediated bacterial killing. Because spermine oxidase (SMO), which back-converts spermine to spermidine, is induced in macrophages by H. pylori, we determined its role in iNOS-dependent host defense. SMO shRNA knockdown in RAW 264.7 murine macrophages resulted in a marked decrease in H. pylori-stimulated iNOS protein, but not mRNA expression, and a 90% reduction in NO levels; NO production was also inhibited in primary murine peritoneal macrophages with SMO knockdown. There was an increase in spermine levels after H. pylori stimulation that rapidly decreased, while SMO knockdown caused a greater increase in spermine that was sustained. With SMO knockdown, L-Arg uptake and killing of H. pylori by macrophages was prevented. The overexpression of SMO by transfection of an expression plasmid prevented the H. pylori-stimulated increase in spermine levels, and led to increased L-Arg uptake, iNOS protein expression and NO production, and H. pylori killing. In two human monocytic cell lines, U937 and THP-1, overexpression of SMO caused a significant enhancement of NO production with H. pylori stimulation. By depleting spermine, SMO can abrogate the inhibitory effect of polyamines on innate immune responses to H. pylori by enhancing antimicrobial NO production.

Nuclear localization of human spermine oxidase isoforms – possible implications in drug response and disease etiology

PubMed Central

Murray-Stewart, Tracy; Wang, Yanlin; Goodwin, Andrew; Hacker, Amy; Meeker, Alan; Casero, Robert A.

2013-01-01

The recent discovery of the direct oxidation of spermine via spermine oxidase (SMO) as a mechanism through which specific antitumor polyamine analogues exert their cytotoxic effects has fueled interest in the study of the polyamine catabolic pathway. A major byproduct of spermine oxidation is H2O2, a source of toxic reactive oxygen species. Recent targeted small interfering RNA studies have confirmed that SMO-produced reactive oxygen species are directly responsible for oxidative stress capable of inducing apoptosis and potentially mutagenic DNA damage. In the present study, we describe a second catalytically active splice variant protein of the human spermine oxidase gene, designated SMO5, which exhibits substrate specificities and affinities comparable to those of the originally identified human spermine oxidase-1, SMO/PAOh1, and, as such, is an additional source of H2O2. Importantly, overexpression of either of these SMO isoforms in NCI-H157 human non-small cell lung carcinoma cells resulted in significant localization of SMO protein in the nucleus, as determined by confocal microscopy. Furthermore, cell lines overexpressing either SMO/PAOh1 or SMO5 demonstrated increased spermine oxidation in the nucleus, with accompanying alterations in individual nuclear polyamine concentrations. This increased oxidation of spermine in the nucleus therefore increases the production of highly reactive H2O2 in close proximity to DNA, as well as decreases nuclear spermine levels, thus altering the protective roles of spermine in free radical scavenging and DNA shielding, and resulting in an overall increased potential for oxidative DNA damage in these cells. The results of these studies therefore have considerable significance both with respect to targeting polyamine oxidation as an antineoplastic strategy, and in regard to the potential role of spermine oxidase in inflammation-induced carcinogenesis. PMID:18422650

Inverse lithography using sparse mask representations

NASA Astrophysics Data System (ADS)

Ionescu, Radu C.; Hurley, Paul; Apostol, Stefan

2015-03-01

We present a novel optimisation algorithm for inverse lithography, based on optimization of the mask derivative, a domain inherently sparse, and for rectilinear polygons, invertible. The method is first developed assuming a point light source, and then extended to general incoherent sources. What results is a fast algorithm, producing manufacturable masks (the search space is constrained to rectilinear polygons), and flexible (specific constraints such as minimal line widths can be imposed). One inherent trick is to treat polygons as continuous entities, thus making aerial image calculation extremely fast and accurate. Requirements for mask manufacturability can be integrated in the optimization without too much added complexity. We also explain how to extend the scheme for phase-changing mask optimization.

A Synthesis Model of Sustainable Market Orientation: Conceptualization, Measurement, and Influence on Academic Accreditation--A Case Study of Egyptian-Accredited Faculties

ERIC Educational Resources Information Center

Abou-Warda, Sherein H.

2014-01-01

Higher education institutions are increasingly concerned about accreditation. Although sustainable market orientation (SMO) bears on academic accreditation, to date, no study has developed a valid scale of SMO or assessed its influence on accreditation. The purpose of this paper is to construct and validate an SMO scale that was developed in…

Single-Molecule Analysis of Pre-mRNA Splicing with Colocalization Single-Molecule Spectroscopy (CoSMoS).

PubMed

Braun, Joerg E; Serebrov, Victor

2017-01-01

Recent development of single-molecule techniques to study pre-mRNA splicing has provided insights into the dynamic nature of the spliceosome. Colocalization single-molecule spectroscopy (CoSMoS) allows following spliceosome assembly in real time at single-molecule resolution in the full complexity of cellular extracts. A detailed protocol of CoSMoS has been published previously (Anderson and Hoskins, Methods Mol Biol 1126:217-241, 2014). Here, we provide an update on the technical advances since the first CoSMoS studies including slide surface treatment, data processing, and representation. We describe various labeling strategies to generate RNA reporters with multiple dyes (or other moieties) at specific locations.

DOE Office of Scientific and Technical Information (OSTI.GOV)

McMillan, Kyle; Marleau, Peter; Brubaker, Erik

In coded aperture imaging, one of the most important factors determining the quality of reconstructed images is the choice of mask/aperture pattern. In many applications, uniformly redundant arrays (URAs) are widely accepted as the optimal mask pattern. Under ideal conditions, thin and highly opaque masks, URA patterns are mathematically constructed to provide artifact-free reconstruction however, the number of URAs for a chosen number of mask elements is limited and when highly penetrating particles such as fast neutrons and high-energy gamma-rays are being imaged, the optimum is seldom achieved. In this case more robust mask patterns that provide better reconstructed imagemore » quality may exist. Through the use of heuristic optimization methods and maximum likelihood expectation maximization (MLEM) image reconstruction, we show that for both point and extended neutron sources a random mask pattern can be optimized to provide better image quality than that of a URA.« less

ILP-based co-optimization of cut mask layout, dummy fill, and timing for sub-14nm BEOL technology

NASA Astrophysics Data System (ADS)

Han, Kwangsoo; Kahng, Andrew B.; Lee, Hyein; Wang, Lutong

2015-10-01

Self-aligned multiple patterning (SAMP), due to its low overlay error, has emerged as the leading option for 1D gridded back-end-of-line (BEOL) in sub-14nm nodes. To form actual routing patterns from a uniform "sea of wires", a cut mask is needed for line-end cutting or realization of space between routing segments. Constraints on cut shapes and minimum cut spacing result in end-of-line (EOL) extensions and non-functional (i.e. dummy fill) patterns; the resulting capacitance and timing changes must be consistent with signoff performance analyses and their impacts should be minimized. In this work, we address the co-optimization of cut mask layout, dummy fill, and design timing for sub-14nm BEOL design. Our central contribution is an optimizer based on integer linear programming (ILP) to minimize the timing impact due to EOL extensions, considering (i) minimum cut spacing arising in sub-14nm nodes; (ii) cut assignment to different cut masks (color assignment); and (iii) the eligibility to merge two unit-size cuts into a bigger cut. We also propose a heuristic approach to remove dummy fills after the ILP-based optimization by extending the usage of cut masks. Our heuristic can improve critical path performance under minimum metal density and mask density constraints. In our experiments, we study the impact of number of cut masks, minimum cut spacing and metal density under various constraints. Our studies of optimized cut mask solutions in these varying contexts give new insight into the tradeoff of performance and cost that is afforded by cut mask patterning technology options.

Methanol Adsorption and Reaction on Samaria Thin Films on Pt(111).

PubMed

Jhang, Jin-Hao; Schaefer, Andreas; Zielasek, Volkmar; Weaver, Jason F; Bäumer, Marcus

2015-09-17

We investigated the adsorption and reaction of methanol on continuous and discontinuous films of samarium oxide (SmO x ) grown on Pt(111) in ultrahigh vacuum. The methanol decomposition was studied by temperature programmed desorption (TPD) and infrared reflection absorption spectroscopy (IRRAS), while structural changes of the oxide surface were monitored by low-energy electron diffraction (LEED). Methanol dehydrogenates to adsorbed methoxy species on both the continuous and discontinuous SmO x films, eventually leading to the desorption of CO and H₂ which desorbs at temperatures in the range 400-600 K. Small quantities of CO₂ are also detected mainly on as-prepared Sm₂O₃ thin films, but the production of CO₂ is limited during repeated TPD runs. The discontinuous film exhibits the highest reactivity compared to the continuous film and the Pt(111) substrate. The reactivity of methanol on reduced and reoxidized films was also investigated, revealing how SmO x structures influence the chemical behavior. Over repeated TPD experiments, a SmO x structural/chemical equilibrium condition is found which can be approached either from oxidized or reduced films. We also observed hydrogen absence in TPD which indicates that hydrogen is stored either in SmO x films or as OH groups on the SmO x surfaces.

Effects of hard mask etch on final topography of advanced phase shift masks

NASA Astrophysics Data System (ADS)

Hortenbach, Olga; Rolff, Haiko; Lajn, Alexander; Baessler, Martin

2017-07-01

Continuous shrinking of the semiconductor device dimensions demands steady improvements of the lithographic resolution on wafer level. These requirements challenge the photomask industry to further improve the mask quality in all relevant printing characteristics. In this paper topography of the Phase Shift Masks (PSM) was investigated. Effects of hard mask etch on phase shift uniformity and mask absorber profile were studied. Design of experiments method (DoE) was used for the process optimization, whereas gas composition, bias power of the hard mask main etch and bias power of the over-etch were varied. In addition, influence of the over-etch time was examined at the end of the experiment. Absorber depth uniformity, sidewall angle (SWA), reactive ion etch lag (RIE lag) and through pitch (TP) dependence were analyzed. Measurements were performed by means of Atomic-force microscopy (AFM) using critical dimension (CD) mode with a boot-shaped tip. Scanning electron microscope (SEM) cross-section images were prepared to verify the profile quality. Finally CD analysis was performed to confirm the optimal etch conditions. Significant dependence of the absorber SWA on hard mask (HM) etch conditions was observed revealing an improvement potential for the mask absorber profile. It was found that hard mask etch can leave a depth footprint in the absorber layer. Thus, the etch depth uniformity of hard mask etch is crucial for achieving a uniform phase shift over the active mask area. The optimized hard mask etch process results in significantly improved mask topography without deterioration of tight CD specifications.

Dissipation of sulfamethoxazole in pasture soils as affected by soil and environmental factors.

PubMed

Srinivasan, Prakash; Sarmah, Ajit K

2014-05-01

The dissipation of sulfamethoxazole (SMO) antibiotic in three different soils was investigated through laboratory incubation studies. The experiments were conducted under different incubation conditions such as initial chemical concentration, soil depth, temperature, and with sterilisation. The results indicate that SMO dissipated rapidly in New Zealand pasture soils, and the 50% dissipation times (DT50) in Hamilton, Te Kowhai and Horotiu soils under non-sterile conditions were 9.24, 4.3 and 13.33 days respectively. During the incubation period for each sampling event the soil dehydrogenase activity (DHA) and the variation in microbial community were monitored thorough phospholipid fatty acid extraction analysis (PLFA). The DHA data correlated well with the dissipation rate constants of SMO antibiotic, an increase in the DHA activity resulted in faster antibiotic dissipation. The PLFA analysis was indicative of higher bacterial presence as compared to fungal community, highlighting the type of microbial community responsible for dissipation. The results indicate that with increasing soil depth, SMO dissipation in soil was slower (except for Horotiu) while with increase in temperature the antibiotic loss was faster, and was noticeable in all the soils. Both the degree of biological activity and the temperature of the soil influenced overall SMO dissipation. SMO is not likely to persist more than 5-6 months in all three soils suggesting that natural biodegradation may be sufficient for the removal of these contaminants from the soil. Its dissipation in sterile soils indicated abiotic factors such as strong sorption onto soil components to play a role in the dissipation of SMO. Copyright © 2014 Elsevier B.V. All rights reserved.

Digging a hole under Hedgehog: downstream inhibition as an emerging anticancer strategy.

PubMed

Di Magno, Laura; Coni, Sonia; Di Marcotullio, Lucia; Canettieri, Gianluca

2015-08-01

Hedgehog signaling is a key regulator of development and stem cell fate and its aberrant activation is a leading cause of a number of tumors. Activating germline or somatic mutations of genes encoding Hh pathway components are found in Basal Cell Carcinoma (BCC) and Medulloblastoma (MB). Ligand-dependent Hedgehog hyperactivation, due to autocrine or paracrine mechanisms, is also observed in a large number of malignancies of the breast, colon, skin, bladder, pancreas and other tissues. The key tumorigenic role of Hedgehog has prompted effort aimed at identifying inhibitors of this signaling. To date, only the antagonists of the membrane transducer Smo have been approved for therapy or are under clinical trials in patients with BCC and MB linked to Ptch or Smo mutations. Despite the good initial response, patients treated with Smo antagonists have eventually developed resistance due to the occurrence of compensating mechanisms. Furthermore, Smo antagonists are not effective in tumors where the Hedgehog hyperactivation is due to mutations of pathway components downstream of Smo, or in case of non-canonical, Smo-independent activation of the Gli transcription factors. For all these reasons, the research of Hh inhibitors acting downstream of Smo is becoming an area of intensive investigation. In this review we illustrate the progresses made in the identification of effective Hedgehog inhibitors and their application in cancer, with a special emphasis on the newly identified downstream inhibitors. We describe in detail the Gli inhibitors and illustrate their mode of action and applications in experimental and/or clinical settings. Copyright © 2015 Elsevier B.V. All rights reserved.

CoSMoMVPA: Multi-Modal Multivariate Pattern Analysis of Neuroimaging Data in Matlab/GNU Octave.

PubMed

Oosterhof, Nikolaas N; Connolly, Andrew C; Haxby, James V

2016-01-01

Recent years have seen an increase in the popularity of multivariate pattern (MVP) analysis of functional magnetic resonance (fMRI) data, and, to a much lesser extent, magneto- and electro-encephalography (M/EEG) data. We present CoSMoMVPA, a lightweight MVPA (MVP analysis) toolbox implemented in the intersection of the Matlab and GNU Octave languages, that treats both fMRI and M/EEG data as first-class citizens. CoSMoMVPA supports all state-of-the-art MVP analysis techniques, including searchlight analyses, classification, correlations, representational similarity analysis, and the time generalization method. These can be used to address both data-driven and hypothesis-driven questions about neural organization and representations, both within and across: space, time, frequency bands, neuroimaging modalities, individuals, and species. It uses a uniform data representation of fMRI data in the volume or on the surface, and of M/EEG data at the sensor and source level. Through various external toolboxes, it directly supports reading and writing a variety of fMRI and M/EEG neuroimaging formats, and, where applicable, can convert between them. As a result, it can be integrated readily in existing pipelines and used with existing preprocessed datasets. CoSMoMVPA overloads the traditional volumetric searchlight concept to support neighborhoods for M/EEG and surface-based fMRI data, which supports localization of multivariate effects of interest across space, time, and frequency dimensions. CoSMoMVPA also provides a generalized approach to multiple comparison correction across these dimensions using Threshold-Free Cluster Enhancement with state-of-the-art clustering and permutation techniques. CoSMoMVPA is highly modular and uses abstractions to provide a uniform interface for a variety of MVP measures. Typical analyses require a few lines of code, making it accessible to beginner users. At the same time, expert programmers can easily extend its functionality. CoSMoMVPA comes with extensive documentation, including a variety of runnable demonstration scripts and analysis exercises (with example data and solutions). It uses best software engineering practices including version control, distributed development, an automated test suite, and continuous integration testing. It can be used with the proprietary Matlab and the free GNU Octave software, and it complies with open source distribution platforms such as NeuroDebian. CoSMoMVPA is Free/Open Source Software under the permissive MIT license. Website: http://cosmomvpa.org Source code: https://github.com/CoSMoMVPA/CoSMoMVPA.

CoSMoMVPA: Multi-Modal Multivariate Pattern Analysis of Neuroimaging Data in Matlab/GNU Octave

PubMed Central

Oosterhof, Nikolaas N.; Connolly, Andrew C.; Haxby, James V.

2016-01-01

Recent years have seen an increase in the popularity of multivariate pattern (MVP) analysis of functional magnetic resonance (fMRI) data, and, to a much lesser extent, magneto- and electro-encephalography (M/EEG) data. We present CoSMoMVPA, a lightweight MVPA (MVP analysis) toolbox implemented in the intersection of the Matlab and GNU Octave languages, that treats both fMRI and M/EEG data as first-class citizens. CoSMoMVPA supports all state-of-the-art MVP analysis techniques, including searchlight analyses, classification, correlations, representational similarity analysis, and the time generalization method. These can be used to address both data-driven and hypothesis-driven questions about neural organization and representations, both within and across: space, time, frequency bands, neuroimaging modalities, individuals, and species. It uses a uniform data representation of fMRI data in the volume or on the surface, and of M/EEG data at the sensor and source level. Through various external toolboxes, it directly supports reading and writing a variety of fMRI and M/EEG neuroimaging formats, and, where applicable, can convert between them. As a result, it can be integrated readily in existing pipelines and used with existing preprocessed datasets. CoSMoMVPA overloads the traditional volumetric searchlight concept to support neighborhoods for M/EEG and surface-based fMRI data, which supports localization of multivariate effects of interest across space, time, and frequency dimensions. CoSMoMVPA also provides a generalized approach to multiple comparison correction across these dimensions using Threshold-Free Cluster Enhancement with state-of-the-art clustering and permutation techniques. CoSMoMVPA is highly modular and uses abstractions to provide a uniform interface for a variety of MVP measures. Typical analyses require a few lines of code, making it accessible to beginner users. At the same time, expert programmers can easily extend its functionality. CoSMoMVPA comes with extensive documentation, including a variety of runnable demonstration scripts and analysis exercises (with example data and solutions). It uses best software engineering practices including version control, distributed development, an automated test suite, and continuous integration testing. It can be used with the proprietary Matlab and the free GNU Octave software, and it complies with open source distribution platforms such as NeuroDebian. CoSMoMVPA is Free/Open Source Software under the permissive MIT license. Website: http://cosmomvpa.org Source code: https://github.com/CoSMoMVPA/CoSMoMVPA PMID:27499741

Utilization of a modified special-cubic design and an electronic tongue for bitterness masking formulation optimization.

PubMed

Li, Lianli; Naini, Venkatesh; Ahmed, Salah U

2007-10-01

A unique modification of simplex design was applied to an electronic tongue (E-Tongue) analysis in bitterness masking formulation optimization. Three formulation variables were evaluated in the simplex design, i.e. concentrations of two taste masking polymers, Amberlite and Carbopol, and pH of the granulating fluid. Response of the design was a bitterness distance measured using an E-Tongue by applying a principle component analysis, which represents taste masking efficiency of the formulation. The smaller the distance, the better the bitterness masking effect. Contour plots and polynomial equations of the bitterness distance response were generated as a function of formulation composition and pH. It was found that interactions between polymer and pH reduced the bitterness of the formulation, attributed to pH-dependent ionization and complexation properties of the ionic polymers, thus keeping the drug out of solution and unavailable to bitterness perception. At pH 4.9 and an Amberlite/Carbopol ratio of 1.4:1 (w/w), the optimal taste masking formulation was achieved and in agreement with human gustatory sensation study results. Therefore, adopting a modified simplex experimental design on response measured using an E-Tongue provided an efficient approach to taste masking formulation optimization using ionic binding polymers. (c) 2007 Wiley-Liss, Inc.

Variability-aware double-patterning layout optimization for analog circuits

NASA Astrophysics Data System (ADS)

Li, Yongfu; Perez, Valerio; Tripathi, Vikas; Lee, Zhao Chuan; Tseng, I.-Lun; Ong, Jonathan Yoong Seang

2018-03-01

The semiconductor industry has adopted multi-patterning techniques to manage the delay in the extreme ultraviolet lithography technology. During the design process of double-patterning lithography layout masks, two polygons are assigned to different masks if their spacing is less than the minimum printable spacing. With these additional design constraints, it is very difficult to find experienced layout-design engineers who have a good understanding of the circuit to manually optimize the mask layers in order to minimize color-induced circuit variations. In this work, we investigate the impact of double-patterning lithography on analog circuits and provide quantitative analysis for our designers to select the optimal mask to minimize the circuit's mismatch. To overcome the problem and improve the turn-around time, we proposed our smart "anchoring" placement technique to optimize mask decomposition for analog circuits. We have developed a software prototype that is capable of providing anchoring markers in the layout, allowing industry standard tools to perform automated color decomposition process.

Combining malaria control with house electrification: adherence to recommended behaviours for proper deployment of solar-powered mosquito trapping systems, Rusinga Island, western Kenya.

PubMed

Oria, Prisca A; Alaii, Jane; Ayugi, Margaret; Takken, Willem; Leeuwis, Cees

2015-08-01

To investigate community adherence to recommended behaviours for proper deployment of solar-powered mosquito trapping systems (SMoTS) after 3- to 10-week use. Solar-powered mosquito trapping system, which also provided power for room lighting and charging mobile phones, were installed in houses in Rusinga Island, western Kenya. We used a structured checklist for observations and a semi-structured questionnaire for interviews in 24 homesteads. We also analysed the subject of 224 community calls to the project team for technical maintenance of SMoTS. Most respondents cared for SMoTS by fencing, emptying and cleaning the trap. Our observations revealed that most traps were fenced, clean and in good working condition. A significantly higher proportion of community calls was lighting-related. Lighting was the main reason respondents liked SMoTS because it reduced or eliminated expenditure on kerosene. However, some respondents observed they no longer heard sounds of mosquitoes inside their houses. All respondents reportedly slept under insecticide-treated nets (ITNs) before receiving SMoTS. After receiving SMoTS, most respondents reportedly continued to use ITNs citing that the project advised them to do so. Some beach residents stopped using ITNs because they no longer heard mosquitoes or due to heat discomfort caused by lights. Electricity-related incentives played a greater role in encouraging adherence to recommended behaviours for proper deployment of SMoTS than the potential health benefits in the early stages of the intervention. Although energy-related financial incentives may play a role, they are insufficient to ensure adherence to health advice, even in the short term. Ongoing community engagement and research monitors and addresses adherence to recommended behaviours including continuation of current malaria control strategies. © 2015 John Wiley & Sons Ltd.

High-Energy Radiation from a Model of Quasars, Active Galactic Nuclei, and the Galactic Center with Magnetic Monopoles

NASA Astrophysics Data System (ADS)

Peng, Qiu-he; Chou, Chih-kang

2001-04-01

The fact that magnetic monopoles may catalyze nucleon decay (the Rubakov-Callan [RC] effect) as predicated by the grand unified theory of particle physics is invoked as the energy source of quasars and active galactic nuclei. Recent study of this model revealed that the radius of the supermassive object (SMO) located at the Galactic center is much larger than its Schwarzschild radius. We propose that this SMOs could be the source of high-energy gamma-ray radiation, although the emitted radiation may be mainly concentrated in the infrared. The surface temperature of the SMO at the Galactic center is taken as 121 K, inferred from the observed maximum of the flux spectrum of Sgr A* at the near infrared (1×1013 Hz); the radius of the SMO is about 8.1×1015 cm or 1.1×104RS (RS is the Schwarzschild radius). The mass of the SMO is derived from the observed total luminosity of Sgr A* (1×1037 ergs s-1) as 2.5×106 Msolar. Strong gamma-ray radiation with energy higher than 0.5 MeV may be emitted from the SMO. The flux of positrons emitted from the SMO is estimated to be 6.5×1042e+ s-1. The content parameter of magnetic monopoles ξ≡[(Nm/NB)/1.9×10- 25](<σβ>/10-27) also may be deduced from observations to be 230. Taking the cross section of the RC effect as 1×10-27 cm2, the strength of the radial magnetic field at the surface of the SMO is estimated to be 20-100 G. Our model also can predict the production of extreme ultra-high-energy cosmic rays.

Molecular Characterization of Bovine SMO Gene and Effects of Its Genetic Variations on Body Size Traits in Qinchuan Cattle (Bos taurus).

PubMed

Zhang, Ya-Ran; Gui, Lin-Sheng; Li, Yao-Kun; Jiang, Bi-Jie; Wang, Hong-Cheng; Zhang, Ying-Ying; Zan, Lin-Sen

2015-07-27

Smoothened (Smo)-mediated Hedgehog (Hh) signaling pathway governs the patterning, morphogenesis and growth of many different regions within animal body plans. This study evaluated the effects of genetic variations of the bovine SMO gene on economically important body size traits in Chinese Qinchuan cattle. Altogether, eight single nucleotide polymorphisms (SNPs: 1-8) were identified and genotyped via direct sequencing covering most of the coding region and 3'UTR of the bovine SMO gene. Both the p.698Ser.>Ser. synonymous mutation resulted from SNP1 and the p.700Ser.>Pro. non-synonymous mutation caused by SNP2 mapped to the intracellular C-terminal tail of bovine Smo protein; the other six SNPs were non-coding variants located in the 3'UTR. The linkage disequilibrium was analyzed, and five haplotypes were discovered in 520 Qinchuan cattle. Association analyses showed that SNP2, SNP3/5, SNP4 and SNP6/7 were significantly associated with some body size traits (p < 0.05) except SNP1/8 (p > 0.05). Meanwhile, cattle with wild-type combined haplotype Hap1/Hap1 had significantly (p < 0.05) greater body length than those with Hap2/Hap2. Our results indicate that variations in the SMO gene could affect body size traits of Qinchuan cattle, and the wild-type haplotype Hap1 together with the wild-type alleles of these detected SNPs in the SMO gene could be used to breed cattle with superior body size traits. Therefore, our results could be helpful for marker-assisted selection in beef cattle breeding programs.

Molecular Characterization of Bovine SMO Gene and Effects of Its Genetic Variations on Body Size Traits in Qinchuan Cattle (Bos taurus)

PubMed Central

Zhang, Ya-Ran; Gui, Lin-Sheng; Li, Yao-Kun; Jiang, Bi-Jie; Wang, Hong-Cheng; Zhang, Ying-Ying; Zan, Lin-Sen

2015-01-01

Smoothened (Smo)-mediated Hedgehog (Hh) signaling pathway governs the patterning, morphogenesis and growth of many different regions within animal body plans. This study evaluated the effects of genetic variations of the bovine SMO gene on economically important body size traits in Chinese Qinchuan cattle. Altogether, eight single nucleotide polymorphisms (SNPs: 1–8) were identified and genotyped via direct sequencing covering most of the coding region and 3ʹUTR of the bovine SMO gene. Both the p.698Ser.>Ser. synonymous mutation resulted from SNP1 and the p.700Ser.>Pro. non-synonymous mutation caused by SNP2 mapped to the intracellular C-terminal tail of bovine Smo protein; the other six SNPs were non-coding variants located in the 3ʹUTR. The linkage disequilibrium was analyzed, and five haplotypes were discovered in 520 Qinchuan cattle. Association analyses showed that SNP2, SNP3/5, SNP4 and SNP6/7 were significantly associated with some body size traits (p < 0.05) except SNP1/8 (p > 0.05). Meanwhile, cattle with wild-type combined haplotype Hap1/Hap1 had significantly (p < 0.05) greater body length than those with Hap2/Hap2. Our results indicate that variations in the SMO gene could affect body size traits of Qinchuan cattle, and the wild-type haplotype Hap1 together with the wild-type alleles of these detected SNPs in the SMO gene could be used to breed cattle with superior body size traits. Therefore, our results could be helpful for marker-assisted selection in beef cattle breeding programs. PMID:26225956

Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, Zhong Xin; Sun, Cong Cong; Wenzhou People's Hospital, Wenzhou, Zhejiang

Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Westernmore » blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.« less

GENERAL VIEW, LOOKING SOUTHEAST, OF STANDARDIZING MAGNETIC OBSERVATORY (SMO) WHICH ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

GENERAL VIEW, LOOKING SOUTHEAST, OF STANDARDIZING MAGNETIC OBSERVATORY (SMO) WHICH IS TO THE RIGHT. THE BUILDING TO THE LEFT IS 'STATION 'A'', ALSO A NON-MAGNETIC STRUCTURE, ONCE USED FOR COMPARISONS OF MAGNETIC INSTRUMENTS WITH THE SMO. THE BUILDING IN THE CENTER CONTAINED A SEARCH-LIGHT USED IN CONJUNCTION WITH MEASUREMENTS OF THE EARTH'S ATMOSPHERE. - Carnegie Institution of Washington, Department of Terrestrial Magnetism, Standardizing Magnetic Observatory, 5241 Broad Branch Drive Northwest, Washington, District of Columbia, DC

Dynamics of a bistable Miura-origami structure

NASA Astrophysics Data System (ADS)

Fang, Hongbin; Li, Suyi; Ji, Huimin; Wang, K. W.

2017-05-01

Origami-inspired structures and materials have shown extraordinary properties and performances originating from the intricate geometries of folding. However, current state of the art studies have mostly focused on static and quasistatic characteristics. This research performs a comprehensive experimental and analytical study on the dynamics of origami folding through investigating a stacked Miura-Ori (SMO) structure with intrinsic bistability. We fabricate and experimentally investigated a bistable SMO prototype with rigid facets and flexible crease lines. Under harmonic base excitation, the SMO exhibits both intrawell and interwell oscillations. Spectrum analyses reveal that the dominant nonlinearities of SMO are quadratic and cubic, which generate rich dynamics including subharmonic and chaotic oscillations. The identified nonlinearities indicate that a third-order polynomial can be employed to approximate the measured force-displacement relationship. Such an approximation is validated via numerical study by qualitatively reproducing the phenomena observed in the experiments. The dynamic characteristics of the bistable SMO resemble those of a Helmholtz-Duffing oscillator (HDO); this suggests the possibility of applying the established tools and insights of HDO to predict origami dynamics. We also show that the bistability of SMO can be programmed within a large design space via tailoring the crease stiffness and initial stress-free configurations. The results of this research offer a wealth of fundamental insights into the dynamics of origami folding, and provide a solid foundation for developing foldable and deployable structures and materials with embedded dynamic functionalities.

Reduced Smoothened level rescues Aβ-induced memory deficits and neuronal inflammation in animal models of Alzheimer's disease.

PubMed

Ma, Weiwei; Wu, Mengnan; Zhou, Siyan; Tao, Ye; Xie, Zuolei; Zhong, Yi

2018-05-20

Emerging evidence suggests that neuro-inflammation begins early and drives the pathogenesis of Alzheimer's disease (AD), and anti-inflammatory therapies are under clinical development. However, several anti-inflammatory compounds failed to improve memory in clinical trials, indicating that reducing inflammation alone might not be enough. On the other hand, neuro-inflammation is implicated in a number of mental disorders which share the same therapeutic targets. Based on these observations, we screened a batch of genes related with mental disorder and neuro-inflammation in a classical olfactory conditioning in an amyloid beta (Aβ) overexpression fly model. A Smoothened (SMO) mutant was identified as a genetic modifier of Aβ toxicity in 3-min memory and downregulation of SMO rescued Aβ-induced 3-min and 1-h memory deficiency. Also, Aβ activated innate inflammatory response in fly by increasing the expression of antimicrobial peptides, which were alleviated by downregulating SMO. Furthermore, pharmaceutical administration of a SMO antagonist LDE rescued Aβ-induced upregulation of SMO in astrocytes of mouse hippocampus, improved memory in Morris water maze (MWM), and reduced expression of astrocyte secreting pro-inflammatory factors IL-1β, TNFα and the microglia marker IBA-1 in an APP/PS1 transgenic mouse model. Our study suggests that SMO is an important conserved modulator of Aβ toxicity in both fly and mouse models of AD. Copyright © 2018. Published by Elsevier Ltd.

On the effectiveness of noise masks: naturalistic vs. un-naturalistic image statistics.

PubMed

Hansen, Bruce C; Hess, Robert F

2012-05-01

It has been argued that the human visual system is optimized for identification of broadband objects embedded in stimuli possessing orientation averaged power spectra fall-offs that obey the 1/f(β) relationship typically observed in natural scene imagery (i.e., β=2.0 on logarithmic axes). Here, we were interested in whether individual spatial channels leading to recognition are functionally optimized for narrowband targets when masked by noise possessing naturalistic image statistics (β=2.0). The current study therefore explores the impact of variable β noise masks on the identification of narrowband target stimuli ranging in spatial complexity, while simultaneously controlling for physical or perceived differences between the masks. The results show that β=2.0 noise masks produce the largest identification thresholds regardless of target complexity, and thus do not seem to yield functionally optimized channel processing. The differential masking effects are discussed in the context of contrast gain control. Copyright © 2012 Elsevier Ltd. All rights reserved.

Patient with Gorlin syndrome and metastatic basal cell carcinoma refractory to smoothened inhibitors.

PubMed

Zhu, Gefei A; Li, Angela S; Chang, Anne Lynn S

2014-08-01

Basal cell carcinomas (BCCs) in patients with Gorlin syndrome have been reported to be extremely sensitive to Smoothened (SMO) inhibitors, a novel targeted therapy against the Hedgehog pathway, because of characteristic mutations in these patients. A few cases of disease refractory to oral therapy with SMO inhibitors have been reported in patients with Gorlin syndrome and nonmetastatic BCCs, but refractory disease in distantly metastatic tumors has not been documented in this high-risk group. A man with Gorlin syndrome and innumerable cutaneous BCCs presented with biopsy-proven BCC in his lungs. After SMO inhibitor therapy, almost all of his cutaneous tumors shrank, but his lung metastases did not. These lung metastases remained refractory to treatment despite institution of a second SMO inhibitor. We report a case of Gorlin syndrome in a patient with metastatic BCC refractory to SMO inhibitors. Furthermore, clinical responses in this patient's cutaneous tumors did not parallel the responses in the distant site. However, serial imaging after diagnosis of metastatic disease can be critical to monitor for response to therapy.

Magnetic and electronic properties of SrMnO3 thin films

NASA Astrophysics Data System (ADS)

Mandal, Arup Kumar; Panchal, Gyanendra; Choudhary, R. J.; Phase, D. M.

2018-05-01

Single phase hexagonal bulk SrMnO3 (SMO) was prepared by solid state route and it was used for depositing thin films by pulsed laser deposition (PLD) technique on single crystalline (100) oriented SrTiO3 (STO) substrate. X-ray diffraction shows that the thin film is deposited in cubic SrMnO3 phase. From X-ray absorption at the Mn L edge we observed the mixed valency of Mn (Mn3+& Mn4+) due to strain induced by the lattice mismatching between SMO and STO. Due to this mixed valency of Mn ion in SMO film, the ferromagnetic nature is observed at lower temperature because of double exchange. After post annealing with very low oxygen partial pressure, magnetic and electronic property of SMO films are effectively modified.

Optimizing the taste-masked formulation of acetaminophen using sodium caseinate and lecithin by experimental design.

PubMed

Hoang Thi, Thanh Huong; Lemdani, Mohamed; Flament, Marie-Pierre

2013-09-10

In a previous study of ours, the association of sodium caseinate and lecithin was demonstrated to be promising for masking the bitterness of acetaminophen via drug encapsulation. The encapsulating mechanisms were suggested to be based on the segregation of multicomponent droplets occurring during spray-drying. The spray-dried particles delayed the drug release within the mouth during the early time upon administration and hence masked the bitterness. Indeed, taste-masking is achieved if, within the frame of 1-2 min, drug substance is either not released or the released amount is below the human threshold for identifying its bad taste. The aim of this work was (i) to evaluate the effect of various processing and formulation parameters on the taste-masking efficiency and (ii) to determine the optimal formulation for optimal taste-masking effect. Four investigated input variables included inlet temperature (X1), spray flow (X2), sodium caseinate amount (X3) and lecithin amount (X4). The percentage of drug release amount during the first 2 min was considered as the response variable (Y). A 2(4)-full factorial design was applied and allowed screening for the most influential variables i.e. sodium caseinate amount and lecithin amount. Optimizing these two variables was therefore conducted by a simplex approach. The SEM and DSC results of spray-dried powder prepared under optimal conditions showed that drug seemed to be well encapsulated. The drug release during the first 2 min significantly decreased, 7-fold less than the unmasked drug particles. Therefore, the optimal formulation that performed the best taste-masking effect was successfully achieved. Copyright © 2013 Elsevier B.V. All rights reserved.

Near-Infrared Spectroscopic Measurement of the Effect of Leg Dominance on Muscle Oxygen Saturation During Cycling

NASA Technical Reports Server (NTRS)

Ellerby, Gwenn E. C.; Lee, Stuart M. C.; Paunescu, Lelia Adelina; Pereira, Chelsea; Smith, Charles P.; Soller, Babs R.

2011-01-01

The effect of leg dominance on the symmetry of the biomechanics during cycling remains uncertain -- asymmetries have been observed in kinematics and kinetics, while symmetries were found in muscle activation. No studies have yet investigated the symmetry of muscle metabolism during cycling. Near-infrared spectroscopy (NIRS) provides a non-invasive method to investigate the metabolic responses of specific muscles during cycling. PURPOSE: To determine whether there was an effect of leg dominance on thigh muscle oxygen saturation (SmO2) during incrementally loaded submaximal cycling using NIRS. METHODS: Eight right leg dominant, untrained subjects (5 men, 3 women; 31+/-2 yrs; 168.6+/-1.0 cm; 67.2+/-1.8 kg, mean +/- SE) volunteered to participate. Spectra were collected bilaterally from the vastus lateralis (VL) during supine rest and cycling. SmO2 was calculated using previously published methods. Subjects pedaled at 65 rpm while resistance to pedaling was increased in 0.5 kp increments from 0.5 kp every 3 min until the subject reached 80% of age-predicted maximal heart rate. SmO2 was averaged over 3 min for each completed stage. A two-way ANOVA was performed to test for leg differences. A priori contrasts were used to compare work levels to rest. RESULTS: VL SmO2 was not different between the dominant and non-dominant legs at rest and during exercise (p=0.57). How SmO2 changed with workload was also not different between legs (p=0.32). SmO2 at 0.5 kp (60.3+/-4.0, p=0.12) and 1.0 kp (59.5+/-4.0, p=0.10) was not different from rest (69.1+/-4.0). SmO2 at 1.5 kp (55.4 4.0, p=0.02), 2.0 kp (55.7+/-5.0, p=0.04), and 2.5 kp (43.4+/-7.9, p=0.01) was significantly lower than rest. CONCLUSION: VL SmO2 during cycling is not different between dominant and non-dominant legs and decreases with moderate workload in untrained cyclists. Assuming blood flow is directed equally to both legs, similar levels of oxygen extraction (as indicated by SmO2) suggests the metabolic load of cycling is not different between legs. This is in agreement with a recent study demonstrating symmetrical increase of muscle activation of the VL during cycling. Leg dominance did not influence VL SmO2 during submaximal cycling, but may have an effect at higher loads or during other forms of exercise, such as walking and running.

Antineoplastic Efficacy of Novel Polyamine Analogues in Human Breast Cancer

DTIC Science & Technology

2005-06-01

Davidson, N.E., and Casero, R.A.. Spermine oxidase SMO(PAOh1), not N1-acetylpolyamine oxidase (PAO) is the primary source of cytotoxic H2O2 in polyamine... spermine oxidase (PAOh1/SMO) mRNA and activity by a polyamine analogue in human breast cancer cell lines. The fourth Era of Hope meeting for the...SMO/PAOh1 Spermine Oxidase DFMO α-difluoromethylornithine BENSpm N1, N11-bis(ethyl)norspermine CHEMSpm N1-(cycloheptylmethyl)-N11-ethyl- 4,8

Tunable wavefront coded imaging system based on detachable phase mask: Mathematical analysis, optimization and underlying applications

NASA Astrophysics Data System (ADS)

Zhao, Hui; Wei, Jingxuan

2014-09-01

The key to the concept of tunable wavefront coding lies in detachable phase masks. Ojeda-Castaneda et al. (Progress in Electronics Research Symposium Proceedings, Cambridge, USA, July 5-8, 2010) described a typical design in which two components with cosinusoidal phase variation operate together to make defocus sensitivity tunable. The present study proposes an improved design and makes three contributions: (1) A mathematical derivation based on the stationary phase method explains why the detachable phase mask of Ojeda-Castaneda et al. tunes the defocus sensitivity. (2) The mathematical derivations show that the effective bandwidth wavefront coded imaging system is also tunable by making each component of the detachable phase mask move asymmetrically. An improved Fisher information-based optimization procedure was also designed to ascertain the optimal mask parameters corresponding to specific bandwidth. (3) Possible applications of the tunable bandwidth are demonstrated by simulated imaging.

Acyl-CoA-Binding Protein ACBP1 Modulates Sterol Synthesis during Embryogenesis1[OPEN

PubMed Central

Hsiao, An-Shan; Xue, Yan

2017-01-01

Fatty acids (FAs) and sterols are primary metabolites that exert interrelated functions as structural and signaling lipids. Despite their common syntheses from acetyl-coenzyme A, homeostatic cross talk remains enigmatic. Six Arabidopsis (Arabidopsis thaliana) acyl-coenzyme A-binding proteins (ACBPs) are involved in FA metabolism. ACBP1 interacts with PHOSPHOLIPASE Dα1 and regulates phospholipid composition. Here, its specific role in the negative modulation of sterol synthesis during embryogenesis is reported. ACBP1, likely in a liganded state, interacts with STEROL C4-METHYL OXIDASE1-1 (SMO1-1), a rate-limiting enzyme in the sterol pathway. Proembryo abortion in the double mutant indicated that the ACBP1-SMO1-1 interaction is synthetic lethal, corroborating with their strong promoter activities in developing ovules. Gas chromatography-mass spectrometry revealed quantitative and compositional changes in FAs and sterols upon overexpression or mutation of ACBP1 and/or SMO1-1. Aberrant levels of these metabolites may account for the downstream defect in lipid signaling. GLABRA2 (GL2), encoding a phospholipid/sterol-binding homeodomain transcription factor, was up-regulated in developing seeds of acbp1, smo1-1, and ACBP1+/−smo1-1 in comparison with the wild type. Consistent with the corresponding transcriptional alteration of GL2 targets, high-oil, low-mucilage phenotypes of gl2 were phenocopied in ACBP1+/−smo1-1. Thus, ACBP1 appears to modulate the metabolism of two important lipid classes (FAs and sterols) influencing cellular signaling. PMID:28500265

Masking Strategies for Image Manifolds.

PubMed

Dadkhahi, Hamid; Duarte, Marco F

2016-07-07

We consider the problem of selecting an optimal mask for an image manifold, i.e., choosing a subset of the pixels of the image that preserves the manifold's geometric structure present in the original data. Such masking implements a form of compressive sensing through emerging imaging sensor platforms for which the power expense grows with the number of pixels acquired. Our goal is for the manifold learned from masked images to resemble its full image counterpart as closely as possible. More precisely, we show that one can indeed accurately learn an image manifold without having to consider a large majority of the image pixels. In doing so, we consider two masking methods that preserve the local and global geometric structure of the manifold, respectively. In each case, the process of finding the optimal masking pattern can be cast as a binary integer program, which is computationally expensive but can be approximated by a fast greedy algorithm. Numerical experiments show that the relevant manifold structure is preserved through the datadependent masking process, even for modest mask sizes.

Validation of Procedures for Monitoring Crewmember Immune Function SDBI-1900, SMO-015 - Integrated Immune

NASA Technical Reports Server (NTRS)

Crucian, Brian; Stowe, Raymond; Mehta, Satish; Uchakin, Peter; Nehlsen-Cannarella, Sandra; Morukov, Boris; Pierson, Duane; Sams, Clarence

2007-01-01

There is ample evidence to suggest that space flight leads to immune system dysregulation. This may be a result of microgravity, confinement, physiological stress, radiation, environment or other mission-associated factors. The clinical risk from prolonged immune dysregulation during space flight are not yet determined, but may include increased incidence of infection, allergy, hypersensitivity, hematological malignancy or altered wound healing. Each of the clinical events resulting from immune dysfunction has the potential to impact mission critical objectives during exploration-class missions. To date, precious little in-flight immune data has been generated to assess this phenomenon. The majority of recent flight immune studies have been post-flight assessments, which may not accurately reflect the in-flight condition. There are no procedures currently in place to monitor immune function or its effect on crew health. The objective of this Supplemental Medical Objective (SMO) is to develop and validate an immune monitoring strategy consistent with operational flight requirements and constraints. This SMO will assess the clinical risks resulting from the adverse effects of space flight on the human immune system and will validate a flight-compatible immune monitoring strategy. Characterization of the clinical risk and the development of a monitoring strategy are necessary prerequisite activities prior to validating countermeasures. This study will determine, to the best level allowed by current technology, the in-flight status of crewmembers immune system. Pre-flight, in-flight and post-flight assessments of immune status, immune function, viral reactivation and physiological stress will be performed. The in-flight samples will allow a distinction between legitimate in-flight alterations and the physiological stresses of landing and readaptation which are believed to alter landing day assessments. The overall status of the immune system during flight (activation, deficiency, dysregulation) and the response of the immune system to specific latent virus reactivation (known to occur during space flight) will be thoroughly assessed. Following completion of the SMO the data will be evaluated to determine the optimal set of assays for routine monitoring of crewmember immune system function, should the clinical risk warrant such monitoring.

Serial robot for the trajectory optimization and error compensation of TMT mask exchange system

NASA Astrophysics Data System (ADS)

Wang, Jianping; Zhang, Feifan; Zhou, Zengxiang; Zhai, Chao

2015-10-01

Mask exchange system is the main part of Multi-Object Broadband Imaging Echellette (MOBIE) on the Thirty Meter Telescope (TMT). According to the conception of the TMT mask exchange system, the pre-design was introduced in the paper which was based on IRB 140 robot. The stiffness model of IRB 140 in SolidWorks was analyzed under different gravity vectors for further error compensation. In order to find the right location and path planning, the robot and the mask cassette model was imported into MOBIE model to perform different schemes simulation. And obtained the initial installation position and routing. Based on these initial parameters, IRB 140 robot was operated to simulate the path and estimate the mask exchange time. Meanwhile, MATLAB and ADAMS software were used to perform simulation analysis and optimize the route to acquire the kinematics parameters and compare with the experiment results. After simulation and experimental research mentioned in the paper, the theoretical reference was acquired which could high efficient improve the structure of the mask exchange system parameters optimization of the path and precision of the robot position.

Dry etching technologies for reflective multilayer

NASA Astrophysics Data System (ADS)

Iino, Yoshinori; Karyu, Makoto; Ita, Hirotsugu; Kase, Yoshihisa; Yoshimori, Tomoaki; Muto, Makoto; Nonaka, Mikio; Iwami, Munenori

2012-11-01

We have developed a highly integrated methodology for patterning Extreme Ultraviolet (EUV) mask, which has been highlighted for the lithography technique at the 14nm half-pitch generation and beyond. The EUV mask is characterized as a reflective-type mask which is completely different compared with conventional transparent-type of photo mask. And it requires not only patterning of absorber layer without damaging the underlying multi reflective layers (40 Si/Mo layers) but also etching multi reflective layers. In this case, the dry etch process has generally faced technical challenges such as the difficulties in CD control, etch damage to quartz substrate and low selectivity to the mask resist. Shibaura Mechatronics ARESTM mask etch system and its optimized etch process has already achieved the maximal etch performance at patterning two-layered absorber. And in this study, our process technologies of multi reflective layers will be evaluated by means of optimal combination of process gases and our optimized plasma produced by certain source power and bias power. When our ARES™ is used for multilayer etching, the user can choose to etch the absorber layer at the same time or etch only the multilayer.

The efficacy of novel anatomical sites for the assessment of muscle oxygenation during central hypovolemia.

PubMed

Sprick, Justin D; Soller, Babs R; Rickards, Caroline A

2016-11-01

Muscle tissue oxygenation (SmO 2 ) can track central blood volume loss associated with hemorrhage. Traditional peripheral measurement sites (e.g., forearm) may not be practical due to excessive movement or injury (e.g., amputation). The aim of this study was to evaluate the efficacy of three novel anatomical sites for the assessment of SmO 2 under progressive central hypovolemia. 10 male volunteers were exposed to stepwise prone lower body negative pressure to decrease central blood volume, while SmO 2 was assessed at four sites-the traditional site of the flexor carpi ulnaris (ARM), and three novel sites not previously investigated during lower body negative pressure, the deltoid, latissimus dorsi, and trapezius. SmO 2 at the novel sites was compared to the ARM sensor and to stroke volume responses. A reduction in SmO 2 was detected by the ARM sensor at the first level of lower body negative pressure (-15 mmHg; P = 0.007), and at -30 (the deltoid), -45 (latissimus dorsi), and -60 mmHg lower body negative pressure (trapezius) at the novel sites (P ≤ 0.04). SmO 2 responses at all novel sites were correlated with responses at the ARM (R ≥ 0.89), and tracked the reduction in stroke volume (R ≥ 0.87); the latissimus dorsi site exhibited the strongest linear correlations (R ≥ 0.96). Of the novel sensor sites, the latissimus dorsi exhibited the strongest linear associations with SmO 2 at the ARM, and with reductions in central blood volume. These findings have important implications for detection of hemorrhage in austere environments (e.g., combat) when use of a peripheral sensor may not be ideal, and may facilitate incorporation of these sensors into uniforms. © 2016 by the Society for Experimental Biology and Medicine.

Infrared spectra and density functional calculations for SMO2 molecules (M = Cr, Mo, W).

PubMed

Wang, Xuefeng; Andrews, Lester

2009-08-06

Infrared absorptions of the matrix isolated SMO2 (M = Cr, Mo, W) molecules were observed following laser-ablated metal atom reactions with SO2 during condensation in solid argon and neon. The symmetric and antisymmetric M-O stretching mode assignments were confirmed by appropriate S18O2 and S(16,18)O2 isotopic shifts. The much weaker Cr-S stretching mode was identified through its 34S shift. Density functional (B3LYP and BPW91) calculations were performed to obtain molecular structures and to reproduce the infrared spectra. Computed pyramidal structures for the SMO2 molecules are very similar to those for the analogous trioxides and this functional group in [MO2S(bdt)]2- complexes. Additional weaker absorptions are assigned to the (SO2)(SMO2) adducts, which are stabilized by a four-membered ring.

Sensorless control of ship propulsion interior permanent magnet synchronous motor based on a new sliding mode observer.

PubMed

Ren, Jun-Jie; Liu, Yan-Cheng; Wang, Ning; Liu, Si-Yuan

2015-01-01

This paper proposes a sensorless speed control strategy for ship propulsion interior permanent magnet synchronous motor (IPMSM) based on a new sliding-mode observer (SMO). In the SMO the low-pass filter and the method of arc-tangent calculation of extended electromotive force (EMF) or phase-locked loop (PLL) technique are not used. The calculation of the rotor speed is deduced from the Lyapunov function stability analysis. In order to reduce system chattering, sigmoid functions with switching gains being adaptively updated by fuzzy logic systems are innovatively incorporated into the SMO. Finally, simulation results for a 4.088 MW ship propulsion IPMSM and experimental results from a 7.5 kW IPMSM drive are provided to verify the effectiveness of the proposed SMO method. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Structure of the human smoothened receptor 7TM bound to an antitumor agent

PubMed Central

Wang, Chong; Wu, Huixian; Katritch, Vsevolod; Han, Gye Won; Huang, Xi-Ping; Liu, Wei; Siu, Fai Yiu; Roth, Bryan L.; Cherezov, Vadim; Stevens, Raymond C.

2013-01-01

The smoothened (SMO) receptor, a key signal transducer in the Hedgehog (Hh) signaling pathway is both responsible for the maintenance of normal embryonic development and implicated in carcinogenesis. The SMO receptor is classified as a class Frizzled (class F) G protein-coupled receptor (GPCR), although the canonical Hh signaling pathway involves the transcription factor Gli and the sequence similarity with class A GPCRs is less than 10%. Here we report the crystal structure at 2.5 Å resolution of the transmembrane domain of the human SMO receptor bound to the small molecule antagonist LY2940680. Although the SMO receptor shares the seven transmembrane helical (7TM) fold, most conserved motifs for class A GPCRs are absent, and the structure reveals an unusually complex arrangement of long extracellular loops stabilized by four disulfide bonds. The ligand binds at the extracellular end of the 7TM bundle and forms extensive contacts with the loops. PMID:23636324

Model-based assist feature insertion for sub-40nm memory device

NASA Astrophysics Data System (ADS)

Suh, Sungsoo; Lee, Suk-joo; Choi, Seong-woon; Lee, Sung-Woo; Park, Chan-hoon

2009-04-01

Many issues need to be resolved for a production-worthy model based assist feature insertion flow for single and double exposure patterning process to extend low k1 process at 193 nm immersion technology. Model based assist feature insertion is not trivial to implement either for single and double exposure patterning compared to rule based methods. As shown in Fig. 1, pixel based mask inversion technology in itself has difficulties in mask writing and inspection although it presents as one of key technology to extend single exposure for contact layer. Thus far, inversion technology is tried as a cooptimization of target mask to simultaneously generate optimized main and sub-resolution assists features for a desired process window. Alternatively, its technology can also be used to optimize for a target feature after an assist feature types are inserted in order to simplify the mask complexity. Simplification of inversion mask is one of major issue with applying inversion technology to device development even if a smaller mask feature can be fabricated since the mask writing time is also a major factor. As shown in Figure 2, mask writing time may be a limiting factor in determining whether or not an inversion solution is viable. It can be reasoned that increased number of shot counts relates to increase in margin for inversion methodology. On the other hand, there is a limit on how complex a mask can be in order to be production worthy. There is also source and mask co-optimization which influences the final mask patterns and assist feature sizes and positions for a given target. In this study, we will discuss assist feature insertion methods for sub 40-nm technology.

Acyl-CoA-Binding Protein ACBP1 Modulates Sterol Synthesis during Embryogenesis.

PubMed

Lung, Shiu-Cheung; Liao, Pan; Yeung, Edward C; Hsiao, An-Shan; Xue, Yan; Chye, Mee-Len

2017-07-01

Fatty acids (FAs) and sterols are primary metabolites that exert interrelated functions as structural and signaling lipids. Despite their common syntheses from acetyl-coenzyme A, homeostatic cross talk remains enigmatic. Six Arabidopsis ( Arabidopsis thaliana ) acyl-coenzyme A-binding proteins (ACBPs) are involved in FA metabolism. ACBP1 interacts with PHOSPHOLIPASE Dα1 and regulates phospholipid composition. Here, its specific role in the negative modulation of sterol synthesis during embryogenesis is reported. ACBP1, likely in a liganded state, interacts with STEROL C4-METHYL OXIDASE1-1 (SMO1-1), a rate-limiting enzyme in the sterol pathway. Proembryo abortion in the double mutant indicated that the ACBP1-SMO1-1 interaction is synthetic lethal, corroborating with their strong promoter activities in developing ovules. Gas chromatography-mass spectrometry revealed quantitative and compositional changes in FAs and sterols upon overexpression or mutation of ACBP1 and/or SMO1-1 Aberrant levels of these metabolites may account for the downstream defect in lipid signaling. GLABRA2 ( GL2 ), encoding a phospholipid/sterol-binding homeodomain transcription factor, was up-regulated in developing seeds of acbp1 , smo1-1 , and ACBP1 +/- smo1-1 in comparison with the wild type. Consistent with the corresponding transcriptional alteration of GL2 targets, high-oil, low-mucilage phenotypes of gl2 were phenocopied in ACBP1 +/- smo1-1 Thus, ACBP1 appears to modulate the metabolism of two important lipid classes (FAs and sterols) influencing cellular signaling. © 2017 American Society of Plant Biologists. All Rights Reserved.

OPC and PSM design using inverse lithography: a nonlinear optimization approach

NASA Astrophysics Data System (ADS)

Poonawala, Amyn; Milanfar, Peyman

2006-03-01

We propose a novel method for the fast synthesis of low complexity model-based optical proximity correction (OPC) and phase shift masks (PSM) to improve the resolution and pattern fidelity of optical microlithography. We use the pixel-based mask representation, a continuous function formulation, and gradient based iterative optimization techniques to solve the above inverse problem. The continuous function formulation allows analytic calculation of the gradient. Pixel-based parametrization provides tremendous liberty in terms of the features possible in the synthesized masks, but also suffers the inherent disadvantage that the masks are very complex and difficult to manufacture. We therefore introduce the regularization framework; a useful tool which provides the flexibility to promote certain desirable properties in the solution. We employ the above framework to ensure that the estimated masks have only two or three (allowable) transmission values and are also comparatively simple and easy to manufacture. The results demonstrate that we are able to bring the CD on target using OPC masks. Furthermore, we were also able to boost the contrast of the aerial image using attenuated, strong, and 100% transmission phase shift masks. Our algorithm automatically (and optimally) adds assist-bars, dog-ears, serifs, anti-serifs, and other custom structures best suited for printing the desired pattern.

Effects of bovine SMO gene polymorphisms on the body measurement and meat quality traits of Qinchuan cattle.

PubMed

Zhang, Y R; Li, Y K; Fu, C Z; Wang, J L; Wang, H B; Zan, L S

2014-10-07

Beef cattle breeding programs focus on improving important economic traits, including growth rates, and meat quantity and quality. Molecular marker-assisted selection based on genetic variation represents a potential method for breeding genetically improved livestock with better economic traits. Smoothened (SMO) protein is a signal transducer that contributes to the regulation of both osteogenesis and adipogenesis through the hedgehog pathway. In this study, we detected polymorphisms in the bovine SMO gene of Qinchuan cattle, and we analyzed their associations with body measurement traits (BMTs) and meat quality traits (MQTs). Using DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism, 3 novel single nucleotide polymorphisms were identified in the SMO gene of 562 cattle: 1 G > C mutation on exon 9 (G21234C) and 2 C > T mutations on exon 11 (C22424T and C22481T). Association analysis showed that polymorphisms on both the G21234C and C22424T loci significantly affected certain BMTs and MQTs (P < 0.05 or P < 0.01), whereas those on the C22481T locus did not (P > 0.05). Therefore, the SMO gene could be used as a candidate gene to alter BMTs and MQTs in Qinchuan cattle or for marker-assisted selection to breed cattle with superior BMTs and MQTs.

Regaining motor control in musician's dystonia by restoring sensorimotor organisation

PubMed Central

Rosenkranz, Karin; Butler, Katherine; Williamon, Aaron; Rothwell, John C.

2010-01-01

Professional musicians are an excellent human model of long term effects of skilled motor training on the structure and function of the motor system. However, such effects are accompanied by an increased risk of developing motor abnormalities, in particular musician's dystonia. Previously we found that there was an expanded spatial integration of proprioceptive input into the hand area of motor cortex (sensorimotor organisation, SMO) in healthy musicians as tested with a transcranial magnetic stimulation (TMS) paradigm. In musician's dystonia, this expansion was even larger, resulting in a complete lack of somatotopic organisation. We hypothesised that the disordered motor control in musician's dystonia is a consequence of the disordered SMO. In the present paper we test this idea by giving pianists with musician's dystonia 15 min experience of a modified proprioceptive training task. This restored SMO towards that seen in healthy pianists. Crucially, motor control of the affected task improved significantly and objectively as measured with a MIDI piano, and the amount of behavioural improvement was significantly correlated to the degree of sensorimotor re-organisation. In healthy pianists and non-musicians, the SMO and motor performance remained essentially unchanged. These findings suggest a link between the differentiation of SMO in the hand motor cortex and the degree of motor control of intensively practiced tasks in highly skilled individuals. PMID:19923295

Identification of optimal mask size parameter for noise filtering in 99mTc-methylene diphosphonate bone scintigraphy images.

PubMed

Pandey, Anil K; Bisht, Chandan S; Sharma, Param D; ArunRaj, Sreedharan Thankarajan; Taywade, Sameer; Patel, Chetan; Bal, Chandrashekhar; Kumar, Rakesh

2017-11-01

Tc-methylene diphosphonate (Tc-MDP) bone scintigraphy images have limited number of counts per pixel. A noise filtering method based on local statistics of the image produces better results than a linear filter. However, the mask size has a significant effect on image quality. In this study, we have identified the optimal mask size that yields a good smooth bone scan image. Forty four bone scan images were processed using mask sizes 3, 5, 7, 9, 11, 13, and 15 pixels. The input and processed images were reviewed in two steps. In the first step, the images were inspected and the mask sizes that produced images with significant loss of clinical details in comparison with the input image were excluded. In the second step, the image quality of the 40 sets of images (each set had input image, and its corresponding three processed images with 3, 5, and 7-pixel masks) was assessed by two nuclear medicine physicians. They selected one good smooth image from each set of images. The image quality was also assessed quantitatively with a line profile. Fisher's exact test was used to find statistically significant differences in image quality processed with 5 and 7-pixel mask at a 5% cut-off. A statistically significant difference was found between the image quality processed with 5 and 7-pixel mask at P=0.00528. The identified optimal mask size to produce a good smooth image was found to be 7 pixels. The best mask size for the John-Sen Lee filter was found to be 7×7 pixels, which yielded Tc-methylene diphosphonate bone scan images with the highest acceptable smoothness.

Sorption of selected veterinary antibiotics onto dairy farming soils of contrasting nature.

PubMed

Srinivasan, Prakash; Sarmah, Ajit K; Manley-Harris, Merilyn

2014-02-15

The sorption potential for three sulfonamides (SAs), sulfamethoxazole (SMO), sulfachloropyridazine (SCP) and sulfamethazine (SM) and a macrolide, tylosin tartrate (TT) was assessed on six New Zealand dairy farming soils of contrasting physico-chemical properties. Kinetics studies showed that the sorption was rapid in the first few hours of the contact time (0-2h for SA and 0-4h for TT) and thereafter apparent equilibrium was achieved. Batch sorption isotherm data revealed that the degree of isotherm linearity (N) for SCP and SM varied between 0.50 and 1.08 in the six soils. Isotherms of both TT and SMO were mostly non-linear with the degree of non-linearity for TT (N=0.38-0.71) being greater than for SMO (0.42-0.75) in all soils except Manawatu (TT) and Te Kowhai (SMO) where a linear pattern was observed. Concentration-dependent effective distribution coefficient (Kd(eff)) values for the SMO, SCP and SM antibiotics in the soils ranged from 0.85 to 16.35 L kg(-1), while that for TT was 1.6 to 1,042 L kg(-1). The sorption affinity for all soils followed an order: TT>SCP>SM>SMO. Remarkable high sorption for tylosin in Matawhero soil as compared to other soils was attributed to the presence of oxygen containing acidic polar functional groups as evident in the FT-IR spectra of the soil. Furthermore, it was hypothesised that sorption of TT onto soils was mostly driven by metal oxide-surface mediated transformations whereas for sulfonamides it was primarily due to hydrophobic interactions. Copyright © 2013 Elsevier B.V. All rights reserved.

The α Subunit of the G Protein G13 Regulates Activity of One or More Gli Transcription Factors Independently of Smoothened*

PubMed Central

Douglas, Andrew E.; Heim, Jennifer A.; Shen, Feng; Almada, Luciana L.; Riobo, Natalia A.; Fernández-Zapico, Martin E.; Manning, David R.

2011-01-01

Smoothened (Smo) is a seven-transmembrane (7-TM) receptor that is essential to most actions of the Hedgehog family of morphogens. We found previously that Smo couples to members of the Gi family of heterotrimeric G proteins, which in some cases are integral although alone insufficient in the activation of Gli transcription factors through Hedgehog signaling. In response to a report that the G12/13 family is relevant to Hedgehog signaling as well, we re-evaluated the coupling of Smo to one member of this family, G13, and investigated the capacity of this and other G proteins to activate one or more of forms of Gli. We found no evidence that Smo couples directly to G13. We found nonetheless that Gα13 and to some extent Gαq and Gα12 are able to effect activation of Gli(s). This capacity is realized in some cells, e.g. C3H10T1/2, MC3T3, and pancreatic cancer cells, but not all cells. The mechanism employed is distinct from that achieved through canonical Hedgehog signaling, as the activation does not involve autocrine signaling or in any other way require active Smo and does not necessarily involve enhanced transcription of Gli1. The activation by Gα13 can be replicated through a Gq/G12/13-coupled receptor, CCKA, and is attenuated by inhibitors of p38 mitogen-activated protein kinase and Tec tyrosine kinases. We posit that G proteins, and perhaps G13 in particular, provide access to Gli that is independent of Smo and that they thus establish a basis for control of at least some forms of Gli-mediated transcription apart from Hedgehogs. PMID:21757753

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ge, Xin; Lyu, Pengwei; Gu, Yuanting

Sonic hesgehog (Shh) signaling has been reported to play an essential role in cancer progression. The mechanism of Shh involved in breast cancer carcinogenesis remains unclear. The present study sought to explore whether Shh signaling could regulate the glycolytic metabolism in breast cancers. Overexpression of the smoothed (Smo) and Gli-1 was found in human primary breast cancers. The expressions of Shh and Gli-1 correlated significantly with tumor size and tumor stage. In vitro, human recombinant Shh (rShh) triggered Smo and Gli-1 expression, promoted glucose utilization and lactate production, and accelerated cell proliferation in MCF-7 and MDA-MB-231 cells. Notably, rShh did notmore » alter 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) expression but augmented PFKFB3 phosphorylation on ser{sup 461}, along with elevated fructose-2,6-bisphosphate (F2,6BP) generation by MCF-7 and MDA-MB-231 cells. This effect could be dampened by Smo siRNA but not by Gli-1 siRNA. In addition, our data showed the upregulated expressions of MAPK by rShh and elevatory PFKFB3 phosphorylation by p38/MAPK activated kinase (MK2). In conclusion, our study characterized a novel role of Shh in promoting glycolysis and proliferation of breast cancer cells via PFKFB3 phosphorylation, which was mediated by Smo and p38/MK2. - Highlights: • Overexpression of Smo and Gli-1 was found in human primary breast cancers. • Shh promoted glucose utilization, lactate production, and cell proliferation. • Shh did not alter PFKFB3 expression but augmented PFKFB3 phosphorylation on ser461. • Shh acts on PFKFB3 phosphorylation via Smo and p38 MAPK/MK2.« less

Synthesis of bilayer MoS{sub 2} nanosheets by a facile hydrothermal method and their methyl orange adsorption capacity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ye, Lijuan; Xu, Haiyan; Zhang, Dingke

2014-07-01

Highlights: • Hexagonal phase of MoS{sub 2} nanosheets was synthesized by a facile hydrothermal method. • FE-SEM and TEM images show the sheets-like morphology of MoS{sub 2}. • Bilayer MoS{sub 2} can be grown under the optimized mole ratio of 2:1 of S:Mo at 180 °C for 50 h. • The MoS{sub 2} nanosheets possess high methyl orange adsorption capacity due to the large surface area. - Abstract: Molybdenum disulfide (MoS{sub 2}) nanosheets have received significant attention recently due to the potential applications for exciting physics and technology. Here we show that MoS{sub 2} nanosheets can be prepared by amore » facile hydrothermal method. The study of the properties of the MoS{sub 2} nanosheets prepared at different conditions suggests that the mole ratio of precursors and hydrothermal time significantly influences the purity, crystalline quality and thermal stability of MoS{sub 2}. X-ray diffraction, Raman spectra and transmission electron microscopy results indicate that bilayer MoS{sub 2} can be grown under an optimized mole ratio of 2:1 of S:Mo at 180 °C for 50 h. Moreover, such ultrathin nanosheets exhibit a prominent photoluminescence and possess high methyl orange adsorption capacity due to the large surface area, which can be potentially used in photodevice and photochemical catalyst.« less

Optimization of a methamphetamine conjugate vaccine for antibody production in mice.

PubMed

Stevens, Misty W; Gunnell, Melinda G; Tawney, Rachel; Owens, S Michael

2016-06-01

There are still no approved medications for treating patients who abuse methamphetamine. Active vaccines for treating abuse of nicotine and cocaine are in clinical studies, but have not proven effective seemingly due to inadequate anti-drug antibody production. The current studies aimed to optimize the composition, adjuvant and route of administration of a methamphetamine conjugate vaccine, ICKLH-SMO9, in mice with the goal of generating significantly higher antibody levels. A range of hapten epitope densities were compared, as were the adjuvants Alhydrogel and a new Toll-like receptor 4 (TLR4) agonist called GLA-SE. While methamphetamine hapten density did not strongly affect the antibody response, the adjuvant did. Glucopyranosyl lipid A in a stable oil-in-water emulsion (GLA-SE) produced much higher levels of antibody in response to immunization compared with Alhydrogel; immunization with GLA-SE also produced antibodies with higher affinities for methamphetamine. GLA-SE has been used in human studies of vaccines for influenza among others and like some other clinical TLR4 agonists, it is safe and elicits a strong immune response. GLA-SE adjuvanted vaccines are typically administered by intramuscular injection and this also proved effective in these mouse studies. Clinical studies of the ICKLH-SMO9 methamphetamine vaccine adjuvanted with GLA-SE have the potential for demonstrating efficacy by generating much higher levels of antibody than substance abuse vaccines that have unsuccessfully used aluminum-based adjuvants. Copyright © 2016 Elsevier B.V. All rights reserved.

Decoding the phosphorylation code in Hedgehog signal transduction

PubMed Central

Chen, Yongbin; Jiang, Jin

2013-01-01

Hedgehog (Hh) signaling plays pivotal roles in embryonic development and adult tissue homeostasis, and its deregulation leads to numerous human disorders including cancer. Binding of Hh to Patched (Ptc), a twelve-transmembrane protein, alleviates its inhibition of Smoothened (Smo), a seven-transmembrane protein related to G-protein-coupled receptors (GPCRs), leading to Smo phosphorylation and activation. Smo acts through intracellular signaling complexes to convert the latent transcription factor Cubitus interruptus (Ci)/Gli from a truncated repressor to a full-length activator, leading to derepression/activation of Hh target genes. Increasing evidence suggests that phosphorylation participates in almost every step in the signal relay from Smo to Ci/Gli, and that differential phosphorylation of several key pathway components may be crucial for translating the Hh morphogen gradient into graded pathway activities. In this review, we focus on the multifaceted roles that phosphorylation plays in Hh signal transduction, and discuss the conservation and difference between Drosophila and mammalian Hh signaling mechanisms. PMID:23337587

Sonic hedgehog signaling regulates actin cytoskeleton via Tiam1-Rac1 cascade during spine formation.

PubMed

Sasaki, Nobunari; Kurisu, Junko; Kengaku, Mineko

2010-12-01

The sonic hedgehog (Shh) pathway has essential roles in several processes during development of the vertebrate central nervous system (CNS). Here, we report that Shh regulates dendritic spine formation in hippocampal pyramidal neurons via a novel pathway that directly regulates the actin cytoskeleton. Shh signaling molecules Patched (Ptc) and Smoothened (Smo) are expressed in several types of postmitotic neurons, including cerebellar Purkinje cells and hippocampal pyramidal neurons. Knockdown of Smo induces dendritic spine formation in cultured hippocampal neurons independently of Gli-mediated transcriptional activity. Smo interacts with Tiam1, a guanine nucleotide exchange factor for Rac1, via its cytoplasmic C-terminal region. Inhibition of Tiam1 or Rac1 activity suppresses spine induction by Smo knockdown. Shh induces remodeling of the actin cytoskeleton independently of transcriptional activation in mouse embryonic fibroblasts. These findings demonstrate a novel Shh pathway that regulates the actin cytoskeleton via Tiam1-Rac1 activation. Copyright © 2010 Elsevier Inc. All rights reserved.

Peptide amphiphile nanofiber hydrogel delivery of sonic hedgehog protein to the cavernous nerve to promote regeneration and prevent erectile dysfunction.

PubMed

Choe, Shawn; Bond, Christopher W; Harrington, Daniel A; Stupp, Samuel I; McVary, Kevin T; Podlasek, Carol A

2017-01-01

Erectile dysfunction (ED) has high impact on quality of life in prostatectomy, diabetic and aging patients. An underlying mechanism is cavernous nerve (CN) injury, which causes ED in up to 80% of prostatectomy patients. We examine how sonic hedgehog (SHH) treatment with innovative peptide amphiphile nanofiber hydrogels (PA), promotes CN regeneration after injury. SHH and its receptors patched (PTCH1) and smoothened (SMO) are localized in PG neurons and glia. SMO undergoes anterograde transport to signal to downstream targets. With crush injury, PG neurons degenerate and undergo apoptosis. SHH protein decreases, SMO localization changes to the neuronal cell surface, and anterograde transport stops. With SHH treatment SHH is taken up at the injury site and undergoes retrograde transport to PG neurons, allowing SMO transport to occur, and neurons remain intact. SHH treatment prevents neuronal degeneration, maintains neuronal, glial and downstream target signaling, and is significant as a regenerative therapy. Published by Elsevier Inc.

Cholesterol activates the G-protein coupled receptor Smoothened to promote Hedgehog signaling

PubMed Central

Luchetti, Giovanni; Sircar, Ria; Kong, Jennifer H; Nachtergaele, Sigrid; Sagner, Andreas; Byrne, Eamon FX; Covey, Douglas F; Siebold, Christian; Rohatgi, Rajat

2016-01-01

Cholesterol is necessary for the function of many G-protein coupled receptors (GPCRs). We find that cholesterol is not just necessary but also sufficient to activate signaling by the Hedgehog (Hh) pathway, a prominent cell-cell communication system in development. Cholesterol influences Hh signaling by directly activating Smoothened (SMO), an orphan GPCR that transmits the Hh signal across the membrane in all animals. Unlike many GPCRs, which are regulated by cholesterol through their heptahelical transmembrane domains, SMO is activated by cholesterol through its extracellular cysteine-rich domain (CRD). Residues shown to mediate cholesterol binding to the CRD in a recent structural analysis also dictate SMO activation, both in response to cholesterol and to native Hh ligands. Our results show that cholesterol can initiate signaling from the cell surface by engaging the extracellular domain of a GPCR and suggest that SMO activity may be regulated by local changes in cholesterol abundance or accessibility. DOI: http://dx.doi.org/10.7554/eLife.20304.001 PMID:27705744

A new predictive model for continuous positive airway pressure in the treatment of obstructive sleep apnea.

PubMed

Ebben, Matthew R; Narizhnaya, Mariya; Krieger, Ana C

2017-05-01

Numerous mathematical formulas have been developed to determine continuous positive airway pressure (CPAP) without an in-laboratory titration study. Recent studies have shown that style of CPAP mask can affect the optimal pressure requirement. However, none of the current models take mask style into account. Therefore, the goal of this study was to develop new predictive models of CPAP that take into account the style of mask interface. Data from 200 subjects with attended CPAP titrations during overnight polysomnograms using nasal masks and 132 subjects using oronasal masks were randomized and split into either a model development or validation group. Predictive models were then created in each model development group and the accuracy of the models was then tested in the model validation groups. The correlation between our new oronasal model and laboratory determined optimal CPAP was significant, r = 0.61, p < 0.001. Our nasal formula was also significantly related to laboratory determined optimal CPAP, r = 0.35, p < 0.001. The oronasal model created in our study significantly outperformed the original CPAP predictive model developed by Miljeteig and Hoffstein, z = 1.99, p < 0.05. The predictive performance of our new nasal model did not differ significantly from Miljeteig and Hoffstein's original model, z = -0.16, p < 0.90. The best predictors for the nasal mask group were AHI, lowest SaO2, and neck size, whereas the top predictors in the oronasal group were AHI and lowest SaO2. Our data show that predictive models of CPAP that take into account mask style can significantly improve the formula's accuracy. Most of the past models likely focused on model development with nasal masks (mask style used for model development was not typically reported in previous investigations) and are not well suited for patients using an oronasal interface. Our new oronasal CPAP prediction equation produced significantly improved performance compared to the well-known Miljeteig and Hoffstein formula in patients titrated on CPAP with an oronasal mask and was also significantly related to laboratory determined optimal CPAP.

Muscle Oxygen Saturation Improves Diagnostic Association Between Initial Vital Signs and Major Hemorrhage: A Prospective Observational Study.

PubMed

Reisner, Andrew T; Edla, Shwetha; Liu, Jianbo; Rubin, John T; Thorsen, Jill E; Kittell, Erin; Smith, Jason B; Yeh, Daniel D; Reifman, Jaques

2016-03-01

During initial assessment of trauma patients, vital signs do not identify all patients with life-threatening hemorrhage. We hypothesized that a novel vital sign, muscle oxygen saturation (SmO2 ), could provide independent diagnostic information beyond routine vital signs for identification of hemorrhaging patients who require packed red blood cell (RBC) transfusion. This was an observational study of adult trauma patients treated at a Level I trauma center. Study staff placed the CareGuide 1100 tissue oximeter (Reflectance Medical Inc., Westborough, MA), and we analyzed average values of SmO2 , systolic blood pressure (sBP), pulse pressure (PP), and heart rate (HR) during 10 minutes of early emergency department evaluation. We excluded subjects without a full set of vital signs during the observation interval. The study outcome was hemorrhagic injury and RBC transfusion ≥ 3 units in 24 hours (24-hr RBC ≥ 3). To test the hypothesis that SmO2 added independent information beyond routine vital signs, we developed one logistic regression model with HR, sBP, and PP and one with SmO2 in addition to HR, sBP, and PP and compared their areas under receiver operating characteristic curves (ROC AUCs) using DeLong's test. We enrolled 487 subjects; 23 received 24-hr RBC ≥ 3. Compared to the model without SmO2 , the regression model with SmO2 had a significantly increased ROC AUC for the prediction of ≥ 3 units of 24-hr RBC volume, 0.85 (95% confidence interval [CI], 0.75-0.91) versus 0.77 (95% CI, 0.66-0.86; p < 0.05 per DeLong's test). Results were similar for ROC AUCs predicting patients (n = 11) receiving 24-hr RBC ≥ 9. SmO2 significantly improved the diagnostic association between initial vital signs and hemorrhagic injury with blood transfusion. This parameter may enhance the early identification of patients who require blood products for life-threatening hemorrhage. © 2016 The Authors. Academic Emergency Medicine published by Wiley Periodicals, Inc. on behalf of Society for Academic Emergency Medicine.

Spontaneous sulfur dioxide activation by Group V metal (V, Nb, Ta) atoms in excess argon at cryogenic temperatures.

PubMed

Liu, Xing; Wang, Xuefeng; Wang, Qiang; Andrews, Lester

2013-06-28

Reactions of laser-ablated V, Nb and Ta atoms with SO2 in excess argon during condensation gave new absorptions in the M=O stretching region, which were assigned to metal sulfide oxides SMO2 and anions SMO2(-) (M = V, Nb, Ta). The metal oxide complex OV(η(2)-SO) was also identified through the V=O and the characteristic side-on coordinated S-O stretching modes. The assignments of major vibrational modes were confirmed by appropriate S(18)O2 and (34)SO2 isotopic shifts, and density functional frequency calculations. DFT calculations were employed to study the behavior of reactions of Group V bare metal atoms with SO2, and a representative profile was derived which not only showed the preferred coordinating fashion of metal atoms but also tracked the path of S-O bond activation. The η(2)-O,O' bridge coordinated complexes are preferred with energy decreases of ca. 50 kcal mol(-1) for all three metals, which facilitate the activation of two S-O bonds in succession and finally direct the reaction to the most stable molecules SMO2 (M = V, Nb, Ta) along the potential energy surface (PES). Finally the SMO2 molecules capture electrons to give anions SMO2(-) with about 3.6 eV electron affinities based on DFT calculations.

The Hedgehog processing pathway is required for NSCLC growth and survival

PubMed Central

Rodriguez-Blanco, Jezabel; Schilling, Neal S.; Tokhunts, Robert; Giambelli, Camilla; Long, Jun; Liang Fei, Dennis; Singh, Samer; Black, Kendall E.; Wang, Zhiqiang; Galimberti, Fabrizio; Bejarano, Pablo A.; Elliot, Sharon; Glassberg, Marilyn K.; Nguyen, Dao M.; Lockwood, William W.; Lam, Wan L.; Dmitrovsky, Ethan; Capobianco, Anthony J.; Robbins, David J.

2013-01-01

Considerable interest has been generated from the results of recent clinical trials using SMOOTHENED (SMO) antagonists to inhibit the growth of HEDGEHOG (HH) signaling dependent tumors. This interest is tempered by the discovery of SMO mutations mediating resistance, underscoring the rationale for developing therapeutic strategies that interrupt HH signaling at levels distinct from those inhibiting SMO function. Here, we demonstrate that HH dependent non-small cell lung carcinoma (NSCLC) growth is sensitive to blockade of the HH pathway upstream of SMO, at the level of HH ligand processing. Individually, the use of different lentivirally delivered shRNA constructs targeting two functionally distinct HH-processing proteins, SKINNY HEDGEHOG (SKN) or DISPATCHED-1 (DISP-1), in NSCLC cell lines produced similar decreases in cell proliferation and increased cell death. Further, providing either an exogenous source of processed HH or a SMO agonist reverses these effects. The attenuation of HH processing, by knocking down either of these gene products, also abrogated tumor growth in mouse xenografts. Finally, we extended these findings to primary clinical specimens, showing that SKN is frequently over-expressed in NSCLC and that higher DISP-1 expression is associated with an unfavorable clinical outcome. Our results show a critical role for HH processing in HH-dependent tumors, identifies two potential druggable targets in the HH pathway, and suggest that similar therapeutic strategies could be explored to treat patients harboring HH ligand dependent cancers. PMID:22733134

Mask etcher data strategy for 45nm and beyond

NASA Astrophysics Data System (ADS)

Lewington, Richard; Ibrahim, Ibrahim M.; Panayil, Sheeba; Kumar, Ajay; Yamartino, John

2006-05-01

Mask Etching for the 45nm technology node and beyond requires a system-level data and diagnostics strategy. This necessity stems from the need to control the performance of the mask etcher to increasingly stringent and diverse requirements of the mask production environment. Increasing mask costs and the capability to acquire and consolidate a wealth of data within the mask etch platform are primary motivators towards harnessing data mines for feedback into the mask etching optimization. There are offline and real-time possibilities and scenarios. Here, we discuss the data architecture, acquisition, and strategies of the Applied Materials Tetra II TM Mask Etch System.

Long range personalized cancer treatment strategies incorporating evolutionary dynamics.

PubMed

Yeang, Chen-Hsiang; Beckman, Robert A

2016-10-22

Current cancer precision medicine strategies match therapies to static consensus molecular properties of an individual's cancer, thus determining the next therapeutic maneuver. These strategies typically maintain a constant treatment while the cancer is not worsening. However, cancers feature complicated sub-clonal structure and dynamic evolution. We have recently shown, in a comprehensive simulation of two non-cross resistant therapies across a broad parameter space representing realistic tumors, that substantial improvement in cure rates and median survival can be obtained utilizing dynamic precision medicine strategies. These dynamic strategies explicitly consider intratumoral heterogeneity and evolutionary dynamics, including predicted future drug resistance states, and reevaluate optimal therapy every 45 days. However, the optimization is performed in single 45 day steps ("single-step optimization"). Herein we evaluate analogous strategies that think multiple therapeutic maneuvers ahead, considering potential outcomes at 5 steps ahead ("multi-step optimization") or 40 steps ahead ("adaptive long term optimization (ALTO)") when recommending the optimal therapy in each 45 day block, in simulations involving both 2 and 3 non-cross resistant therapies. We also evaluate an ALTO approach for situations where simultaneous combination therapy is not feasible ("Adaptive long term optimization: serial monotherapy only (ALTO-SMO)"). Simulations utilize populations of 764,000 and 1,700,000 virtual patients for 2 and 3 drug cases, respectively. Each virtual patient represents a unique clinical presentation including sizes of major and minor tumor subclones, growth rates, evolution rates, and drug sensitivities. While multi-step optimization and ALTO provide no significant average survival benefit, cure rates are significantly increased by ALTO. Furthermore, in the subset of individual virtual patients demonstrating clinically significant difference in outcome between approaches, by far the majority show an advantage of multi-step or ALTO over single-step optimization. ALTO-SMO delivers cure rates superior or equal to those of single- or multi-step optimization, in 2 and 3 drug cases respectively. In selected virtual patients incurable by dynamic precision medicine using single-step optimization, analogous strategies that "think ahead" can deliver long-term survival and cure without any disadvantage for non-responders. When therapies require dose reduction in combination (due to toxicity), optimal strategies feature complex patterns involving rapidly interleaved pulses of combinations and high dose monotherapy. This article was reviewed by Wendy Cornell, Marek Kimmel, and Andrzej Swierniak. Wendy Cornell and Andrzej Swierniak are external reviewers (not members of the Biology Direct editorial board). Andrzej Swierniak was nominated by Marek Kimmel.

Design Architecture of field-effect transistor with back gate electrode for biosensor application

NASA Astrophysics Data System (ADS)

Fathil, M. F. M.; Arshad, M. K. Md.; Hashim, U.; Ruslinda, A. R.; Gopinath, Subash C. B.; M. Nuzaihan M., N.; Ayub, R. M.; Adzhri, R.; Zaki, M.; Azman, A. H.

2016-07-01

This paper presents the preparation method of photolithography chrome mask design used in fabrication process of field-effect transistor with back gate biasing based biosensor. Initially, the chrome masks are designed by studying the process flow of the biosensor fabrication, followed by drawing of the actual chrome mask using the AutoCAD software. The overall width and length of the device is optimized at 16 mm and 16 mm, respectively. Fabrication processes of the biosensor required five chrome masks, which included source and drain formation mask, the back gate area formation mask, electrode formation mask, front gate area formation mask, and passivation area formation mask. The complete chrome masks design will be sent for chrome mask fabrication and for future use in biosensor fabrication.

Advanced EUV mask and imaging modeling

NASA Astrophysics Data System (ADS)

Evanschitzky, Peter; Erdmann, Andreas

2017-10-01

The exploration and optimization of image formation in partially coherent EUV projection systems with complex source shapes requires flexible, accurate, and efficient simulation models. This paper reviews advanced mask diffraction and imaging models for the highly accurate and fast simulation of EUV lithography systems, addressing important aspects of the current technical developments. The simulation of light diffraction from the mask employs an extended rigorous coupled wave analysis (RCWA) approach, which is optimized for EUV applications. In order to be able to deal with current EUV simulation requirements, several additional models are included in the extended RCWA approach: a field decomposition and a field stitching technique enable the simulation of larger complex structured mask areas. An EUV multilayer defect model including a database approach makes the fast and fully rigorous defect simulation and defect repair simulation possible. A hybrid mask simulation approach combining real and ideal mask parts allows the detailed investigation of the origin of different mask 3-D effects. The image computation is done with a fully vectorial Abbe-based approach. Arbitrary illumination and polarization schemes and adapted rigorous mask simulations guarantee a high accuracy. A fully vectorial sampling-free description of the pupil with Zernikes and Jones pupils and an optimized representation of the diffraction spectrum enable the computation of high-resolution images with high accuracy and short simulation times. A new pellicle model supports the simulation of arbitrary membrane stacks, pellicle distortions, and particles/defects on top of the pellicle. Finally, an extension for highly accurate anamorphic imaging simulations is included. The application of the models is demonstrated by typical use cases.

Strategy optimization for mask rule check in wafer fab

NASA Astrophysics Data System (ADS)

Yang, Chuen Huei; Lin, Shaina; Lin, Roger; Wang, Alice; Lee, Rachel; Deng, Erwin

2015-07-01

Photolithography process is getting more and more sophisticated for wafer production following Moore's law. Therefore, for wafer fab, consolidated and close cooperation with mask house is a key to achieve silicon wafer success. However, generally speaking, it is not easy to preserve such partnership because many engineering efforts and frequent communication are indispensable. The inattentive connection is obvious in mask rule check (MRC). Mask houses will do their own MRC at job deck stage, but the checking is only for identification of mask process limitation including writing, etching, inspection, metrology, etc. No further checking in terms of wafer process concerned mask data errors will be implemented after data files of whole mask are composed in mask house. There are still many potential data errors even post-OPC verification has been done for main circuits. What mentioned here are the kinds of errors which will only occur as main circuits combined with frame and dummy patterns to form whole reticle. Therefore, strategy optimization is on-going in UMC to evaluate MRC especially for wafer fab concerned errors. The prerequisite is that no impact on mask delivery cycle time even adding this extra checking. A full-mask checking based on job deck in gds or oasis format is necessary in order to secure acceptable run time. Form of the summarized error report generated by this checking is also crucial because user friendly interface will shorten engineers' judgment time to release mask for writing. This paper will survey the key factors of MRC in wafer fab.

A reduced-order nonlinear sliding mode observer for vehicle slip angle and tyre forces

NASA Astrophysics Data System (ADS)

Chen, Yuhang; Ji, Yunfeng; Guo, Konghui

2014-12-01

In this paper, a reduced-order sliding mode observer (RO-SMO) is developed for vehicle state estimation. Several improvements are achieved in this paper. First, the reference model accuracy is improved by considering vehicle load transfers and using a precise nonlinear tyre model 'UniTire'. Second, without the reference model accuracy degraded, the computing burden of the state observer is decreased by a reduced-order approach. Third, nonlinear system damping is integrated into the SMO to speed convergence and reduce chattering. The proposed RO-SMO is evaluated through simulation and experiments based on an in-wheel motor electric vehicle. The results show that the proposed observer accurately predicts the vehicle states.

Lithographic process window optimization for mask aligner proximity lithography

NASA Astrophysics Data System (ADS)

Voelkel, Reinhard; Vogler, Uwe; Bramati, Arianna; Erdmann, Andreas; Ünal, Nezih; Hofmann, Ulrich; Hennemeyer, Marc; Zoberbier, Ralph; Nguyen, David; Brugger, Juergen

2014-03-01

We introduce a complete methodology for process window optimization in proximity mask aligner lithography. The commercially available lithography simulation software LAB from GenISys GmbH was used for simulation of light propagation and 3D resist development. The methodology was tested for the practical example of lines and spaces, 5 micron half-pitch, printed in a 1 micron thick layer of AZ® 1512HS1 positive photoresist on a silicon wafer. A SUSS MicroTec MA8 mask aligner, equipped with MO Exposure Optics® was used in simulation and experiment. MO Exposure Optics® is the latest generation of illumination systems for mask aligners. MO Exposure Optics® provides telecentric illumination and excellent light uniformity over the full mask field. MO Exposure Optics® allows the lithography engineer to freely shape the angular spectrum of the illumination light (customized illumination), which is a mandatory requirement for process window optimization. Three different illumination settings have been tested for 0 to 100 micron proximity gap. The results obtained prove, that the introduced process window methodology is a major step forward to obtain more robust processes in mask aligner lithography. The most remarkable outcome of the presented study is that a smaller exposure gap does not automatically lead to better print results in proximity lithography - what the "good instinct" of a lithographer would expect. With more than 5'000 mask aligners installed in research and industry worldwide, the proposed process window methodology might have significant impact on yield improvement and cost saving in industry.

CoSMoS: Conserved Sequence Motif Search in the proteome

PubMed Central

Liu, Xiao I; Korde, Neeraj; Jakob, Ursula; Leichert, Lars I

2006-01-01

Background With the ever-increasing number of gene sequences in the public databases, generating and analyzing multiple sequence alignments becomes increasingly time consuming. Nevertheless it is a task performed on a regular basis by researchers in many labs. Results We have now created a database called CoSMoS to find the occurrences and at the same time evaluate the significance of sequence motifs and amino acids encoded in the whole genome of the model organism Escherichia coli K12. We provide a precomputed set of multiple sequence alignments for each individual E. coli protein with all of its homologues in the RefSeq database. The alignments themselves, information about the occurrence of sequence motifs together with information on the conservation of each of the more than 1.3 million amino acids encoded in the E. coli genome can be accessed via the web interface of CoSMoS. Conclusion CoSMoS is a valuable tool to identify highly conserved sequence motifs, to find regions suitable for mutational studies in functional analyses and to predict important structural features in E. coli proteins. PMID:16433915

GLI activation by atypical protein kinase C ι/λ regulates the growth of basal cell carcinomas.

PubMed

Atwood, Scott X; Li, Mischa; Lee, Alex; Tang, Jean Y; Oro, Anthony E

2013-02-28

Growth of basal cell carcinomas (BCCs) requires high levels of hedgehog (HH) signalling through the transcription factor GLI. Although inhibitors of membrane protein smoothened (SMO) effectively suppress HH signalling, early tumour resistance illustrates the need for additional downstream targets for therapy. Here we identify atypical protein kinase C ι/λ (aPKC-ι/λ) as a novel GLI regulator in mammals. aPKC-ι/λ and its polarity signalling partners co-localize at the centrosome and form a complex with missing-in-metastasis (MIM), a scaffolding protein that potentiates HH signalling. Genetic or pharmacological loss of aPKC-ι/λ function blocks HH signalling and proliferation of BCC cells. Prkci is a HH target gene that forms a positive feedback loop with GLI and exists at increased levels in BCCs. Genome-wide transcriptional profiling shows that aPKC-ι/λ and SMO control the expression of similar genes in tumour cells. aPKC-ι/λ functions downstream of SMO to phosphorylate and activate GLI1, resulting in maximal DNA binding and transcriptional activation. Activated aPKC-ι/λ is upregulated in SMO-inhibitor-resistant tumours and targeting aPKC-ι/λ suppresses signalling and growth of resistant BCC cell lines. These results demonstrate that aPKC-ι/λ is critical for HH-dependent processes and implicates aPKC-ι/λ as a new, tumour-selective therapeutic target for the treatment of SMO-inhibitor-resistant cancers.

CoSMoS and TwinPaW: initial report on two new German twin studies.

PubMed

Spinath, Frank M; Wolf, Heike

2006-12-01

After briefly recapitulating two earlier German twin studies (BiLSAT and GOSAT), we present two new German twin studies with a longitudinal perspective: CoSMoS and TwinPaW. The twin study on Cognitive ability, Self-reported Motivation and School performance (CoSMoS) aims to investigate predictors and influences of school performance in a genetically sensitive design, beginning with children in late elementary school. The Twin study on Personality And Wellbeing (TwinPaW) focuses on adult personality and its relation to physical health as well as health-related behavior in an adult sample of twins. Both studies are characterized by an effort to recruit new large twin samples through a novel recruitment procedure aimed at reducing self-selective sampling. In two German federal states, contact information on persons born on the same day and with the same name was retrieved from record sections. From the resulting pool of more than 36,000 addresses we contacted approximately 2000 parents of twins aged 9 and 10 for CoSMoS, as well as 2000 adult twin pairs for TwinPaW by telephone and mail. Personal contact by telephone proved to be more efficient with agreement rates of 63% in the children sample and 65% in the adult sample. In this article we briefly describe the rationale and the study aims of CoSMoS and TwinPaW as well as the characteristics of the sample we have recruited so far.

Optimal mask characterization by Surrogate Wafer Print (SWaP) method

NASA Astrophysics Data System (ADS)

Kimmel, Kurt R.; Hoellein, Ingo; Peters, Jan Hendrick; Ackmann, Paul; Connolly, Brid; West, Craig

2008-10-01

Traditionally, definition of mask specifications is done completely by the mask user, while characterization of the mask relative to the specifications is done completely by the mask maker. As the challenges of low-k1 imaging continue to grow in scope of designs and in absolute complexity, the inevitable partnership between wafer lithographers and mask makers has strengthened as well. This is reflected in the jointly owned mask facilities and device manufacturers' continued maintenance of fully captive mask shops which foster the closer mask-litho relationships. However, while some device manufacturers have leveraged this to optimize mask specifications before the mask is built and, therefore, improve mask yield and cost, the opportunity for post-fabrication partnering on mask characterization is more apparent and compelling. The Advanced Mask Technology Center (AMTC) has been investigating the concept of assessing how a mask images, rather than the mask's physical attributes, as a technically superior and lower-cost method to characterize a mask. The idea of printing a mask under its intended imaging conditions, then characterizing the imaged wafer as a surrogate for traditional mask inspections and measurements represents the ultimate method to characterize a mask's performance, which is most meaningful to the user. Surrogate wafer print (SWaP) is already done as part of leading-edge wafer fab mask qualification to validate defect and dimensional performance. In the past, the prospect of executing this concept has generally been summarily discarded as technically untenable and logistically intractable. The AMTC published a paper at BACUS 2007 successfully demonstrating the performance of SWaP for the characterization of defects as an alternative to traditional mask inspection [1]. It showed that this concept is not only feasible, but, in some cases, desirable. This paper expands on last year's work at AMTC to assess the full implementation of SWaP as an enhancement to mask characterization quality including defectivity, dimensional control, pattern fidelity, and in-plane distortion. We present a thorough analysis of both the technical and logistical challenges coupled with an objective view of the advantages and disadvantages from both the technical and financial perspectives. The analysis and model used by the AMTC will serve to provoke other mask shops to prepare their own analyses then consider this new paradigm for mask characterization and qualification.

Stenotrophomonas maltophilia responds to exogenous AHL signals through the LuxR solo SmoR (Smlt1839).

PubMed

Martínez, Paula; Huedo, Pol; Martinez-Servat, Sònia; Planell, Raquel; Ferrer-Navarro, Mario; Daura, Xavier; Yero, Daniel; Gibert, Isidre

2015-01-01

Quorum Sensing (QS) mediated by Acyl Homoserine Lactone (AHL) molecules are probably the most widespread and studied among Gram-negative bacteria. Canonical AHL systems are composed by a synthase (LuxI family) and a regulator element (LuxR family), whose genes are usually adjacent in the genome. However, incomplete AHL-QS machinery lacking the synthase LuxI is frequently observed in Proteobacteria, and the regulator element is then referred as LuxR solo. It has been shown that certain LuxR solos participate in interspecific communication by detecting signals produced by different organisms. In the case of Stenotrophomonas maltophilia, a preliminary genome sequence analysis revealed numerous putative luxR genes, none of them associated to a luxI gene. From these, the hypothetical LuxR solo Smlt1839, here designated SmoR, presents a conserved AHL binding domain and a helix-turn-helix DNA binding motif. Its genomic organization-adjacent to hchA gene-indicate that SmoR belongs to the new family "LuxR regulator chaperone HchA-associated." AHL-binding assays revealed that SmoR binds to AHLs in-vitro, at least to oxo-C8-homoserine lactone, and it regulates operon transcription, likely by recognizing a conserved palindromic regulatory box in the hchA upstream region. Supplementation with concentrated supernatants from Pseudomonas aeruginosa, which contain significant amounts of AHLs, promoted swarming motility in S. maltophilia. Contrarily, no swarming stimulation was observed when the P. aeruginosa supernatant was treated with the lactonase AiiA from Bacillus subtilis, confirming that AHL contributes to enhance the swarming ability of S. maltophilia. Finally, mutation of smoR resulted in a swarming alteration and an apparent insensitivity to the exogenous AHLs provided by P. aeruginosa. In conclusion, our results demonstrate that S. maltophilia senses AHLs produced by neighboring bacteria through the LuxR solo SmoR, regulating population behaviors such as swarming motility.

Design of aerosol face masks for children using computerized 3D face analysis.

PubMed

Amirav, Israel; Luder, Anthony S; Halamish, Asaf; Raviv, Dan; Kimmel, Ron; Waisman, Dan; Newhouse, Michael T

2014-08-01

Aerosol masks were originally developed for adults and downsized for children. Overall fit to minimize dead space and a tight seal are problematic, because children's faces undergo rapid and marked topographic and internal anthropometric changes in their first few months/years of life. Facial three-dimensional (3D) anthropometric data were used to design an optimized pediatric mask. Children's faces (n=271, aged 1 month to 4 years) were scanned with 3D technology. Data for the distance from the bridge of the nose to the tip of the chin (H) and the width of the mouth opening (W) were used to categorize the scans into "small," "medium," and "large" "clusters." "Average" masks were developed from each cluster to provide an optimal seal with minimal dead space. The resulting computerized contour, W and H, were used to develop the SootherMask® that enables children, "suckling" on their own pacifier, to keep the mask on their face, mainly by means of subatmospheric pressure. The relatively wide and flexible rim of the mask accommodates variations in facial size within and between clusters. Unique pediatric face masks were developed based on anthropometric data obtained through computerized 3D face analysis. These masks follow facial contours and gently seal to the child's face, and thus may minimize aerosol leakage and dead space.

Amine oxidase-based biosensors for spermine and spermidine determination.

PubMed

Boffi, Alberto; Favero, Gabriele; Federico, Rodolfo; Macone, Alberto; Antiochia, Riccarda; Tortolini, Cristina; Sanzó, Gabriella; Mazzei, Franco

2015-02-01

The present work describes the development and optimization of electrochemical biosensors for specific determination of the biogenic polyamine spermine (Spm) and spermidine (Spmd) whose assessment represents a novel important analytical tool in food analysis and human diagnostics. These biosensors have been prepared using novel engineered enzymes: polyamine oxidase (PAO) endowed with selectivity towards Spm and Spmd and spermine oxidase (SMO) characterized by strict specificity towards Spm. The current design entails biosensors in which the enzymes were entrapped in poly(vinyl alcohol) bearing styrylpyridinium groups (PVA-SbQ), a photocrosslinkable gel, onto an electrode surface. Screen-printed electrodes (SPEs) were used as electrochemical transducers for enzymatically produced hydrogen peroxide, operating at different potential vs Ag/AgCl according to the material of the working electrode (WE): +700 mV for graphite (GP) or -100 mV for Prussian blue (PB)-modified SPE, respectively. Biosensor performances were evaluated by means of flow injection amperometric (FIA) measurements. The modified electrodes showed good sensitivity, long-term stability and reproducibility. Under optimal conditions, the PAO biosensor showed a linear range 0.003-0.3 mM for Spm and 0.01-0.4 mM for Spmd, while with the SMO biosensor, a linear range of 0.004-0.5 mM for Spm has been obtained. The main kinetic parameters apparent Michaelis constant (K M), turnover number (K cat) and steady-state current (I max) were determined. The proposed device was then applied to the determination of biogenic amines in blood samples. The results obtained were in good agreement with those obtained with the GC-MS reference method.

The influence of negative training set size on machine learning-based virtual screening.

PubMed

Kurczab, Rafał; Smusz, Sabina; Bojarski, Andrzej J

2014-01-01

The paper presents a thorough analysis of the influence of the number of negative training examples on the performance of machine learning methods. The impact of this rather neglected aspect of machine learning methods application was examined for sets containing a fixed number of positive and a varying number of negative examples randomly selected from the ZINC database. An increase in the ratio of positive to negative training instances was found to greatly influence most of the investigated evaluating parameters of ML methods in simulated virtual screening experiments. In a majority of cases, substantial increases in precision and MCC were observed in conjunction with some decreases in hit recall. The analysis of dynamics of those variations let us recommend an optimal composition of training data. The study was performed on several protein targets, 5 machine learning algorithms (SMO, Naïve Bayes, Ibk, J48 and Random Forest) and 2 types of molecular fingerprints (MACCS and CDK FP). The most effective classification was provided by the combination of CDK FP with SMO or Random Forest algorithms. The Naïve Bayes models appeared to be hardly sensitive to changes in the number of negative instances in the training set. In conclusion, the ratio of positive to negative training instances should be taken into account during the preparation of machine learning experiments, as it might significantly influence the performance of particular classifier. What is more, the optimization of negative training set size can be applied as a boosting-like approach in machine learning-based virtual screening.

The influence of negative training set size on machine learning-based virtual screening

PubMed Central

2014-01-01

Background The paper presents a thorough analysis of the influence of the number of negative training examples on the performance of machine learning methods. Results The impact of this rather neglected aspect of machine learning methods application was examined for sets containing a fixed number of positive and a varying number of negative examples randomly selected from the ZINC database. An increase in the ratio of positive to negative training instances was found to greatly influence most of the investigated evaluating parameters of ML methods in simulated virtual screening experiments. In a majority of cases, substantial increases in precision and MCC were observed in conjunction with some decreases in hit recall. The analysis of dynamics of those variations let us recommend an optimal composition of training data. The study was performed on several protein targets, 5 machine learning algorithms (SMO, Naïve Bayes, Ibk, J48 and Random Forest) and 2 types of molecular fingerprints (MACCS and CDK FP). The most effective classification was provided by the combination of CDK FP with SMO or Random Forest algorithms. The Naïve Bayes models appeared to be hardly sensitive to changes in the number of negative instances in the training set. Conclusions In conclusion, the ratio of positive to negative training instances should be taken into account during the preparation of machine learning experiments, as it might significantly influence the performance of particular classifier. What is more, the optimization of negative training set size can be applied as a boosting-like approach in machine learning-based virtual screening. PMID:24976867

EUVL back-insertion layout optimization

NASA Astrophysics Data System (ADS)

Civay, D.; Laffosse, E.; Chesneau, A.

2018-03-01

Extreme ultraviolet lithography (EUVL) is targeted for front-up insertion at advanced technology nodes but will be evaluated for back insertion at more mature nodes. EUVL can put two or more mask levels back on one mask, depending upon what level(s) in the process insertion occurs. In this paper, layout optimization methods are discussed that can be implemented when EUVL back insertion is implemented. The layout optimizations can be focused on improving yield, reliability or density, depending upon the design needs. The proposed methodology modifies the original two or more colored layers and generates an optimized single color EUVL layout design.

Regaining motor control in musician's dystonia by restoring sensorimotor organization.

PubMed

Rosenkranz, Karin; Butler, Katherine; Williamon, Aaron; Rothwell, John C

2009-11-18

Professional musicians are an excellent model of long-term motor learning effects on structure and function of the sensorimotor system. However, intensive motor skill training has been associated with task-specific deficiency in hand motor control, which has a higher prevalence among musicians (musician's dystonia) than in the general population. Using a transcranial magnetic stimulation paradigm, we previously found an expanded spatial integration of proprioceptive input into the hand motor cortex [sensorimotor organization (SMO)] in healthy musicians. In musician's dystonia, however, this expansion was even larger. Whereas motor skills of musicians are likely to be supported by a spatially expanded SMO, we hypothesized that in musician's dystonia this might have developed too far and now disrupts rather than assists task-specific motor control. If so, motor control should be regained by reversing the excessive reorganization in musician's dystonia. Here, we test this hypothesis and show that a 15 min intervention with proprioceptive input (proprioceptive training) restored SMO in pianists with musician's dystonia to the pattern seen in healthy pianists. Crucially, task-specific motor control improved significantly and objectively as measured with a MIDI (musical instrument digital interface) piano, and the amount of behavioral improvement was significantly correlated to the degree of sensorimotor reorganization. In healthy pianists and nonmusicians, the SMO and motor performance remained essentially unchanged. These findings suggest that the differentiation of SMO in the hand motor cortex and the degree of motor control of intensively practiced tasks are significantly linked and finely balanced. Proprioceptive training restored this balance in musician's dystonia to the behaviorally beneficial level of healthy musicians.

Suppression of hedgehog signaling regulates hepatic stellate cell activation and collagen secretion.

PubMed

Li, Tao; Leng, Xi-Sheng; Zhu, Ji-Ye; Wang, Gang

2015-01-01

Hepatic stellate cells (HSCs) play an important role in liver fibrosis. This study investigates the expression of hedgehog in HSC and the role of hedgehog signaling on activation and collagen secretion of HSC. Liver ex vivo perfusion with collagenase IV and density gradient centrifugation were used to isolate HSC. Expression of hedgehog signaling components Ihh, Smo, Ptc, Gli2 and Gli3 in HSC were detected by RT-PCR. Hedgehog siRNA vectors targeting Ihh, Smo and Gli2 were constructed and transfected into HSC respectively. Suppression of hedgehog signaling were detected by SYBR Green fluorescence quantitative RT-PCR. Effects of hedgehog signaling inhibition on HSC activation and collagen I secretion were analyzed. Hedgehog signaling components Ihh, Smo, Ptc, Gli2 and Gli3 were expressed in HSC. siRNA vectors targeting Ihh, Smo and Gli2 were successfully constructed and decreased target gene expression. Suppression of hedgehog signaling significantly decreased the expression of α-SMA in HSC (P<0.01). Collagen type I secretion of HSC were also significantly decreased (P<0.01). In summary, HSC activation and collagen secretion can be regulated by hedgehog signaling. Hedgehog may play a role in the pathogenesis of liver fibrosis.

Bariatric surgery outcomes in black patients with super morbid obesity: a 1-year postoperative review.

PubMed

Onyewu, Samuel C; Ogundimu, Ololade O; Ortega, Gezzer; Bauer, Edward S; Emenari, Chijindu C; Molyneaux, Neh D; Layne, Sylvonne A; Changoor, Navin R; Tapscott, Denia; Tran, Daniel D; Fullum, Terrence M

2017-01-01

Super morbid obesity (body mass index [BMI] > 50 kg/m 2 ) is associated with significant comorbidities and is disparagingly prevalent among the black population. There is paucity of data regarding bariatric surgery outcomes among super morbid obese (SMO) blacks. Our aim is to evaluate the reduction in weight and resolution of comorbidities after bariatric surgery among SMO black patients at an urban academic institution. A retrospective review of SMO black patients who underwent bariatric surgery from August 2008 to June 2013 at Howard University Hospital. Outcomes of interest include weight loss, improvement or resolution of hypertension, type 2 diabetes, and hyperlipidemia at 12 months. Eighty-seven patients met our inclusion criteria. Mean preoperative weight and BMI were 347.2 lbs and 56.8 kg/m 2 , respectively. At 12 months, mean weight and BMI were 245.3 lbs and 40.1 kg/m 2 , respectively. There was also significant improvement or resolution of hypertension, type 2 diabetes, and hyperlipidemia. Bariatric surgery may result in significant weight loss and improvement or resolution of comorbidities in SMO black patients. Copyright © 2016. Published by Elsevier Inc.

Fully optimized shaped pupils: preparation for a test at the Subaru Telescope

NASA Astrophysics Data System (ADS)

Carlotti, Alexis; Kasdin, N. Jeremy; Martinache, Frantz; Vanderbei, Robert J.; Young, Elizabeth J.; Che, George; Groff, Tyler D.; Guyon, Olivier

2012-09-01

The SCExAO instrument at the Subaru telescope, mainly based on a PIAA coronagraph can benefit from the addition of a robust and simple shaped pupil coronagraph. New shaped pupils, fully optimized in 2 dimensions, make it possible to design optimal apodizers for arbitrarily complex apertures, for instance on-axis telescopes such as the Subaru telescope. We have designed several masks with inner working angles as small as 2.5 λ / D, and for high-contrast regions with different shapes. Using Princeton University nanofabrication facilities, we have manufactured two masks by photolithography. These masks have been tested in the laboratory, both in Princeton and in the facilities of the National Astronomical Observatory of Japan (NAOJ) in Hilo. The goal of this work is to prepare tests on the sky of a shaped pupil coronagraph in 2012.

An iterative sinogram gap-filling method with object- and scanner-dedicated discrete cosine transform (DCT)-domain filters for high resolution PET scanners.

PubMed

Kim, Kwangdon; Lee, Kisung; Lee, Hakjae; Joo, Sungkwan; Kang, Jungwon

2018-01-01

We aimed to develop a gap-filling algorithm, in particular the filter mask design method of the algorithm, which optimizes the filter to the imaging object by an adaptive and iterative process, rather than by manual means. Two numerical phantoms (Shepp-Logan and Jaszczak) were used for sinogram generation. The algorithm works iteratively, not only on the gap-filling iteration but also on the mask generation, to identify the object-dedicated low frequency area in the DCT-domain that is to be preserved. We redefine the low frequency preserving region of the filter mask at every gap-filling iteration, and the region verges on the property of the original image in the DCT domain. The previous DCT2 mask for each phantom case had been manually well optimized, and the results show little difference from the reference image and sinogram. We observed little or no difference between the results of the manually optimized DCT2 algorithm and those of the proposed algorithm. The proposed algorithm works well for various types of scanning object and shows results that compare to those of the manually optimized DCT2 algorithm without perfect or full information of the imaging object.

Laser-assisted electrochemical micromachining of mould cavity on the stainless steel surface

NASA Astrophysics Data System (ADS)

Li, Xiaohai; Wang, Shuming; Wang, Dong; Tong, Han

2018-02-01

In order to fabricate the micro mould cavities with complex structures on 304 stainless steel, laser-assisted electrochemical micromachining (EMM) based on surface modification by fiber laser masking was studied,and a new device of laser-assisted EMM was developed. Laser marking on the surface of 304 stainless steel can first be realized by fiber laser heating scanning. Through analysis of X ray diffraction analysis (XRD), metal oxide layer with predefined pattern can be formed by laser marking, and phase transformation can also occur on the 304 stainless steel surface, which produce the laser masking layer with corrosion resistance. The stainless steel surface with laser masking layer is subsequently etched by EMM, the laser masking layer severs as the temporary protective layer without relying on lithography mask, the fabrication of formed electrodes is also avoided, so micro pattern cavities can fast be fabricated. The impacts on machining accuracy during EMM with laser masking were discussed to optimize machining parameters, such as machining voltage, electrolyte concentration, duty cycle of pulse power supply and electrode gap size, the typical mould cavities 23μm deep were fabricated under the optimized parameters.

Masks in Imaging Flow Cytometry

PubMed Central

Dominical, Venina; Samsel, Leigh; McCoy, J. Philip

2016-01-01

Data analysis in imaging flow cytometry incorporates elements of flow cytometry together with other aspects of morphological analysis of images. A crucial early step in this analysis is the creation of a mask to distinguish the portion of the image upon which further examination of specified features can be performed. Default masks are provided by the manufacturer of the imaging flow cytometer but additional custom masks can be created by the individual user for specific applications. Flawed or inaccurate masks can have a substantial negative impact on the overall analysis of a sample, thus great care must be taken to ensure the accuracy of masks. Here we discuss various types of masks and cite examples of their use. Furthermore we provide our insight for how to approach selecting and assessing the optimal mask for a specific analysis. PMID:27461256

Metacontrast masking is processed before grapheme-color synesthesia.

PubMed

Bacon, Michael Patrick; Bridgeman, Bruce; Ramachandran, Vilayanur S

2013-01-01

We investigated the physiological mechanism of grapheme-color synesthesia using metacontrast masking. A metacontrast target is rendered invisible by a mask that is delayed by about 60 ms; the target and mask do not overlap in space or time. Little masking occurs, however, if the target and mask are simultaneous. This effect must be cortical, because it can be obtained dichoptically. To compare the data for synesthetes and controls, we developed a metacontrast design in which nonsynesthete controls showed weaker dichromatic masking (i.e., the target and mask were in different colors) than monochromatic masking. We accomplished this with an equiluminant target, mask, and background for each observer. If synesthetic color affected metacontrast, synesthetes should show monochromatic masking more similar to the weak dichromatic masking among controls, because synesthetes could add their synesthetic color to the monochromatic condition. The target-mask pairs used for each synesthete were graphemes that elicited strong synesthetic colors. We found stronger monochromatic than dichromatic U-shaped metacontrast for both synesthetes and controls, with optimal masking at an asynchrony of 66 ms. The difference in performance between the monochromatic and dichromatic conditions in the synesthetes indicates that synesthesia occurs at a later processing stage than does metacontrast masking.

Improving the CD linearity and proximity performance of photomasks written on the Sigma7500-II DUV laser writer through embedded OPC

NASA Astrophysics Data System (ADS)

Österberg, Anders; Ivansen, Lars; Beyerl, Angela; Newman, Tom; Bowhill, Amanda; Sahouria, Emile; Schulze, Steffen

2007-10-01

Optical proximity correction (OPC) is widely used in wafer lithography to produce a printed image that best matches the design intent while optimizing CD control. OPC software applies corrections to the mask pattern data, but in general it does not compensate for the mask writer and mask process characteristics. The Sigma7500-II deep-UV laser mask writer projects the image of a programmable spatial light modulator (SLM) using partially coherent optics similar to wafer steppers, and the optical proximity effects of the mask writer are in principle correctable with established OPC methods. To enhance mask patterning, an embedded OPC function, LinearityEqualize TM, has been developed for the Sigma7500- II that is transparent to the user and which does not degrade mask throughput. It employs a Calibre TM rule-based OPC engine from Mentor Graphics, selected for the computational speed necessary for mask run-time execution. A multinode cluster computer applies optimized table-based CD corrections to polygonized pattern data that is then fractured into an internal writer format for subsequent data processing. This embedded proximity correction flattens the linearity behavior for all linewidths and pitches, which targets to improve the CD uniformity on production photomasks. Printing results show that the CD linearity is reduced to below 5 nm for linewidths down to 200 nm, both for clear and dark and for isolated and dense features, and that sub-resolution assist features (SRAF) are reliably printed down to 120 nm. This reduction of proximity effects for main mask features and the extension of the practical resolution for SRAFs expands the application space of DUV laser mask writing.

An improved principal component analysis based region matching method for fringe direction estimation

NASA Astrophysics Data System (ADS)

He, A.; Quan, C.

2018-04-01

The principal component analysis (PCA) and region matching combined method is effective for fringe direction estimation. However, its mask construction algorithm for region matching fails in some circumstances, and the algorithm for conversion of orientation to direction in mask areas is computationally-heavy and non-optimized. We propose an improved PCA based region matching method for the fringe direction estimation, which includes an improved and robust mask construction scheme, and a fast and optimized orientation-direction conversion algorithm for the mask areas. Along with the estimated fringe direction map, filtered fringe pattern by automatic selective reconstruction modification and enhanced fast empirical mode decomposition (ASRm-EFEMD) is used for Hilbert spiral transform (HST) to demodulate the phase. Subsequently, windowed Fourier ridge (WFR) method is used for the refinement of the phase. The robustness and effectiveness of proposed method are demonstrated by both simulated and experimental fringe patterns.

Modeling of thermomechanical changes of extreme-ultraviolet mask and their dependence on absorber variation

NASA Astrophysics Data System (ADS)

Ban, Chung-Hyun; Park, Eun-Sang; Park, Jae-Hun; Oh, Hye-Keun

2018-06-01

Thermal and structural deformation of extreme-ultraviolet lithography (EUVL) masks during the exposure process may become important issues as these masks are subject to rigorous image placement and flatness requirements. The reflective masks used for EUVL absorb energy during exposure, and the temperature of the masks rises as a result. This can cause thermomechanical deformation that can reduce the pattern quality. The use of very thick low-thermal-expansion substrate materials (LTEMs) may reduce energy absorption, but they do not completely eliminate mask deformation. Therefore, it is necessary to predict and optimize the effects of energy transferred from the extreme-ultraviolet (EUV) light source and the resultant patterns of structured EUV masks with complex multilayers. Our study shows that heat accumulates in the masks as exposure progresses. It has been found that a higher absorber ratio (pattern density) applied to the patterning of EUV masks exacerbates the problem, especially in masks with more complex patterns.

Combinatorial algorithms for design of DNA arrays.

PubMed

Hannenhalli, Sridhar; Hubell, Earl; Lipshutz, Robert; Pevzner, Pavel A

2002-01-01

Optimal design of DNA arrays requires the development of algorithms with two-fold goals: reducing the effects caused by unintended illumination (border length minimization problem) and reducing the complexity of masks (mask decomposition problem). We describe algorithms that reduce the number of rectangles in mask decomposition by 20-30% as compared to a standard array design under the assumption that the arrangement of oligonucleotides on the array is fixed. This algorithm produces provably optimal solution for all studied real instances of array design. We also address the difficult problem of finding an arrangement which minimizes the border length and come up with a new idea of threading that significantly reduces the border length as compared to standard designs.

Medical students as teachers at CoSMO, Columbia University's student-run clinic: a pilot study and literature review.

PubMed

Hamso, Magni; Ramsdell, Amanda; Balmer, Dorene; Boquin, Cyrus

2012-01-01

Although medical students are expected to teach as soon as they begin residency, medical schools have just recently begun adding teacher training to their curricula. Student-run clinics (SRCs) may provide opportunities in clinical teaching before residency. The aim of this pilot study was to examine students' experiences in clinical teaching at Columbia Student Medical Outreach (CoSMO), Columbia University's SRC, during the 2009-2010 school year. A mixed-methods approach was used. Data included closed and open-ended surveys (n = 34), combined interviews with preclinical and clinical student pairs (n = 5), individual interviews (n = 10), and focus groups (n = 3). The transcripts were analyzed using the principles of grounded theory. Many students had their first clinical teaching experience while volunteering at CoSMO. Clinical students' ability to teach affected the quality of the learning experience for their preclinical peers. Preclinical students who asked questions and engaged in patient care challenged their clinical peers to balance teaching with patient care. Clinical students began to see themselves as teachers while volunteering at CoSMO. The practical experiences in clinical teaching that students have at SRCs can supplement classroom-based trainings. Medical schools might revisit their SRCs as places for exposure to clinical teaching.

Overlay improvement by exposure map based mask registration optimization

NASA Astrophysics Data System (ADS)

Shi, Irene; Guo, Eric; Chen, Ming; Lu, Max; Li, Gordon; Li, Rivan; Tian, Eric

2015-03-01

Along with the increased miniaturization of semiconductor electronic devices, the design rules of advanced semiconductor devices shrink dramatically. [1] One of the main challenges of lithography step is the layer-to-layer overlay control. Furthermore, DPT (Double Patterning Technology) has been adapted for the advanced technology node like 28nm and 14nm, corresponding overlay budget becomes even tighter. [2][3] After the in-die mask registration (pattern placement) measurement is introduced, with the model analysis of a KLA SOV (sources of variation) tool, it's observed that registration difference between masks is a significant error source of wafer layer-to-layer overlay at 28nm process. [4][5] Mask registration optimization would highly improve wafer overlay performance accordingly. It was reported that a laser based registration control (RegC) process could be applied after the pattern generation or after pellicle mounting and allowed fine tuning of the mask registration. [6] In this paper we propose a novel method of mask registration correction, which can be applied before mask writing based on mask exposure map, considering the factors of mask chip layout, writing sequence, and pattern density distribution. Our experiment data show if pattern density on the mask keeps at a low level, in-die mask registration residue error in 3sigma could be always under 5nm whatever blank type and related writer POSCOR (position correction) file was applied; it proves random error induced by material or equipment would occupy relatively fixed error budget as an error source of mask registration. On the real production, comparing the mask registration difference through critical production layers, it could be revealed that registration residue error of line space layers with higher pattern density is always much larger than the one of contact hole layers with lower pattern density. Additionally, the mask registration difference between layers with similar pattern density could also achieve under 5nm performance. We assume mask registration excluding random error is mostly induced by charge accumulation during mask writing, which may be calculated from surrounding exposed pattern density. Multi-loading test mask registration result shows that with x direction writing sequence, mask registration behavior in x direction is mainly related to sequence direction, but mask registration in y direction would be highly impacted by pattern density distribution map. It proves part of mask registration error is due to charge issue from nearby environment. If exposure sequence is chip by chip for normal multi chip layout case, mask registration of both x and y direction would be impacted analogously, which has also been proved by real data. Therefore, we try to set up a simple model to predict the mask registration error based on mask exposure map, and correct it with the given POSCOR (position correction) file for advanced mask writing if needed.

Improved techniques reduce face mask leak during simulated neonatal resuscitation: study 2.

PubMed

Wood, Fiona E; Morley, Colin J; Dawson, Jennifer A; Kamlin, C Omar F; Owen, Louise S; Donath, Susan; Davis, Peter G

2008-05-01

Techniques of positioning and holding neonatal face masks vary. Studies have shown that leak at the face mask is common and often substantial irrespective of operator experience. (1) To identify a technique for face mask placement and hold which will minimise mask leak. (2) To investigate the effect of written instruction and demonstration of the identified technique on mask leak for two round face masks. Three experienced neonatologists compared methods of placing and holding face masks to minimise the leak for Fisher & Paykel 60 mm and Laerdal size 0/1 masks. 50 clinical staff gave positive pressure ventilation to a modified manikin designed to measure leak at the face mask. They were provided with written instructions on how to position and hold each mask and then received a demonstration. Face mask leak was measured after each teaching intervention. A technique of positioning and holding the face masks was identified which minimised leak. The mean (SD) mask leaks before instruction, after instruction and after demonstration were 55% (31), 49% (30), 33% (26) for the Laerdal mask and 57% (25), 47% (28), 32% (30) for the Fisher & Paykel mask. There was no significant difference in mask leak between the two masks. Written instruction alone reduced leak by 8.8% (CI 1.4% to 16.2%) for either mask; when combined with a demonstration mask leak was reduced by 24.1% (CI 16.4% to 31.8%). Written instruction and demonstration of the identified optimal technique resulted in significantly reduced face mask leak.

Dead space variability of face masks for valved holding chambers.

PubMed

Amirav, Israel; Newhouse, Michael T

2008-03-01

Valved holding chambers with masks are commonly used to deliver inhaled medications to young children with asthma. Optimal mask properties such as their dead space volume have received little attention. The smaller the mask the more likely it is that a greater proportion of the dose in the VHC will be inhaled with each breath, thus speeding VHC emptying and improving overall aerosol delivery efficiency and dose. Masks may have different DSV and thus different performance. To compare both physical dead space and functional dead space of different face masks under various applied pressures. The DSV of three commonly used face masks of VHCs was measured by water displacement both under various pressures (to simulate real-life application, dynamic DSV) and under no pressure (static DSV). There was a great variability of both static and dynamic dead space among various face mask for VHCs, which is probably related to their flexibility. Different masks have different DSV characteristics. This variability should be taken into account when comparing the clinical efficacy of various VHCs.

A Counter-Social Movement Approach to Deconstructing Daesh

DTIC Science & Technology

alternative, the US military could view Daesh as a transnational social movement organization (SMO), and by doing so, planners could develop a more effective... social movement theory (SMT) to determine lines of effort (LOE) against which US military forces could best apply resources to counteract the SMO. This... study is divided into four sections. The first section constitutes an overview of SMT as a form of contentious politics. The second section presents a

Crevice Corrosion Behavior of 45 Molybdenum-Containing Stainless Steels in Seawater.

DTIC Science & Technology

1981-12-01

Armco, Avesta Jernverks, Cabot, Carpenter Technology, Crucible, Eastern, Firth-Brown, Huntington, Jessup, Langley Alloys, and Uddeholm. 16...Department of Energy, Report ANL/OTEC-BCM-022. 7. Wallen, B., and M. Liljas, " Avesta 254 SMO - A New, High Molybdenum Stainless Steel," presented at NKM8...1977).; 11. Wallen, B., " Avesta 254 SMO - A Stainless Steel for Seawater Service," presented at the Advanced Stainless Steels for Turbine Condensors

Vectorial mask optimization methods for robust optical lithography

NASA Astrophysics Data System (ADS)

Ma, Xu; Li, Yanqiu; Guo, Xuejia; Dong, Lisong; Arce, Gonzalo R.

2012-10-01

Continuous shrinkage of critical dimension in an integrated circuit impels the development of resolution enhancement techniques for low k1 lithography. Recently, several pixelated optical proximity correction (OPC) and phase-shifting mask (PSM) approaches were developed under scalar imaging models to account for the process variations. However, the lithography systems with larger-NA (NA>0.6) are predominant for current technology nodes, rendering the scalar models inadequate to describe the vector nature of the electromagnetic field that propagates through the optical lithography system. In addition, OPC and PSM algorithms based on scalar models can compensate for wavefront aberrations, but are incapable of mitigating polarization aberrations in practical lithography systems, which can only be dealt with under the vector model. To this end, we focus on developing robust pixelated gradient-based OPC and PSM optimization algorithms aimed at canceling defocus, dose variation, wavefront and polarization aberrations under a vector model. First, an integrative and analytic vector imaging model is applied to formulate the optimization problem, where the effects of process variations are explicitly incorporated in the optimization framework. A steepest descent algorithm is then used to iteratively optimize the mask patterns. Simulations show that the proposed algorithms can effectively improve the process windows of the optical lithography systems.

Propagation of resist heating mask error to wafer level

NASA Astrophysics Data System (ADS)

Babin, S. V.; Karklin, Linard

2006-10-01

As technology is approaching 45 nm and below the IC industry is experiencing a severe product yield hit due to rapidly shrinking process windows and unavoidable manufacturing process variations. Current EDA tools are unable by their nature to deliver optimized and process-centered designs that call for 'post design' localized layout optimization DFM tools. To evaluate the impact of different manufacturing process variations on final product it is important to trace and evaluate all errors through design to manufacturing flow. Photo mask is one of the critical parts of this flow, and special attention should be paid to photo mask manufacturing process and especially to mask tight CD control. Electron beam lithography (EBL) is a major technique which is used for fabrication of high-end photo masks. During the writing process, resist heating is one of the sources for mask CD variations. Electron energy is released in the mask body mainly as heat, leading to significant temperature fluctuations in local areas. The temperature fluctuations cause changes in resist sensitivity, which in turn leads to CD variations. These CD variations depend on mask writing speed, order of exposure, pattern density and its distribution. Recent measurements revealed up to 45 nm CD variation on the mask when using ZEP resist. The resist heating problem with CAR resists is significantly smaller compared to other types of resists. This is partially due to higher resist sensitivity and the lower exposure dose required. However, there is no data yet showing CD errors on the wafer induced by CAR resist heating on the mask. This effect can be amplified by high MEEF values and should be carefully evaluated at 45nm and below technology nodes where tight CD control is required. In this paper, we simulated CD variation on the mask due to resist heating; then a mask pattern with the heating error was transferred onto the wafer. So, a CD error on the wafer was evaluated subject to only one term of the mask error budget - the resist heating CD error. In simulation of exposure using a stepper, variable MEEF was considered.

Design architecture of double spiral interdigitated electrode with back gate electrode for biosensor application

NASA Astrophysics Data System (ADS)

Fathil, M. F. M.; Arshad, M. K. Md.; Hashim, U.; Ruslinda, A. R.; Gopinath, Subash C. B.; M. Nuzaihan M., N.; Ayub, R. M.; Adzhri, R.; Zaki, M.; Azman, A. H.

2016-07-01

This paper presents the preparation method of photolithography chrome mask design used in fabrication process of double spiral interdigitated electrode with back gate biasing based biosensor. By learning the fabrication process flow of the biosensor, the chrome masks are designed through drawing using the AutoCAD software. The overall width and length of the device is optimized at 7.0 mm and 10.0 mm, respectively. Fabrication processes of the biosensor required three chrome masks, which included back gate opening, spiral IDE formation, and passivation area formation. The complete chrome masks design will be sent for chrome mask fabrication and for future use in biosensor fabrication.

Lithographic performance comparison with various RET for 45-nm node with hyper NA

NASA Astrophysics Data System (ADS)

Adachi, Takashi; Inazuki, Yuichi; Sutou, Takanori; Kitahata, Yasuhisa; Morikawa, Yasutaka; Toyama, Nobuhito; Mohri, Hiroshi; Hayashi, Naoya

2006-05-01

In order to realize 45 nm node lithography, strong resolution enhancement technology (RET) and water immersion will be needed. In this research, we discussed about various RET performance comparison for 45 nm node using 3D rigorous simulation. As a candidate, we chose binary mask (BIN), several kinds of attenuated phase-shifting mask (att-PSM) and chrome-less phase-shifting lithography mask (CPL). The printing performance was evaluated and compared for each RET options, after the optimizing illumination conditions, mask structure and optical proximity correction (OPC). The evaluation items of printing performance were CD-DOF, contrast-DOF, conventional ED-window and MEEF, etc. It's expected that effect of mask 3D topography becomes important at 45 nm node, so we argued about not only the case of ideal structures, but also the mask topography error effects. Several kinds of mask topography error were evaluated and we confirmed how these errors affect to printing performance.

Innovative method to suppress local geometry distortions for fabrication of interdigitated electrode arrays with nano gaps

NASA Astrophysics Data System (ADS)

Partel, S.; Urban, G.

2016-03-01

In this paper we present a method to optimize the lithography process for the fabrication of interdigitated electrode arrays (IDA) for a lift-off free electrochemical biosensor. The biosensor is based on amperometric method to allow a signal amplification by redox cycling. We already demonstrated a method to fabricate IDAs with nano gaps with conventional mask aligner lithography and two subsequent deposition processes. By decreasing the distance down to the nanometer range the linewidth variation is becoming the most critical factor and can result in a short circuit of the electrodes. Therefore, the light propagation and the resist pattern of the mask aligner lithography process are simulated to optimize the lithography process. To optimize the outer finger structure assistant features (AsFe) were introduced. The AsFe allow an optimization of the intensity distribution at the electrode fingers. Hence, the periodicity is expanded and the outer structure of the IDA is practically a part of the periodic array. The better CD uniformity can be obtained by adding three assistant features which generate an equal intensity distributions for the complete finger pattern. Considering a mask optimization of the outer structures would also be feasible. However, due to the strong impact of the gap between mask and wafer at contact lithography it is not practicable. The better choice is to create the same intensity distribution for all finger structures. With the introduction of the assistant features large areas with electrode gap sizes in the sub 100 nm region are demonstrated.

JWST-MIRI spectrometer main optics design and main results

NASA Astrophysics Data System (ADS)

Navarro, Ramón; Schoenmaker, Ton; Kroes, Gabby; Oudenhuysen, Ad; Jager, Rieks; Venema, Lars

2017-11-01

MIRI ('Mid InfraRed Instrument') is the combined imager and integral field spectrometer for the 5-29 micron wavelength range under development for the James Webb Space Telescope JWST. The flight acceptance tests of the Spectrometer Main Optics flight models (SMO), part of the MIRI spectrometer, are completed in the summer of 2008 and the system is delivered to the MIRI-JWST consortium. The two SMO arms contain 14 mirrors and form the MIRI optical system together with 12 selectable gratings on grating wheels. The entire system operates at a temperature of 7 Kelvin and is designed on the basis of a 'no adjustments' philosophy. This means that the optical alignment precision depends strongly on the design, tolerance analysis and detailed knowledge of the manufacturing process. Because in principle no corrections are needed after assembly, continuous tracking of the alignment performance during the design and manufacturing phases is important. The flight hardware is inspected with respect to performance parameters like alignment and image quality. The stability of these parameters is investigated after exposure to various vibration levels and successive cryogenic cool downs. This paper describes the philosophy behind the acceptance tests, the chosen test strategy and reports the results of these tests. In addition the paper covers the design of the optical test setup, focusing on the simulation of the optical interfaces of the SMO. Also the relation to the SMO qualification and verification program is addressed.

Efficacy of Asparaginase Erwinia chrysanthemi With and Without Temozolomide Against Glioma Cells and Intracranial Mouse Medulloblastoma.

PubMed

Sanghez, Valentina; Chen, Mengqing; Li, Shan; Chou, Tsui-Fen; Iacovino, Michelina; Lin, Henry J; Lasky, Joseph L; Panosyan, Eduard H

2018-05-01

Anti-metabolites are less-myelosuppressive than DNA-damaging anticancer drugs and may be useful against brain tumors. We evaluated the asparagine/glutamine-deaminating agent Erwinaze with/without temozolomide against brain tumor cells and mouse medulloblastomas. Erwinaze treatment of cell lines and neurospheres led to dose-dependent reductions of cells (reversible by L-glutamine), with half maximal inhibitory concentrations (IC 50 s) of 0.12->10 IU/ml. Erwinaze at <1 IU/ml reduced temozolomide IC 50 s by 3.6- to 13-fold (300-1,200 μM to 40-330 μM). Seven-week-old SMO/SMO mice treated with Erwinaze (regardless of temozolomide treatment) had better survival 11 weeks post-therapy, compared to those not treated with Erwinaze (81.25% vs. 46.15, p=0.08). Temozolomide-treated mice developed 10% weight loss, impairing survival. All 16 mice treated with temozolomide (regardless of Erwinaze treatment) succumbed by 40-weeks of age, whereas 5/8 animals treated with Erwinaze alone and 2/6 controls survived (p=0.035). Erwinaze enhances cytotoxicity of temozolomide in vitro, and improves survival in SMO/SMO mice, likely by reducing cerebrospinal fluid glutamine. Temozolomide-associated toxicity prevented demonstration of any potential combinatorial advantage with Erwinaze in vivo. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

A New Sample Transect through the Sierra Madre Occidental Silicic Large Igneous Province in Southern Chihuahua State, Mexico: First Stratigraphic, Petrologic, and Geochemical Results

NASA Astrophysics Data System (ADS)

Andrews, G. D.; Davila Harris, P.; Brown, S. R.; Anderson, L.; Moreno, N.

2014-12-01

We completed a field sampling transect across the northern Sierra Madre Occidental silicic large igneous province (SMO) in December 2013. Here we present the first stratigraphic, petrological, and geochemical data from the transect between Hidalgo del Parral and Guadalupe y Calvo, Chihuahua, Mexico. This is the first new transect across the SMO in 25 years and the only one between existing NE - SW transects at Chihuahua - Hermosillo and Durango - Mazatlan. The 245 km-long transect along Mexican Highway 24 crosses the boundary between the extended (Basin and Range) and non-extended (Sierra Madre Occidental plateau) parts of the SMO, and allows sampling of previously undescribed Oligocene (?) - early Miocene (?) rhyolitic ignimbrites and lavas, and occasional post-rhyolite, Miocene (?) SCORBA basaltic andesite lavas. 54 samples of rhyolitic ignimbrites (40) and lavas (7), and basaltic andesite lavas (7) were sampled along the transect, including 8 canyon sections with more than one unit. The ignimbrites are overwhelming rhyodacitic (plagioclase and hornblende or biotite phyric) or rhyolitic (quartz (+/- sanidine) in additon to plagioclase and hornblende or biotite phyric) and sparsely to highly phyric. Preliminary petrographic (phenocryst abundances) and geochemical (major and trace element) will be presented and compared to existing data from elsewhere in the SMO. Future work will include U-Pb zircon dating and whole rock and in-zircon radiogenic isotopes analyses.

MicroRNA-1271 inhibits proliferation and promotes apoptosis of multiple myeloma cells through inhibiting smoothened-mediated Hedgehog signaling pathway.

PubMed

Xu, Zhengwei; Huang, Chen; Hao, Dingjun

2017-02-01

MicroRNAs (miRNAs) have emerged as important regulators in multiple myeloma (MM). miR-1271 is a tumor suppressor in many cancer types. However, the biological role of miR-1271 in MM remains unclear. In the present study, we elucidated the biological role of miR-1271 in MM. Results showed that miR-1271 was significantly decreased in primary MM cells from MM patients and MM cell lines. Overexpression of miR-1271 inhibited proliferation and promoted apoptosis of MM cells. Conversely, suppression of miR-1271 showed the opposite effect. Bioinformatics algorithm analysis predicted that smoothened (SMO), the activator of Hedgehog (HH) signaling pathway, was a direct target of miR-1271 that was experimentally verified by a dual-luciferase reporter assay. Furthermore, overexpression of miR-1271 inhibited SMO expression and HH signaling pathway. Conversely, the restoration of SMO expression markedly abolished the effect of miR-1271 overexpression on cell proliferation, apoptosis and HH signaling pathway in MM cells. Taken together, the present study suggests that miR-1271 functions as a tumor suppressor that inhibits proliferation and promotes apoptosis of MM cells through inhibiting SMO-mediated HH signaling pathway. This finding implies that miR-1271 is a potential therapeutic target for the treatment of MM.

Validating high-resolution California coastal flood modeling with Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR)

NASA Astrophysics Data System (ADS)

O'Neill, A.

2015-12-01

The Coastal Storm Modeling System (CoSMoS) is a numerical modeling scheme used to predict coastal flooding due to sea level rise and storms influenced by climate change, currently in use in central California and in development for Southern California (Pt. Conception to the Mexican border). Using a framework of circulation, wave, analytical, and Bayesian models at different geographic scales, high-resolution results are translated as relevant hazards projections at the local scale that include flooding, wave heights, coastal erosion, shoreline change, and cliff failures. Ready access to accurate, high-resolution coastal flooding data is critical for further validation and refinement of CoSMoS and improved coastal hazard projections. High-resolution Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR) provides an exceptional data source as appropriately-timed flights during extreme tides or storms provide a geographically-extensive method for determining areas of inundation and flooding extent along expanses of complex and varying coastline. Landward flood extents are numerically identified via edge-detection in imagery from single flights, and can also be ascertained via change detection using additional flights and imagery collected during average wave/tide conditions. The extracted flooding positions are compared against CoSMoS results for similar tide, water level, and storm-intensity conditions, allowing for robust testing and validation of CoSMoS and providing essential feedback for supporting regional and local model improvement.

Three-dimensional polarization marked multiple-QR code encryption by optimizing a single vectorial beam

NASA Astrophysics Data System (ADS)

Lin, Chao; Shen, Xueju; Hua, Binbin; Wang, Zhisong

2015-10-01

We demonstrate the feasibility of three dimensional (3D) polarization multiplexing by optimizing a single vectorial beam using a multiple-signal window multiple-plane (MSW-MP) phase retrieval algorithm. Original messages represented with multiple quick response (QR) codes are first partitioned into a series of subblocks. Then, each subblock is marked with a specific polarization state and randomly distributed in 3D space with both longitudinal and transversal adjustable freedoms. A generalized 3D polarization mapping protocol is established to generate a 3D polarization key. Finally, multiple-QR code is encrypted into one phase only mask and one polarization only mask based on the modified Gerchberg-Saxton (GS) algorithm. We take the polarization mask as the cyphertext and the phase only mask as additional dimension of key. Only when both the phase key and 3D polarization key are correct, original messages can be recovered. We verify our proposal with both simulation and experiment evidences.

Comparison of cloud optical depth and cloud mask applying BRDF model-based background surface reflectance

NASA Astrophysics Data System (ADS)

Kim, H. W.; Yeom, J. M.; Woo, S. H.

2017-12-01

Over the thin cloud region, satellite can simultaneously detect the reflectance from thin clouds and land surface. Since the mixed reflectance is not the exact cloud information, the background surface reflectance should be eliminated to accurately distinguish thin cloud such as cirrus. In the previous research, Kim et al (2017) was developed the cloud masking algorithm using the Geostationary Ocean Color Imager (GOCI), which is one of significant instruments for Communication, Ocean, and Meteorology Satellite (COMS). Although GOCI has 8 spectral channels including visible and near infra-red spectral ranges, the cloud masking has quantitatively reasonable result when comparing with MODIS cloud mask (Collection 6 MYD35). Especially, we noticed that this cloud masking algorithm is more specialized in thin cloud detections through the validation with Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) data. Because this cloud masking method was concentrated on eliminating background surface effects from the top-of-atmosphere (TOA) reflectance. Applying the difference between TOA reflectance and the bi-directional reflectance distribution function (BRDF) model-based background surface reflectance, cloud areas both thick cloud and thin cloud can be discriminated without infra-red channels which were mostly used for detecting clouds. Moreover, when the cloud mask result was utilized as the input data when simulating BRDF model and the optimized BRDF model-based surface reflectance was used for the optimized cloud masking, the probability of detection (POD) has higher value than POD of the original cloud mask. In this study, we examine the correlation between cloud optical depth (COD) and its cloud mask result. Cloud optical depths mostly depend on the cloud thickness, the characteristic of contents, and the size of cloud contents. COD ranges from less than 0.1 for thin clouds to over 1000 for the huge cumulus due to scattering by droplets. With the cloud optical depth of CALIPSO, the cloud masking result can be more improved since we can figure out how deep cloud is. To validate the cloud mask and the correlation result, the atmospheric retrieval will be computed to compare the difference between TOA reflectance and the simulated surface reflectance.

Ecosystem service trade-offs and their influencing factors: A case study in the Loess Plateau of China.

PubMed

Feng, Qiang; Zhao, Wenwu; Fu, Bojie; Ding, Jingyi; Wang, Shuai

2017-12-31

Soil erosion control (SEC), carbon sequestration (CAS), and soil moisture (SMO) strongly interact in the semi-arid Loess Plateau. Since SMO has supportive effects on SEC and CAS, it can be considered as ecosystem service (ES), and there is an immediate need to coordinate the relationships among these ecosystem services (ESs) to promote the sustainability of vegetation recovery. In this study, we quantified the ESs, ES trade-offs, and the environmental factors in 151 sample plots in the Ansai watershed, and we used a redundancy analysis (RDA) to clarify the effects of environmental factors on these ESs and their trade-offs. The results were as follows: (1) the general trend in the SEC of vegetation types was Robinia pseudoacacia (CH)>native grass (NG)>small arbor (ST)>Hippophae rhamnoides (SJ)>artificial grass (AG)>Caragana korshinskii (NT)>apple orchard (GY)>crop (CP); the CAS trend was CH>SJ>NT>AG>CP>ST>GY>NG; and the SMO trend was CP>NG>GY>AG>SJ>ST>CH>NT. (2) For SEC-SMO trade-offs, the influence of vegetation type, altitude, silt and sand composition was dominant. The arrangement of NG, AG, and SJ could decrease the extent of the trade-offs. (3) For CAS-SMO trade-offs, vegetation coverage and types were the dominant factors, but the effects were not complex. The extent of these trade-offs was lowest for NT, and that for SJ was the second lowest. (4) Considering the relationships among the three ESs, SJ was the most appropriate afforestation plant. Combing the vegetation types, slope position, slope gradient, and soil properties could regulate these ES relationships. The dominant factors influencing ES trade-offs varied among the different soil layers, so we must consider the corresponding influencing factors to regulate ESs. Moreover, manual management measures were also important for coordinating the ES relationships. Our research provides a better understanding of the mechanisms influencing the relationships among ESs. Copyright © 2017 Elsevier B.V. All rights reserved.

Validating the WHO maternal near miss tool: comparing high- and low-resource settings.

PubMed

Witteveen, Tom; Bezstarosti, Hans; de Koning, Ilona; Nelissen, Ellen; Bloemenkamp, Kitty W; van Roosmalen, Jos; van den Akker, Thomas

2017-06-19

WHO proposed the WHO Maternal Near Miss (MNM) tool, classifying women according to several (potentially) life-threatening conditions, to monitor and improve quality of obstetric care. The objective of this study is to analyse merged data of one high- and two low-resource settings where this tool was applied and test whether the tool may be suitable for comparing severe maternal outcome (SMO) between these settings. Using three cohort studies that included SMO cases, during two-year time frames in the Netherlands, Tanzania and Malawi we reassessed all SMO cases (as defined by the original studies) with the WHO MNM tool (five disease-, four intervention- and seven organ dysfunction-based criteria). Main outcome measures were prevalence of MNM criteria and case fatality rates (CFR). A total of 3172 women were studied; 2538 (80.0%) from the Netherlands, 248 (7.8%) from Tanzania and 386 (12.2%) from Malawi. Total SMO detection was 2767 (87.2%) for disease-based criteria, 2504 (78.9%) for intervention-based criteria and 1211 (38.2%) for organ dysfunction-based criteria. Including every woman who received ≥1 unit of blood in low-resource settings as life-threatening, as defined by organ dysfunction criteria, led to more equally distributed populations. In one third of all Dutch and Malawian maternal death cases, organ dysfunction criteria could not be identified from medical records. Applying solely organ dysfunction-based criteria may lead to underreporting of SMO. Therefore, a tool based on defining MNM only upon establishing organ failure is of limited use for comparing settings with varying resources. In low-resource settings, lowering the threshold of transfused units of blood leads to a higher detection rate of MNM. We recommend refined disease-based criteria, accompanied by a limited set of intervention- and organ dysfunction-based criteria to set a measure of severity.

Role of Polyamine Oxidase (PAOh1/SMO) in Human Breast Cancer

DTIC Science & Technology

2007-04-01

polyamine spermidine , 3-aminopropanal, and the reactive oxygen species, H2O2. Previous work by our research group has shown that SMO can be induced by...spermine/ spermidine N1-acetyltransferase (SSAT). Treatment of MCF-10a cells with CSE resulted in a rapid 3-fold induction of SSAT mRNA at the one hour time...and spermine/ spermidine N1 acetyl- transferase (SSAT, open bars) in MCF- 10a human breast cancer cells by cigarette smoke extract (CSE) at the

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lemaire, H.; Barat, E.; Carrel, F.

In this work, we tested Maximum likelihood expectation-maximization (MLEM) algorithms optimized for gamma imaging applications on two recent coded mask gamma cameras. We respectively took advantage of the characteristics of the GAMPIX and Caliste HD-based gamma cameras: noise reduction thanks to mask/anti-mask procedure but limited energy resolution for GAMPIX, high energy resolution for Caliste HD. One of our short-term perspectives is the test of MAPEM algorithms integrating specific prior values for the data to reconstruct adapted to the gamma imaging topic. (authors)

Machine learning for inverse lithography: using stochastic gradient descent for robust photomask synthesis

NASA Astrophysics Data System (ADS)

Jia, Ningning; Y Lam, Edmund

2010-04-01

Inverse lithography technology (ILT) synthesizes photomasks by solving an inverse imaging problem through optimization of an appropriate functional. Much effort on ILT is dedicated to deriving superior masks at a nominal process condition. However, the lower k1 factor causes the mask to be more sensitive to process variations. Robustness to major process variations, such as focus and dose variations, is desired. In this paper, we consider the focus variation as a stochastic variable, and treat the mask design as a machine learning problem. The stochastic gradient descent approach, which is a useful tool in machine learning, is adopted to train the mask design. Compared with previous work, simulation shows that the proposed algorithm is effective in producing robust masks.

Molecular evolution of the polyamine oxidase gene family in Metazoa

PubMed Central

2012-01-01

Background Polyamine oxidase enzymes catalyze the oxidation of polyamines and acetylpolyamines. Since polyamines are basic regulators of cell growth and proliferation, their homeostasis is crucial for cell life. Members of the polyamine oxidase gene family have been identified in a wide variety of animals, including vertebrates, arthropodes, nematodes, placozoa, as well as in plants and fungi. Polyamine oxidases (PAOs) from yeast can oxidize spermine, N1-acetylspermine, and N1-acetylspermidine, however, in vertebrates two different enzymes, namely spermine oxidase (SMO) and acetylpolyamine oxidase (APAO), specifically catalyze the oxidation of spermine, and N1-acetylspermine/N1-acetylspermidine, respectively. Little is known about the molecular evolutionary history of these enzymes. However, since the yeast PAO is able to catalyze the oxidation of both acetylated and non acetylated polyamines, and in vertebrates these functions are addressed by two specialized polyamine oxidase subfamilies (APAO and SMO), it can be hypothesized an ancestral reference for the former enzyme from which the latter would have been derived. Results We analysed 36 SMO, 26 APAO, and 14 PAO homologue protein sequences from 54 taxa including various vertebrates and invertebrates. The analysis of the full-length sequences and the principal domains of vertebrate and invertebrate PAOs yielded consensus primary protein sequences for vertebrate SMOs and APAOs, and invertebrate PAOs. This analysis, coupled to molecular modeling techniques, also unveiled sequence regions that confer specific structural and functional properties, including substrate specificity, by the different PAO subfamilies. Molecular phylogenetic trees revealed a basal position of all the invertebrates PAO enzymes relative to vertebrate SMOs and APAOs. PAOs from insects constitute a monophyletic clade. Two PAO variants sampled in the amphioxus are basal to the dichotomy between two well supported monophyletic clades including, respectively, all the SMOs and APAOs from vertebrates. The two vertebrate monophyletic clades clustered strictly mirroring the organismal phylogeny of fishes, amphibians, reptiles, birds, and mammals. Evidences from comparative genomic analysis, structural evolution and functional divergence in a phylogenetic framework across Metazoa suggested an evolutionary scenario where the ancestor PAO coding sequence, present in invertebrates as an orthologous gene, has been duplicated in the vertebrate branch to originate the paralogous SMO and APAO genes. A further genome evolution event concerns the SMO gene of placental, but not marsupial and monotremate, mammals which increased its functional variation following an alternative splicing (AS) mechanism. Conclusions In this study the explicit integration in a phylogenomic framework of phylogenetic tree construction, structure prediction, and biochemical function data/prediction, allowed inferring the molecular evolutionary history of the PAO gene family and to disambiguate paralogous genes related by duplication event (SMO and APAO) and orthologous genes related by speciation events (PAOs, SMOs/APAOs). Further, while in vertebrates experimental data corroborate SMO and APAO molecular function predictions, in invertebrates the finding of a supported phylogenetic clusters of insect PAOs and the co-occurrence of two PAO variants in the amphioxus urgently claim the need for future structure-function studies. PMID:22716069

Molecular evolution of the polyamine oxidase gene family in Metazoa.

PubMed

Polticelli, Fabio; Salvi, Daniele; Mariottini, Paolo; Amendola, Roberto; Cervelli, Manuela

2012-06-20

Polyamine oxidase enzymes catalyze the oxidation of polyamines and acetylpolyamines. Since polyamines are basic regulators of cell growth and proliferation, their homeostasis is crucial for cell life. Members of the polyamine oxidase gene family have been identified in a wide variety of animals, including vertebrates, arthropodes, nematodes, placozoa, as well as in plants and fungi. Polyamine oxidases (PAOs) from yeast can oxidize spermine, N1-acetylspermine, and N1-acetylspermidine, however, in vertebrates two different enzymes, namely spermine oxidase (SMO) and acetylpolyamine oxidase (APAO), specifically catalyze the oxidation of spermine, and N1-acetylspermine/N1-acetylspermidine, respectively. Little is known about the molecular evolutionary history of these enzymes. However, since the yeast PAO is able to catalyze the oxidation of both acetylated and non acetylated polyamines, and in vertebrates these functions are addressed by two specialized polyamine oxidase subfamilies (APAO and SMO), it can be hypothesized an ancestral reference for the former enzyme from which the latter would have been derived. We analysed 36 SMO, 26 APAO, and 14 PAO homologue protein sequences from 54 taxa including various vertebrates and invertebrates. The analysis of the full-length sequences and the principal domains of vertebrate and invertebrate PAOs yielded consensus primary protein sequences for vertebrate SMOs and APAOs, and invertebrate PAOs. This analysis, coupled to molecular modeling techniques, also unveiled sequence regions that confer specific structural and functional properties, including substrate specificity, by the different PAO subfamilies. Molecular phylogenetic trees revealed a basal position of all the invertebrates PAO enzymes relative to vertebrate SMOs and APAOs. PAOs from insects constitute a monophyletic clade. Two PAO variants sampled in the amphioxus are basal to the dichotomy between two well supported monophyletic clades including, respectively, all the SMOs and APAOs from vertebrates. The two vertebrate monophyletic clades clustered strictly mirroring the organismal phylogeny of fishes, amphibians, reptiles, birds, and mammals. Evidences from comparative genomic analysis, structural evolution and functional divergence in a phylogenetic framework across Metazoa suggested an evolutionary scenario where the ancestor PAO coding sequence, present in invertebrates as an orthologous gene, has been duplicated in the vertebrate branch to originate the paralogous SMO and APAO genes. A further genome evolution event concerns the SMO gene of placental, but not marsupial and monotremate, mammals which increased its functional variation following an alternative splicing (AS) mechanism. In this study the explicit integration in a phylogenomic framework of phylogenetic tree construction, structure prediction, and biochemical function data/prediction, allowed inferring the molecular evolutionary history of the PAO gene family and to disambiguate paralogous genes related by duplication event (SMO and APAO) and orthologous genes related by speciation events (PAOs, SMOs/APAOs). Further, while in vertebrates experimental data corroborate SMO and APAO molecular function predictions, in invertebrates the finding of a supported phylogenetic clusters of insect PAOs and the co-occurrence of two PAO variants in the amphioxus urgently claim the need for future structure-function studies.

Wafer hot spot identification through advanced photomask characterization techniques

NASA Astrophysics Data System (ADS)

Choi, Yohan; Green, Michael; McMurran, Jeff; Ham, Young; Lin, Howard; Lan, Andy; Yang, Richer; Lung, Mike

2016-10-01

As device manufacturers progress through advanced technology nodes, limitations in standard 1-dimensional (1D) mask Critical Dimension (CD) metrics are becoming apparent. Historically, 1D metrics such as Mean to Target (MTT) and CD Uniformity (CDU) have been adequate for end users to evaluate and predict the mask impact on the wafer process. However, the wafer lithographer's process margin is shrinking at advanced nodes to a point that the classical mask CD metrics are no longer adequate to gauge the mask contribution to wafer process error. For example, wafer CDU error at advanced nodes is impacted by mask factors such as 3-dimensional (3D) effects and mask pattern fidelity on subresolution assist features (SRAFs) used in Optical Proximity Correction (OPC) models of ever-increasing complexity. These items are not quantifiable with the 1D metrology techniques of today. Likewise, the mask maker needs advanced characterization methods in order to optimize the mask process to meet the wafer lithographer's needs. These advanced characterization metrics are what is needed to harmonize mask and wafer processes for enhanced wafer hot spot analysis. In this paper, we study advanced mask pattern characterization techniques and their correlation with modeled wafer performance.

The Mask Designs for Space Interferometer Mission (SIM)

NASA Technical Reports Server (NTRS)

Wang, Xu

2008-01-01

The Space Interferometer Mission (SIM) consists of three interferometers (science, guide1, and guide2) and two optical paths (metrology and starlight). The system requirements for each interferometer/optical path combination are different and sometimes work against each other. A diffraction model is developed to design and optimize various masks to simultaneously meet the system requirements of three interferometers. In this paper, the details of this diffraction model will be described first. Later, the mask design for each interferometer will be presented to demonstrate the system performance compliance. In the end, a tolerance sensitivity study on the geometrical dimension, shape, and the alignment of these masks will be discussed.

Second medical opinions: the views of oncology patients and their physicians.

PubMed

Philip, Jennifer; Gold, Michelle; Schwarz, Max; Komesaroff, Paul

2010-09-01

Second medical opinions (SMOs) are common in oncology practice, but the nature of these consultations has received relatively little attention. This study examines the views of patients with advanced cancer and their physicians of SMOs. Parallel, concurrent surveys were developed for patients and physicians. The first was distributed to outpatients with advanced cancer-attending specialist clinics in an Australian quaternary hospital. The second survey, developed on the basis of results of exploratory interviews with medical oncologists, was distributed to medical oncologists in Australia. Seventeen of fifty two (33%) patients had sought a SMO, most commonly prompted by concerns around communication with their first doctor, the extreme and desperate nature of their medical condition and the need for reassurance. Most (94%) patients found the SMO helpful, with satisfaction related to improved communication and reassurance. Patients were concerned that seeking a second medical opinion may affect their relationship with their primary doctor. Most physicians (82%) reported seeing between one and five SMO per month, with patients being motivated by the need for additional information and reassurance. Physicians regarded SMO patients as having greater information needs (84%), greater psychosocial needs (58%) and requiring more of the physician's time and energy (77%) than other patients. SMOs are common in cancer care with most patients motivated by the need for improved communication, additional information and reassurance. Physicians identify patients who seek SMOs as having additional psychosocial needs compared with other oncology patients.

Matching OPC and masks on 300-mm lithography tools utilizing variable illumination settings

NASA Astrophysics Data System (ADS)

Palitzsch, Katrin; Kubis, Michael; Schroeder, Uwe P.; Schumacher, Karl; Frangen, Andreas

2004-05-01

CD control is crucial to maximize product yields on 300mm wafers. This is particularly true for DRAM frontend lithography layers, like gate level, and deep trench (capacitor) level. In the DRAM process, large areas of the chip are taken up by array structures, which are difficult to structure due to aggressive pitch requirements. Consequently, the lithography process is centered such that the array structures are printed on target. Optical proximity correction is applied to print gate level structures in the periphery circuitry on target. Only slight differences of the different Zernike terms can cause rather large variations of the proximity curves, resulting in a difference of isolated and semi-isolated lines printed on different tools. If the deviations are too large, tool specific OPC is needed. The same is true for deep trench level, where the length to width ratio of elongated contact-like structures is an important parameter to adjust the electrical properties of the chip. Again, masks with specific biases for tools with different Zernikes are needed to optimize product yield. Additionally, mask making contributes to the CD variation of the process. Theoretically, the CD deviation caused by an off-centered mask process can easily eat up the majority of the CD budget of a lithography process. In practice, masks are very often distributed intelligently among production tools, such that lens and mask effects cancel each other. However, only dose adjusting and mask allocation may still result in a high CD variation with large systematical contributions. By adjusting the illumination settings, we have successfully implemented a method to reduce CD variation on our advanced processes. Especially inner and outer sigma for annular illumination, and the numerical aperture, can be optimized to match mask and stepper properties. This process will be shown to overcome slight lens and mask differences effectively. The effects on lithography process windows have to be considered, nonetheless.

Marquardt's Phi mask: pitfalls of relying on fashion models and the golden ratio to describe a beautiful face.

PubMed

Holland, E

2008-03-01

Stephen Marquardt has derived a mask from the golden ratio that he claims represents the "ideal" facial archetype. Many have found his mask convincing, including cosmetic surgeons. However, Marquardt's mask is associated with numerous problems. The method used to examine goodness of fit with the proportions in the mask is faulty. The mask is ill-suited for non-European populations, especially sub-Saharan Africans and East Asians. The mask also appears to approximate the face shape of masculinized European women. Given that the general public strongly and overwhelmingly prefers above average facial femininity in women, white women seeking aesthetic facial surgery would be ill-advised to aim toward a better fit with Marquardt's mask. This article aims to show the proper way of assessing goodness of fit with Marquardt's mask, to address the shape of the mask as it pertains to masculinity-femininity, and to discuss the broader issue of an objective assessment of facial attractiveness. Generalized Procrustes analysis is used to show how goodness of fit with Marquardt's mask can be assessed. Thin-plate spline analysis is used to illustrate visually how sample faces, including northwestern European averages, differ from Marquardt's mask. Marquardt's mask best describes the facial proportions of masculinized white women as seen in fashion models. Marquardt's mask does not appear to describe "ideal" face shape even for white women because its proportions are inconsistent with the optimal preferences of most people, especially with regard to femininity.

Optimization of wavefront coding imaging system using heuristic algorithms

NASA Astrophysics Data System (ADS)

González-Amador, E.; Padilla-Vivanco, A.; Toxqui-Quitl, C.; Zermeño-Loreto, O.

2017-08-01

Wavefront Coding (WFC) systems make use of an aspheric Phase-Mask (PM) and digital image processing to extend the Depth of Field (EDoF) of computational imaging systems. For years, several kinds of PM have been designed to produce a point spread function (PSF) near defocus-invariant. In this paper, the optimization of the phase deviation parameter is done by means of genetic algorithms (GAs). In this, the merit function minimizes the mean square error (MSE) between the diffraction limited Modulated Transfer Function (MTF) and the MTF of the system that is wavefront coded with different misfocus. WFC systems were simulated using the cubic, trefoil, and 4 Zernike polynomials phase-masks. Numerical results show defocus invariance aberration in all cases. Nevertheless, the best results are obtained by using the trefoil phase-mask, because the decoded image is almost free of artifacts.

Optimized phase mask to realize retro-reflection reduction for optical systems

NASA Astrophysics Data System (ADS)

He, Sifeng; Gong, Mali

2017-10-01

Aiming at the threats to the active laser detection systems of electro-optical devices due to the cat-eye effect, a novel solution is put forward to realize retro-reflection reduction in this paper. According to the demands of both cat-eye effect reduction and the image quality maintenance of electro-optical devices, a symmetric phase mask is achieved from a stationary phase method and a fast Fourier transform algorithm. Then, based on a comparison of peak normalized cross-correlation (PNCC) between the different defocus parameters, the optimal imaging position can be obtained. After modification with the designed phase mask, the cat-eye effect peak intensity can be reduced by two orders of magnitude while maintaining good image quality and high modulation transfer function (MTF). Furthermore, a practical design example is introduced to demonstrate the feasibility of our proposed approach.

Wafer hot spot identification through advanced photomask characterization techniques: part 2

NASA Astrophysics Data System (ADS)

Choi, Yohan; Green, Michael; Cho, Young; Ham, Young; Lin, Howard; Lan, Andy; Yang, Richer; Lung, Mike

2017-03-01

Historically, 1D metrics such as Mean to Target (MTT) and CD Uniformity (CDU) have been adequate for mask end users to evaluate and predict the mask impact on the wafer process. However, the wafer lithographer's process margin is shrinking at advanced nodes to a point that classical mask CD metrics are no longer adequate to gauge the mask contribution to wafer process error. For example, wafer CDU error at advanced nodes is impacted by mask factors such as 3-dimensional (3D) effects and mask pattern fidelity on sub-resolution assist features (SRAFs) used in Optical Proximity Correction (OPC) models of ever-increasing complexity. To overcome the limitation of 1D metrics, there are numerous on-going industry efforts to better define wafer-predictive metrics through both standard mask metrology and aerial CD methods. Even with these improvements, the industry continues to struggle to define useful correlative metrics that link the mask to final device performance. In part 1 of this work, we utilized advanced mask pattern characterization techniques to extract potential hot spots on the mask and link them, theoretically, to issues with final wafer performance. In this paper, part 2, we complete the work by verifying these techniques at wafer level. The test vehicle (TV) that was used for hot spot detection on the mask in part 1 will be used to expose wafers. The results will be used to verify the mask-level predictions. Finally, wafer performance with predicted and verified mask/wafer condition will be shown as the result of advanced mask characterization. The goal is to maximize mask end user yield through mask-wafer technology harmonization. This harmonization will provide the necessary feedback to determine optimum design, mask specifications, and mask-making conditions for optimal wafer process margin.

The Effects of Screw Configuration and Polymeric Carriers on Hot-Melt Extruded Taste-Masked Formulations Incorporated into Orally Disintegrating Tablets

PubMed Central

Morott, Joseph T.; Pimparade, Manjeet; Park, Jun-Bom; Worley, Chelsea P.; Majumdar, Soumyajit; Lian, Zhuoyang; Pinto, Elanor; Bi, Yunxia; Durig, Thomas; Repka, Michael A.

2015-01-01

The primary aim of this research was to produce successfully taste masked formulations of Sildenafil Citrate (SC) using hot-melt extrusion (HME) technology. Multiple screw configurations and polymeric carriers were evaluated for their effects on taste masking efficiency, which was assessed by both E-tongue analysis and in vitro dissolution in simulated salivary fluid (SSF, pH 6.8 artificial saliva). The screw configurations were further assessed for their effects on the morphology of the API using PXRD, FT-IR and mid-infrared chemical imaging. It was determined that the screw configuration had a profound effect on the taste masking efficiency of the formulations as a result of altering the physical state of the API. Selected extruded formulations using ethylcellulose (EC) with a pore former were further formulated into orally disintegrating tablets (ODTs), which were optimized by varying the grade and percentage of the superdisintegrant used. An optimized disintegration time of approximately 8 seconds was achieved. The final ODT formulation exhibited excellent taste masking properties with over 85% drug release in gastric media as well as physical tablet properties. Interestingly, friability, which tends to be a common concern when formulating ODTs, was well within the acceptable limits (<1%) for common tablets. PMID:25410968

Design and Optimization of a Light-Emitting Diode Projection Micro-Stereolithography Three-Dimensional Manufacturing System

DTIC Science & Technology

2012-12-11

ment, and difficulties creating high aspect ratio features. In addition, conventional mask-based lithography cannot create curved surfaces in the...There are three types of digital mask technologies: (1) liquid crystal display (LCD); (2) digital micromirror device (DMD); and (3) LCoS. LCD is the

Assessment of molecular contamination in mask pod

NASA Astrophysics Data System (ADS)

Foray, Jean Marie; Dejaune, Patrice; Sergent, Pierre; Gough, Stuart; Cheung, D.; Davenet, Magali; Favre, Arnaud; Rude, C.; Trautmann, T.; Tissier, Michel; Fontaine, H.; Veillerot, M.; Avary, K.; Hollein, I.; Lerit, R.

2008-04-01

Context/ study Motivation: Contamination and especially Airbone Molecular Contamination (AMC) is a critical issue for mask material flow with a severe and fairly unpredictable risk of induced contamination and damages especially for 193 nm lithography. It is therefore essential to measure, to understand and then try to reduce AMC in mask environment. Mask material flow was studied in a global approach by a pool of European partners, especially within the frame of European MEDEA+ project, so called "MUSCLE". This paper deals with results and assessment of mask pod environment in term of molecular contamination in a first step, then in a second step preliminary studies to reduce mask pod influence and contamination due to material out gassing. Approach and techniques: A specific assessment of environmental / molecular contamination along the supply chain was performed by all partners. After previous work presented at EMLC 07, further studies were performed on real time contamination measurement pod at different sites locations (including Mask manufacturing site, blank manufacturing sites, IC fab). Studies were linked to the main critical issues: cleaning, storage, handling, materials and processes. Contamination measurement campaigns were carried out along the mask supply chain using specific Adixen analyzer in order to monitor in real time organic contaminants (ppb level) in mask pods. Key results would be presented: VOC, AMC and humidity level on different kinds of mask carriers, impact of basic cleaning on pod outgassing measurement (VOC, NH3), and process influence on pod contamination... In a second step, preliminary specific pod conditioning studies for better pod environment were performed based on Adixen vacuum process. Process influence had been experimentally measured in term of molecular outgassing from mask pods. Different AMC experimental characterization methods had been carried out leading to results on a wide range of organic and inorganic contaminants: by inline techniques based on Adixen humidity, also VOC and organic sensors, together by off-line techniques already used in the extensive previous mask pods benchmark (TD-GCMS & Ionic Chromatography). Humidity and VOC levels from mask carriers had shown significant reduction after Adixen pod conditioning process. Focus had been made on optimized vacuum step (for AMC) after particles carrier cleaning cycle. Based upon these key results new procedures, as well as guidelines for mask carrier cleaning optimization are proposed to improve pod contamination control. Summary results/next steps: This paper reports molecular contamination measurement campaigns performed by a pool of European partners along the mask supply chain. It allows us to investigate, identify and quantify critical molecular contamination in mask pod, as well as VOC and humidity, issues depending on locations, uses, and carrier's type. Preliminary studies highlight initial process solutions for pods conditioning that are being used for short term industrialization and further industrialized.

Optical inspection of NGL masks

NASA Astrophysics Data System (ADS)

Pettibone, Donald W.; Stokowski, Stanley E.

2004-12-01

For the last five years KLA-Tencor and our joint venture partners have pursued a research program studying the ability of optical inspection tools to meet the inspection needs of possible NGL lithographies. The NGL technologies that we have studied include SCALPEL, PREVAIL, EUV lithography, and Step and Flash Imprint Lithography. We will discuss the sensitivity of the inspection tools and mask design factors that affect tool sensitivity. Most of the work has been directed towards EUV mask inspection and how to optimize the mask to facilitate inspection. Our partners have succeeded in making high contrast EUV masks ranging in contrast from 70% to 98%. Die to die and die to database inspection of EUV masks have been achieved with a sensitivity that is comparable to what can be achieved with conventional photomasks, approximately 80nm defect sensitivity. We have inspected SCALPEL masks successfully. We have found a limitation of optical inspection when applied to PREVAIL stencil masks. We have run inspections on SFIL masks in die to die, reflected light, in an effort to provide feedback to improve the masks. We have used a UV inspection system to inspect both unpatterned EUV substrates (no coatings) and blanks (with EUV multilayer coatings). These inspection results have proven useful in driving down the substrate and blank defect levels.

Investigating gas sensing mechanism of graphene oxide (GO) thin films through cross-selectivity to various gases

NASA Astrophysics Data System (ADS)

Kumar, Shani; Dhingra, Vishal; Garg, Amit; Chowdhuri, Arijit

2016-05-01

Worldwide researchers are actively engaged in utilizing Graphene and its related materials in gas sensing applications. A high surface-to-volume ratio that offers scope of optimization leading to enhanced sensing performance besides lower sensor operating temperatures are some advantages that graphene based sensors possess over conventional semiconducting metal oxide (SMO) sensors. Conventional SMO based gas sensors are known to suffer from problems of cross-selectivity where selectivity is understood to be a gas sensor's ability to preferentially detect one particular gas without responding to or experiencing interference from other gases present in the ambient. In the current study gas sensing mechanism of Graphene oxide (GO) thin films is investigated by repeatedly exposing the sensing configuration to various gases and its cross-selectivity response to the same is examined. In the investigation typical gas sensing response characteristics of the sensor configuration are studied in both oxidizing as well as reducing environments. The gas sensing data is acquired by means of Keithley 6487 picoammeter which is interfaced with a customized Gas Sensing Test Rig (GSTR) that provides a controlled ambient to the sensors for measurement of reproducible characteristics. GSTR further provided the option of varying the operating temperature and gas concentration for the different sensor configurations under study. XRD studies indicate formation of GO with typical crystallite size of 4.2 nm. UV-Vis investigations reveal a typical band-gap of 4.42 (eV) which is in conformity with those reported in the available literature.1,2

Optimizing defect inspection strategy through the use of design-aware database control layers

NASA Astrophysics Data System (ADS)

Stoler, Dvori; Ruch, Wayne; Ma, Weimin; Chakravarty, Swapnajit; Liu, Steven; Morgan, Ray; Valadez, John; Moore, Bill; Burns, John

2007-10-01

Resolution limitations in the mask making process can cause differences between the features that appear in a database and those printed to a reticle. These differences may result from intentional or unintentional features in the database exceeding the resolution limit of the mask making process such as small gaps or lines in the data, line end shortening on small sub-resolution assist features etc creating challenges to both mask writing and mask inspection. Areas with high variance from design to mask, often referred to as high MEEF areas (mask error enhancement factor), become highly problematic and can directly impact mask and device yield, mask manufacturing cycle time and ultimately mask costs. Specific to mask inspection it may be desirable to inspect certain non-critical or non-relevant features at reduced sensitivity so as not to detect real, but less significant process defects. In contrast there may also be times where increased sensitivity is required for critical mask features or areas. Until recently, this process was extremely manual, creating added time and cost to the mask inspection cycle. Shifting to more intelligent and automated inspection flows is the key focus of this paper. A novel approach to importing design data directly into the mask inspection to include both MDP generated MRC errors files and LRC generated MEEF files. The results of recently developed inspection and review capability based upon controlling defect inspection using design aware data base control layers on a pixel basis are discussed. Typical mask shop applications and implementations will be shown.

Trends in pharmaceutical taste masking technologies: a patent review.

PubMed

Ayenew, Zelalem; Puri, Vibha; Kumar, Lokesh; Bansal, Arvind K

2009-01-01

According to the year 2003 survey of pediatricians by the American Association of Pediatrics, unpleasant taste was the biggest barrier for completing treatment in pediatrics. The field of taste masking of active pharmaceutical ingredients (API) has been continuously evolving with varied technologies and new excipients. The article reviews the trends in taste masking technologies by studying the current state of the art patent database for the span of year 1997 to 2007. The worldwide database of European patent office (http://ep.espacenet.com) was employed to collect the patents and patent applications. It also discusses the possible reasons for the change of preferences in the taste masking technologies with time. The prime factors critical to the selection of an optimal taste masking technique such as the extent of drug bitterness, solubility, particle characteristics, dosage form and dose are briefly discussed.

Cryogenic Etching of High Aspect Ratio 400 nm Pitch Silicon Gratings.

PubMed

Miao, Houxun; Chen, Lei; Mirzaeimoghri, Mona; Kasica, Richard; Wen, Han

2016-10-01

The cryogenic process and Bosch process are two widely used processes for reactive ion etching of high aspect ratio silicon structures. This paper focuses on the cryogenic deep etching of 400 nm pitch silicon gratings with various etching mask materials including polymer, Cr, SiO 2 and Cr-on-polymer. The undercut is found to be the key factor limiting the achievable aspect ratio for the direct hard masks of Cr and SiO 2 , while the etch selectivity responds to the limitation of the polymer mask. The Cr-on-polymer mask provides the same high selectivity as Cr and reduces the excessive undercut introduced by direct hard masks. By optimizing the etching parameters, we etched a 400 nm pitch grating to ≈ 10.6 μ m depth, corresponding to an aspect ratio of ≈ 53.

Thyroid hormone regulates the expression of the sonic hedgehog signaling pathway in the embryonic and adult Mammalian brain.

PubMed

Desouza, Lynette A; Sathanoori, Malini; Kapoor, Richa; Rajadhyaksha, Neha; Gonzalez, Luis E; Kottmann, Andreas H; Tole, Shubha; Vaidya, Vidita A

2011-05-01

Thyroid hormone is important for development and plasticity in the immature and adult mammalian brain. Several thyroid hormone-responsive genes are regulated during specific developmental time windows, with relatively few influenced across the lifespan. We provide novel evidence that thyroid hormone regulates expression of the key developmental morphogen sonic hedgehog (Shh), and its coreceptors patched (Ptc) and smoothened (Smo), in the early embryonic and adult forebrain. Maternal hypo- and hyperthyroidism bidirectionally influenced Shh mRNA in embryonic forebrain signaling centers at stages before fetal thyroid hormone synthesis. Further, Smo and Ptc expression were significantly decreased in the forebrain of embryos derived from hypothyroid dams. Adult-onset thyroid hormone perturbations also regulated expression of the Shh pathway bidirectionally, with a significant induction of Shh, Ptc, and Smo after hyperthyroidism and a decline in Smo expression in the hypothyroid brain. Short-term T₃ administration resulted in a significant induction of cortical Shh mRNA expression and also enhanced reporter gene expression in Shh(+/LacZ) mice. Further, acute T₃ treatment of cortical neuronal cultures resulted in a rapid and significant increase in Shh mRNA, suggesting direct effects. Chromatin immunoprecipitation assays performed on adult neocortex indicated enhanced histone acetylation at the Shh promoter after acute T₃ administration, providing further support that Shh is a thyroid hormone-responsive gene. Our results indicate that maternal and adult-onset perturbations of euthyroid status cause robust and region-specific changes in the Shh pathway in the embryonic and adult forebrain, implicating Shh as a possible mechanistic link for specific neurodevelopmental effects of thyroid hormone.

Current twin studies in Germany: report on CoSMoS, SOEP, and ChronoS.

PubMed

Hahn, Elisabeth; Gottschling, Juliana; Spinath, Frank M

2013-02-01

This article summarizes the status of three recent German twin studies: CoSMoS, SOEP, and ChronoS. The German twin study on Cognitive Ability, Self-Reported Motivation, and School Achievement (CoSMoS) is a three-wave longitudinal study of monozygotic and dizygotic twins reared together, and aims to investigate predictors of and influences on school performance. In the first wave of the data collection in 2005, 408 pairs of twins aged between 7 and 11 as well as their parents participated in CoSMoS. The SOEP twin study is an extended twin study, which has combined data from monozygotic and dizygotic twins reared together with additional data from full sibling pairs, mother-child, and grandparent-child dyads who participated in the German Socio-Economic Panel (GSOEP) study. The SOEP twin project comprises about 350 twin and 950 non-twin pairs aged between 17 and 70. Data were collected between 2009 and 2010, with a focus on personality traits, wellbeing, education, employment, income, living situation, life-satisfaction, and several attitudes. The aim of the Chronotype twin study (ChronoS) was to examine genetic and environmental influences on chronotype (morningness and eveningness), coping strategies, and several aspects of the previous SOEP twin project in a sample of 301 twin pairs aged between 19 and 76 years, recruited in 2010 and 2011. Part of the ChronoS twin sample also participated in the earlier SOEP twin study, representing a second wave of assessments. We briefly describe the design and contents of these three studies as well as selected recent findings.

Model-based virtual VSB mask writer verification for efficient mask error checking and optimization prior to MDP

NASA Astrophysics Data System (ADS)

Pack, Robert C.; Standiford, Keith; Lukanc, Todd; Ning, Guo Xiang; Verma, Piyush; Batarseh, Fadi; Chua, Gek Soon; Fujimura, Akira; Pang, Linyong

2014-10-01

A methodology is described wherein a calibrated model-based `Virtual' Variable Shaped Beam (VSB) mask writer process simulator is used to accurately verify complex Optical Proximity Correction (OPC) and Inverse Lithography Technology (ILT) mask designs prior to Mask Data Preparation (MDP) and mask fabrication. This type of verification addresses physical effects which occur in mask writing that may impact lithographic printing fidelity and variability. The work described here is motivated by requirements for extreme accuracy and control of variations for today's most demanding IC products. These extreme demands necessitate careful and detailed analysis of all potential sources of uncompensated error or variation and extreme control of these at each stage of the integrated OPC/ MDP/ Mask/ silicon lithography flow. The important potential sources of variation we focus on here originate on the basis of VSB mask writer physics and other errors inherent in the mask writing process. The deposited electron beam dose distribution may be examined in a manner similar to optical lithography aerial image analysis and image edge log-slope analysis. This approach enables one to catch, grade, and mitigate problems early and thus reduce the likelihood for costly long-loop iterations between OPC, MDP, and wafer fabrication flows. It moreover describes how to detect regions of a layout or mask where hotspots may occur or where the robustness to intrinsic variations may be improved by modification to the OPC, choice of mask technology, or by judicious design of VSB shots and dose assignment.

Projected 21st century coastal flooding in the Southern California Bight. Part 1: Development of the third generation CoSMoS model

USGS Publications Warehouse

O'Neill, Andrea; Erikson, Li; Barnard, Patrick; Limber, Patrick; Vitousek, Sean; Warrick, Jonathan; Foxgrover, Amy C.; Lovering, Jessica

2018-01-01

Due to the effects of climate change over the course of the next century, the combination of rising sea levels, severe storms, and coastal change will threaten the sustainability of coastal communities, development, and ecosystems as we know them today. To clearly identify coastal vulnerabilities and develop appropriate adaptation strategies due to projected increased levels of coastal flooding and erosion, coastal managers need local-scale hazards projections using the best available climate and coastal science. In collaboration with leading scientists world-wide, the USGS designed the Coastal Storm Modeling System (CoSMoS) to assess the coastal impacts of climate change for the California coast, including the combination of sea-level rise, storms, and coastal change. In this project, we directly address the needs of coastal resource managers in Southern California by integrating a vast range of global climate change projections in a thorough and comprehensive numerical modeling framework. In Part 1 of a two-part submission on CoSMoS, methods and the latest improvements are discussed, and an example of hazard projections is presented.

Metabolites in vertebrate Hedgehog signaling.

PubMed

Roberg-Larsen, Hanne; Strand, Martin Frank; Krauss, Stefan; Wilson, Steven Ray

2014-04-11

The Hedgehog (HH) signaling pathway is critical in embryonic development, stem cell biology, tissue homeostasis, chemoattraction and synapse formation. Irregular HH signaling is associated with a number of disease conditions including congenital disorders and cancer. In particular, deregulation of HH signaling has been linked to skin, brain, lung, colon and pancreatic cancers. Key mediators of the HH signaling pathway are the 12-pass membrane protein Patched (PTC), the 7-pass membrane protein Smoothened (SMO) and the GLI transcription factors. PTC shares homology with the RND family of small-molecule transporters and it has been proposed that it interferes with SMO through metabolites. Although a conclusive picture is lacking, substantial efforts are made to identify and understand natural metabolites/sterols, including cholesterol, vitamin D3, oxysterols and glucocorticoides, that may be affected by, or influence the HH signaling cascade at the level of PTC and SMO. In this review we will elaborate the role of metabolites in HH signaling with a focus on oxysterols, and discuss advancements in modern analytical approaches in the field. Copyright © 2014 Elsevier Inc. All rights reserved.

Primary Cilia Negatively Regulate Melanogenesis in Melanocytes and Pigmentation in a Human Skin Model.

PubMed

Choi, Hyunjung; Shin, Ji Hyun; Kim, Eun Sung; Park, So Jung; Bae, Il-Hong; Jo, Yoon Kyung; Jeong, In Young; Kim, Hyoung-June; Lee, Youngjin; Park, Hea Chul; Jeon, Hong Bae; Kim, Ki Woo; Lee, Tae Ryong; Cho, Dong-Hyung

2016-01-01

The primary cilium is an organelle protruding from the cell body that senses external stimuli including chemical, mechanical, light, osmotic, fluid flow, and gravitational signals. Skin is always exposed to the external environment and responds to external stimuli. Therefore, it is possible that primary cilia have an important role in skin. Ciliogenesis was reported to be involved in developmental processes in skin, such as keratinocyte differentiation and hair formation. However, the relation between skin pigmentation and primary cilia is largely unknown. Here, we observed that increased melanogenesis in melanocytes treated with a melanogenic inducer was inhibited by a ciliogenesis inducer, cytochalasin D, and serum-free culture. However, these inhibitory effects disappeared in GLI2 knockdown cells. In addition, activation of sonic hedgehog (SHH)-smoothened (Smo) signaling pathway by a Smo agonist, SAG inhibited melanin synthesis in melanocytes and pigmentation in a human skin model. On the contrary, an inhibitor of primary cilium formation, ciliobrevin A1, activated melanogenesis in melanocytes. These results suggest that skin pigmentation may be regulated partly by the induction of ciliogenesis through Smo-GLI2 signaling.

PMJ panel discussion overview on mask complexities, cost, and cycle time in 32-nm system LSI generation: conflict or concurrent?

NASA Astrophysics Data System (ADS)

Hosono, Kunihiro; Kato, Kokoro

2008-10-01

This is a report on a panel discussion organized in Photomask Japan 2008, where the challenges about "Mask Complexities, Cost, and Cycle Time in 32-nm System LSI Generation" were addressed to have a look over the possible solutions from the standpoints of chipmaker, commercial mask shop, DA tool vendor and equipments makers. The wrap-up is as follows: Mask complexities justify the mask cost, while the acceptable increase rate of 32nm-mask cost significantly differs between mask suppliers or users side. The efficiency progress by new tools or DFM has driven their cycle-time reductions. Mask complexities and cost will be crucial issues prior to cycle time, and there seems to be linear correlation between them. Controlling complexity and cycle time requires developing a mix of advanced technologies, and especially for cost reduction, shot prices in writers and processing rates in inspection tools have been improved remarkably by tool makers. In addition, activities of consortium in Japan (Mask D2I) are expected to enhance the total optimization of mask design, writing and inspection. The cycle-time reduction potentially drives the lowering of mask cost, and, on the other, the pattern complexities and tighter mask specifications get in the way to 32nm generation as well as the nano-economics and market challenges. There are still many difficult problems in mask manufacturing now, and we are sure to go ahead to overcome a 32nm hurdle with the advances of technologies and collaborations by not only technologies but also finance.

Program and Project Management Framework

NASA Technical Reports Server (NTRS)

Butler, Cassandra D.

2002-01-01

The primary objective of this project was to develop a framework and system architecture for integrating program and project management tools that may be applied consistently throughout Kennedy Space Center (KSC) to optimize planning, cost estimating, risk management, and project control. Project management methodology used in building interactive systems to accommodate the needs of the project managers is applied as a key component in assessing the usefulness and applicability of the framework and tools developed. Research for the project included investigation and analysis of industrial practices, KSC standards, policies, and techniques, Systems Management Office (SMO) personnel, and other documented experiences of project management experts. In addition, this project documents best practices derived from the literature as well as new or developing project management models, practices, and techniques.

Machine learning based detection of age-related macular degeneration (AMD) and diabetic macular edema (DME) from optical coherence tomography (OCT) images

PubMed Central

Wang, Yu; Zhang, Yaonan; Yao, Zhaomin; Zhao, Ruixue; Zhou, Fengfeng

2016-01-01

Non-lethal macular diseases greatly impact patients’ life quality, and will cause vision loss at the late stages. Visual inspection of the optical coherence tomography (OCT) images by the experienced clinicians is the main diagnosis technique. We proposed a computer-aided diagnosis (CAD) model to discriminate age-related macular degeneration (AMD), diabetic macular edema (DME) and healthy macula. The linear configuration pattern (LCP) based features of the OCT images were screened by the Correlation-based Feature Subset (CFS) selection algorithm. And the best model based on the sequential minimal optimization (SMO) algorithm achieved 99.3% in the overall accuracy for the three classes of samples. PMID:28018716

Underwater acoustic positioning system for the SMO and KM3NeT - Italia projects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Viola, S.; Barbagallo, G.; Cacopardo, G.

In the underwater neutrino telescopes, the positions of the Cherenkov light sensors and their movements must be known with an accuracy of few tens of centimetres. In this work, the activities of the SMO and KM3NeT-Italia teams for the development of an acoustic positioning system for KM3NeT-Italia project are presented. The KM3NeT-Italia project foresees the construction, within two years, of 8 towers in the view of the several km{sup 3}-scale neutrino telescope KM3NeT.

Facial and ocular deposition of nebulized budesonide: effects of face mask design.

PubMed

Harris, Keith W; Smaldone, Gerald C

2008-02-01

In vivo case reports and in vitro studies have indicated that aerosol therapy using face masks can result in drug deposition on the face and in the eyes, and that face mask design may affect drug delivery. To test different mask/nebulizer combinations for budesonide, a nebulized steroid used to treat pediatric patients with asthma. Using high-performance liquid chromatography, drug delivery (inhaled mass), facial, and ocular deposition of budesonide aerosols were studied in vitro using a ventilated face facsimile (tidal volume, 50 mL; rate, 25 breaths/min, duty cycle 0.4), a tight-fitting test mask, a standard commercial mask, and a prototype mask designed to optimize delivery by reducing particle inertia. Nebulizer insertion into the mask (front loaded vs bottom loaded) was also tested. Particle size was measured by cascade impaction. Pari LC Plus (PARI Respiratory Equipment; Midlothian, VA) and MistyNeb (Allegiance; McGaw Park, IL) nebulizers were tested. Inhaled mass for tight-fitting and prototype masks was similar (13.2 +/- 1.85% vs 14.4 +/- 0.67% [percentage of nebulizer charge], p = 0.58) and significantly greater than for the commercial mask (3.03 +/- 0.26%, p = 0.005). Mask insertion of nebulizer was a key factor (inhaled mass: front loaded vs bottom loaded, 8.23 +/- 0.18% vs 3.03 +/- 0.26%; p = 0.005). Ocular deposition varied by an order of magnitude and was a strong function of mask design (4.77 +/- 0.24% vs 0.35 +/- 0.05%, p = 0.002, tight fitting vs prototype). Particle sizes (7.3 to 9 microm) were larger than previously reported for budesonide. For pediatric breathing patterns, mask design is a key factor defining budesonide delivery to the lungs, face, and eyes. Front-loaded nebulizer mask combinations are more efficient than bottom-loaded systems.

Efficacy of a new device to optimize positive pressure ventilation via face mask in edentulous patients: a randomized trial.

PubMed

Niño, Maria C; Pauwels, Andres; Raffan, Fernando; Arango, Enrique; Romero, David J; Benitez, Daniel

2017-04-01

Mask ventilation is routinely performed during anesthesia. Under some circumstances, it might be difficult to perform, such as in edentulous patients, due to inadequate mask seal. We developed a new device called NIPARA and studied its use For ventilation optimization in edentulous patients. This randomized controlled trial included edentulous adults who had no other predictors of difficult airway, scheduled to undergo general anesthesia. Patients were assigned either to the NIPARA device group or to the control group (oral airway only). The primary outcomes were peak inspiratory pressure and tidal volume values of the first 14 breaths. The secondary outcome was the incidence of complications. Data from 37 patients were collected during a one-year period (twenty in the NIPARA device group and 17 in the control group). The difference in mean PIP was not statistically significant. The tidal volume was 1.5 times greater in the NIPARA group than in the control group. One patient from the intervention group had minimal oral trauma. In the administration of face mask ventilation, NIPARA is an effective device that significantly improves the tidal volume administered in edentulous patients.

Development and Evaluation of Taste Masked Granular Formulation of Satranidazole by Melt Granulation Technique

PubMed Central

Pawar, Harshal Ashok; Joshi, Pooja Rasiklal

2014-01-01

Drugs from nitroimidazole category are generally bitter in taste. Oral formulation with bitter taste is not palatable. Geriatrics and pediatrics patients usually suffer from swallowing difficulties. Many other patients in some disease conditions avoid swallowing tablets. Satranidazole is a new nitro-imidazole derivative with bitter taste and is available in market as film coated tablet. The purpose of this research was to mask the bitter taste of Satranidazole by coating complexation with low melting point wax and Eudragit EPO. Different types of wax (glyceryl monostearate, stearic acid and cetyl alcohol) were tried for taste masking. The drug to stearic acid ratio 1 : 2 was found to be optimum on the basis of taste evaluation and in vitro release. The formulated granules were found to possess good flow property. FTIR studies confirmed that there was no interaction between drug and excipients. Scanning Electron Microscopy of drug and the optimized batch of granules was performed. The in vitro release of drug from granules was compared with marketed tablet formulation. The taste masked granules of optimized batch showed 87.65% release of drug in 1 hr which is comparable to that of marketed tablet formulation. PMID:26556200

Fabrication of a novel quartz micromachined gyroscope

NASA Astrophysics Data System (ADS)

Xie, Liqiang; Xing, Jianchun; Wang, Haoxu; Wu, Xuezhong

2015-04-01

A novel quartz micromachined gyroscope is proposed in this paper. The novel gyroscope is realized by quartz anisotropic wet etching and 3-dimensional electrodes deposition. In the quartz wet etching process, the quality of Cr/Au mask films affecting the process are studied by experiment. An excellent mask film with 100 Å Cr and 2000 Å Au is achieved by optimization of experimental parameters. Crystal facets after etching seriously affect the following sidewall electrodes deposition process and the structure's mechanical behaviours. Removal of crystal facets is successfully implemented by increasing etching time based on etching rate ratios between facets and crystal planes. In the electrodes deposition process, an aperture mask evaporation method is employed to prepare electrodes on 3-dimensional surfaces of the gyroscope structure. The alignments among the aperture masks are realized by the ABM™ Mask Aligner System. Based on the processes described above, a z-axis quartz gyroscope is fabricated successfully.

Efficient three-dimensional resist profile-driven source mask optimization optical proximity correction based on Abbe-principal component analysis and Sylvester equation

NASA Astrophysics Data System (ADS)

Lin, Pei-Chun; Yu, Chun-Chang; Chen, Charlie Chung-Ping

2015-01-01

As one of the critical stages of a very large scale integration fabrication process, postexposure bake (PEB) plays a crucial role in determining the final three-dimensional (3-D) profiles and lessening the standing wave effects. However, the full 3-D chemically amplified resist simulation is not widely adopted during the postlayout optimization due to the long run-time and huge memory usage. An efficient simulation method is proposed to simulate the PEB while considering standing wave effects and resolution enhancement techniques, such as source mask optimization and subresolution assist features based on the Sylvester equation and Abbe-principal component analysis method. Simulation results show that our algorithm is 20× faster than the conventional Gaussian convolution method.

Several organic parameters on underlying hazardous constituents list can not be measured at the universal treatment standards

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, H.C.

1998-07-01

The Idaho National Engineering and Environmental Laboratory (INEEL) has several permitted treatment, storage and disposal facilities. The INEEL Sample Management Office (SMO) conducts all analysis subcontracting activities for Department of Energy Environmental Management programs at the INEEL. In this role, the INEEL SMO has had the opportunity to subcontract the analyses of various wastes (including ash from an interim status incinerator) requesting a target analyte list equivalent to the constituents listed in 40 Code of Federal Regulations. These analyses are required to ensure that treated wastes do not contain underlying hazardous constituents (UHC) at concentrations greater than the universal treatmentmore » standards (UTS) prior to land disposal. The INEEL SMO has conducted a good-faith effort by negotiating with several commercial laboratories to identify the lowest possible quantitation and detection limits that can be achieved for the organic UHC analytes. The results of this negotiating effort has been the discovery that no single laboratory (currently under subcontract with the INEEL SMO) can achieve a detection level that is within an order of magnitude of the UTS for all organic parameters on a clean sample matrix (e.g., sand). This does not mean that there is no laboratory that can achieve the order of magnitude requirements for all organic UHCs on a clean sample matrix. The negotiations held to date indicate that it is likely that no laboratory can achieve the order of magnitude requirements for a difficult sample matrix (e.g., an incinerator ash). The authors suggest that the regulation needs to be revised to address the disparity between what is achievable in the laboratory and the regulatory levels required by the UTS.« less

Development of the Coastal Storm Modeling System (CoSMoS) for predicting the impact of storms on high-energy, active-margin coasts

USGS Publications Warehouse

Barnard, Patrick; Maarten van Ormondt,; Erikson, Li H.; Jodi Eshleman,; Hapke, Cheryl J.; Peter Ruggiero,; Peter Adams,; Foxgrover, Amy C.

2014-01-01

The Coastal Storm Modeling System (CoSMoS) applies a predominantly deterministic framework to make detailed predictions (meter scale) of storm-induced coastal flooding, erosion, and cliff failures over large geographic scales (100s of kilometers). CoSMoS was developed for hindcast studies, operational applications (i.e., nowcasts and multiday forecasts), and future climate scenarios (i.e., sea-level rise + storms) to provide emergency responders and coastal planners with critical storm hazards information that may be used to increase public safety, mitigate physical damages, and more effectively manage and allocate resources within complex coastal settings. The prototype system, developed for the California coast, uses the global WAVEWATCH III wave model, the TOPEX/Poseidon satellite altimetry-based global tide model, and atmospheric-forcing data from either the US National Weather Service (operational mode) or Global Climate Models (future climate mode), to determine regional wave and water-level boundary conditions. These physical processes are dynamically downscaled using a series of nested Delft3D-WAVE (SWAN) and Delft3D-FLOW (FLOW) models and linked at the coast to tightly spaced XBeach (eXtreme Beach) cross-shore profile models and a Bayesian probabilistic cliff failure model. Hindcast testing demonstrates that, despite uncertainties in preexisting beach morphology over the ~500 km alongshore extent of the pilot study area, CoSMoS effectively identifies discrete sections of the coast (100s of meters) that are vulnerable to coastal hazards under a range of current and future oceanographic forcing conditions, and is therefore an effective tool for operational and future climate scenario planning.

Vismodegib Exerts Targeted Efficacy Against Recurrent Sonic Hedgehog–Subgroup Medulloblastoma: Results From Phase II Pediatric Brain Tumor Consortium Studies PBTC-025B and PBTC-032

PubMed Central

Robinson, Giles W.; Orr, Brent A.; Wu, Gang; Gururangan, Sridharan; Lin, Tong; Qaddoumi, Ibrahim; Packer, Roger J.; Goldman, Stewart; Prados, Michael D.; Desjardins, Annick; Chintagumpala, Murali; Takebe, Naoko; Kaste, Sue C.; Rusch, Michael; Allen, Sariah J.; Onar-Thomas, Arzu; Stewart, Clinton F.; Fouladi, Maryam; Boyett, James M.; Gilbertson, Richard J.; Curran, Tom; Ellison, David W.; Gajjar, Amar

2015-01-01

Purpose Two phase II studies assessed the efficacy of vismodegib, a sonic hedgehog (SHH) pathway inhibitor that binds smoothened (SMO), in pediatric and adult recurrent medulloblastoma (MB). Patients and Methods Adult patients enrolled onto PBTC-025B and pediatric patients enrolled onto PBTC-032 were treated with vismodegib (150 to 300 mg/d). Protocol-defined response, which had to be sustained for 8 weeks, was confirmed by central neuroimaging review. Molecular tests to identify patterns of response and insensitivity were performed when tissue was available. Results A total of 31 patients were enrolled onto PBTC-025B, and 12 were enrolled onto PBTC-032. Three patients in PBTC-025B and one in PBTC-032, all with SHH-subgroup MB (SHH-MB), exhibited protocol-defined responses. Progression-free survival (PFS) was longer in those with SHH-MB than in those with non-SHH–MB, and prolonged disease stabilization occurred in 41% of patient cases of SHH-MB. Among those with SHH-MB, loss of heterozygosity of PTCH1 was associated with prolonged PFS, and diffuse staining of P53 was associated with reduced PFS. Whole-exome sequencing identified mutations in SHH genes downstream from SMO in four of four tissue samples from nonresponders and upstream of SMO in two of four patients with favorable responses. Conclusion Vismodegib exhibits activity against adult recurrent SHH-MB but not against recurrent non-SHH–MB. Inadequate accrual of pediatric patients precluded conclusions in this population. Molecular analyses support the hypothesis that SMO inhibitor activity depends on the genomic aberrations within the tumor. Such inhibitors should be advanced in SHH-MB studies; however, molecular and genomic work remains imperative to identify target populations that will truly benefit. PMID:26169613

Widespread GLI expression but limited canonical hedgehog signaling restricted to the ductular reaction in human chronic liver disease

PubMed Central

Tirnitz-Parker, Janina Elke Eleonore; Hamson, Elizabeth Jane; Warren, Alessandra; Maneck, Bharvi; Chen, Jinbiao; Patkunanathan, Bramilla; Boland, Jade; Cheng, Robert; Shackel, Nicholas Adam; Seth, Devanshi; Bowen, David Geoffrey; Martelotto, Luciano Gastón; Watkins, D. Neil; McCaughan, Geoffrey William

2017-01-01

Canonical Hedgehog (Hh) signaling in vertebrate cells occurs following Smoothened activation/translocation into the primary cilia (Pc), followed by a GLI transcriptional response. Nonetheless, GLI activation can occur independently of the canonical Hh pathway. Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations. This study extends these observations to human liver tissue, and analyses the effect of GLI inhibition on LPC viability/gene expression. Human donor and cirrhotic liver tissue specimens were evaluated for SHH, GLI2 and Pc expression using immunofluorescence and qRT-PCR. Changes to viability and gene expression in LPCs in vitro were assessed following GLI inhibition. Identification of Pc (as a marker of canonical Hh signaling) in human cirrhosis was predominantly confined to the ductular reaction and LPCs. In contrast, GLI2 was expressed in multiple cell populations including Pc-ve endothelium, hepatocytes, and leukocytes. HSCs/myofibroblasts (>99%) expressed GLI2, with only 1.92% displaying Pc. In vitro GLI signals maintained proliferation/viability within LPCs and GLI inhibition affected the expression of genes related to stemness, hepatocyte/biliary differentiation and Hh/Wnt signaling. At least two mechanisms of GLI signaling (Pc/SMO-dependent and Pc/SMO-independent) mediate chronic liver disease pathogenesis. This may have significant ramifications for the choice of Hh inhibitor (anti-SMO or anti-GLI) suitable for clinical trials. We also postulate GLI delivers a pro-survival signal to LPCs whilst maintaining stemness. PMID:28187190

Widespread GLI expression but limited canonical hedgehog signaling restricted to the ductular reaction in human chronic liver disease.

PubMed

Grzelak, Candice Alexandra; Sigglekow, Nicholas David; Tirnitz-Parker, Janina Elke Eleonore; Hamson, Elizabeth Jane; Warren, Alessandra; Maneck, Bharvi; Chen, Jinbiao; Patkunanathan, Bramilla; Boland, Jade; Cheng, Robert; Shackel, Nicholas Adam; Seth, Devanshi; Bowen, David Geoffrey; Martelotto, Luciano Gastón; Watkins, D Neil; McCaughan, Geoffrey William

2017-01-01

Canonical Hedgehog (Hh) signaling in vertebrate cells occurs following Smoothened activation/translocation into the primary cilia (Pc), followed by a GLI transcriptional response. Nonetheless, GLI activation can occur independently of the canonical Hh pathway. Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations. This study extends these observations to human liver tissue, and analyses the effect of GLI inhibition on LPC viability/gene expression. Human donor and cirrhotic liver tissue specimens were evaluated for SHH, GLI2 and Pc expression using immunofluorescence and qRT-PCR. Changes to viability and gene expression in LPCs in vitro were assessed following GLI inhibition. Identification of Pc (as a marker of canonical Hh signaling) in human cirrhosis was predominantly confined to the ductular reaction and LPCs. In contrast, GLI2 was expressed in multiple cell populations including Pc-ve endothelium, hepatocytes, and leukocytes. HSCs/myofibroblasts (>99%) expressed GLI2, with only 1.92% displaying Pc. In vitro GLI signals maintained proliferation/viability within LPCs and GLI inhibition affected the expression of genes related to stemness, hepatocyte/biliary differentiation and Hh/Wnt signaling. At least two mechanisms of GLI signaling (Pc/SMO-dependent and Pc/SMO-independent) mediate chronic liver disease pathogenesis. This may have significant ramifications for the choice of Hh inhibitor (anti-SMO or anti-GLI) suitable for clinical trials. We also postulate GLI delivers a pro-survival signal to LPCs whilst maintaining stemness.

Thyroid Hormone Regulates the Expression of the Sonic Hedgehog Signaling Pathway in the Embryonic and Adult Mammalian Brain

PubMed Central

Desouza, Lynette A.; Sathanoori, Malini; Kapoor, Richa; Rajadhyaksha, Neha; Gonzalez, Luis E.; Kottmann, Andreas H.; Tole, Shubha

2011-01-01

Thyroid hormone is important for development and plasticity in the immature and adult mammalian brain. Several thyroid hormone-responsive genes are regulated during specific developmental time windows, with relatively few influenced across the lifespan. We provide novel evidence that thyroid hormone regulates expression of the key developmental morphogen sonic hedgehog (Shh), and its coreceptors patched (Ptc) and smoothened (Smo), in the early embryonic and adult forebrain. Maternal hypo- and hyperthyroidism bidirectionally influenced Shh mRNA in embryonic forebrain signaling centers at stages before fetal thyroid hormone synthesis. Further, Smo and Ptc expression were significantly decreased in the forebrain of embryos derived from hypothyroid dams. Adult-onset thyroid hormone perturbations also regulated expression of the Shh pathway bidirectionally, with a significant induction of Shh, Ptc, and Smo after hyperthyroidism and a decline in Smo expression in the hypothyroid brain. Short-term T3 administration resulted in a significant induction of cortical Shh mRNA expression and also enhanced reporter gene expression in Shh+/LacZ mice. Further, acute T3 treatment of cortical neuronal cultures resulted in a rapid and significant increase in Shh mRNA, suggesting direct effects. Chromatin immunoprecipitation assays performed on adult neocortex indicated enhanced histone acetylation at the Shh promoter after acute T3 administration, providing further support that Shh is a thyroid hormone-responsive gene. Our results indicate that maternal and adult-onset perturbations of euthyroid status cause robust and region-specific changes in the Shh pathway in the embryonic and adult forebrain, implicating Shh as a possible mechanistic link for specific neurodevelopmental effects of thyroid hormone. PMID:21363934

Overactivation of hedgehog signaling alters development of the ovarian vasculature in mice.

PubMed

Ren, Yi; Cowan, Robert G; Migone, Fernando F; Quirk, Susan M

2012-06-01

The hedgehog (HH) signaling pathway is critical for ovarian function in Drosophila, but its role in the mammalian ovary has not been defined. Previously, expression of a dominant active allele of the HH signal transducer protein smoothened (SMO) in Amhr2(cre/+)SmoM2 mice caused anovulation in association with a lack of smooth muscle in the theca of developing follicles. The current study examined events during the first 2 wk of life in Amhr2(cre/+)SmoM2 mice to gain insight into the cause of anovulation. Expression of transcriptional targets of HH signaling, Gli1, Ptch1, and Hhip, which are used as measures of pathway activity, were elevated during the first several days of life in Amhr2(cre/+)SmoM2 mice compared to controls but were similar to controls in older mice. Microarray analysis showed that genes with increased expression in 2-day-old mutants compared to controls were enriched for the processes of vascular and tube development and steroidogenesis. The density of platelet endothelial cell adhesion molecule (PECAM)-labeled endothelial tubes was increased in the cortex of newborn ovaries of mutant mice. Costaining of preovulatory follicles for PECAM and smooth muscle actin showed that muscle-type vascular support cells are deficient in theca of mutant mice. Expression of genes for steroidogenic enzymes that are normally expressed in the fetal adrenal gland were elevated in newborn ovaries of mutant mice. In summary, overactivation of HH signaling during early life alters gene expression and vascular development and this is associated with the lifelong development of anovulatory follicles in which the thecal vasculature fails to mature appropriately.

Overactivation of Hedgehog Signaling Alters Development of the Ovarian Vasculature in Mice1

PubMed Central

Ren, Yi; Cowan, Robert G.; Migone, Fernando F.; Quirk, Susan M.

2012-01-01

ABSTRACT The hedgehog (HH) signaling pathway is critical for ovarian function in Drosophila, but its role in the mammalian ovary has not been defined. Previously, expression of a dominant active allele of the HH signal transducer protein smoothened (SMO) in Amhr2cre/+SmoM2 mice caused anovulation in association with a lack of smooth muscle in the theca of developing follicles. The current study examined events during the first 2 wk of life in Amhr2cre/+SmoM2 mice to gain insight into the cause of anovulation. Expression of transcriptional targets of HH signaling, Gli1, Ptch1, and Hhip, which are used as measures of pathway activity, were elevated during the first several days of life in Amhr2cre/+SmoM2 mice compared to controls but were similar to controls in older mice. Microarray analysis showed that genes with increased expression in 2-day-old mutants compared to controls were enriched for the processes of vascular and tube development and steroidogenesis. The density of platelet endothelial cell adhesion molecule (PECAM)-labeled endothelial tubes was increased in the cortex of newborn ovaries of mutant mice. Costaining of preovulatory follicles for PECAM and smooth muscle actin showed that muscle-type vascular support cells are deficient in theca of mutant mice. Expression of genes for steroidogenic enzymes that are normally expressed in the fetal adrenal gland were elevated in newborn ovaries of mutant mice. In summary, overactivation of HH signaling during early life alters gene expression and vascular development and this is associated with the lifelong development of anovulatory follicles in which the thecal vasculature fails to mature appropriately. PMID:22402963

Transcriptional profiles of SHH pathway genes in keratocystic odontogenic tumor and ameloblastoma.

PubMed

Gurgel, Clarissa Araújo Silva; Buim, Marcilei Eliza Cavichiolli; Carvalho, Kátia Cândido; Sales, Caroline Brandi Schlaepfer; Reis, Mitermayer Galvão; de Souza, Renata Oliveira; de Faro Valverde, Ludmila; de Azevedo, Roberto Almeida; Dos Santos, Jean Nunes; Soares, Fernando Augusto; Ramos, Eduardo Antônio Gonçalves

2014-09-01

Sonic hedgehog (SHH) pathway activation has been identified as a key factor in the development of many types of tumors, including odontogenic tumors. Our study examined the expression of genes in the SHH pathway to characterize their roles in the pathogenesis of keratocystic odontogenic tumors (KOT) and ameloblastomas (AB). We quantified the expression of SHH, SMO, PTCH1, SUFU, GLI1, CCND1, and BCL2 genes by qPCR in a total of 23 KOT, 11 AB, and three non-neoplastic oral mucosa (NNM). We also measured the expression of proteins related to this pathway (CCND1 and BCL2) by immunohistochemistry. We observed overexpression of SMO, PTCH1, GLI1, and CCND1 genes in both KOT (23/23) and AB (11/11). However, we did not detect expression of the SHH gene in 21/23 KOT and 10/11 AB tumors. Low levels of the SUFU gene were expressed in KOT (P = 0.0199) and AB (P = 0.0127) relative to the NNM. Recurrent KOT exhibited high levels of SMO (P = 0.035), PTCH1 (P = 0.048), CCND1 (P = 0.048), and BCL2 (P = 0.045) transcripts. Using immunolabeling of CCND1, we observed no statistical difference between primary and recurrent KOT (P = 0.8815), sporadic and NBCCS-KOT (P = 0.7688), and unicystic and solid AB (P = 0.7521). Overexpression of upstream (PTCH1 and SMO) and downstream (GLI1, CCND1 and BCL2) genes in the SHH pathway leads to the constitutive activation of this pathway in KOT and AB and may suggest a mechanism for the development of these types of tumors. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Beetroot-based gel supplementation improves handgrip strength, forearm muscle O2 saturation but not exercise tolerance and blood volume in jiu-jitsu athletes.

PubMed

de Oliveira, Gustavo Vieira; Nascimento, Luiz; Volino-Souza, Mônica; Mesquita, Jacilene; Alvares, Thiago

2018-03-22

The ergogenic effect of beetroot on the exercise performance of trained cyclists, runners, kayakers, and swimmers has been demonstrated. However, whether or not beetroot supplementation presents a beneficial effect on the exercise performance of jiu-jitsu athletes (JJA) remains inconclusive. Therefore, present study assessed the effect of beetroot-based gel (BG) supplementation on maximal voluntary contraction (MVC), exercise time until fatigue (ETF), muscle O2 saturation (SmO2), blood volume (tHb), and plasma nitrate and lactate in response to handgrip isotonic exercise (HIE) in JJA. In a randomized, crossover, double-blind design, 12 JJA performed three sets of HIE at 40% of the MVC until fatigue after 8 days (8th dose was offered 120 min previous exercise) of BG supplementation or a nitrate-depleted gel (PLA), and forearm SmO2 and tHb were continuously monitored by using near-infrared spectroscopy. Blood samples were taken before, immediately after exercise, and 20 min after exercise recovery in PLA and BG condition. MVC was evaluated at baseline and 20 min after HIE. There was a significant reduction in ∆MVC decline after HIE in BG condition. Forearm SmO2 during exercise recovery was significantly greater only after BG supplementation. No significant difference in ETF and tHb were observed between both BG and PLA in response to HIE. Plasma nitrate increased only after BG, whereas the exercise-induced increase in plasma lactate was significantly lower in BG when compared to PLA. In conclusion, BG supplementation may be a good nutritional strategy to improve forearm SmO2 and prevent force decline in response to exercise in JJA.

Lithographic qualification of high-transmission mask blank for 10nm node and beyond

NASA Astrophysics Data System (ADS)

Xu, Yongan; Faure, Tom; Viswanathan, Ramya; Lobb, Granger; Wistrom, Richard; Burns, Sean; Hu, Lin; Graur, Ioana; Bleiman, Ben; Fischer, Dan; Mignot, Yann; Sakamoto, Yoshifumi; Toda, Yusuke; Bolton, John; Bailey, Todd; Felix, Nelson; Arnold, John; Colburn, Matthew

2016-04-01

In this paper, we discuss the lithographic qualification of high transmission (High T) mask for Via and contact hole applications in 10nm node and beyond. First, the simulated MEEF and depth of focus (DoF) data are compared between the 6% and High T attnPSM masks with the transmission of High T mask blank varying from 12% to 20%. The 12% High T blank shows significantly better MEEF and larger DoF than those of 6% attnPSM mask blank, which are consistent with our wafer data. However, the simulations show no obvious advantage in MEEF and DoF when the blank transmittance is larger than 12%. From our wafer data, it has been seen that the common process window from High T mask is 40nm bigger than that from the 6% attnPSM mask. In the elongated bar structure with smaller aspect ratio, 1.26, the 12% High T mask shows significantly less develop CD pull back in the major direction. Compared to the High T mask, the optimized new illumination condition for 6% attnPSM shows limited improvement in MEEF and the DoF through pitch. In addition, by using the High T mask blank, we have also investigated the SRAF printing, side lobe printing and the resist profile through cross sections, and no patterning risk has been found for manufacturing. As part of this work new 12% High T mask blank materials and processes were developed, and a brief overview of key mask technology development results have been shared. Overall, it is concluded that the High T mask, 12% transmission, provides the most robust and extendable lithographic solution for 10nm node and beyond.

Manufacturability study of masks created by inverse lithography technology (ILT)

NASA Astrophysics Data System (ADS)

Martin, Patrick M.; Progler, C. J.; Xiao, G.; Gray, R.; Pang, L.; Liu, Y.

2005-11-01

As photolithography is pushed to fabricate deep-sub wavelength devices for 90nm, 65nm and smaller technology nodes using available exposure tools (i.e., 248nm, 193nm steppers), photomask capability is becoming extremely critical. For example, PSM masks require more complicated processing; aggressive OPC makes the writing time longer and sometimes unpredictable; and, high MEEF imposes much more stringent demands on mask quality. Therefore, in order for any new lithography technology to be adopted into production, mask manufacturability must be studied thoroughly and carefully. In this paper we will present the mask manufacturability study on mask patterns created using Inverse Lithography Technology (ILT). Unlike conventional OPC methodologies, ILT uses a unique outcome-based technology to mathematically determine the mask features that produce the desired on-wafer results. ILT solves the most critical litho challenges of the deep sub-wavelength era. Potential benefits include: higher yield; expanded litho process windows; superb pattern fidelity at 90, 65 & 45-nm nodes; and reduced time-to-silicon - all without changing the existing lithography infrastructure and design-to-silicon flow. In this study a number of cell structures were selected and used as test patterns. "Luminized patterns" were generated for binary mask and attenuated phase-shift mask. Both conventional OPC patterns and "luminized patterns" were put on a test reticle side by side, and they all have a number of variations in term of correction aggressivity level and mask complexity. Mask manufacturability, including data fracturing, writing time, mask inspection, and metrology were studied. The results demonstrate that, by optimizing the inspection recipe, masks created using ILT technology can be made and qualified using current processes with a reasonable turn-around time.

Extraction and utilization of the repeating patterns for CP writing in mask making

NASA Astrophysics Data System (ADS)

Shoji, Masahiro; Inoue, Tadao; Yamabe, Masaki

2010-05-01

In May 2006, the Mask Design, Drawing, and Inspection Technology Research Department (Mask D2I) at the Association of Super-Advanced Electronics Technologies (ASET) launched a 4-year program for reducing mask manufacturing cost and TAT by concurrent optimization of Mask Data Preparation (MDP), mask writing, and mask inspection [1]. Figure 1 shows an outline of the project at Mask D2I at ASET. As one of the tasks being pursued at the Mask Design Data Technology Research Laboratory we have evaluated the effect of reducing the writing shot counts by utilizing the repeating patterns, and that showed positive impact on mask making by using CP writing. During the past four years, we have developed a software to extract repeating patterns from fractured OPCed mask data and have evaluated the efficiency of reducing the writing shot counts using the repeating patterns with this software. In this evaluation, we have used many actual device production data obtained from the member companies of Mask D2I. To the extraction software, we added new functions for extracting common repeating patterns from a set of multiple masks, and studied how this step affects the ratio of reducing the shot counts in comparison to the case of utilization of the repeating patterns for single mask. We have also developed a software that uses the result of extracting repeating patterns and prepares writing-data for the MCC/CP writing system which has been developed at the Mask Writing Equipment Technology Research Laboratory. With this software, we have examined how EB proximity effect on CP writing affects in reducing the shot count where CP shots with large CD errors have to be divided into VSB shots. In this paper we will report on making common CP mask from a set of multiple actual device data by using these software, and will also report on the results of CP writing and calculation of writing-TAT by MCC/CP writing system.

Integration of mask and silicon metrology in DFM

NASA Astrophysics Data System (ADS)

Matsuoka, Ryoichi; Mito, Hiroaki; Sugiyama, Akiyuki; Toyoda, Yasutaka

2009-03-01

We have developed a highly integrated method of mask and silicon metrology. The method adopts a metrology management system based on DBM (Design Based Metrology). This is the high accurate contouring created by an edge detection algorithm used in mask CD-SEM and silicon CD-SEM. We have inspected the high accuracy, stability and reproducibility in the experiments of integration. The accuracy is comparable with that of the mask and silicon CD-SEM metrology. In this report, we introduce the experimental results and the application. As shrinkage of design rule for semiconductor device advances, OPC (Optical Proximity Correction) goes aggressively dense in RET (Resolution Enhancement Technology). However, from the view point of DFM (Design for Manufacturability), the cost of data process for advanced MDP (Mask Data Preparation) and mask producing is a problem. Such trade-off between RET and mask producing is a big issue in semiconductor market especially in mask business. Seeing silicon device production process, information sharing is not completely organized between design section and production section. Design data created with OPC and MDP should be linked to process control on production. But design data and process control data are optimized independently. Thus, we provided a solution of DFM: advanced integration of mask metrology and silicon metrology. The system we propose here is composed of followings. 1) Design based recipe creation: Specify patterns on the design data for metrology. This step is fully automated since they are interfaced with hot spot coordinate information detected by various verification methods. 2) Design based image acquisition: Acquire the images of mask and silicon automatically by a recipe based on the pattern design of CD-SEM.It is a robust automated step because a wide range of design data is used for the image acquisition. 3) Contour profiling and GDS data generation: An image profiling process is applied to the acquired image based on the profiling method of the field proven CD metrology algorithm. The detected edges are then converted to GDSII format, which is a standard format for a design data, and utilized for various DFM systems such as simulation. Namely, by integrating pattern shapes of mask and silicon formed during a manufacturing process into GDSII format, it makes it possible to bridge highly accurate pattern profile information over to the design field of various EDA systems. These are fully integrated into design data and automated. Bi-directional cross probing between mask data and process control data is allowed by linking them. This method is a solution for total optimization that covers Design, MDP, mask production and silicon device producing. This method therefore is regarded as a strategic DFM approach in the semiconductor metrology.

Silicon Solar Cell Optimization.

DTIC Science & Technology

1981-06-01

from the surface. (b) Oxide mask formation Etching grooves into the silicon requires an effective alkaline-resistant mask which will withstand the...face. This technique employs a very viscous photoresist, Furt #206, in conjunction with multiple spin-applications and bake periods, to effectively ...175 80 125 78 75 74 To compare the effects of groove depth, substrate thick- ness and bulk resistivity, an experiment was conducted. Using identical

ScAlN etch mask for highly selective silicon etching

DOE PAGES

Henry, Michael David; Young, Travis R.; Griffin, Ben

2017-09-08

Here, this work reports the utilization of a recently developed film, ScAlN, as a silicon etch mask offering significant improvements in high etch selectivity to silicon. Utilization of ScAlN as a fluorine chemistry based deep reactive ion etch mask demonstrated etch selectivity at 23 550:1, four times better than AlN, 11 times better than Al 2O 3, and 148 times better than silicon dioxide with significantly less resputtering at high bias voltage than either Al 2O 3 or AlN. Ellipsometry film thickness measurements show less than 0.3 nm/min mask erosion rates for ScAlN. Micromasking of resputtered Al for Al 2Omore » 3, AlN, and ScAlN etch masks is also reported here, utilizing cross-sectional scanning electron microscope and confocal microscope roughness measurements. With lower etch bias, the reduced etch rate can be optimized to achieve a trench bottom surface roughness that is comparable to SiO 2 etch masks. Etch mask selectivity enabled by ScAlN is likely to make significant improvements in microelectromechanical systems, wafer level packaging, and plasma dicing of silicon.« less

Model of visual contrast gain control and pattern masking

NASA Technical Reports Server (NTRS)

Watson, A. B.; Solomon, J. A.

1997-01-01

We have implemented a model of contrast gain and control in human vision that incorporates a number of key features, including a contrast sensitivity function, multiple oriented bandpass channels, accelerating nonlinearities, and a devisive inhibitory gain control pool. The parameters of this model have been optimized through a fit to the recent data that describe masking of a Gabor function by cosine and Gabor masks [J. M. Foley, "Human luminance pattern mechanisms: masking experiments require a new model," J. Opt. Soc. Am. A 11, 1710 (1994)]. The model achieves a good fit to the data. We also demonstrate how the concept of recruitment may accommodate a variant of this model in which excitatory and inhibitory paths have a common accelerating nonlinearity, but which include multiple channels tuned to different levels of contrast.

An economic analysis for optimal distributed computing resources for mask synthesis and tape-out in production environment

NASA Astrophysics Data System (ADS)

Cork, Chris; Lugg, Robert; Chacko, Manoj; Levi, Shimon

2005-06-01

With the exponential increase in output database size due to the aggressive optical proximity correction (OPC) and resolution enhancement technique (RET) required for deep sub-wavelength process nodes, the CPU time required for mask tape-out continues to increase significantly. For integrated device manufacturers (IDMs), this can impact the time-to-market for their products where even a few days delay could have a huge commercial impact and loss of market window opportunity. For foundries, a shorter turnaround time provides a competitive advantage in their demanding market, too slow could mean customers looking elsewhere for these services; while a fast turnaround may even command a higher price. With FAB turnaround of a mature, plain-vanilla CMOS process of around 20-30 days, a delay of several days in mask tapeout would contribute a significant fraction to the total time to deliver prototypes. Unlike silicon processing, masks tape-out time can be decreased by simply purchasing extra computing resources and software licenses. Mask tape-out groups are taking advantage of the ever-decreasing hardware cost and increasing power of commodity processors. The significant distributability inherent in some commercial Mask Synthesis software can be leveraged to address this critical business issue. Different implementations have different fractions of the code that cannot be parallelized and this affects the efficiency with which it scales, as is described by Amdahl"s law. Very few are efficient enough to allow the effective use of 1000"s of processors, enabling run times to drop from days to only minutes. What follows is a cost aware methodology to quantify the scalability of this class of software, and thus act as a guide to estimating the optimal investment in terms of hardware and software licenses.

Sensorless sliding mode observer for a five-phase permanent magnet synchronous motor drive.

PubMed

Hosseyni, Anissa; Trabelsi, Ramzi; Mimouni, Med Faouzi; Iqbal, Atif; Alammari, Rashid

2015-09-01

This paper deals with the sensorless vector controlled five-phase permanent magnet synchronous motor (PMSM) drive based on a sliding mode observer (SMO). The observer is designed considering the back electromotive force (EMF) of five-phase permanent magnet synchronous motor. The SMO structure and design are illustrated. Stability of the proposed observer is demonstrated using Lyapunov stability criteria. The proposed strategy is asymptotically stable in the context of Lyapunov theory. Simulated results on a five-phase PMSM drive are displayed to validate the feasibility and the effectiveness of the proposed control strategy. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

Robust In-Flight Sensor Fault Diagnostics for Aircraft Engine Based on Sliding Mode Observers

PubMed Central

Chang, Xiaodong; Huang, Jinquan; Lu, Feng

2017-01-01

For a sensor fault diagnostic system of aircraft engines, the health performance degradation is an inevitable interference that cannot be neglected. To address this issue, this paper investigates an integrated on-line sensor fault diagnostic scheme for a commercial aircraft engine based on a sliding mode observer (SMO). In this approach, one sliding mode observer is designed for engine health performance tracking, and another for sensor fault reconstruction. Both observers are employed in in-flight applications. The results of the former SMO are analyzed for post-flight updating the baseline model of the latter. This idea is practical and feasible since the updating process does not require the algorithm to be regulated or redesigned, so that ground-based intervention is avoided, and the update process is implemented in an economical and efficient way. With this setup, the robustness of the proposed scheme to the health degradation is much enhanced and the latter SMO is able to fulfill sensor fault reconstruction over the course of the engine life. The proposed sensor fault diagnostic system is applied to a nonlinear simulation of a commercial aircraft engine, and its effectiveness is evaluated in several fault scenarios. PMID:28398255

Robust In-Flight Sensor Fault Diagnostics for Aircraft Engine Based on Sliding Mode Observers.

PubMed

Chang, Xiaodong; Huang, Jinquan; Lu, Feng

2017-04-11

For a sensor fault diagnostic system of aircraft engines, the health performance degradation is an inevitable interference that cannot be neglected. To address this issue, this paper investigates an integrated on-line sensor fault diagnostic scheme for a commercial aircraft engine based on a sliding mode observer (SMO). In this approach, one sliding mode observer is designed for engine health performance tracking, and another for sensor fault reconstruction. Both observers are employed in in-flight applications. The results of the former SMO are analyzed for post-flight updating the baseline model of the latter. This idea is practical and feasible since the updating process does not require the algorithm to be regulated or redesigned, so that ground-based intervention is avoided, and the update process is implemented in an economical and efficient way. With this setup, the robustness of the proposed scheme to the health degradation is much enhanced and the latter SMO is able to fulfill sensor fault reconstruction over the course of the engine life. The proposed sensor fault diagnostic system is applied to a nonlinear simulation of a commercial aircraft engine, and its effectiveness is evaluated in several fault scenarios.

Cryptotermes brevis (Isoptera: Kalotermitidae) in the Azores: Lessons After 2 yr of Monitoring in the Archipelago

PubMed Central

Borges, Paulo A. V.; Guerreiro, Orlando; Ferreira, Maria T.; Borges, Annabella; Ferreira, Filomena; Bicudo, Nuno; Nunes, Lina; Marcos, Rita S.; Arroz, Ana M.; Scheffrahn, Rudolf H.; Myles, Timothy G.

2014-01-01

Abstract The dispersal flights of West Indian drywood termite, Cryptotermes brevis (Walker) (Isoptera: Kalotermitidae) were surveyed in the major cities of Azores. The sampling device used to estimate termite density consisted of a yellow adhesive trap (size 45 by 24 cm), placed with an artificial or natural light source in a dark attic environment. In addition, data from two other projects were used to improve the knowledge about the geographical distribution of the species. The level of infestation in the two main Azorean towns differed, with high levels in the houses of Angra do Heroísmo, whereas in Ponta Delgada, there are fewer houses with high levels of infestation. The infestation in Ponta Delgada shows a pattern of spreading from the center outward to the city’s periphery, whereas in Angra do Heroísmo, there was a pattern of spreading outward from several foci. The heavy infestation observed in Angra do Heroísmo and the clear increase of infestation levels observed from 2010 to 2011 is a reason for concern and calls for an urgent application of an Integrated Pest Management (IPM) control strategy. PMID:25368085

A semantic web ontology for small molecules and their biological targets.

PubMed

Choi, Jooyoung; Davis, Melissa J; Newman, Andrew F; Ragan, Mark A

2010-05-24

A wide range of data on sequences, structures, pathways, and networks of genes and gene products is available for hypothesis testing and discovery in biological and biomedical research. However, data describing the physical, chemical, and biological properties of small molecules have not been well-integrated with these resources. Semantically rich representations of chemical data, combined with Semantic Web technologies, have the potential to enable the integration of small molecule and biomolecular data resources, expanding the scope and power of biomedical and pharmacological research. We employed the Semantic Web technologies Resource Description Framework (RDF) and Web Ontology Language (OWL) to generate a Small Molecule Ontology (SMO) that represents concepts and provides unique identifiers for biologically relevant properties of small molecules and their interactions with biomolecules, such as proteins. We instanced SMO using data from three public data sources, i.e., DrugBank, PubChem and UniProt, and converted to RDF triples. Evaluation of SMO by use of predetermined competency questions implemented as SPARQL queries demonstrated that data from chemical and biomolecular data sources were effectively represented and that useful knowledge can be extracted. These results illustrate the potential of Semantic Web technologies in chemical, biological, and pharmacological research and in drug discovery.

Ground-based FTIR retrievals of SF6 on Reunion Island

NASA Astrophysics Data System (ADS)

Zhou, Minqiang; Langerock, Bavo; Vigouroux, Corinne; Wang, Pucai; Hermans, Christian; Stiller, Gabriele; Walker, Kaley A.; Dutton, Geoff; Mahieu, Emmanuel; De Mazière, Martine

2018-02-01

SF6 total columns were successfully retrieved from FTIR (Fourier transform infrared) measurements (Saint Denis and Maïdo) on Reunion Island (21° S, 55° E) between 2004 and 2016 using the SFIT4 algorithm: the retrieval strategy and the error budget were presented. The FTIR SF6 retrieval has independent information in only one individual layer, covering the whole of the troposphere and the lower stratosphere. The trend in SF6 was analysed based on the FTIR-retrieved dry-air column-averaged mole fractions (XSF6) on Reunion Island, the in situ measurements at America Samoa (SMO) and the collocated satellite measurements (Michelson Interferometer for Passive Atmospheric Sounding, MIPAS, and Atmospheric Chemistry Experiment Fourier Transform Spectrometer, ACE-FTS) in the southern tropics. The SF6 annual growth rate from FTIR retrievals is 0.265 ± 0.013 pptv year-1 for 2004-2016, which is slightly weaker than that from the SMO in situ measurements (0.285 ± 0.002 pptv year-1) for the same time period. The SF6 trend in the troposphere from MIPAS and ACE-FTS observations is also close to the ones from the FTIR retrievals and the SMO in situ measurements.

Coatings masking in near, medium, and far infrared used for ship camouflage

NASA Astrophysics Data System (ADS)

Milewski, S.; Dulski, R.; Kastek, M.; Trzaskawka, P.; Barela, J.; Firmanty, K.

2011-11-01

The increasing range of naval engagements results in development of camouflages applied on warships that mask their signatures first in visible and next in and IR spectra. Camouflage applied on warships that mask their IR signatures is one of the most basic countermeasure methods against attacks by heat-seeking missiles. A set of special coatings applied to the ship's hull allows misidentification by enemies weapon and so make the ship harder to destroy. Thus the knowledge on actual thermal contrast between the ship and surrounding background is required in order to provide an effective antimissile defense. The paper presents selected aspects related to ship's camouflage realized by altering its thermal signature as well as the results of radiometric measurement of thermal radiation of IR-masking coatings. Measurements were performed using IR imaging spectrometers in near, medium and far infrared spectra. The presented measurement results constitute the basis for the assessment of the effectiveness of IR masking methods and additionally provide the opportunity to effectively simulate the properties of masking coatings and further to optimize their radiometric properties in the infrared range.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henry, Michael David; Young, Travis R.; Griffin, Ben

Here, this work reports the utilization of a recently developed film, ScAlN, as a silicon etch mask offering significant improvements in high etch selectivity to silicon. Utilization of ScAlN as a fluorine chemistry based deep reactive ion etch mask demonstrated etch selectivity at 23 550:1, four times better than AlN, 11 times better than Al 2O 3, and 148 times better than silicon dioxide with significantly less resputtering at high bias voltage than either Al 2O 3 or AlN. Ellipsometry film thickness measurements show less than 0.3 nm/min mask erosion rates for ScAlN. Micromasking of resputtered Al for Al 2Omore » 3, AlN, and ScAlN etch masks is also reported here, utilizing cross-sectional scanning electron microscope and confocal microscope roughness measurements. With lower etch bias, the reduced etch rate can be optimized to achieve a trench bottom surface roughness that is comparable to SiO 2 etch masks. Etch mask selectivity enabled by ScAlN is likely to make significant improvements in microelectromechanical systems, wafer level packaging, and plasma dicing of silicon.« less

Green clay and aloe vera peel-off facial masks: response surface methodology applied to the formulation design.

PubMed

O'Reilly Beringhs, André; Rosa, Julia Macedo; Stulzer, Hellen Karine; Budal, Rosane Maria; Sonaglio, Diva

2013-03-01

This article describes the optimization of a peel-off facial mask formulation. An investigation was carried out on the parameters of the formulation that most affect the desirable characteristics of peel-off facial masks. Cereal alcohol had a significant effect on the drying time at concentrations of 1-12% (w/w). The applicability of the evaluated formulations was influenced by both carbomer (0-2.4%; w/w) and polyvinyl alcohol (PVA; 2.5-17.5%; w/w) content due to their ability to alter the formulation viscosity. Inverse concentrations of carbomer and PVA led to formulations with optimum viscosity for facial application. Film-forming performance was influenced only by the PVA concentration, achieving maximum levels at concentrations of around 11% (w/w). The optimized formulation, determined mathematically, contained 13% (w/w) PVA and 10% (w/w) cereal alcohol with no addition of carbomer. This formulation provided high levels of applicability and film-forming performance, the lowest drying time possible and excellent homogeneity of the green clay particles and aloe vera before and after drying. The preliminary stability study indicated that the optimized formulation is stable under normal storage conditions. The microbiological stability evaluation indicated that the preservative was efficient in terms of avoiding microbial growth. RSM was shown to be a useful statistical tool for the determination of the behavior of different compounds and their concentrations for the responses studied, allowing the investigation of the optimum conditions for the production of green clay and aloe vera peel-off facial masks.

Melt-in-Mouth Multi-particulate System for the Treatment of ADHD: A Convenient Platform for Pediatric Use.

PubMed

Patadia, Jalashri; Tripathi, Rahul; Joshi, Amita

2016-08-01

Generally, pellets obtained from extrusion/spheronization, containing microcrystalline cellulose (MCC), do not disintegrate. An attempt has been made to develop melt-in-mouth pellets of taste-masked atomoxetine hydrochloride, using extrusion-spheronization, for pediatric patients. Melt-in-mouth pellets were prepared using extrusion-spheronization method and optimized using 3(3) FFD. MCC (X1, %), mannitol (X2, %) and Indion 414: Pharmaburst 500 ratio (X3, ratio) were the factors (independent variables) studied, whereas responses studied (dependent variables) were friability (Y1, %), yield (Y2, %) shape (Y3, roundness) in vitro disintegration time (Y4, seconds). The optimized formulation obtained from FFD was characterized for friability, shape and morphology, in vitro disintegration time, porosity, moisture uptake, in vitro release study and in vivo taste and disintegration time in healthy human volunteers. Randomized, two-treatment, two-sequence, two-period, single dose, crossover sensory evaluation study of taste-masked melt-in-mouth pellet was carried out in 10 healthy human subjects. A statistically significant polynomial mathematical relationship was generated between the factors and responses to obtain an optimized formulation. The optimized formulation was characterized (in vitro and in vivo) and exhibited a rapid drug release in vitro attributed to fast disintegration of pellets and high solubility of drug in 0.1 N HCl and buffer (pH 6.8). In vivo, 40% of volunteers ranked taste-masked optimized formulation as slightly bitter while 60% ranked it as no taste. The optimized pellets were conveniently administered in volunteers and exhibited rapid in-vivo disintegration in the oral cavity. Melt-in-mouth pellets can be a used as a platform technology for administering drugs to paediatric patients accurately and conveniently resulting in patient compliance.

Effects of annealing temperature on the H2-sensing properties of Pd-decorated WO3 nanorods

NASA Astrophysics Data System (ADS)

Lee, Sangmin; Lee, Woo Seok; Lee, Jae Kyung; Hyun, Soong Keun; Lee, Chongmu; Choi, Seungbok

2018-03-01

The temperature of the post-annealing treatment carried out after noble metal deposition onto semiconducting metal oxides (SMOs) must be carefully optimized to maximize the sensing performance of the metal-decorated SMO sensors. WO3 nanorods were synthesized by thermal evaporation of WO3 powders and decorated with Pd nanoparticles using a sol-gel method, followed by an annealing process. The effects of the annealing temperature on the hydrogen gas-sensing properties of the Pd-decorated WO3 nanorods were then examined; the optimal annealing temperature, leading to the highest response of the WO3 nanorod sensor to H2, was determined to be 600 °C. Post-annealing at 600 °C resulted in nanorods with the highest surface area-to-volume ratio, as well as in the optimal size and the largest number of deposited Pd nanoparticles, leading to the highest response and the shortest response/recovery times toward H2. The improved H2-sensing performance of the Pd-decorated WO3 nanorod sensor, compared to a sensor based on pristine WO3 nanorods, is attributed to the enhanced catalytic activity, increased surface area-to-volume ratio, and higher amounts of surface defects.

Optimized distributed computing environment for mask data preparation

NASA Astrophysics Data System (ADS)

Ahn, Byoung-Sup; Bang, Ju-Mi; Ji, Min-Kyu; Kang, Sun; Jang, Sung-Hoon; Choi, Yo-Han; Ki, Won-Tai; Choi, Seong-Woon; Han, Woo-Sung

2005-11-01

As the critical dimension (CD) becomes smaller, various resolution enhancement techniques (RET) are widely adopted. In developing sub-100nm devices, the complexity of optical proximity correction (OPC) is severely increased and applied OPC layers are expanded to non-critical layers. The transformation of designed pattern data by OPC operation causes complexity, which cause runtime overheads to following steps such as mask data preparation (MDP), and collapse of existing design hierarchy. Therefore, many mask shops exploit the distributed computing method in order to reduce the runtime of mask data preparation rather than exploit the design hierarchy. Distributed computing uses a cluster of computers that are connected to local network system. However, there are two things to limit the benefit of the distributing computing method in MDP. First, every sequential MDP job, which uses maximum number of available CPUs, is not efficient compared to parallel MDP job execution due to the input data characteristics. Second, the runtime enhancement over input cost is not sufficient enough since the scalability of fracturing tools is limited. In this paper, we will discuss optimum load balancing environment that is useful in increasing the uptime of distributed computing system by assigning appropriate number of CPUs for each input design data. We will also describe the distributed processing (DP) parameter optimization to obtain maximum throughput in MDP job processing.

Utilizing Hierarchical Segmentation to Generate Water and Snow Masks to Facilitate Monitoring Change with Remotely Sensed Image Data

NASA Technical Reports Server (NTRS)

Tilton, James C.; Lawrence, William T.; Plaza, Antonio J.

2006-01-01

The hierarchical segmentation (HSEG) algorithm is a hybrid of hierarchical step-wise optimization and constrained spectral clustering that produces a hierarchical set of image segmentations. This segmentation hierarchy organizes image data in a manner that makes the image's information content more accessible for analysis by enabling region-based analysis. This paper discusses data analysis with HSEG and describes several measures of region characteristics that may be useful analyzing segmentation hierarchies for various applications. Segmentation hierarchy analysis for generating landwater and snow/ice masks from MODIS (Moderate Resolution Imaging Spectroradiometer) data was demonstrated and compared with the corresponding MODIS standard products. The masks based on HSEG segmentation hierarchies compare very favorably to the MODIS standard products. Further, the HSEG based landwater mask was specifically tailored to the MODIS data and the HSEG snow/ice mask did not require the setting of a critical threshold as required in the production of the corresponding MODIS standard product.

Phase-field simulations of GaN growth by selective area epitaxy on complex mask geometries

DOE PAGES

Aagesen, Larry K.; Coltrin, Michael Elliott; Han, Jung; ...

2015-05-15

Three-dimensional phase-field simulations of GaN growth by selective area epitaxy were performed. Furthermore, this model includes a crystallographic-orientation-dependent deposition rate and arbitrarily complex mask geometries. The orientation-dependent deposition rate can be determined from experimental measurements of the relative growth rates of low-index crystallographic facets. Growth on various complex mask geometries was simulated on both c-plane and a-plane template layers. Agreement was observed between simulations and experiment, including complex phenomena occurring at the intersections between facets. The sources of the discrepancies between simulated and experimental morphologies were also investigated. We found that the model provides a route to optimize masks andmore » processing conditions during materials synthesis for solar cells, light-emitting diodes, and other electronic and opto-electronic applications.« less

Undersampling strategies for compressed sensing accelerated MR spectroscopic imaging

NASA Astrophysics Data System (ADS)

Vidya Shankar, Rohini; Hu, Houchun Harry; Bikkamane Jayadev, Nutandev; Chang, John C.; Kodibagkar, Vikram D.

2017-03-01

Compressed sensing (CS) can accelerate magnetic resonance spectroscopic imaging (MRSI), facilitating its widespread clinical integration. The objective of this study was to assess the effect of different undersampling strategy on CS-MRSI reconstruction quality. Phantom data were acquired on a Philips 3 T Ingenia scanner. Four types of undersampling masks, corresponding to each strategy, namely, low resolution, variable density, iterative design, and a priori were simulated in Matlab and retrospectively applied to the test 1X MRSI data to generate undersampled datasets corresponding to the 2X - 5X, and 7X accelerations for each type of mask. Reconstruction parameters were kept the same in each case(all masks and accelerations) to ensure that any resulting differences can be attributed to the type of mask being employed. The reconstructed datasets from each mask were statistically compared with the reference 1X, and assessed using metrics like the root mean square error and metabolite ratios. Simulation results indicate that both the a priori and variable density undersampling masks maintain high fidelity with the 1X up to five-fold acceleration. The low resolution mask based reconstructions showed statistically significant differences from the 1X with the reconstruction failing at 3X, while the iterative design reconstructions maintained fidelity with the 1X till 4X acceleration. In summary, a pilot study was conducted to identify an optimal sampling mask in CS-MRSI. Simulation results demonstrate that the a priori and variable density masks can provide statistically similar results to the fully sampled reference. Future work would involve implementing these two masks prospectively on a clinical scanner.

Implementation of random contact hole design with CPL mask by using IML technology

NASA Astrophysics Data System (ADS)

Hsu, Michael; Van Den Broeke, Doug; Hsu, Stephen; Chen, J. Fung; Shi, Xuelong; Corcoran, Noel; Yu, Linda

2005-11-01

The contact hole imaging is a very challenge task for the optical lithography process during IC manufacturing. Lots of RETs were proposed to improve the contrast of small opening hole. Scattering Bar (SB) OPC, together with optimized illumination, is no doubt one of the critical enablers for low k1 contact imaging. In this study, an effective model-based SB OPC based on IML technology is implemented for contact layer at 90nm, 65nm, and 45nm nodes. For our full-chip implementation flow, the first step is to determine the critical design area and then to proceed with NA and illumination optimization. Then, we selected the best NA in combination with optimum illumination via a Diffraction Optical Element (DOE). With optimized illumination, it is now possible to construct an interference map for the full-chip mask pattern. Utilizing the interference map, the model-based SB OPC is performed. Next, model OPC can be applied with the presence of SB for the entire chip. It is important to note that, for patterning at k1 near 0.35 or below, it may be necessary to include 3D mask effects with a high NA OPC model. With enhanced DOF by IML and immersion process, the low k1 production worthy contact process is feasible.

EUVL masks: paving the path for commercialization

NASA Astrophysics Data System (ADS)

Mangat, Pawitter J. S.; Hector, Scott D.

2001-09-01

Optical projection lithography has been the principal vehicle of semiconductor manufacturing for more than 20 years and is marching aggressively to satisfy the needs of semiconductor manufacturers for 100nm devices. However, the complexity of optical lithography continues to increase as wavelength reduction continues to 157nm. Extreme Ultraviolet Lithography (EUVL), with wavelength from 13-14 nm, is evolving as a leading next generation lithography option for semiconductor industry to stay on the path laid by Moore's Law. Masks are a critical part of the success of any technology and are considered to be high risk both for optical lithography and NGL technologies for sub-100nm lithography. Two key areas of EUV mask fabrication are reflective multilayer deposition and absorber patterning. In the case of reflective multilayers, delivering defect free multilayers for mask blanks is the biggest challenge. Defect mitigation is being explored as a possible option to smooth the multilayer defects in addition to optimization of the deposition process to reduce defect density. The mask patterning process needs focus on the defect-free absorber stack patterning process, mask cleaning, inspection and repair. In addition, there is considerable effort to understand by simulations, the defect printability, thermal and mechanical distortions, and non-telecentric illumination, to mention a few. To protect the finished mask from defects added during use, a removable pellicle strategy combined with thermophoretic protection during exposure is being developed. Recent migration to square form factor using low thermal expansion material (LTEM) is advantageous as historical developments in optical masks can be applied to EUV mask patterning. This paper addresses recent developments in the EUV mask patterning and highlights critical manufacturing process controls needed to fabricate defect-free full field masks with CD and image placement specifications for sub-70nm node lithography. No technology can be implemented without establishing the commercial infrastructure. The rising cost seems to be a major issue affecting the technology development. With respect to mask fabrication for commercial availability, a virtual mask shop analysis is presented that indicates that the process cost for EUVL masks are comparable to the high end optical mask with a reasonable yield. However, the cost for setting up a new mask facility is considerably high.

Defining defect specifications to optimize photomask production and requalification

NASA Astrophysics Data System (ADS)

Fiekowsky, Peter

2006-10-01

Reducing defect repairs and accelerating defect analysis is becoming more important as the total cost of defect repairs on advanced masks increases. Photomask defect specs based on printability, as measured on AIMS microscopes has been used for years, but the fundamental defect spec is still the defect size, as measured on the photomask, requiring the repair of many unprintable defects. ADAS, the Automated Defect Analysis System from AVI is now available in most advanced mask shops. It makes the use of pure printability specs, or "Optimal Defect Specs" practical. This software uses advanced algorithms to eliminate false defects caused by approximations in the inspection algorithm, classify each defect, simulate each defect and disposition each defect based on its printability and location. This paper defines "optimal defect specs", explains why they are now practical and economic, gives a method of determining them and provides accuracy data.

Atomic-scale distortion of optically activated Sm dopants identified with site-selective X-ray absorption spectroscopy

NASA Astrophysics Data System (ADS)

Ishii, Masashi; Crowe, Iain F.; Halsall, Matthew P.; Hamilton, Bruce; Hu, Yongfeng; Sham, Tsun-Kong; Harako, Susumu; Zhao, Xin-Wei; Komuro, Shuji

2013-10-01

The local structure of luminescent Sm dopants was investigated using an X-ray absorption fine-structure technique with X-ray-excited optical luminescence. Because this technique evaluates X-ray absorption from luminescence, only optically active sites are analyzed. The Sm L3 near-edge spectrum contains split 5d states and a shake-up transition that are specific to luminescent Sm. Theoretical calculations using cluster models identified an atomic-scale distortion that can reproduce the split 5d states. The model with C4v local symmetry and compressive bond length of Sm-O of a six-fold oxygen (SmO6) cluster is most consistent with the experimental results.

Noncanonical Hedgehog Signaling

PubMed Central

Brennan, Donna; Chen, Xiaole; Cheng, Lan; Mahoney, My; Riobo, Natalia A.

2012-01-01

The notion of noncanonical hedgehog (Hh) signaling in mammals has started to receive support from numerous observations. By noncanonical, we refer to all those cellular and tissue responses to any of the Hh isoforms that are independent of transcriptional changes mediated by the Gli family of transcription factors. In this chapter, we discuss the most recent findings that suggest that Patched1 can regulate cell proliferation and apoptosis independently of Smoothened (Smo) and Gli and the reports that Smo modulates actin cytoskeleton-dependent processes such as fibroblast migration, endothelial cell tubulogenesis, axonal extension, and neurite formation by diverse mechanisms that exclude any involvement of Gli-dependent transcription. We also acknowledge the existence of less stronger evidence of noncanonical signaling in Drosophila. PMID:22391299

Semiconductor metal oxide compounds based gas sensors: A literature review

NASA Astrophysics Data System (ADS)

Patil, Sunil Jagannath; Patil, Arun Vithal; Dighavkar, Chandrakant Govindrao; Thakare, Kashinath Shravan; Borase, Ratan Yadav; Nandre, Sachin Jayaram; Deshpande, Nishad Gopal; Ahire, Rajendra Ramdas

2015-03-01

This paper gives a statistical view about important contributions and advances on semiconductor metal oxide (SMO) compounds based gas sensors developed to detect the air pollutants such as liquefied petroleum gas (LPG), H2S, NH3, CO2, acetone, ethanol, other volatile compounds and hazardous gases. Moreover, it is revealed that the alloy/composite made up of SMO gas sensors show better gas response than their counterpart single component gas sensors, i.e., they are found to enhance the 4S characteristics namely speed, sensitivity, selectivity and stability. Improvement of such types of sensors used for detection of various air pollutants, which are reported in last two decades, is highlighted herein.

Techniques for the analysis of data from coded-mask X-ray telescopes

NASA Technical Reports Server (NTRS)

Skinner, G. K.; Ponman, T. J.; Hammersley, A. P.; Eyles, C. J.

1987-01-01

Several techniques useful in the analysis of data from coded-mask telescopes are presented. Methods of handling changes in the instrument pointing direction are reviewed and ways of using FFT techniques to do the deconvolution considered. Emphasis is on techniques for optimally-coded systems, but it is shown that the range of systems included in this class can be extended through the new concept of 'partial cycle averaging'.

Formulation and evaluation of sublingual tablets containing Sumatriptan succinate

PubMed Central

Prajapati, Shailesh T; Patel, Parth B; Patel, Chhagan N

2012-01-01

Objective: Sumatriptan succinate is a selective 5-hydroxytryptamine-1 receptor agonist effective in the acute treatment of migraine headaches, having low bioavailability of about 15% orally due to first-pass metabolism. The purpose of this research was to mask the intensely bitter taste of Sumatriptan succinate and to formulate fast-acting, taste-masked sublingual tablet formulation. Materials and Methods: Taste masking was performed by solid dispersion method with mannitol and ion exchange with Kyron T 114 because it releases the drug in salivary pH. The resultant batches were evaluated for in-vivo taste masking as well compatability study (Fourier transform infrared (FTIR) and differential scanning calorimetry (DSC)). For a better feel in the mouth, menthol and sweetener Na saccharine were added to the tablet formulation. The tablets were prepared by direct compression and evaluated for weight variation, thickness, friability, drug content, hardness, disintegration time, wetting time, in vitro drug release, and in vitro permeation study. Results and Discussion: Optimized batches disintegrated in vitro within 28-34 s. Maximum drug release could be achieved with in 10 min for the solid dispersion batches and 14-15 min for the ion-exchange batches with Kyron T 114. The optimized tablet formulation showed better taste and the formulated sublingual tablets may act as a potential alternate for the Sumatriptan succinate oral tablet. Conclusion: Sumatriptan succinate can be successfully taste-masked by both the solid dispersion method using mannitol by the melting method and Ion exchange resin with Kyron T114. It was also concluded that prepared formulation improve bioavailability by prevention of first pass metabolism. PMID:23373008

Masked priming effect reflects evidence accumulated by the prime.

PubMed

Kinoshita, Sachiko; Norris, Dennis

2010-01-01

In the same-different match task, masked priming is observed with the same responses but not different responses. Norris and Kinoshita's (2008) Bayesian reader account of masked priming explains this pattern based on the same principle as that explaining the absence of priming for nonwords in the lexical decision task. The pattern of priming follows from the way the model makes optimal decisions in the two tasks; priming does not depend on first activating the prime and then the target. An alternative explanation is in terms of a bias towards responding "same" that exactly counters the facilitatory effect of lexical access. The present study tested these two views by varying both the degree to which the prime predicts the response and the visibility of the prime. Unmasked primes produced effects expected from the view that priming is influenced by the degree to which the prime predicts the response. In contrast, with masked primes, the size of priming for the same response was completely unaffected by predictability. These results rule out response bias as an explanation of the absence of masked priming for different responses and, in turn, indicate that masked priming is not a consequence of automatic lexical access of the prime.

Patterning of light-extraction nanostructures on sapphire substrates using nanoimprint and ICP etching with different masking materials.

PubMed

Chen, Hao; Zhang, Qi; Chou, Stephen Y

2015-02-27

Sapphire nanopatterning is the key solution to GaN light emitting diode (LED) light extraction. One challenge is to etch deep nanostructures with a vertical sidewall in sapphire. Here, we report a study of the effects of two masking materials (SiO2 and Cr) and different etching recipes (the reaction gas ratio, the reaction pressure and the inductive power) in a chlorine-based (BCl3 and Cl2) inductively coupled plasma (ICP) etching of deep nanopillars in sapphire, and the etching process optimization. The masking materials were patterned by nanoimprinting. We have achieved high aspect ratio sapphire nanopillar arrays with a much steeper sidewall than the previous etching methods. We discover that the SiO2 mask has much slower erosion rate than the Cr mask under the same etching condition, leading to the deep cylinder-shaped nanopillars (122 nm diameter, 200 nm pitch, 170 nm high, flat top, and a vertical sidewall of 80° angle), rather than the pyramid-shaped shallow pillars (200 nm based diameter, 52 nm height, and 42° sidewall) resulted by using Cr mask. The processes developed are scalable to large volume LED manufacturing.

Cryptotermes brevis (Isoptera: Kalotermitidae) in the Azores: lessons after 2 yr of monitoring in the Archipelago.

PubMed

Borges, Paulo A V; Guerreiro, Orlando; Ferreira, Maria T; Borges, Annabella; Ferreira, Filomena; Bicudo, Nuno; Nunes, Lina; Marcos, Rita S; Arroz, Ana M; Scheffrahn, Rudolf H; Myles, Timothy G

2014-01-01

The dispersal flights of West Indian drywood termite, Cryptotermes brevis (Walker) (Isoptera: Kalotermitidae) were surveyed in the major cities of Azores. The sampling device used to estimate termite density consisted of a yellow adhesive trap (size 45 by 24 cm), placed with an artificial or natural light source in a dark attic environment. In addition, data from two other projects were used to improve the knowledge about the geographical distribution of the species. The level of infestation in the two main Azorean towns differed, with high levels in the houses of Angra do Heroísmo, whereas in Ponta Delgada, there are fewer houses with high levels of infestation. The infestation in Ponta Delgada shows a pattern of spreading from the center outward to the city's periphery, whereas in Angra do Heroísmo, there was a pattern of spreading outward from several foci. The heavy infestation observed in Angra do Heroísmo and the clear increase of infestation levels observed from 2010 to 2011 is a reason for concern and calls for an urgent application of an Integrated Pest Management (IPM) control strategy. © The Author 2014. Published by Oxford University Press on behalf of the Entomological Society of America.

Protein-bound Polysaccharide-K Inhibits Hedgehog Signaling Through Down-regulation of MAML3 and RBPJ Transcription Under Hypoxia, Suppressing the Malignant Phenotype in Pancreatic Cancer.

PubMed

Yamasaki, Akio; Onishi, Hideya; Imaizumi, Akira; Kawamoto, Makoto; Fujimura, Akiko; Oyama, Yasuhiro; Katano, Mitsuo

2016-08-01

Hedgehog signaling is activated in pancreatic cancer and could be a therapeutic target. We previously demonstrated that recombination signal binding protein for immunoglobulin-kappa-J region (RBPJ) and mastermind-like 3 (MAML3) contribute to the hypoxia-induced up-regulation of Smoothened (SMO) transcription. We have also shown that protein-bound polysaccharide-K (PSK) could be effective for refractory pancreatic cancer that down-regulates SMO transcription under hypoxia. In this study, we evaluated whether the anticancer mechanism of PSK involves inhibiting RBPJ and MAML3 expression under hypoxia. PSK reduced SMO, MAML3 and RBPJ expression in pancreatic cancer cells under hypoxia. PSK also blocked RBPJ-induced invasiveness under hypoxia by inhibiting matrix metalloproteinase expression. Lastly, we showed that PSK attenuated RBPJ-induced proliferation both in vitro and in vivo. These results suggest that PSK suppresses Hedgehog signaling through down-regulation of MAML3 and RBPJ transcription under hypoxia, inhibiting the induction of a malignant phenotype in pancreatic cancer. Our results may lead to development of new treatments for refractory pancreatic cancer using PSK as a Hedgehog inhibitor. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Mutations in the human SC4MOL gene encoding a methyl sterol oxidase cause psoriasiform dermatitis, microcephaly, and developmental delay

PubMed Central

He, Miao; Kratz, Lisa E.; Michel, Joshua J.; Vallejo, Abbe N.; Ferris, Laura; Kelley, Richard I.; Hoover, Jacqueline J.; Jukic, Drazen; Gibson, K. Michael; Wolfe, Lynne A.; Ramachandran, Dhanya; Zwick, Michael E.; Vockley, Jerry

2011-01-01

Defects in cholesterol synthesis result in a wide variety of symptoms, from neonatal lethality to the relatively mild dysmorphic features and developmental delay found in individuals with Smith-Lemli-Opitz syndrome. We report here the identification of mutations in sterol-C4-methyl oxidase–like gene (SC4MOL) as the cause of an autosomal recessive syndrome in a human patient with psoriasiform dermatitis, arthralgias, congenital cataracts, microcephaly, and developmental delay. This gene encodes a sterol-C4-methyl oxidase (SMO), which catalyzes demethylation of C4-methylsterols in the cholesterol synthesis pathway. C4-Methylsterols are meiosis-activating sterols (MASs). They exist at high concentrations in the testis and ovary and play roles in meiosis activation. In this study, we found that an accumulation of MASs in the patient led to cell overproliferation in both skin and blood. SMO deficiency also substantially altered immunocyte phenotype and in vitro function. MASs serve as ligands for liver X receptors α and β (LXRα and LXRβ), which are important in regulating not only lipid transport in the epidermis, but also innate and adaptive immunity. Deficiency of SMO represents a biochemical defect in the cholesterol synthesis pathway, the clinical spectrum of which remains to be defined. PMID:21285510

Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond.

PubMed

Bakshi, Anshika; Chaudhary, Sandeep C; Rana, Mehtab; Elmets, Craig A; Athar, Mohammad

2017-12-01

Basal cell carcinoma (BCC) of the skin is driven by aberrant hedgehog signaling. Thus blocking this signaling pathway by small molecules such as vismodegib inhibits tumor growth. Primary cilium in the epidermal cells plays an integral role in the processing of hedgehog signaling-related proteins. Recent genomic studies point to the involvement of additional genetic mutations that might be associated with the development of BCCs, suggesting significance of other signaling pathways, such as WNT, NOTCH, mTOR, and Hippo, aside from hedgehog in the pathogenesis of this human neoplasm. Some of these pathways could be regulated by noncoding microRNA. Altered microRNA expression profile is recognized with the progression of these lesions. Stopping treatment with Smoothened (SMO) inhibitors often leads to tumor reoccurrence in the patients with basal cell nevus syndrome, who develop 10-100 of BCCs. In addition, the initial effectiveness of these SMO inhibitors is impaired due to the onset of mutations in the drug-binding domain of SMO. These data point to a need to develop strategies to overcome tumor recurrence and resistance and to enhance efficacy by developing novel single agent-based or multiple agents-based combinatorial approaches. Immunotherapy and photodynamic therapy could be additional successful approaches particularly if developed in combination with chemotherapy for inoperable and metastatic BCCs. © 2017 Wiley Periodicals, Inc.

Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond

PubMed Central

Bakshi, Anshika; Chaudhary, Sandeep C.; Rana, Mehtab; Elmets, Craig A.; Athar, Mohammad

2018-01-01

Basal cell carcinoma (BCC) of the skin is driven by aberrant hedgehog signaling. Thus blocking this signaling pathway by small molecules such as vismodegib inhibits tumor growth. Primary cilium in the epidermal cells plays an integral role in the processing of hedgehog signaling-related proteins. Recent genomic studies point to the involvement of additional genetic mutations that might be associated with the development of BCCs, suggesting significance of other signaling pathways, such as WNT, NOTCH, mTOR, and Hippo, aside from hedgehog in the pathogenesis of this human neoplasm. Some of these pathways could be regulated by noncoding microRNA. Altered microRNA expression profile is recognized with the progression of these lesions. Stopping treatment with Smoothened (SMO) inhibitors often leads to tumor reoccurrence in the patients with basal cell nevus syndrome, who develop 10–100 of BCCs. In addition, the initial effectiveness of these SMO inhibitors is impaired due to the onset of mutations in the drug-binding domain of SMO. These data point to a need to develop strategies to overcome tumor recurrence and resistance and to enhance efficacy by developing novel single agent-based or multiple agents-based combinatorial approaches. Immunotherapy and photodynamic therapy could be additional successful approaches particularly if developed in combination with chemotherapy for inoperable and metastatic BCCs. PMID:28574612

Dry etching technologies for the advanced binary film

NASA Astrophysics Data System (ADS)

Iino, Yoshinori; Karyu, Makoto; Ita, Hirotsugu; Yoshimori, Tomoaki; Azumano, Hidehito; Muto, Makoto; Nonaka, Mikio

2011-11-01

ABF (Advanced Binary Film) developed by Hoya as a photomask for 32 (nm) and larger specifications provides excellent resistance to both mask cleaning and 193 (nm) excimer laser and thereby helps extend the lifetime of the mask itself compared to conventional photomasks and consequently reduces the semiconductor manufacturing cost [1,2,3]. Because ABF uses Ta-based films, which are different from Cr film or MoSi films commonly used for photomask, a new process is required for its etching technology. A patterning technology for ABF was established to perform the dry etching process for Ta-based films by using the knowledge gained from absorption layer etching for EUV mask that required the same Ta-film etching process [4]. Using the mask etching system ARES, which is manufactured by Shibaura Mechatronics, and its optimized etching process, a favorable CD (Critical Dimension) uniformity, a CD linearity and other etching characteristics were obtained in ABF patterning. Those results are reported here.

The oxidation of alkylaryl sulfides and benzo[b]thiophenes by Escherichia coli cells expressing wild-type and engineered styrene monooxygenase from Pseudomonas putida CA-3.

PubMed

Nikodinovic-Runic, Jasmina; Coulombel, Lydie; Francuski, Djordje; Sharma, Narain D; Boyd, Derek R; Ferrall, Rory Moore O; O'Connor, Kevin E

2013-06-01

Nine different sulfur-containing compounds were biotransformed to the corresponding sulfoxides by Escherichia coli Bl21(DE3) cells expressing styrene monooxygenase (SMO) from Pseudomonas putida CA-3. Thioanisole was consumed at 83.3 μmoles min(-1) g cell dry weight(-1) resulting mainly in the formation of R-thioanisole sulfoxide with an enantiomeric excess (ee) value of 45 %. The rate of 2-methyl-, 2-chloro- and 2-bromo-thioanisole consumption was 2-fold lower than that of thioanisole. Surprisingly, the 2-methylthioanisole sulfoxide product had the opposite (S) configuration to that of the other 2-substituted thioanisole derivatives and had a higher ee value (84 %). The rate of oxidation of 4-substituted thioanisoles was higher than the corresponding 2-substituted substrates but the ee values of the products were consistently lower (10-23 %). The rate of benzo[b]thiophene and 2-methylbenzo[b]thiophene sulfoxidation was approximately 10-fold lower than that of thioanisole. The ee value of the benzo[b]thiophene sulfoxide could not be determined as the product racemized rapidly. E. coli cells expressing an engineered SMO (SMOeng R3-11) oxidised 2-substituted thioanisoles between 1.8- and 2.8-fold faster compared to cells expressing the wild-type enzyme. SMOeng R3-11 oxidised benzo[b]thiophene and 2-methylbenzo[b]thiophene 10.1 and 5.6 times faster that the wild-type enzyme. The stereospecificity of the reaction catalysed by SMOeng was unchanged from that of the wild type. Using the X-ray crystal structure of the P. putida S12 SMO, it was evident that the entrance of substrates into the SMO active site is limited by the binding pocket bottleneck formed by the side chains of Val-211 and Asn-46 carboxyamide group.

An orbital angular momentum radio communication system optimized by intensity controlled masks effectively: Theoretical design and experimental verification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Xinlu; Applied Optics Beijing Area Major Laboratory, Department of Physics, Beijing Normal University, Beijing 100875; Huang, Shanguo, E-mail: shghuang@bupt.edu.cn

A system of generating and receiving orbital angular momentum (OAM) radio beams, which are collectively formed by two circular array antennas (CAAs) and effectively optimized by two intensity controlled masks, is proposed and experimentally investigated. The scheme is effective in blocking of the unwanted OAM modes and enhancing the power of received radio signals, which results in the capacity gain of system and extended transmission distance of the OAM radio beams. The operation principle of the intensity controlled masks, which can be regarded as both collimator and filter, is feasible and simple to realize. Numerical simulations of intensity and phasemore » distributions at each key cross-sectional plane of the radio beams demonstrate the collimated results. The experimental results match well with the theoretical analysis and the receive distance of the OAM radio beam at radio frequency (RF) 20 GHz is extended up to 200 times of the wavelength of the RF signals, the measured distance is 5 times of the original measured distance. The presented proof-of-concept experiment demonstrates the feasibility of the system.« less

Near-Infrared Spectroscopic Measurements of Calf Muscle during Walking at Simulated Reduced Gravity - Preliminary Results

NASA Technical Reports Server (NTRS)

Ellerby, Gwenn E. C.; Lee, Stuart M. C.; Stroud, Leah; Norcross, Jason; Gernhardt, Michael; Soller, Babs R.

2008-01-01

Consideration for lunar and planetary exploration space suit design can be enhanced by investigating the physiologic responses of individual muscles during locomotion in reduced gravity. Near-infrared spectroscopy (NIRS) provides a non-invasive method to study the physiology of individual muscles in ambulatory subjects during reduced gravity simulations. PURPOSE: To investigate calf muscle oxygen saturation (SmO2) and pH during reduced gravity walking at varying treadmill inclines and added mass conditions using NIRS. METHODS: Four male subjects aged 42.3 +/- 1.7 years (mean +/- SE) and weighing 77.9 +/- 2.4 kg walked at a moderate speed (3.2 +/- 0.2 km/h) on a treadmill at inclines of 0, 10, 20, and 30%. Unsuited subjects were attached to a partial gravity simulator which unloaded the subject to simulate body weight plus the additional weight of a space suit (121 kg) in lunar gravity (0.17G). Masses of 0, 11, 23, and 34 kg were added to the subject and then unloaded to maintain constant weight. Spectra were collected from the lateral gastrocnemius (LG), and SmO2 and pH were calculated using previously published methods (Yang et al. 2007 Optics Express ; Soller et al. 2008 J Appl Physiol). The effects of incline and added mass on SmO2 and pH were analyzed through repeated measures ANOVA. RESULTS: SmO2 and pH were both unchanged by added mass (p>0.05), so data from trials at the same incline were averaged. LG SmO2 decreased significantly with increasing incline (p=0.003) from 61.1 +/- 2.0% at 0% incline to 48.7 +/- 2.6% at 30% incline, while pH was unchanged by incline (p=0.12). CONCLUSION: Increasing the incline (and thus work performed) during walking causes the LG to extract more oxygen from the blood supply, presumably to support the increased metabolic cost of uphill walking. The lack of an effect of incline on pH may indicate that, while the intensity of exercise has increased, the LG has not reached a level of work above the anaerobic threshold. In these preliminary studies, 30% incline walking at reduced gravity may not require anaerobic LG activity due to the low exercise intensity (42.8 +/- 1.6% of VO(sub 2max)). It is also possible that at reduced gravity additional work is being done by muscle groups other than the calf.

Modeling high-efficiency extreme ultraviolet etched multilayer phase-shift masks

NASA Astrophysics Data System (ADS)

Sherwin, Stuart; Neureuther, Andrew; Naulleau, Patrick

2017-10-01

Achieving high-throughput extreme ultraviolet (EUV) patterning remains a major challenge due to low source power; phase-shift masks can help solve this challenge for dense features near the resolution limit by creating brighter images than traditional absorber masks when illuminated with the same source power. We explore applications of etched multilayer phase-shift masks for EUV lithography, both in the current-generation 0.33 NA and next-generation 0.55 NA systems. We derive analytic formulas for the thin-mask throughput gains, which are 2.42× for lines and spaces and 5.86× for contacts compared with an absorber mask with dipole and quadrupole illumination, respectively. Using rigorous finite-difference time-domain simulations, we quantify variations in these gains by pitch and orientation, finding 87% to 113% of the thin-mask value for lines and spaces and a 91% to 99% for contacts. We introduce an edge placement error metric, which accounts for CD errors, relative feature motion, and telecentricity errors, and use this metric both to optimize mask designs for individual features and to explore which features can be printed on the same mask. Furthermore, we find that although partial coherence shrinks the process window, at an achievable sigma of 0.2 we obtain a depth of focus of 340 nm and an exposure latitude of 39.2%, suggesting that partial coherence will not limit the feasibility of this technology. Finally, we show that many problems such as sensitivity to etch uniformity can be greatly mitigated using a central obscuration in the imaging pupil.

The edge of awareness: Mask spatial density, but not color, determines optimal temporal frequency for continuous flash suppression.

PubMed

Drewes, Jan; Zhu, Weina; Melcher, David

2018-01-01

The study of how visual processing functions in the absence of visual awareness has become a major research interest in the vision-science community. One of the main sources of evidence that stimuli that do not reach conscious awareness-and are thus "invisible"-are still processed to some degree by the visual system comes from studies using continuous flash suppression (CFS). Why and how CFS works may provide more general insight into how stimuli access awareness. As spatial and temporal properties of stimuli are major determinants of visual perception, we hypothesized that these properties of the CFS masks would be of significant importance to the achieved suppression depth. In previous studies however, the spatial and temporal properties of the masks themselves have received little study, and masking parameters vary widely across studies, making a metacomparison difficult. To investigate the factors that determine the effectiveness of CFS, we varied both the temporal frequency and the spatial density of Mondrian-style masks. We consistently found the longest suppression duration for a mask temporal frequency of around 6 Hz. In trials using masks with reduced spatial density, suppression was weaker and frequency tuning was less precise. In contrast, removing color reduced mask effectiveness but did not change the pattern of suppression strength as a function of frequency. Overall, this pattern of results stresses the importance of CFS mask parameters and is consistent with the idea that CFS works by disrupting the spatiotemporal mechanisms that underlie conscious access to visual input.

A large format membrane-based x-ray mask for microfluidic chip fabrication

NASA Astrophysics Data System (ADS)

Wang, Lin; Zhang, Min; Desta, Yohannes; Melzak, J.; Wu, C. H.; Peng, Zhengchun

2006-02-01

X-ray lithography is a very good option for the fabrication of micro-devices especially when high aspect ratio patterns are required. Membrane-based x-ray masks are commonly used for high-resolution x-ray lithography. A thin layer of silicon nitride (Si3N4) or silicon carbide (SiC) film (1-2 µm) is normally used as the membrane material for x-ray mask fabrication (Wells G M, Reilly M, Nachman R, Cerrina F, El-Khakani M A and Chaker M 1993 Mater. Res. Soc. Conf. Proc. 306 81-9 Shoki T, Nagasawa H, Kosuga H, Yamaguchi Y, Annaka N, Amemiya I and Nagarekawa O 1993 SPIE Proc. 1924 450-6). The freestanding membrane window of an x-ray mask, which defines the exposing area of the x-ray mask, can be obtained by etching a pre-defined area on a silicon wafer from the backside (Wang L, Desta Y, Fettig R K, Goettert J, Hein H, Jakobs P and Chulz J 2004 J. Micromech. Microeng. 14 722-6). Usually, the window size of an x-ray mask is around 20 × 20 mm because of the low tensile stress of the membrane (10-100 MPa), and the larger window dimension of an x-ray mask may cause the deformation of membranes and lower the mask quality. However, x-ray masks with larger windows are preferred for micro-device fabrication in order to increase the productivity. We analyzed the factors which influence the flatness of large format x-ray masks and fabricated x-ray masks with a window size of 55 × 55 mm and 46 × 65 mm on 1 µm thick membranes by increasing the tensile stress of the membranes (>300 MPa) and optimizing the stress of the absorber layer. The large format x-ray mask was successfully applied for the fabrication of microfluidic chips.

N-terminus determines activity and specificity of styrene monooxygenase reductases.

PubMed

Heine, Thomas; Scholtissek, Anika; Westphal, Adrie H; van Berkel, Willem J H; Tischler, Dirk

2017-12-01

Styrene monooxygenases (SMOs) are two-enzyme systems that catalyze the enantioselective epoxidation of styrene to (S)-styrene oxide. The FADH 2 co-substrate of the epoxidase component (StyA) is supplied by an NADH-dependent flavin reductase (StyB). The genome of Rhodococcus opacus 1CP encodes two SMO systems. One system, which we define as E1-type, displays homology to the SMO from Pseudomonas taiwanensis VLB120. The other system, originally reported as a fused system (RoStyA2B), is defined as E2-type. Here we found that E1-type RoStyB is inhibited by FMN, while RoStyA2B is known to be active with FMN. To rationalize the observed specificity of RoStyB for FAD, we generated an artificial reductase, designated as RoStyBart, in which the first 22 amino acid residues of RoStyB were joined to the reductase part of RoStyA2B, while the oxygenase part (A2) was removed. RoStyBart mainly purified as apo-protein and mimicked RoStyB in being inhibited by FMN. Pre-incubation with FAD yielded a turnover number at 30°C of 133.9±3.5s -1 , one of the highest rates observed for StyB reductases. RoStyBart holo-enzyme switches to a ping-pong mechanism and fluorescence analysis indicated for unproductive binding of FMN to the second (co-substrate) binding site. In summary, it is shown for the first time that optimization of the N-termini of StyB reductases allows the evolution of their activity and specificity. Copyright © 2017 Elsevier B.V. All rights reserved.

Spatial Attention Enhances Perceptual Processing of Single-Element Displays

NASA Technical Reports Server (NTRS)

Bacon, William; Johnston, James C.; Remington, Roger W.; Null, Cynthia H. (Technical Monitor)

1994-01-01

Shiu and Pashler (1993) reported that precueing masked, single-element displays had negligible effects on identification accuracy. They argued that spatial attention does not actually enhance stimulus perceptibility, but only reduces decision noise. Alternatively, such negative results may arise if cues are sub-optimal, or if masks place an insufficient premium on timely deployment of attention. We report results showing that valid cueing enhances processing of even single-element displays. Spatial attention does indeed enhance perceptual processes.

Identifying typical physical activity on smartphone with varying positions and orientations.

PubMed

Miao, Fen; He, Yi; Liu, Jinlei; Li, Ye; Ayoola, Idowu

2015-04-13

Traditional activity recognition solutions are not widely applicable due to a high cost and inconvenience to use with numerous sensors. This paper aims to automatically recognize physical activity with the help of the built-in sensors of the widespread smartphone without any limitation of firm attachment to the human body. By introducing a method to judge whether the phone is in a pocket, we investigated the data collected from six positions of seven subjects, chose five signals that are insensitive to orientation for activity classification. Decision trees (J48), Naive Bayes and Sequential minimal optimization (SMO) were employed to recognize five activities: static, walking, running, walking upstairs and walking downstairs. The experimental results based on 8,097 activity data demonstrated that the J48 classifier produced the best performance with an average recognition accuracy of 89.6% during the three classifiers, and thus would serve as the optimal online classifier. The utilization of the built-in sensors of the smartphone to recognize typical physical activities without any limitation of firm attachment is feasible.

Statistical mechanics of image processing by digital halftoning

NASA Astrophysics Data System (ADS)

Inoue, Jun-Ichi; Norimatsu, Wataru; Saika, Yohei; Okada, Masato

2009-03-01

We consider the problem of digital halftoning (DH). The DH is an image processing representing each grayscale in images in terms of black and white dots, and it is achieved by making use of the threshold dither mask, namely, each pixel is determined as black if the grayscale pixel is greater than or equal to the mask value and as white vice versa. To determine the mask for a given grayscale image, we assume that human-eyes might recognize the BW dots as the corresponding grayscale by linear filters. Then, the Hamiltonian is constructed as a distance between the original and recognized images which is written in terms of the mask. Finding the ground state of the Hamiltonian via deterministic annealing, we obtain the optimal mask and the BW dots simultaneously. From the spectrum analysis, we find that the BW dots are desirable from the view point of human-eyes modulation properties. We also show that the lower bound of the mean square error for the inverse process of the DH is minimized on the Nishimori line which is well-known in the research field of spin glasses.

Antigen Masking During Fixation and Embedding, Dissected

PubMed Central

Scalia, Carla Rossana; Boi, Giovanna; Bolognesi, Maddalena Maria; Riva, Lorella; Manzoni, Marco; DeSmedt, Linde; Bosisio, Francesca Maria; Ronchi, Susanna; Leone, Biagio Eugenio; Cattoretti, Giorgio

2016-01-01

Antigen masking in routinely processed tissue is a poorly understood process caused by multiple factors. We sought to dissect the effect on antigenicity of each step of processing by using frozen sections as proxies of the whole tissue. An equivalent extent of antigen masking occurs across variable fixation times at room temperature. Most antigens benefit from longer fixation times (>24 hr) for optimal detection after antigen retrieval (AR; for example, Ki-67, bcl-2, ER). The transfer to a graded alcohol series results in an enhanced staining effect, reproduced by treating the sections with detergents, possibly because of a better access of the polymeric immunohistochemical detection system to tissue structures. A second round of masking occurs upon entering the clearing agent, mostly at the paraffin embedding step. This may depend on the non-freezable water removal. AR fully reverses the masking due both to the fixation time and the paraffin embedding. AR itself destroys some epitopes which do not survive routine processing. Processed frozen sections are a tool to investigate fixation and processing requirements for antigens in routine specimens. PMID:27798289

Coded aperture ptychography: uniqueness and reconstruction

NASA Astrophysics Data System (ADS)

Chen, Pengwen; Fannjiang, Albert

2018-02-01

Uniqueness of solution is proved for any ptychographic scheme with a random mask under a minimum overlap condition and local geometric convergence analysis is given for the alternating projection (AP) and Douglas-Rachford (DR) algorithms. DR is shown to possess a unique fixed point in the object domain and for AP a simple criterion for distinguishing the true solution among possibly many fixed points is given. A minimalist scheme, where the adjacent masks overlap 50% of the area and each pixel of the object is illuminated by exactly four illuminations, is conveniently parametrized by the number q of shifted masks in each direction. The lower bound 1  -  C/q 2 is proved for the geometric convergence rate of the minimalist scheme, predicting a poor performance with large q which is confirmed by numerical experiments. The twin-image ambiguity is shown to arise for certain Fresnel masks and degrade the performance of reconstruction. Extensive numerical experiments are performed to explore the general features of a well-performing mask, the optimal value of q and the robustness with respect to measurement noise.

Photomask etch system and process for 10nm technology node and beyond

NASA Astrophysics Data System (ADS)

Chandrachood, Madhavi; Grimbergen, Michael; Yu, Keven; Leung, Toi; Tran, Jeffrey; Chen, Jeff; Bivens, Darin; Yalamanchili, Rao; Wistrom, Richard; Faure, Tom; Bartlau, Peter; Crawford, Shaun; Sakamoto, Yoshifumi

2015-10-01

While the industry is making progress to offer EUV lithography schemes to attain ultimate critical dimensions down to 20 nm half pitch, an interim optical lithography solution to address an immediate need for resolution is offered by various integration schemes using advanced PSM (Phase Shift Mask) materials including thin e-beam resist and hard mask. Using the 193nm wavelength to produce 10nm or 7nm patterns requires a range of optimization techniques, including immersion and multiple patterning, which place a heavy demand on photomask technologies. Mask schemes with hard mask certainly help attain better selectivity and hence better resolution but pose integration challenges and defectivity issues. This paper presents a new photomask etch solution for attenuated phase shift masks that offers high selectivity (Cr:Resist > 1.5:1), tighter control on the CD uniformity with a 3sigma value approaching 1 nm and controllable CD bias (5-20 nm) with excellent CD linearity performance (<5 nm) down to the finer resolution. The new system has successfully demonstrated capability to meet the 10 nm node photomask CD requirements without the use of more complicated hard mask phase shift blanks. Significant improvement in post wet clean recovery performance was demonstrated by the use of advanced chamber materials. Examples of CD uniformity, linearity, and minimum feature size, and etch bias performance on 10 nm test site and production mask designs will be shown.

Use of simulation to optimize the pinhole diameter and mask thickness for an x-ray backscatter imaging system

NASA Astrophysics Data System (ADS)

Vella, A.; Munoz, Andre; Healy, Matthew J. F.; Lane, David; Lockley, D.

2017-08-01

The PENELOPE Monte Carlo simulation code was used to determine the optimum thickness and aperture diameter of a pinhole mask for X-ray backscatter imaging in a security application. The mask material needs to be thick enough to absorb most X-rays, and the pinhole must be wide enough for sufficient field of view whilst narrow enough for sufficient image spatial resolution. The model consisted of a fixed geometry test object, various masks with and without pinholes, and a 1040 x 1340 pixels' area detector inside a lead lined camera housing. The photon energy distribution incident upon masks was flat up to selected energy limits. This artificial source was used to avoid the optimisation being specific to any particular X-ray source technology. The pixelated detector was modelled by digitising the surface area represented by the PENELOPE phase space file and integrating the energies of the photons impacting within each pixel; a MATLAB code was written for this. The image contrast, signal to background ratio, spatial resolution, and collimation effect were calculated at the simulated detector as a function of pinhole diameter and various thicknesses of mask made of tungsten, tungsten/epoxy composite or bismuth alloy. A process of elimination was applied to identify suitable masks for a viable X-ray backscattering security application.

Full-chip level MEEF analysis using model based lithography verification

NASA Astrophysics Data System (ADS)

Kim, Juhwan; Wang, Lantian; Zhang, Daniel; Tang, Zongwu

2005-11-01

MEEF (Mask Error Enhancement Factor) has become a critical factor in CD uniformity control since optical lithography process moved to sub-resolution era. A lot of studies have been done by quantifying the impact of the mask CD (Critical Dimension) errors on the wafer CD errors1-2. However, the benefits from those studies were restricted only to small pattern areas of the full-chip data due to long simulation time. As fast turn around time can be achieved for the complicated verifications on very large data by linearly scalable distributed processing technology, model-based lithography verification becomes feasible for various types of applications such as post mask synthesis data sign off for mask tape out in production and lithography process development with full-chip data3,4,5. In this study, we introduced two useful methodologies for the full-chip level verification of mask error impact on wafer lithography patterning process. One methodology is to check MEEF distribution in addition to CD distribution through process window, which can be used for RET/OPC optimization at R&D stage. The other is to check mask error sensitivity on potential pinch and bridge hotspots through lithography process variation, where the outputs can be passed on to Mask CD metrology to add CD measurements on those hotspot locations. Two different OPC data were compared using the two methodologies in this study.

An optimized OPC and MDP flow for reducing mask write time and mask cost

NASA Astrophysics Data System (ADS)

Yang, Ellyn; Li, Cheng He; Park, Se Jin; Zhu, Yu; Guo, Eric

2010-09-01

In the process of optical proximity correction, layout edge or fragment is migrating to proper position in order to minimize edge placement error (EPE). During this fragment migration, several factors other than EPE can be also taken into account as a part of cost function for optimal fragment displacement. Several factors are devised in favor of OPC stability, which can accommodate room for high mask error enhancement factor (MEEF), lack of process window, catastrophic pattern failure such as pinch/bridge and improper fragmentation. As technology node becomes finer, there happens conflict between OPC accuracy and stability. Especially for metal layers, OPC has focused on the stability by loss of accurate OPC results. On this purpose, several techniques have been introduced, which are target smoothing, process window aware OPC, model-based retargeting and adaptive OPC. By utilizing those techniques, OPC enables more stabilized patterning, instead of realizing design target exactly on wafer. Inevitably, post-OPC layouts become more complicated because those techniques invoke additional edge, or fragments prior to correction or during OPC iteration. As a result, jogs of post OPC layer can be dramatically increased, which results in huge number of shot count after data fracturing. In other words, there is trade-off relationship between data complexity and various methods for OPC stability. In this paper, those relationships have been investigated with respect to several technology nodes. The mask shot count reduction is achieved by reducing the number of jogs with which EPE difference are within pre-specified value. The effect of jog smoothing on OPC output - in view of OPC performance and mask data preparation - was studied quantitatively for respective technology nodes.

VizieR Online Data Catalog: Radial velocities in A1914 (Barrena+, 2013)

NASA Astrophysics Data System (ADS)

Barrena, R.; Girardi, M.; Boschin, W.

2014-04-01

We performed observations of A1914 using Device Optimized for the Low Resolution (DOLORES) multi-object spectrograph at the TNG telescope in 2010 March. We used the LR-B grism, which provides a dispersion of 187Å/mm. DOLORES works with a 2048x2048 pixels E2V CCD. The pixel size is 13.5um. We retrieved a total of four multi-object spectroscopy (MOS) masks containing 146 slits. We exposed 3600s for each mask. (1 data file).

VizieR Online Data Catalog: Velocities in ZwCl2341.1+0000 field (Boschin+, 2013)

NASA Astrophysics Data System (ADS)

Boschin, W.; Girardi, M.; Barrena, R.

2014-07-01

Multi-object spectroscopic observations of ZwCl 2341+00 were carried out at the TNG in 2009 October, 2011 August and 2011 December. We used the instrument Device Optimized for the Low Resolution (DOLORES) in multi-object spectroscopy (MOS) mode with the LR-B Grism. In summary, we observed four MOS masks for a total of 142 slits. The total exposure time was 3600s for three masks and 5400s for the last one. (1 data file).

Tradeoff between insensitivity to depth-induced spherical aberration and resolution of 3D fluorescence imaging due to the use of wavefront encoding with a radially symmetric phase mask

NASA Astrophysics Data System (ADS)

Doblas, Ana; Dutta, Ananya; Saavedra, Genaro; Preza, Chrysanthe

2018-02-01

Previously, a wavefront encoded (WFE) imaging system implemented using a squared cubic (SQUBIC) phase mask has been verified to reduce the sensitivity of the imaging system to spherical aberration (SA). The strength of the SQUBIC phase mask and, as consequence, the performance of the WFE system are controlled by a design parameter, A. Although the higher the A-value, the more tolerant the WFE system is to SA, this is accomplished at the expense of the effective imaging resolution. In this contribution, we investigate this tradeoff in order to find an optimal A-value to balance the effect of SA and loss of resolution.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aagesen, Larry K.; Coltrin, Michael Elliott; Han, Jung

Three-dimensional phase-field simulations of GaN growth by selective area epitaxy were performed. Furthermore, this model includes a crystallographic-orientation-dependent deposition rate and arbitrarily complex mask geometries. The orientation-dependent deposition rate can be determined from experimental measurements of the relative growth rates of low-index crystallographic facets. Growth on various complex mask geometries was simulated on both c-plane and a-plane template layers. Agreement was observed between simulations and experiment, including complex phenomena occurring at the intersections between facets. The sources of the discrepancies between simulated and experimental morphologies were also investigated. We found that the model provides a route to optimize masks andmore » processing conditions during materials synthesis for solar cells, light-emitting diodes, and other electronic and opto-electronic applications.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aagesen, Larry K.; Thornton, Katsuyo, E-mail: kthorn@umich.edu; Coltrin, Michael E.

Three-dimensional phase-field simulations of GaN growth by selective area epitaxy were performed. The model includes a crystallographic-orientation-dependent deposition rate and arbitrarily complex mask geometries. The orientation-dependent deposition rate can be determined from experimental measurements of the relative growth rates of low-index crystallographic facets. Growth on various complex mask geometries was simulated on both c-plane and a-plane template layers. Agreement was observed between simulations and experiment, including complex phenomena occurring at the intersections between facets. The sources of the discrepancies between simulated and experimental morphologies were also investigated. The model provides a route to optimize masks and processing conditions during materialsmore » synthesis for solar cells, light-emitting diodes, and other electronic and opto-electronic applications.« less

Study of shape evaluation for mask and silicon using large field of view

NASA Astrophysics Data System (ADS)

Matsuoka, Ryoichi; Mito, Hiroaki; Shinoda, Shinichi; Toyoda, Yasutaka

2010-09-01

We have developed a highly integrated method of mask and silicon metrology. The aim of this integration is evaluating the performance of the silicon corresponding to Hotspot on a mask. It can use the mask shape of a large field, besides. The method adopts a metrology management system based on DBM (Design Based Metrology). This is the high accurate contouring created by an edge detection algorithm used in mask CD-SEM and silicon CD-SEM. Currently, as semiconductor manufacture moves towards even smaller feature size, this necessitates more aggressive optical proximity correction (OPC) to drive the super-resolution technology (RET). In other words, there is a trade-off between highly precise RET and mask manufacture, and this has a big impact on the semiconductor market that centers on the mask business. As an optimal solution to these issues, we provide a DFM solution that extracts 2-dimensional data for a more realistic and error-free simulation by reproducing accurately the contour of the actual mask, in addition to the simulation results from the mask data. On the other hand, there is roughness in the silicon form made from a mass-production line. Moreover, there is variation in the silicon form. For this reason, quantification of silicon form is important, in order to estimate the performance of a pattern. In order to quantify, the same form is equalized in two dimensions. And the method of evaluating based on the form is popular. In this study, we conducted experiments for averaging method of the pattern (Measurement Based Contouring) as two-dimensional mask and silicon evaluation technique. That is, observation of the identical position of a mask and a silicon was considered. The result proved its detection accuracy and reliability of variability on two-dimensional pattern (mask and silicon) and is adaptable to following fields of mask quality management. •Discrimination of nuisance defects for fine pattern. •Determination of two-dimensional variability of pattern. •Verification of the performance of the pattern of various kinds of Hotspots. In this report, we introduce the experimental results and the application. We expect that the mask measurement and the shape control on mask production will make a huge contribution to mask yield-enhancement and that the DFM solution for mask quality control process will become much more important technology than ever. It is very important to observe the form of the same location of Design, Mask, and Silicon in such a viewpoint. And we report it about algorithm of the image composition in Large Field.

DfM requirements and ROI analysis for system-on-chip

NASA Astrophysics Data System (ADS)

Balasinski, Artur

2005-11-01

DfM (Design-for-Manufacturability) has become staple requirement beyond 100 nm technology node for efficient generation of mask data, cost reduction, and optimal circuit performance. Layout pattern has to comply to many requirements pertaining to database structure and complexity, suitability for image enhancement by the optical proximity correction, and mask data pattern density and distribution over the image field. These requirements are of particular complexity for Systems-on-Chip (SoC). A number of macro-, meso-, and microscopic effects such as reticle macroloading, planarization dishing, and pattern bridging or breaking would compromise fab yield, device performance, or both. In order to determine the optimal set of DfM rules applicable to the particular designs, Return-on-Investment and Failure Mode and Effect Analysis (FMEA) are proposed.

An automatic iris occlusion estimation method based on high-dimensional density estimation.

PubMed

Li, Yung-Hui; Savvides, Marios

2013-04-01

Iris masks play an important role in iris recognition. They indicate which part of the iris texture map is useful and which part is occluded or contaminated by noisy image artifacts such as eyelashes, eyelids, eyeglasses frames, and specular reflections. The accuracy of the iris mask is extremely important. The performance of the iris recognition system will decrease dramatically when the iris mask is inaccurate, even when the best recognition algorithm is used. Traditionally, people used the rule-based algorithms to estimate iris masks from iris images. However, the accuracy of the iris masks generated this way is questionable. In this work, we propose to use Figueiredo and Jain's Gaussian Mixture Models (FJ-GMMs) to model the underlying probabilistic distributions of both valid and invalid regions on iris images. We also explored possible features and found that Gabor Filter Bank (GFB) provides the most discriminative information for our goal. Finally, we applied Simulated Annealing (SA) technique to optimize the parameters of GFB in order to achieve the best recognition rate. Experimental results show that the masks generated by the proposed algorithm increase the iris recognition rate on both ICE2 and UBIRIS dataset, verifying the effectiveness and importance of our proposed method for iris occlusion estimation.

A randomised controlled trial on the effect of mask choice on residual respiratory events with continuous positive airway pressure treatment.

PubMed

Ebben, Matthew R; Narizhnaya, Mariya; Segal, Alan Z; Barone, Daniel; Krieger, Ana C

2014-06-01

It has been found that mask style can affect the amount of continuous positive airway pressure (CPAP) required to reduce an apnoea/hyponoea index (AHI) to < 5/h on a titration study. However, it was not previously known whether switching from one CPAP mask style to another post titration could affect the residual AHI with CPAP. The purpose of this study was to investigate the differences in residual AHI with CPAP treatment between oronasal and nasal masks. Twenty-one subjects (age mean (M)=62.9, body mass index (BMI) M=29.6 kg/m2) were randomised (14 subjects completed the protocol) to undergo an in-laboratory CPAP titration with either a nasal mask or an oronasal mask. Subjects were then assigned this mask for 3weeks of at-home CPAP use with the optimal treatment pressure determined on the laboratory study (CPAP M=8.4 cm of H2O). At the end of this 3-week period, data were collected from the CPAP machine and the subject was given the other mask to use with the same CPAP settings for the next 3weeks at home (if the nasal mask was given initially, the oronasal one was given later and vice versa). On completion of the second 3-week period, data on residual AHI were again collected and compared with the first 3-week period on CPAP. A Wilcoxon Signed-Rank Test (two-tailed) revealed that residual AHI with CPAP treatment was significantly higher with the oronasal compared with the nasal mask (z = -3.296, p<0.001). All 14 subjects had a higher residual AHI with the oronasal versus nasal mask, and 50% of the subjects had a residual AHI >10/h in the oronasal mask condition, even though all of these subjects were titrated to an AHI of < 5/h in the laboratory. A higher residual AHI was seen in all patients with the use of an oronasal mask compared with a nasal mask. Switching to an oronasal mask post titration results in an increase in residual AHI with CPAP treatment, and pressure adjustment may be warranted. Copyright © 2014 Elsevier B.V. All rights reserved.

Severe maternal morbidity and near miss due to postpartum hemorrhage in a national multicenter surveillance study.

PubMed

Rocha Filho, Edilberto A; Costa, Maria L; Cecatti, Jose G; Parpinelli, Mary A; Haddad, Samira M; Pacagnella, Rodolfo C; Sousa, Maria H; Melo, Elias F; Surita, Fernanda G; Souza, Joao P

2015-02-01

To assess the occurrence of severe maternal complications owing to postpartum hemorrhage (PPH) and its associated factors. A secondary analysis of data from a multicenter cross-sectional prospective surveillance study included 9555 cases of severe maternal morbidity at 27 centers in Brazil between July 2009 and June 2010. Complications of PPH, conditions of severity management, and sociodemographic and obstetric characteristics were assessed. Factors independently associated with severe maternal outcome (SMO) were identified using multiple regression analysis. Overall, 1192 (12.5%) of the 9555 women experienced complications owing to PPH (981 had potentially life-threatening conditions, 181 maternal near miss, and 30 had died). The SMO ratio was 2.6 per 1000 live births among women with PPH and 8.5 per 1000 live births among women with other complications. Women with PPH had a higher risk of blood transfusion and return to the operating theater than did those with complications from other causes. Maternal age, length of pregnancy, previous uterine scar, and cesarean delivery were the main factors associated with an increased risk of SMO secondary to PPH. PPH frequently leads to severe maternal morbidity. A surveillance system can identify the main causes of morbidity and could help to improve care, especially among women identified as being at high risk of PPH. Copyright © 2014 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Rescue therapy by switching to total face mask after failure of face mask-delivered noninvasive ventilation in do-not-intubate patients in acute respiratory failure.

PubMed

Lemyze, Malcolm; Mallat, Jihad; Nigeon, Olivier; Barrailler, Stéphanie; Pepy, Florent; Gasan, Gaëlle; Vangrunderbeeck, Nicolas; Grosset, Philippe; Tronchon, Laurent; Thevenin, Didier

2013-02-01

To evaluate the impact of switching to total face mask in cases where face mask-delivered noninvasive mechanical ventilation has already failed in do-not-intubate patients in acute respiratory failure. Prospective observational study in an ICU and a respiratory stepdown unit over a 12-month study period. Switching to total face mask, which covers the entire face, when noninvasive mechanical ventilation using facial mask (oronasal mask) failed to reverse acute respiratory failure. Seventy-four patients with a do-not-intubate order and treated by noninvasive mechanical ventilation for acute respiratory failure. Failure of face mask-delivered noninvasive mechanical ventilation was associated with a three-fold increase in in-hospital mortality (36% vs. 10.5%; p = 0.009). Nevertheless, 23 out of 36 patients (64%) in whom face mask-delivered noninvasive mechanical ventilation failed to reverse acute respiratory failure and, therefore, switched to total face mask survived hospital discharge. Reasons for switching from facial mask to total face mask included refractory hypercapnic acute respiratory failure (n = 24, 66.7%), painful skin breakdown or facial mask intolerance (n = 11, 30%), and refractory hypoxemia (n = 1, 2.7%). In the 24 patients switched from facial mask to total face mask because of refractory hypercapnia, encephalopathy score (3 [3-4] vs. 2 [2-3]; p < 0.0001), PaCO2 (87 ± 25 mm Hg vs. 70 ± 17 mm Hg; p < 0.0001), and pH (7.24 ± 0.1 vs. 7.32 ± 0.09; p < 0.0001) significantly improved after 2 hrs of total face mask-delivered noninvasive ventilation. Patients switched early to total face mask (in the first 12 hrs) developed less pressure sores (n = 5, 24% vs. n = 13, 87%; p = 0.0002), despite greater length of noninvasive mechanical ventilation within the first 48 hrs (44 hrs vs. 34 hrs; p = 0.05) and less protective dressings (n = 2, 9.5% vs. n = 8, 53.3%; p = 0.007). The optimal cutoff value for face mask-delivered noninvasive mechanical ventilation duration in predicting facial pressure sores was 11 hrs (area under the receiver operating characteristic curve, 0.86 ± 0.04; 95% confidence interval 0.76-0.93; p < 0.0001; sensitivity, 84%; specificity, 71%). In patients in hypercapnic acute respiratory failure, for whom escalation to intubation is deemed inappropriate, switching to total face mask can be proposed as a last resort therapy when face mask-delivered noninvasive mechanical ventilation has already failed to reverse acute respiratory failure. This strategy is particularly adapted to provide prolonged periods of continuous noninvasive mechanical ventilation while preventing facial pressure sores.

Coma measurement by use of an alternating phase-shifting mask mark with a specific phase width

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu Zicheng; Wang Xiangzhao; Yuan Qiongyan

2009-01-10

The correlation between the coma sensitivity of the alternating phase-shifting mask (Alt-PSM) mark and the mark's structure is studied based on the Hopkins theory of partially coherent imaging and positive resist optical lithography (PROLITH) simulation. It is found that an optimized Alt-PSM mark with its phase width being two-thirds its pitch has a higher sensitivity to coma than Alt-PSM marks with the same pitch and the different phase widths. The pitch of the Alt-PSM mark is also optimized by PROLITH simulation, and the structure of p=1.92{lambda}/NA and pw=2p/3 proves to be with the highest sensitivity. The optimized Alt-PSM mark ismore » used as a measurement mark to retrieve coma aberration from the projection optics in lithographic tools. In comparison with an ordinary Alt-PSM mark with its phase width being a half its pitch, the measurement accuracies of Z7 and Z14 apparently increase.« less

Robust resolution enhancement optimization methods to process variations based on vector imaging model

NASA Astrophysics Data System (ADS)

Ma, Xu; Li, Yanqiu; Guo, Xuejia; Dong, Lisong

2012-03-01

Optical proximity correction (OPC) and phase shifting mask (PSM) are the most widely used resolution enhancement techniques (RET) in the semiconductor industry. Recently, a set of OPC and PSM optimization algorithms have been developed to solve for the inverse lithography problem, which are only designed for the nominal imaging parameters without giving sufficient attention to the process variations due to the aberrations, defocus and dose variation. However, the effects of process variations existing in the practical optical lithography systems become more pronounced as the critical dimension (CD) continuously shrinks. On the other hand, the lithography systems with larger NA (NA>0.6) are now extensively used, rendering the scalar imaging models inadequate to describe the vector nature of the electromagnetic field in the current optical lithography systems. In order to tackle the above problems, this paper focuses on developing robust gradient-based OPC and PSM optimization algorithms to the process variations under a vector imaging model. To achieve this goal, an integrative and analytic vector imaging model is applied to formulate the optimization problem, where the effects of process variations are explicitly incorporated in the optimization framework. The steepest descent algorithm is used to optimize the mask iteratively. In order to improve the efficiency of the proposed algorithms, a set of algorithm acceleration techniques (AAT) are exploited during the optimization procedure.

A novel and discriminative method of in vitro disintegration time for preparation and optimization of taste-masked orally disintegrating tablets of carbinoxamine maleate.

PubMed

Liu, Yali; Li, Peng; Qian, Rong; Sun, Tianyu; Fang, Fangzhi; Wang, Zonghua; Ke, Xue; Xu, Bohui

2018-08-01

The primary objective of this study was to mask bitter taste and decrease the disintegration time of carbinoxamine maleate (CAM) orally disintegrating tablets (ODTs). In order to screen the prescription of ODTs, a novel modified in vitro disintegration method (MIVDM) was developed to measure the in vitro disintegration time. In this method, different concentrations of ethanol served as disintegration medium in order to delay the in vitro water absorption and disintegration process of tablets. The MIVDM demonstrated good in vitro and in vivo correlation and proved more precise and discriminative than other reported methods. In this research, ion exchange resins (IERs) were used to mask bitter taste for improving mouthfeel. The drug-resin ratio and reaction temperature were investigated to obtain the optimum carbinoxamine resin complexes (CRCs). The characterization of CRCs revealed an amorphous state. ODTs were prepared by direct compression. Superdisintegrants and diluents of ODTs were screened first. Further optimization was carried out by using Box-Behnken design. The effect of (X 1 ) mannitol/microcrystalline cellulose ratio, (X 2 ) the amount of low-substituted hydroxypropylcellulose and (X 3 ) the hardness was investigated for achieving the lowest (Y) in vitro disintegration time. Technological characterization, wetting time, water absorption ratio, and roughness degree were evaluated. The CRCs and ODTs proved successful taste-masking efficiency. The end product improved patients' compliance. The developed MIVDM was practical for commercial use.

A Deep Ensemble Learning Method for Monaural Speech Separation.

PubMed

Zhang, Xiao-Lei; Wang, DeLiang

2016-03-01

Monaural speech separation is a fundamental problem in robust speech processing. Recently, deep neural network (DNN)-based speech separation methods, which predict either clean speech or an ideal time-frequency mask, have demonstrated remarkable performance improvement. However, a single DNN with a given window length does not leverage contextual information sufficiently, and the differences between the two optimization objectives are not well understood. In this paper, we propose a deep ensemble method, named multicontext networks, to address monaural speech separation. The first multicontext network averages the outputs of multiple DNNs whose inputs employ different window lengths. The second multicontext network is a stack of multiple DNNs. Each DNN in a module of the stack takes the concatenation of original acoustic features and expansion of the soft output of the lower module as its input, and predicts the ratio mask of the target speaker; the DNNs in the same module employ different contexts. We have conducted extensive experiments with three speech corpora. The results demonstrate the effectiveness of the proposed method. We have also compared the two optimization objectives systematically and found that predicting the ideal time-frequency mask is more efficient in utilizing clean training speech, while predicting clean speech is less sensitive to SNR variations.

Bayesian cloud detection for MERIS, AATSR, and their combination

NASA Astrophysics Data System (ADS)

Hollstein, A.; Fischer, J.; Carbajal Henken, C.; Preusker, R.

2014-11-01

A broad range of different of Bayesian cloud detection schemes is applied to measurements from the Medium Resolution Imaging Spectrometer (MERIS), the Advanced Along-Track Scanning Radiometer (AATSR), and their combination. The cloud masks were designed to be numerically efficient and suited for the processing of large amounts of data. Results from the classical and naive approach to Bayesian cloud masking are discussed for MERIS and AATSR as well as for their combination. A sensitivity study on the resolution of multidimensional histograms, which were post-processed by Gaussian smoothing, shows how theoretically insufficient amounts of truth data can be used to set up accurate classical Bayesian cloud masks. Sets of exploited features from single and derived channels are numerically optimized and results for naive and classical Bayesian cloud masks are presented. The application of the Bayesian approach is discussed in terms of reproducing existing algorithms, enhancing existing algorithms, increasing the robustness of existing algorithms, and on setting up new classification schemes based on manually classified scenes.

ArF halftone PSM cleaning process optimization for next-generation lithography

NASA Astrophysics Data System (ADS)

Son, Yong-Seok; Jeong, Seong-Ho; Kim, Jeong-Bae; Kim, Hong-Seok

2000-07-01

ArF lithography which is expected for the next generation optical lithography is adapted for 0.13 micrometers design-rule and beyond. ArF half-tone phase shift mask (HT PSM) will be applied as 1st generation of ArF lithography. Also ArF PSM cleaning demands by means of tighter controls related to phase angle, transmittance and contamination on the masks. Phase angle on ArF HT PSM should be controlled within at least +/- 3 degree and transmittance controlled within at least +/- 3 percent after cleaning process and pelliclization. In the cleaning process of HT PSM, requires not only the remove the particle on mask, but also control to half-tone material for metamorphosis. Contamination defects on the Qz of half tone type PSM is not easy to remove on the photomask surface. New technology and methods of cleaning will be developed in near future, but we try to get out for limit contamination on the mask, without variation of phase angle and transmittance after cleaning process.

Controlling bridging and pinching with pixel-based mask for inverse lithography

NASA Astrophysics Data System (ADS)

Kobelkov, Sergey; Tritchkov, Alexander; Han, JiWan

2016-03-01

Inverse Lithography Technology (ILT) has become a viable computational lithography candidate in recent years as it can produce mask output that results in process latitude and CD control in the fab that is hard to match with conventional OPC/SRAF insertion approaches. An approach to solving the inverse lithography problem as a nonlinear, constrained minimization problem over a domain mask pixels was suggested in the paper by Y. Granik "Fast pixel-based mask optimization for inverse lithography" in 2006. The present paper extends this method to satisfy bridging and pinching constraints imposed on print contours. Namely, there are suggested objective functions expressing penalty for constraints violations, and their minimization with gradient descent methods is considered. This approach has been tested with an ILT-based Local Printability Enhancement (LPTM) tool in an automated flow to eliminate hotspots that can be present on the full chip after conventional SRAF placement/OPC and has been applied in 14nm, 10nm node production, single and multiple-patterning flows.

Process optimization for particle removal on blank chrome mask plates in preparation for resist application

NASA Astrophysics Data System (ADS)

Osborne, Stephen; Smith, Eryn; Woster, Eric; Pelayo, Anthony

2002-03-01

As integrated circuits require smaller lines to provide the memory and processing capability for tomorrow's marketplace, the photomask industry is adopting higher contrast resists to improve photomask lithography. Photomask yield for several high-contrast resist recipes may be improved by coating masks at the mask shop. When coating at a mask shop, an effective method is available that uses coat/bake cluster tools to ensure blanks are clean prior to coating. Many high-contrast resists are available, and some are more susceptible to time-dependent performance factors than conventional resists. One of these factors is the time between coating and writing. Although future methods may reduce the impact of this factor, one current trend is to reduce this time by coating plates at the mask shop just prior to writing. Establishing an effective process to clean blanks prior to coating is necessary for product quality control and is a new task that is critical for maskmakers who previously purchased mask plates but have decided to begin coating them within their facility. This paper provides a strategy and method to be used within coat/bake cluster tools to remove particle contamination from mask blanks. The process uses excimer-UV ionizing radiation and ozone to remove organic contaminants, and then uses a wet process combined with megasonic agitation, surfactant, and spin forces. Megasonic agitation with surfactant lifts up particles, while the convective outflow of water enhances centripetal shear without accumulating harmful charge.

New method of contour-based mask-shape compiler

NASA Astrophysics Data System (ADS)

Matsuoka, Ryoichi; Sugiyama, Akiyuki; Onizawa, Akira; Sato, Hidetoshi; Toyoda, Yasutaka

2007-10-01

We have developed a new method of accurately profiling a mask shape by utilizing a Mask CD-SEM. The method is intended to realize high accuracy, stability and reproducibility of the Mask CD-SEM adopting an edge detection algorithm as the key technology used in CD-SEM for high accuracy CD measurement. In comparison with a conventional image processing method for contour profiling, it is possible to create the profiles with much higher accuracy which is comparable with CD-SEM for semiconductor device CD measurement. In this report, we will introduce the algorithm in general, the experimental results and the application in practice. As shrinkage of design rule for semiconductor device has further advanced, an aggressive OPC (Optical Proximity Correction) is indispensable in RET (Resolution Enhancement Technology). From the view point of DFM (Design for Manufacturability), a dramatic increase of data processing cost for advanced MDP (Mask Data Preparation) for instance and surge of mask making cost have become a big concern to the device manufacturers. In a sense, it is a trade-off between the high accuracy RET and the mask production cost, while it gives a significant impact on the semiconductor market centered around the mask business. To cope with the problem, we propose the best method for a DFM solution in which two dimensional data are extracted for an error free practical simulation by precise reproduction of a real mask shape in addition to the mask data simulation. The flow centering around the design data is fully automated and provides an environment where optimization and verification for fully automated model calibration with much less error is available. It also allows complete consolidation of input and output functions with an EDA system by constructing a design data oriented system structure. This method therefore is regarded as a strategic DFM approach in the semiconductor metrology.

Plasma-Induced, Self-Masking, One-Step Approach to an Ultrabroadband Antireflective and Superhydrophilic Subwavelength Nanostructured Fused Silica Surface.

PubMed

Ye, Xin; Shao, Ting; Sun, Laixi; Wu, Jingjun; Wang, Fengrui; He, Junhui; Jiang, Xiaodong; Wu, Wei-Dong; Zheng, Wanguo

2018-04-25

In this work, antireflective and superhydrophilic subwavelength nanostructured fused silica surfaces have been created by one-step, self-masking reactive ion etching (RIE). Bare fused silica substrates with no mask were placed in a RIE vacuum chamber, and then nanoscale fluorocarbon masks and subwavelength nanostructures (SWSs) automatically formed on these substrate after the appropriate RIE plasma process. The mechanism of plasma-induced self-masking SWS has been proposed in this paper. Plasma parameter effects on the morphology of SWS have been investigated to achieve perfect nanocone-like SWS for excellent antireflection, including process time, reactive gas, and pressure of the chamber. Optical properties, i.e., antireflection and optical scattering, were simulated by the finite difference time domain (FDTD) method. Calculated data agree well with the experiment results. The optimized SWS show ultrabroadband antireflective property (up to 99% from 500 to 1360 nm). An excellent improvement of transmission was achieved for the deep-ultraviolet (DUV) range. The proposed low-cost, highly efficient, and maskless method was applied to achieve ultrabroadband antireflective and superhydrophilic SWSs on a 100 mm optical window, which promises great potential for applications in the automotive industry, goggles, and optical devices.

Phase-shifting coronagraph

NASA Astrophysics Data System (ADS)

Hénault, François; Carlotti, Alexis; Vérinaud, Christophe

2017-09-01

With the recent commissioning of ground instruments such as SPHERE or GPI and future space observatories like WFIRST-AFTA, coronagraphy should probably become the most efficient tool for identifying and characterizing extrasolar planets in the forthcoming years. Coronagraphic instruments such as Phase mask coronagraphs (PMC) are usually based on a phase mask or plate located at the telescope focal plane, spreading the starlight outside the diameter of a Lyot stop that blocks it. In this communication is investigated the capability of a PMC to act as a phase-shifting wavefront sensor for better control of the achieved star extinction ratio in presence of the coronagraphic mask. We discuss the two main implementations of the phase-shifting process, either introducing phase-shifts in a pupil plane and sensing intensity variations in an image plane, or reciprocally. Conceptual optical designs are described in both cases. Numerical simulations allow for better understanding of the performance and limitations of both options, and optimizing their fundamental parameters. In particular, they demonstrate that the phase-shifting process is a bit more efficient when implemented into an image plane, and is compatible with the most popular phase masks currently employed, i.e. fourquadrants and vortex phase masks.

Design of a Multistep Phase Mask for High-Energy Terahertz Pulse Generation by Optical Rectification

NASA Astrophysics Data System (ADS)

Avetisyan, Y.; Makaryan, A.; Tadevosyan, V.; Tonouchi, M.

2017-12-01

A new scheme for generating high-energy terahertz (THz) pulses based on using a multistep phase mask (MSPM) is suggested and analyzed. The mask is placed on the entrance surface of the nonlinear optical (NLO) crystal eliminating the necessity of the imaging optics. In contrast to the contact grating method, introduction of large amounts of angular dispersion is avoided. The operation principle of the suggested scheme is based on the fact that the MSPM splits a single input beam into many smaller time-delayed "beamlets," which together form a discretely tilted-front laser pulse in NLO crystal. The analysis of THz-pulse generation in ZnTe and lithium niobate (LN) crystals shows that application of ZnTe crystal is more preferable, especially when long-wavelength pump sources are used. The dimensions of the mask's steps required for high-energy THz-pulse generation in ZnTe and LN crystals are calculated. The optimal number of steps is estimated, taking into account individual beamlet's spatial broadening and problems related to the mask fabrication. The proposed method is a promising way to develop high-energy, monolithic, and alignment-free THz-pulse sources.

Pharmaceutical optimization of lipid-based dosage forms for the improvement of taste-masking, chemical stability and solubilizing capacity of phenobarbital.

PubMed

Monteagudo, Ezequiel; Langenheim, Mariana; Salerno, Claudia; Buontempo, Fabián; Bregni, Carlos; Carlucci, Adriana

2014-06-01

Microemulsions (MEs) and self-emulsifying drug delivery systems (SEEDS) containing phenobarbital (Phe) were developed to improve its chemical stability, solubilizing capacity and taste-masking in oral liquid dosage forms. Cremophor® RH40 and Labrasol® were used as surfactants for the screening of ME regions, Capmul® MCM L, Captex® 355, Imwitor® 408, Myglyol® 840 and Isopropyl myristate were the oil phases assayed; Transcutol® P, Polyethylene-glycol 400, glycerol, Propylene-glycol and ethanol the cosurfactants. Phe stability assay was carried out (20:4:20:56% and 20:4:35:41% (w/w); surfactant:oily phase:cosurfactant:water) for both surfactants; only one containing ethanol showed significant dismissing in its drug content. Solubility capacity for these selected formulations were also evaluated, an amount between 17 and 58 mg/mL of Phe could be loaded. At last, an optimized ME formulation with Cremophor® RH40 20%, Capmul® MCM L 4%, PEG 400 35% and sucralose 2% (w/w) was chosen in order to optimize taste-masking using an electronic tongue. Strawberry along with banana and tutti-frutti flavors plus mint flavor proved to be the best ones. Labrasol-based pre-concentrates were tested for (micro)emulsifying properties; all of them resulted to behave as SEDDS. In summary, a rationale experimental design conducted to an optimized ME for Phe oral pediatric administration which was able to load 5-fold times the currently used dose (4 mg/mL), with no sign of physical or chemical instability and with improved taste; SEDDS for capsule filling were also obtained. The biopharmaceutical advantages described for these dosage forms encourage furthering in vivo evaluation.

Topology-changing shape optimization with the genetic algorithm

NASA Astrophysics Data System (ADS)

Lamberson, Steven E., Jr.

The goal is to take a traditional shape optimization problem statement and modify it slightly to allow for prescribed changes in topology. This modification enables greater flexibility in the choice of parameters for the topology optimization problem, while improving the direct physical relevance of the results. This modification involves changing the optimization problem statement from a nonlinear programming problem into a form of mixed-discrete nonlinear programing problem. The present work demonstrates one possible way of using the Genetic Algorithm (GA) to solve such a problem, including the use of "masking bits" and a new modification to the bit-string affinity (BSA) termination criterion specifically designed for problems with "masking bits." A simple ten-bar truss problem proves the utility of the modified BSA for this type of problem. A more complicated two dimensional bracket problem is solved using both the proposed approach and a more traditional topology optimization approach (Solid Isotropic Microstructure with Penalization or SIMP) to enable comparison. The proposed approach is able to solve problems with both local and global constraints, which is something traditional methods cannot do. The proposed approach has a significantly higher computational burden --- on the order of 100 times larger than SIMP, although the proposed approach is able to offset this with parallel computing.

Engineering the on-axis intensity of Bessel beam by a feedback tuning loop

NASA Astrophysics Data System (ADS)

Li, Runze; Yu, Xianghua; Yang, Yanlong; Peng, Tong; Yao, Baoli; Zhang, Chunmin; Ye, Tong

2018-02-01

The Bessel beam belongs to a typical class of non-diffractive optical fields that are characterized by their invariant focal profiles along the propagation direction. However, ideal Bessel beams only rigorously exist in theory; Bessel beams generated in the lab are quasi-Bessel beams with finite focal extensions and varying intensity profiles along the propagation axis. The ability to engineer the on-axis intensity profile to the desired shape is essential for many applications. Here we demonstrate an iterative optimization-based approach to engineering the on-axis intensity of Bessel beams. The genetic algorithm is used to demonstrate this approach. Starting with a traditional axicon phase mask, in the design process, the computed on-axis beam profile is fed into a feedback tuning loop of an iterative optimization process, which searches for an optimal radial phase distribution that can generate a generalized Bessel beam with the desired onaxis intensity profile. The experimental implementation involves a fine-tuning process that adjusts the originally targeted profile so that the optimization process can optimize the phase mask to yield an improved on-axis profile. Our proposed method has been demonstrated in engineering several zeroth-order Bessel beams with customized on-axis profiles. High accuracy and high energy throughput merit its use in many applications.

Blood pressure and calf muscle oxygen extraction during plantar flexion exercise in peripheral artery disease.

PubMed

Luck, J Carter; Miller, Amanda J; Aziz, Faisal; Radtka, John F; Proctor, David N; Leuenberger, Urs A; Sinoway, Lawrence I; Muller, Matthew D

2017-07-01

Peripheral artery disease (PAD) is an atherosclerotic vascular disease that affects 200 million people worldwide. Although PAD primarily affects large arteries, it is also associated with microvascular dysfunction, an exaggerated blood pressure (BP) response to exercise, and high cardiovascular mortality. We hypothesized that fatiguing plantar flexion exercise that evokes claudication elicits a greater reduction in skeletal muscle oxygenation (SmO 2 ) and a higher rise in BP in PAD compared with age-matched healthy subjects, but low-intensity steady-state plantar flexion elicits similar responses between groups. In the first experiment, eight patients with PAD and eight healthy controls performed fatiguing plantar flexion exercise (from 0.5 to 7 kg for up to 14 min). In the second experiment, seven patients with PAD and seven healthy controls performed low-intensity plantar flexion exercise (2.0 kg for 14 min). BP, heart rate (HR), and SmO 2 were measured continuously using near-infrared spectroscopy (NIRS). SmO 2 is the ratio of oxygenated hemoglobin to total hemoglobin, expressed as a percent. At fatigue, patients with PAD had a greater increase in mean arterial BP (18 ± 2 vs. vs. 10 ± 2 mmHg, P = 0.029) and HR (14 ± 2 vs. 6 ± 2 beats/min, P = 0.033) and a greater reduction in SmO 2 (-54 ± 10 vs. -12 ± 4%, P = 0.001). However, both groups had similar physiological responses to low-intensity, nonpainful plantar flexion exercise. These data suggest that patients with PAD have altered oxygen uptake and/or utilization during fatiguing exercise coincident with an augmented BP response. NEW & NOTEWORTHY In this laboratory study, patients with peripheral artery disease performed plantar flexion exercise in the supine posture until symptoms of claudication occurred. Relative to age- and sex-matched healthy subjects we found that patients had a higher blood pressure response, a higher heart rate response, and a greater reduction in skeletal muscle oxygenation as determined by near-infrared spectroscopy. Our data suggest that muscle ischemia contributes to the augmented exercise pressor reflex in peripheral artery disease. Copyright © 2017 the American Physiological Society.

Ringfield lithographic camera

DOEpatents

Sweatt, W.C.

1998-09-08

A projection lithography camera is presented with a wide ringfield optimized so as to make efficient use of extreme ultraviolet radiation from a large area radiation source (e.g., D{sub source} {approx_equal} 0.5 mm). The camera comprises four aspheric mirrors optically arranged on a common axis of symmetry. The camera includes an aperture stop that is accessible through a plurality of partial aperture stops to synthesize the theoretical aperture stop. Radiation from a mask is focused to form a reduced image on a wafer, relative to the mask, by reflection from the four aspheric mirrors. 11 figs.

Measurements from preterm infants to guide face mask size.

PubMed

O'Shea, Joyce E; Thio, Marta; Owen, Louise S; Wong, Connie; Dawson, Jennifer A; Davis, Peter G

2016-07-01

International guidelines recommend that an appropriately sized face mask for providing positive pressure ventilation should cover the mouth and nose but not the eyes and should not overlap the chin. This study aimed to measure the dimensions of preterm infants' faces and compare these with the size of the most commonly available face masks (external diameter 50 mm) and the smallest masks available (external diameters 35 and 42 mm). Infants 24-33 weeks' postmenstrual age (PMA) were photographed in a standardised manner. Images were analysed using ImageJ software (National Institute of Health, USA) to calculate the distance from the nasofrontal groove to the mental protuberance. This facial measurement corresponds to the external diameter of an optimally fitting mask. A cohort of 107 infants between 24 and 33 weeks' gestational age, including at least 10 infants per week of gestation, was photographed within 72 h after birth and weekly until 33 weeks' PMA. 347 photographs were analysed. Infants of 24, 26, 28, 30 and 32 weeks' PMA had mean (SD) facial measurements of 32 (2), 36 (3), 38 (4), 41 (2) and 43 (4) mm, respectively. There were no significant differences when examined by gender or when small for gestational age infants were excluded. The smallest size of some brands of mask is too large for many preterm infants. Masks of 35 mm diameter are suitable for infants <29 weeks' PMA or 1000 g. Masks of 42 mm diameter are suitable for infants 27-33 weeks' PMA or 750-2500 g. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Development for 2D pattern quantification method on mask and wafer

NASA Astrophysics Data System (ADS)

Matsuoka, Ryoichi; Mito, Hiroaki; Toyoda, Yasutaka; Wang, Zhigang

2010-03-01

We have developed the effective method of mask and silicon 2-dimensional metrology. The aim of this method is evaluating the performance of the silicon corresponding to Hotspot on a mask. The method adopts a metrology management system based on DBM (Design Based Metrology). This is the high accurate contouring created by an edge detection algorithm used in mask CD-SEM and silicon CD-SEM. Currently, as semiconductor manufacture moves towards even smaller feature size, this necessitates more aggressive optical proximity correction (OPC) to drive the super-resolution technology (RET). In other words, there is a trade-off between highly precise RET and mask manufacture, and this has a big impact on the semiconductor market that centers on the mask business. 2-dimensional Shape quantification is important as optimal solution over these problems. Although 1-dimensional shape measurement has been performed by the conventional technique, 2-dimensional shape management is needed in the mass production line under the influence of RET. We developed the technique of analyzing distribution of shape edge performance as the shape management technique. On the other hand, there is roughness in the silicon shape made from a mass-production line. Moreover, there is variation in the silicon shape. For this reason, quantification of silicon shape is important, in order to estimate the performance of a pattern. In order to quantify, the same shape is equalized in two dimensions. And the method of evaluating based on the shape is popular. In this study, we conducted experiments for averaging method of the pattern (Measurement Based Contouring) as two-dimensional mask and silicon evaluation technique. That is, observation of the identical position of a mask and a silicon was considered. It is possible to analyze variability of the edge of the same position with high precision. The result proved its detection accuracy and reliability of variability on two-dimensional pattern (mask and silicon) and is adaptable to following fields of mask quality management. - Estimate of the correlativity of shape variability and a process margin. - Determination of two-dimensional variability of pattern. - Verification of the performance of the pattern of various kinds of Hotspots. In this report, we introduce the experimental results and the application. We expect that the mask measurement and the shape control on mask production will make a huge contribution to mask yield-enhancement and that the DFM solution for mask quality control process will become much more important technology than ever. It is very important to observe the shape of the same location of Design, Mask, and Silicon in such a viewpoint.

Prognostic value of hedgehog signaling pathway in digestive system cancers: A systematic review and meta-analysis.

PubMed

Wang, Yihan; Peng, Qian; Jia, Hongyuan; Du, Xiao

2016-01-01

The Hedgehog (Hh) signaling pathway has recently been reported to be associated with the prognosis of digestive system cancers. However, the results are inconsistent. This study aimed to investigate the association between Hh pathway components and survival outcomes in patients with digestive system cancers. We conducted a comprehensive retrieval in PubMed, EMBASE and Cochrane library for relevant literatures until May 1st, 2015. The pooled hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS) with 95% confidence intervals (CIs) were calculated to clarify the prognostic value of Hh pathway components, including Shh, Gli1, Gli2, Smo and Ptch1. A total of 16 eligible articles with 3222 patients were included in the meta-analysis. Pooled HR suggested that over-expression of Shh and Gli1 were both associated with poor OS (HR = 1.87, 95% CI: 1.14-3.07 and HR = 1.96, 95% CI: 1.66-2.32, respectively) and DFS (HR = 2.37, 95% CI: 1.19-4.72 and HR = 2.18, 95% CI: 1.61-2.96, respectively). In addition, over-expression of Smo was associated with poor DFS (HR = 1.38, 95% CI: 1.08-1.75). This study reveals that over-expressed Hh pathway components, including Shh, Gli1 and Smo, are associated with poor prognosis in digestive system cancer patients. Hh signaling pathway may become a potential therapeutic target in digestive system cancers.

Application of advanced structure to multi-tone mask for FPD process

NASA Astrophysics Data System (ADS)

Song, Jin-Han; Jeong, Jin-Woong; Kim, Kyu-Sik; Jeong, Woo-Gun; Yun, Sang-Pil; Lee, Dong-Heok; Choi, Sang-Soo

2017-07-01

In accordance with improvement of FPD technology, masks such as phase shift mask (PSM) and multi-tone mask (MTM) for a particular purpose also have been developed. Above all, the MTM consisted of more than tri-tone transmittance has a substantial advantage which enables to reduce the number of mask demand in FPD fabrication process contrast to normal mask of two-tone transmittance.[1,2] A chromium (Cr)-based MTM (Typically top type) is being widely employed because of convenience of etch process caused by its only Cr-based structure consisted of Cr absorber layer and Cr half-tone layer. However, the top type of Cr-based MTM demands two Cr sputtering processes after each layer etching process and writing process. For this reason, a different material from the Cr-based MTM is required for reduction of mask fabrication time and cost. In this study, we evaluate a MTM which has a structure combined Cr with molybdenum silicide (MoSi) to resolve the issues mentioned above. The MoSi which is demonstrated by integrated circuit (IC) process is a suitable material for MTM evaluation. This structure could realize multi-transmittance in common with the Cr-based MTM. Moreover, it enables to reduce the number of sputtering process. We investigate a optimized structure upon consideration of productivity along with performance such as critical dimension (CD) variation and transmittance range of each structure. The transmittance is targeted at h-line wavelength (405 nm) in the evaluation. Compared with Cr-based MTM, the performances of all Cr-/MoSi-based MTMs are considered.

Design of wavefront coding optical system with annular aperture

NASA Astrophysics Data System (ADS)

Chen, Xinhua; Zhou, Jiankang; Shen, Weimin

2016-10-01

Wavefront coding can extend the depth of field of traditional optical system by inserting a phase mask into the pupil plane. In this paper, the point spread function (PSF) of wavefront coding system with annular aperture are analyzed. Stationary phase method and fast Fourier transform (FFT) method are used to compute the diffraction integral respectively. The OTF invariance is analyzed for the annular aperture with cubic phase mask under different obscuration ratio. With these analysis results, a wavefront coding system using Maksutov-Cassegrain configuration is designed finally. It is an F/8.21 catadioptric system with annular aperture, and its focal length is 821mm. The strength of the cubic phase mask is optimized with user-defined operand in Zemax. The Wiener filtering algorithm is used to restore the images and the numerical simulation proves the validity of the design.

SU-E-T-65: A Prospective Trial of Open Face Masks for Head and Neck Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiant, D; Squire, S; Maurer, J

Purpose: Open face head and neck masks allow for active patient monitoring during treatment and may reduced claustrophobia and anxiety compared to closed masks. The ability of open masks to limit intrafraction motion and to preserve the patient shape/position from simulation over protracted treatments should be considered. Methods: Thirty-two head and neck patients were prospectively randomized to treatment in a closed mask or a novel open face mask. All patients received daily volumetric imaging. The daily images were automatically rigidly registered to the planning CT’s offline using a commercial image processing tool. The shifts needed to optimize the registration, themore » mutual information coefficient (MI), and the Pearson correlation (PC) coefficients were recorded to evaluate shape preservation. The open group was set-up and monitored with surface imaging at treatment. The real time surface imaging information was recorded to evaluate intrafraction motion. Results: Sixteen patients were included in each group. Evaluations were made over a total of 984 fractions. The mean MI and PC showed significantly higher shape preservation for the open group than for the closed group (p = 0). The mean rotations for the open group were smaller or < 0.15° larger versus the closed group. The mean intrafraction motion for the open group was 0.93 +/−0.99 mm (2 SD). The maximum single fraction displacement was 3.2 mm. Fourteen of 16 patients showed no significant correlation of motion with fraction number (p > 0.05). Conclusion: The open masks preserved shape as well as the closed masks, and they limited motion to < 2 mm for 95% of the treated fractions. These results are consistent over treatment courses of up to 35 fractions. The open mask is suitable for treatment with or without active monitoring. This work was partially supported by Qfix.« less

Precision process calibration and CD predictions for low-k1 lithography

NASA Astrophysics Data System (ADS)

Chen, Ting; Park, Sangbong; Berger, Gabriel; Coskun, Tamer H.; de Vocht, Joep; Chen, Fung; Yu, Linda; Hsu, Stephen; van den Broeke, Doug; Socha, Robert; Park, Jungchul; Gronlund, Keith; Davis, Todd; Plachecki, Vince; Harris, Tom; Hansen, Steve; Lambson, Chuck

2005-06-01

Leading resist calibration for sub-0.3 k1 lithography demands accuracy <2nm for CD through pitch. An accurately calibrated resist process is the prerequisite for establishing production-worthy manufacturing under extreme low k1. From an integrated imaging point of view, the following key components must be simultaneously considered during the calibration - high numerical aperture (NA>0.8) imaging characteristics, customized illuminations (measured vs. modeled pupil profiles), resolution enhancement technology (RET) mask with OPC, reticle metrology, and resist thin film substrate. For imaging at NA approaching unity, polarized illumination can impact significantly the contrast formation in the resist film stack, and therefore it is an important factor to consider in the CD-based resist calibration. For aggressive DRAM memory core designs at k1<0.3, pattern-specific illumination optimization has proven to be critical for achieving the required imaging performance. Various optimization techniques from source profile optimization with fixed mask design to the combined source and mask optimization have been considered for customer designs and available imaging capabilities. For successful low-k1 process development, verification of the optimization results can only be made with a sufficiently tunable resist model that can predicate the wafer printing accurately under various optimized process settings. We have developed, for resist patterning under aggressive low-k1 conditions, a novel 3D diffusion model equipped with double-Gaussian convolution in each dimension. Resist calibration with the new diffusion model has demonstrated a fitness and CD predication accuracy that rival or outperform the traditional 3D physical resist models. In this work, we describe our empirical approach to achieving the nm-scale precision for advanced lithography process calibrations, using either measured 1D CD through-pitch or 2D memory core patterns. We show that for ArF imaging, the current resist development and diffusion modeling can readily achieve ~1-2nm max CD errors for common 1D through-pitch and aggressive 2D memory core resist patterns. Sensitivities of the calibrated models to various process parameters are analyzed, including the comparison between the measured and modeled (Gaussian or GRAIL) pupil profiles. We also report our preliminary calibration results under selected polarized illumination conditions.

Utilization of optical emission endpoint in photomask dry etch processing

NASA Astrophysics Data System (ADS)

Faure, Thomas B.; Huynh, Cuc; Lercel, Michael J.; Smith, Adam; Wagner, Thomas

2002-03-01

Use of accurate and repeatable endpoint detection during dry etch processing of photomask is very important for obtaining good mask mean-to-target and CD uniformity performance. It was found that the typical laser reflectivity endpoint detecting system used on photomask dry etch systems had several key limitations that caused unnecessary scrap and non-optimum image size performance. Consequently, work to develop and implement use of a more robust optical emission endpoint detection system for chrome dry etch processing of photomask was performed. Initial feasibility studies showed that the emission technique was sensitive enough to monitor pattern loadings on contact and via level masks down to 3 percent pattern coverage. Additional work was performed to further improve this to 1 percent pattern coverage by optimizing the endpoint detection parameters. Comparison studies of mask mean-to-target performance and CD uniformity were performed with the use of optical emission endpoint versus laser endpoint for masks built using TOK IP3600 and ZEP 7000 resist systems. It was found that an improvement in mean-to-target performance and CD uniformity was realized on several types of production masks. In addition, part-to-part endpoint time repeatability was found to be significantly improved with the use of optical emission endpoint.

Masking release for words in amplitude-modulated noise as a function of modulation rate and task

PubMed Central

Buss, Emily; Whittle, Lisa N.; Grose, John H.; Hall, Joseph W.

2009-01-01

For normal-hearing listeners, masked speech recognition can improve with the introduction of masker amplitude modulation. The present experiments tested the hypothesis that this masking release is due in part to an interaction between the temporal distribution of cues necessary to perform the task and the probability of those cues temporally coinciding with masker modulation minima. Stimuli were monosyllabic words masked by speech-shaped noise, and masker modulation was introduced via multiplication with a raised sinusoid of 2.5–40 Hz. Tasks included detection, three-alternative forced-choice identification, and open-set identification. Overall, there was more masking release associated with the closed than the open-set tasks. The best rate of modulation also differed as a function of task; whereas low modulation rates were associated with best performance for the detection and three-alternative identification tasks, performance improved with modulation rate in the open-set task. This task-by-rate interaction was also observed when amplitude-modulated speech was presented in a steady masker, and for low- and high-pass filtered speech presented in modulated noise. These results were interpreted as showing that the optimal rate of amplitude modulation depends on the temporal distribution of speech cues and the information required to perform a particular task. PMID:19603883

Modeling of intense pulsed ion beam heated masked targets for extreme materials characterization

DOE PAGES

Barnard, John J.; Schenkel, Thomas

2017-11-15

Intense, pulsed ion beams locally heat materials and deliver dense electronic excitations that can induce material modifications and phase transitions. Material properties can potentially be stabilized by rapid quenching. Pulsed ion beams with pulse lengths of order ns have recently become available for materials processing. Here, we optimize mask geometries for local modification of materials by intense ion pulses. The goal is to rapidly excite targets volumetrically to the point where a phase transition or local lattice reconstruction is induced followed by rapid cooling that stabilizes desired material's properties fast enough before the target is altered or damaged by, e.g.,more » hydrodynamic expansion. By using a mask, the longitudinal dimension can be large compared to the transverse dimension, allowing the possibility of rapid transverse cooling. We performed HYDRA simulations that calculate peak temperatures for a series of excitation conditions and cooling rates of silicon targets with micro-structured masks and compare these to a simple analytical model. In conclusion, the model gives scaling laws that can guide the design of targets over a wide range of pulsed ion beam parameters.« less

Modeling of intense pulsed ion beam heated masked targets for extreme materials characterization

NASA Astrophysics Data System (ADS)

Barnard, John J.; Schenkel, Thomas

2017-11-01

Intense, pulsed ion beams locally heat materials and deliver dense electronic excitations that can induce material modifications and phase transitions. Material properties can potentially be stabilized by rapid quenching. Pulsed ion beams with pulse lengths of order ns have recently become available for materials processing. Here, we optimize mask geometries for local modification of materials by intense ion pulses. The goal is to rapidly excite targets volumetrically to the point where a phase transition or local lattice reconstruction is induced followed by rapid cooling that stabilizes desired material's properties fast enough before the target is altered or damaged by, e.g., hydrodynamic expansion. By using a mask, the longitudinal dimension can be large compared to the transverse dimension, allowing the possibility of rapid transverse cooling. We performed HYDRA simulations that calculate peak temperatures for a series of excitation conditions and cooling rates of silicon targets with micro-structured masks and compare these to a simple analytical model. The model gives scaling laws that can guide the design of targets over a wide range of pulsed ion beam parameters.

Ringfield lithographic camera

DOEpatents

Sweatt, William C.

1998-01-01

A projection lithography camera is presented with a wide ringfield optimized so as to make efficient use of extreme ultraviolet radiation from a large area radiation source (e.g., D.sub.source .apprxeq.0.5 mm). The camera comprises four aspheric mirrors optically arranged on a common axis of symmetry with an increased etendue for the camera system. The camera includes an aperture stop that is accessible through a plurality of partial aperture stops to synthesize the theoretical aperture stop. Radiation from a mask is focused to form a reduced image on a wafer, relative to the mask, by reflection from the four aspheric mirrors.

Printability Optimization For Fine Pitch Solder Bonding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kwon, Sang-Hyun; Lee, Chang-Woo; Yoo, Sehoon

2011-01-17

Effect of metal mask and pad design on solder printability was evaluated by DOE in this study. The process parameters were stencil thickness, squeegee angle, squeegee speed, mask separating speed, and pad angle of PCB. The main process parameters for printability were stencil thickness and squeegee angle. The response surface showed that maximum printability of 1005 chip was achieved at the stencil thickness of 0.12 mm while the maximum printability of 0603 and 0402 chip was obtained at the stencil thickness of 0.05 mm. The bonding strength of the MLCC chips was also directly related with the printability.

Improvement in defect classification efficiency by grouping disposition for reticle inspection

NASA Astrophysics Data System (ADS)

Lai, Rick; Hsu, Luke T. H.; Chang, Peter; Ho, C. H.; Tsai, Frankie; Long, Garrett; Yu, Paul; Miller, John; Hsu, Vincent; Chen, Ellison

2005-11-01

As the lithography design rule of IC manufacturing continues to migrate toward more advanced technology nodes, the mask error enhancement factor (MEEF) increases and necessitates the use of aggressive OPC features. These aggressive OPC features pose challenges to reticle inspection due to high false detection, which is time-consuming for defect classification and impacts the throughput of mask manufacturing. Moreover, higher MEEF leads to stricter mask defect capture criteria so that new generation reticle inspection tool is equipped with better detection capability. Hence, mask process induced defects, which were once undetectable, are now detected and results in the increase of total defect count. Therefore, how to review and characterize reticle defects efficiently is becoming more significant. A new defect review system called ReviewSmart has been developed based on the concept of defect grouping disposition. The review system intelligently bins repeating or similar defects into defect groups and thus allows operators to review massive defects more efficiently. Compared to the conventional defect review method, ReviewSmart not only reduces defect classification time and human judgment error, but also eliminates desensitization that is formerly inevitable. In this study, we attempt to explore the most efficient use of ReviewSmart by evaluating various defect binning conditions. The optimal binning conditions are obtained and have been verified for fidelity qualification through inspection reports (IRs) of production masks. The experiment results help to achieve the best defect classification efficiency when using ReviewSmart in the mask manufacturing and development.

The SomnuSeal Oral Mask Is Reasonably Tolerated by Otherwise CPAP Noncompliant Patients with OSA

PubMed Central

Katz, N.; Adir, Y.; Etzioni, T.; Kurtz, E.; Pillar, G.

2013-01-01

Compliance with CPAP is the major limiting factor in treating patients with OSA. The novel SomnuSeal mask is an oral self-adaptable mask located between the teeth and the lips ensuring that there are no air leaks or skin abrasions. Fifty patients with AHI > 20, who failed previous CPAP trials, were asked to sleep with the mask for one month. In all patients, the mask was connected to an AutoPAP machine with a heated humidifier. Efficacy, convenience, and compliance (average usage for 4 or more hours per night) were monitored. Fifty patients (41 m and 9 f, mean age 57 ± 12 years, BMI 33.6 ± 4.9 kg/m2, and AHI 47 ± 23/h) participated. Eleven were classified as compliant (average mask usage of 26 nights, 4.7 hours per night), five were only partially compliant (average usage of 13 nights, 2.9 hours per night), and 34 could not comply with it. In all patients who slept with it, the efficacy (assessed by residual AHI derived from the CPAP device) was good with an AHI of less than 8/hour. Interestingly, the required optimal pressure decreased from an average of 9.3 cmH2O to 4.6 cmH2O. The SomnuSeal oral interface is effective and may result in converting noncompliant untreated patients with OSA into well-treated ones. PMID:24228181

Mobile geographic information system solution for pavement condition surveys [summary].

DOT National Transportation Integrated Search

2012-01-01

The State Materials Office (SMO) of the Florida : Department of Transportation (FDOT) performs : annual Pavement Condition Surveys (PCS) of : the Departments extensive pavement network. : This work is performed by single-person crews in : inertial...

Semiconducting Metal Oxide Based Sensors for Selective Gas Pollutant Detection

PubMed Central

Kanan, Sofian M.; El-Kadri, Oussama M.; Abu-Yousef, Imad A.; Kanan, Marsha C.

2009-01-01

A review of some papers published in the last fifty years that focus on the semiconducting metal oxide (SMO) based sensors for the selective and sensitive detection of various environmental pollutants is presented. PMID:22408500

New strain states and radical property tuning of metal oxides using a nanocomposite thin film approach

DOE PAGES

MacManus-Driscoll, Judith; Suwardi, Ady; Kursumovic, Ahmed; ...

2015-05-05

Auxetic-like strain states were generated in self-assembled nanocomposite thin films of (Ba 0.6Sr 0.4TiO 3) 1–x – (Sm 2O 3) x(BSTO – SmO). A switch from auxetic-like to elastic-like strain behavior was observed for x > 0.50, when the SmO switched from being nanopillars in the BSTO matrix to being the matrix with BSTO nanopillars embedded in it. A simple model was adopted to explain how in-plane strain varies with x. At high x (0.75), strongly enhanced ferroelectric properties were obtained compared to pure BSTO films. Furthermore, the nanocomposite method represents a powerful new way to tune the properties ofmore » a wide range of strongly correlated metal oxides whose properties are very sensitive to strain.« less

Janus Monolayer Transition-Metal Dichalcogenides.

PubMed

Zhang, Jing; Jia, Shuai; Kholmanov, Iskandar; Dong, Liang; Er, Dequan; Chen, Weibing; Guo, Hua; Jin, Zehua; Shenoy, Vivek B; Shi, Li; Lou, Jun

2017-08-22

The crystal configuration of sandwiched S-Mo-Se structure (Janus SMoSe) at the monolayer limit has been synthesized and carefully characterized in this work. By controlled sulfurization of monolayer MoSe 2 , the top layer of selenium atoms is substituted by sulfur atoms, while the bottom selenium layer remains intact. The structure of this material is systematically investigated by Raman, photoluminescence, transmission electron microscopy, and X-ray photoelectron spectroscopy and confirmed by time-of-flight secondary ion mass spectrometry. Density functional theory (DFT) calculations are performed to better understand the Raman vibration modes and electronic structures of the Janus SMoSe monolayer, which are found to correlate well with corresponding experimental results. Finally, high basal plane hydrogen evolution reaction activity is discovered for the Janus monolayer, and DFT calculation implies that the activity originates from the synergistic effect of the intrinsic defects and structural strain inherent in the Janus structure.

Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand

NASA Astrophysics Data System (ADS)

Zhang, Xianjun; Zhao, Fei; Wu, Yiran; Yang, Jun; Han, Gye Won; Zhao, Suwen; Ishchenko, Andrii; Ye, Lintao; Lin, Xi; Ding, Kang; Dharmarajan, Venkatasubramanian; Griffin, Patrick R.; Gati, Cornelius; Nelson, Garrett; Hunter, Mark S.; Hanson, Michael A.; Cherezov, Vadim; Stevens, Raymond C.; Tan, Wenfu; Tao, Houchao; Xu, Fei

2017-05-01

The Smoothened receptor (SMO) belongs to the Class Frizzled of the G protein-coupled receptor (GPCR) superfamily, constituting a key component of the Hedgehog signalling pathway. Here we report the crystal structure of the multi-domain human SMO, bound and stabilized by a designed tool ligand TC114, using an X-ray free-electron laser source at 2.9 Å. The structure reveals a precise arrangement of three distinct domains: a seven-transmembrane helices domain (TMD), a hinge domain (HD) and an intact extracellular cysteine-rich domain (CRD). This architecture enables allosteric interactions between the domains that are important for ligand recognition and receptor activation. By combining the structural data, molecular dynamics simulation, and hydrogen-deuterium-exchange analysis, we demonstrate that transmembrane helix VI, extracellular loop 3 and the HD play a central role in transmitting the signal employing a unique GPCR activation mechanism, distinct from other multi-domain GPCRs.

Janus Monolayer Transition-Metal Dichalcogenides

DOE PAGES

Zhang, Jing; Jia, Shuai; Kholmanov, Iskandar; ...

2017-08-03

In this work, the crystal configuration of sandwiched S–Mo–Se structure (Janus SMoSe) at the monolayer limit has been synthesized and carefully characterized. By controlled sulfurization of monolayer MoSe 2, the top layer of selenium atoms is substituted by sulfur atoms, while the bottom selenium layer remains intact. Furthermore, the structure of this material is systematically investigated by Raman, photoluminescence, transmission electron microscopy, and X-ray photoelectron spectroscopy and confirmed by time-of-flight secondary ion mass spectrometry. Density functional theory (DFT) calculations are performed to better understand the Raman vibration modes and electronic structures of the Janus SMoSe monolayer, which are found tomore » correlate well with corresponding experimental results. Finally, high basal plane hydrogen evolution reaction activity is discovered for the Janus monolayer, and DFT calculation implies that the activity originates from the synergistic effect of the intrinsic defects and structural strain inherent in the Janus structure.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xianjun; Zhao, Fei; Wu, Yiran

Here, the Smoothened receptor (SMO) belongs to the Class Frizzled of the G protein-coupled receptor (GPCR) superfamily, constituting a key component of the Hedgehog signalling pathway. Here we report the crystal structure of the multi-domain human SMO, bound and stabilized by a designed tool ligand TC114, using an X-ray free-electron laser source at 2.9 Å. The structure reveals a precise arrangement of three distinct domains: a seven-transmembrane helices domain (TMD), a hinge domain (HD) and an intact extracellular cysteine-rich domain (CRD). This architecture enables allosteric interactions between the domains that are important for ligand recognition and receptor activation. By combiningmore » the structural data, molecular dynamics simulation, and hydrogen-deuterium-exchange analysis, we demonstrate that transmembrane helix VI, extracellular loop 3 and the HD play a central role in transmitting the signal employing a unique GPCR activation mechanism, distinct from other multi-domain GPCRs.« less

Single image super-resolution using self-optimizing mask via fractional-order gradient interpolation and reconstruction.

PubMed

Yang, Qi; Zhang, Yanzhu; Zhao, Tiebiao; Chen, YangQuan

2017-04-04

Image super-resolution using self-optimizing mask via fractional-order gradient interpolation and reconstruction aims to recover detailed information from low-resolution images and reconstruct them into high-resolution images. Due to the limited amount of data and information retrieved from low-resolution images, it is difficult to restore clear, artifact-free images, while still preserving enough structure of the image such as the texture. This paper presents a new single image super-resolution method which is based on adaptive fractional-order gradient interpolation and reconstruction. The interpolated image gradient via optimal fractional-order gradient is first constructed according to the image similarity and afterwards the minimum energy function is employed to reconstruct the final high-resolution image. Fractional-order gradient based interpolation methods provide an additional degree of freedom which helps optimize the implementation quality due to the fact that an extra free parameter α-order is being used. The proposed method is able to produce a rich texture detail while still being able to maintain structural similarity even under large zoom conditions. Experimental results show that the proposed method performs better than current single image super-resolution techniques. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

Designing to win in sub-90nm mask production

NASA Astrophysics Data System (ADS)

Zhang, Yuan

2005-11-01

An informal survey conducted with key customers by Photronics indicates that the time gap between technology nodes has accelerated in recent years. Previously the cycle was three years. However, between 130nm and 90nm there was less than a 2 year gap, and between 90nm and 65nm a 1.5 year gap exists. As a result, the technical challenges have increased substantially. In addition, mask costs are rising exponentially due to high capital equipment cost, a shrinking customer base, long write times and increased applications of 193nm EAPSM or AAPSM. Collaboration among EDA companies, mask houses and wafer manufacturers is now more important than ever. This paper will explore avenues for reducing mask costs, mainly in the areas of: write-time reduction through design for manufacturing (DFM), and yield improvement through specification relaxation. Our study conducted through layout vertex modeling suggests that a simple design shape such as a square versus a circle or an angled structure helps reduce shot count and write time. Shot count reduction through mask layout optimization, and advancement in new generation E-beam writers can reduce write time up to 65%. An advanced laser writer can produce those less critical E-beam layers in less than half the time of an e-beam writer. Additionally, the emerging imprint lithography brings new life and new challenges to the photomask industry with applications in many fields outside of the semiconductor industry. As immersion lithography is introduced for 45nm device production, polarization and MEEF effects due to the mask will become severe. Larger magnification not only provides benefits on CD control and MEEF, but also extends the life time of current 90nm/65nm tool sets where 45nm mask sets can be produced at a lower cost.

An in-vitro-in-vivo taste assessment of bitter drug: comparative electronic tongues study.

PubMed

Maniruzzaman, Mohammed; Douroumis, Dennis

2015-01-01

The efficiency of the Astree e-tongue and Taste Sensing system TS5000Z for the evaluation of the taste masking effect of hot melt extruded formulations was investigated in this study. Hot melt extrusion (HME) processing was optimized using Randcastle single screw extruder (USA) to manufacture extrudates with desirable characteristics. Cationic model drug propranolol HCl (PRP) was processed with the anionic polymers - Eudragit L100 (L100) and Eudragit L100-55 (Acryl-EZE). Solid state of the drug in polymer matrices was evaluated by scanning electron microscopy (SEM), differential scanning calorimetry, particle size analysis, Fourier transform infrared (FTIR) and Nuclear magnetic resonance (NMR) analysis. In-vitro taste masking efficiency of the two polymers was performed by using two different e-tongues (Astree e-tongue and TS5000Z). The results obtained from both e-tongues were further compared and contrast to find out the sensor outputs in all formulations. Solid state analysis of the extruded formulations revealed the presence of amorphous PRP. Both e-tongues were able to detect the taste masking variations of the extrudates and were in good agreement with the in-vivo results obtained from a panel of six healthy human volunteers (R(2)  > 0.84). However, each e-tongue sensor demonstrated different sensitivity, suggesting a careful consideration of the experimental findings during melt extrusion, is necessary for the development of taste-masked formulations. Furthermore, FTIR spectroscopy and NMR studies revealed possible drug polymer intermolecular interactions as the mechanism of successful taste masking. HME can effectively be used to manufacture taste-masked extruded formulations, while both e-tongues demonstrated satisfactory taste analysis for the development of taste-masked formulations. © 2014 Royal Pharmaceutical Society.

Poisson-Spot Intensity Reduction with a Partially-Transparent Petal-Shaped Optical Mask

NASA Technical Reports Server (NTRS)

Shiri, Shahram; Wasylkiwskyj, Wasyl

2013-01-01

The presence of Poisson's spot, also known as the spot of Arago, formed along the optical axis in the geometrical shadow behind an obstruction, has been known since the 18th century. The presence of this spot can best be described as the consequence of constructive interference of light waves diffracted on the edge of the obstruction where its central position can··be determined by the symmetry of the object More recently, the elimination of this spot has received attention in the fields of particle physics, high-energy lasers, astronomy and lithography. In this paper, we introduce a novel, partially transparent petaled mask shape that suppresses the bright spot by up to 10 orders of magnitude in intensity, with powerful applications to many of the above fields. The optimization technique formulated in this design can identify mask shapes having partial transparency only near the petal tips.

Micropellets coated with Kollicoat® Smartseal 30D for taste masking in liquid oral dosage forms.

PubMed

Dashevskiy, Andriy; Mohylyuk, Valentyn; Ahmed, Abid Riaz; Kolter, Karl; Guth, Felicitas; Bodmeier, Roland

2017-09-01

The objective of this study was to develop delivery systems for taste masking based on multiparticulates coated with Kollicoat ® Smartseal 30D formulated as liquid oral suspensions. Coating of particles containing bitter drugs with Kollicoat ® Smartseal reduced drug leaching into aqueous medium, especially when increasing pH, therefore can be used for the formulation of liquid dosage forms. Application of an intermediate layer of ion exchange resins between drug layer and coating can further decrease drug leaching into aqueous vehicle that is beneficial in terms of taste masking. Using optimized compositions of liquid vehicles such as addition of sugar alcohols and ion exchange resin, reconstitutable or ready-to-use liquid dosage forms with micropellets can be developed with bitter taste protection after redispersion lasting longer than 3 weeks, which exceeds the usual period of application.

A combined spectroscopic and plasma chemical kinetic analysis of ionospheric samarium releases

NASA Astrophysics Data System (ADS)

Holmes, Jeffrey M.; Dressler, Rainer A.; Pedersen, Todd R.; Caton, Ronald G.; Miller, Daniel

2017-05-01

Two rocket-borne releases of samarium vapor in the upper atmosphere occurred in May 2013, as part of the Metal Oxide Space Clouds experiment. The releases were characterized by a combination of optical and RF diagnostic instruments located at the Roi-Namur launch site and surrounding islands and atolls. The evolution of the optical spectrum of the solar-illuminated cloud was recorded with a spectrograph covering a 400-800 nm spectral range. The spectra exhibit two distinct spectral regions centered at 496 and 636 nm within which the relative intensities change insignificantly. The ratio between the integrated intensities within these regions, however, changes with time, suggesting that they are associated with different species. With the help of an equilibrium plasma spectral model we attribute the region centered at 496 nm to neutral samarium atoms (Sm I radiance) and features peaking at 649 nm to a molecular species. No evidence for structure due to Sm+ (Sm II) is identified. The persistence of the Sm I radiance suggests a high dissociative recombination rate for the chemi-ionization product, SmO+. A one-dimensional plasma chemical kinetic model of the evolution of the density ratio NSmO/NSm(t) demonstrates that the molecular feature peaking at 649 nm can be attributed to SmO radiance. SmO+ radiance is not identified. By adjusting the Sm vapor mass of the chemical kinetic model input to match the evolution of the total electron density determined by ionosonde data, we conclude that less than 5% of the payload samarium was vaporized.

Conditional loss of hepatocellular Hedgehog signaling in female mice leads to the persistence of hepatic steroidogenesis, androgenization and infertility.

PubMed

Rennert, Christiane; Eplinius, Franziska; Hofmann, Ute; Johänning, Janina; Rolfs, Franziska; Schmidt-Heck, Wolfgang; Guthke, Reinhardt; Gebhardt, Rolf; Ricken, Albert M; Matz-Soja, Madlen

2017-11-01

The Hedgehog signaling pathway is known to be involved in embryogenesis, tissue remodeling, and carcinogenesis. Because of its involvement in carcinogenesis, it seems an interesting target for cancer therapy. Indeed, Sonidegib, an approved inhibitor of the Hedgehog receptor Smoothened (Smo), is highly active against diverse carcinomas, but its use is also reported to be associated with several systemic side effects. Our former work in adult mice demonstrated hepatic Hedgehog signaling to play a key role in the insulin-like growth factor axis and lipid metabolism. The current work using mice with an embryonic and hepatocyte-specific Smo deletion describes an adverse impact of the hepatic Hedgehog pathway on female fertility. In female SAC-KO mice, we detected androgenization characterized by a 3.3-fold increase in testosterone at 12 weeks of age based on an impressive induction of steroidogenic gene expression in hepatocytes, but not in the classic steroidogenic organs (ovary and adrenal gland). Along with the elevated level of testosterone, the female SAC-KO mice showed infertility characterized by juvenile reproductive organs and acyclicity. The endocrine and reproductive alterations resembled polycystic ovarian syndrome and could be confirmed in a second mouse model with conditional deletion of Smo at 8 weeks of age after an extended period of 8 months. We conclude that the down-regulation of hepatic Hedgehog signaling leads to an impaired hormonal balance by the induction of steroidogenesis in the liver. These effects of Hedgehog signaling inhibition should be considered when using Hedgehog inhibitors as anti-cancer drugs.

Enabling laboratory EUV research with a compact exposure tool

NASA Astrophysics Data System (ADS)

Brose, Sascha; Danylyuk, Serhiy; Tempeler, Jenny; Kim, Hyun-su; Loosen, Peter; Juschkin, Larissa

2016-03-01

In this work we present the capabilities of the designed and realized extreme ultraviolet laboratory exposure tool (EUVLET) which has been developed at the RWTH-Aachen, Chair for the Technology of Optical Systems (TOS), in cooperation with the Fraunhofer Institute for Laser Technology (ILT) and Bruker ASC GmbH. Main purpose of this laboratory setup is the direct application in research facilities and companies with small batch production, where the fabrication of high resolution periodic arrays over large areas is required. The setup can also be utilized for resist characterization and evaluation of its pre- and post-exposure processing. The tool utilizes a partially coherent discharge produced plasma (DPP) source and minimizes the number of other critical components to a transmission grating, the photoresist coated wafer and the positioning system for wafer and grating and utilizes the Talbot lithography approach. To identify the limits of this approach first each component is analyzed and optimized separately and relations between these components are identified. The EUV source has been optimized to achieve the best values for spatial and temporal coherence. Phase-shifting and amplitude transmission gratings have been fabricated and exposed. Several commercially available electron beam resists and one EUV resist have been characterized by open frame exposures to determine their contrast under EUV radiation. Cold development procedure has been performed to further increase the resist contrast. By analyzing the exposure results it can be demonstrated that only a 1:1 copy of the mask structure can be fully resolved by the utilization of amplitude masks. The utilized phase-shift masks offer higher 1st order diffraction efficiency and allow a demagnification of the mask structure in the achromatic Talbot plane.

Coastal hazards in a changing world: projecting and communicating future coastal flood risk at the local-scale using the Coastal Storm Modeling System (CoSMoS)

NASA Astrophysics Data System (ADS)

O'Neill, Andrea; Barnard, Patrick; Erikson, Li; Foxgrover, Amy; Limber, Patrick; Vitousek, Sean; Fitzgibbon, Michael; Wood, Nathan

2017-04-01

The risk of coastal flooding will increase for many low-lying coastal regions as predominant contributions to flooding, including sea level, storm surge, wave setup, and storm-related fluvial discharge, are altered with climate change. Community leaders and local governments therefore look to science to provide insight into how climate change may affect their areas. Many studies of future coastal flooding vulnerability consider sea level and tides, but ignore other important factors that elevate flood levels during storm events, such as waves, surge, and discharge. Here we present a modelling approach that considers a broad range of relevant processes contributing to elevated storm water levels for open coast and embayment settings along the U.S. West Coast. Additionally, we present online tools for communicating community-relevant projected vulnerabilities. The Coastal Storm Modeling System (CoSMoS) is a numerical modeling system developed to predict coastal flooding due to both sea-level rise (SLR) and plausible 21st century storms for active-margin settings like the U.S. West Coast. CoSMoS applies a predominantly deterministic framework of multi-scale models encompassing large geographic scales (100s to 1000s of kilometers) to small-scale features (10s to 1000s of meters), resulting in flood extents that can be projected at a local resolution (2 meters). In the latest iteration of CoSMoS applied to Southern California, U.S., efforts were made to incorporate water level fluctuations in response to regional storm impacts, locally wind-generated waves, coastal river discharge, and decadal-scale shoreline and cliff changes. Coastal hazard projections are available in a user-friendly web-based tool (www.prbo.org/ocof), where users can view variations in flood extent, maximum flood depth, current speeds, and wave heights in response to a range of potential SLR and storm combinations, providing direct support to adaptation and management decisions. In order to capture the societal aspect of the hazard, projections are combined with socioeconomic exposure to produce clear, actionable information (https://www.usgs.gov/apps/hera/); this integrated approach to hazard displays provides an example of how to effectively translate complex climate impacts projections into simple, societally-relevant information.

To repair or not to repair: with FAVOR there is no question

NASA Astrophysics Data System (ADS)

Garetto, Anthony; Schulz, Kristian; Tabbone, Gilles; Himmelhaus, Michael; Scheruebl, Thomas

2016-10-01

In the mask shop the challenges associated with today's advanced technology nodes, both technical and economic, are becoming increasingly difficult. The constant drive to continue shrinking features means more masks per device, smaller manufacturing tolerances and more complexity along the manufacturing line with respect to the number of manufacturing steps required. Furthermore, the extremely competitive nature of the industry makes it critical for mask shops to optimize asset utilization and processes in order to maximize their competitive advantage and, in the end, profitability. Full maximization of profitability in such a complex and technologically sophisticated environment simply cannot be achieved without the use of smart automation. Smart automation allows productivity to be maximized through better asset utilization and process optimization. Reliability is improved through the minimization of manual interactions leading to fewer human error contributions and a more efficient manufacturing line. In addition to these improvements in productivity and reliability, extra value can be added through the collection and cross-verification of data from multiple sources which provides more information about our products and processes. When it comes to handling mask defects, for instance, the process consists largely of time consuming manual interactions that are error prone and often require quick decisions from operators and engineers who are under pressure. The handling of defects itself is a multiple step process consisting of several iterations of inspection, disposition, repair, review and cleaning steps. Smaller manufacturing tolerances and features with higher complexity contribute to a higher number of defects which must be handled as well as a higher level of complexity. In this paper the recent efforts undertaken by ZEISS to provide solutions which address these challenges, particularly those associated with defectivity, will be presented. From automation of aerial image analysis to the use of data driven decision making to predict and propose the optimized back end of line process flow, productivity and reliability improvements are targeted by smart automation. Additionally the generation of the ideal aerial image from the design and several repair enhancement features offer additional capabilities to improve the efficiency and yield associated with defect handling.

Microstructural investigation using synchrotron radiation X-ray microtomography reveals taste-masking mechanism of acetaminophen microspheres.

PubMed

Guo, Zhen; Yin, Xianzhen; Liu, Congbiao; Wu, Li; Zhu, Weifeng; Shao, Qun; York, Peter; Patterson, Laurence; Zhang, Jiwen

2016-02-29

The structure of solid drug delivery systems has considerable influence on drug release behaviors from particles and granules and also impacts other properties relevant to release characteristics such as taste. In this study, lipid-based microspheres of acetaminophen were prepared to mask the undesirable taste of drug and therefore to identify the optimal formulation for drug release. Synchrotron radiation X-ray computed microtomography (SR-μCT) was used to investigate the fine structural architectures of microspheres non-destructively at different sampling times during drug release test, which were simultaneously determined to quantitatively correlate the structural data with drug release behaviors. The results demonstrated that the polymeric formulation component, namely, cationic polymethacrylate (Eudragit E100), was the key factor to mask the bitter taste of acetaminophen by inhibiting immediate drug release thereby reducing the interaction intensity of the bitter material with the oral cavity taste buds. The structure and morphology of the microspheres were found to be influenced by the shape and particle size of the drug, which was also an important factor for taste-masking performance. The quantitative analysis generated detailed structural information which was correlated well with drug release behaviors. Thus, SR-μCT has been proved as a powerful tool to investigate the fine microstructure of particles and provides a new approach in the design of particles for taste masking. Copyright © 2015 Elsevier B.V. All rights reserved.

Hot melt extrusion of ion-exchange resin for taste masking.

PubMed

Tan, David Cheng Thiam; Ong, Jeremy Jianming; Gokhale, Rajeev; Heng, Paul Wan Sia

2018-05-30

Taste masking is important for some unpleasant tasting bioactives in oral dosage forms. Among many methods available for taste-masking, use of ion-exchange resin (IER) holds promise. IER combined with hot melt extrusion (HME) may offer additional advantages over solvent methods. IER provides taste masking by complexing with the drug ions and preventing drug dissolution in the mouth. Drug-IER complexation approaches described in literatures are mainly based either on batch processing or column eluting. These methods of drug-IER complexation have obvious limitations such as high solvent volume requirements, multiprocessing steps and extended processing time. Thus, the objective of this study was to develop a single-step, solvent-free, continuous HME process for complexation of drug-IER. The screening study evaluated drug to IER ratio, types of IER and drug complexation methods. In the screening study, a potassium salt of a weakly acidic carboxylate-based cationic IER was found suitable for the HME method. Thereafter, optimization study was conducted by varying HME process parameters such as screw speed, extrusion temperature and drug to IER ratio. It was observed that extrusion temperature and drug to IER ratio are imperative in drug-IER complexation through HME. In summary, this study has established the feasibility of a continuous complexation method for drug to IER using HME for taste masking. Copyright © 2018 Elsevier B.V. All rights reserved.

Mobile geographic information system (GIS) solution for pavement condition surveys.

DOT National Transportation Integrated Search

2012-06-28

This report discusses the design and implementation of a software-based solution that will improve the data collection processes during the Pavement Condition Surveys (PCS) conducted by the State Materials Office (SMO) of the Florida Department of Tr...

SU-E-T-541: Bolus Effect of Thermoplastic Masks in IMRT and VMAT Head and Neck Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhen, H; Nedzi, L; Chen, S

2014-06-01

Purpose: To quantitatively evaluate the bolus effect of thermoplalstic mask on patient skin dose during multi-field IMRT and VMAT treatment. Methods: The clinically approved target contours for five head and neck patients were deformably registered to an anthropomorphic Rando phantom. Two plans: Multifield IMRT plan with 7-9 beams and VMAT plan with 2-4 arcs were created for each patient following same dose constraints. 3mm skin was excluded from PTVs but not constrained during optimization. The prescription dose was 200-220 cGy/fraction. A thermoplastic head and shoulder mask was customized for the Rando phantom. Each plan was delivered to the phantom twicemore » with and without mask. During each delivery, two rectangular strips of EBT3 films (1cm x 6.8cm) were placed across the anterior upper and lower neck near PTVs to measure the surface dose. For consistency films were positioned at same locations for same patient. A total of 8 film strips were obtained for each patient. Film dose was calibrated in the range of 0-400cGy on the day of plan delivery. For dose comparison 3 regions of interests (ROIs) of 1×1 cm{sup 2} were selected at left, right and middle part of each film, resulting in 6 point doses at each plan delivery. Results: The films without mask show relatively uniform dose distribution while those with mask clearly show mesh pattern of mask, usually indicating an increase in skin dose. On average the increase in skin dose over all ROIs with mask was 31.9%(±14.8%) with a range of 11.4%- 58.4%. There is no statistically significant difference (p=0.44) between skin dose increase in VMAT (30.8%±15.3%) and IMRT delivery (33.0%±14.9%). Conclusion: Thermoplastic immobilization masks increase surface dose for HN patient by around 30%. The magnitude is comparable between multi-field IMRT and VMAT. Radiochromic EBT3 film serves as an effective tool to quantify bolus effect.« less

Paving the way to a full chip gate level double patterning application

NASA Astrophysics Data System (ADS)

Haffner, Henning; Meiring, Jason; Baum, Zachary; Halle, Scott

2007-10-01

Double patterning lithography processes can offer significant yield enhancement for challenging circuit designs. Many decomposition (i.e. the process of dividing the layout design into first and second exposures) techniques are possible, but the focus of this paper is on the use of a secondary "cut" mask to trim away extraneous features left from the first exposure. This approach has the advantage that each exposure only needs to support a subset of critical features (e.g. dense lines with the first exposure, isolated spaces with the second one). The extraneous features ("printing assist features" or PrAFs) are designed to support the process window of critical features much like the role of the subresolution assist features (SRAFs) in conventional processes. However, the printing nature of PrAFs leads to many more design options, and hence a greater process and decomposition parameter exploration space, than are available for SRAFs. A decomposition scheme using PRAFs was developed for a gate level process. A critical driver of the work was to deliver improved across-chip linewidth variation (ACLV) performance versus an optimized single exposure process while providing support for a larger range of critical features. A variety of PRAF techniques were investigated by simulation, with a PrAF scheme similar to standard SRAF rules being chosen as the optimal solution [1]. This paper discusses aspects of the code development for an automated PrAF generation and placement scheme and the subsequent decomposition of a layout into two mask levels. While PrAF placement and decomposition is straightforward for layouts with pitch and orientation restrictions, it becomes rather complex for unrestricted layout styles. Because this higher complexity yields more irregularly shaped PrAFs, mask making becomes another critical driver of the optimum placement and clean-up strategies. Examples are given of how those challenges are met or can be successfully circumvented. During subsequent decomposition of the PrAF-enhanced layout into two independent mask levels, various geometric decomposition parameters have to be considered. As an example, the removal of PrAFs has to be guaranteed by a minimum required overlap of the cut mask opening past any PrAF edge. It is discussed that process assumptions such as CD tolerances and overlay as well as inter-level relationship ground rules need to be considered to successfully optimize the final decomposition scheme. Furthermore, simulation and experimental results regarding not only ACLV but also across-device linewidth variation (ADLV) are analyzed.

[Carotid plaque assessment using inversion recovery T1 weighted-3 dimensions variable refocus flip angle turbo spin echo sampling perfection with application optimized contrast using different angle evolutions black blood imaging].

PubMed

Inoue, Yuji; Yoneyama, Masami; Nakamura, Masanobu; Ozaki, Satoshi; Ito, Kenjiro; Hiura, Mikio

2012-01-01

Vulnerable plaque can be attributed to induction of ischemic symptoms and magnetic resonance imaging of carotid artery is valuable to detect the plaque. Magnetization prepared rapid acquisition with gradient echo (MPRAGE) method could detect hemorrhagic vulnerable plaque as high intensity signal; however, blood flow is not sufficiently masked by this method. The contrast for plaque in T1 weighted image (T1WI) could not be obtained sufficiently with black blood image (BBI) by sampling perfection with application optimized contrast using different angle evolutions (SPACE) method as turbo spin echo (TSE). In addition, an appearance of artifact by slow flow is a problem. Considering these controversial situations in plaque imaging, we examined the modified BBI inversion recovery (IR)-SPACE in which IR was added for SPACE method so that the contrast for plaque in T1WI was optimized. We investigated the application of this method in plaque imaging. As a result of phantom imaging, the contrast for plaque in T1WI was definitely obtained by choosing an appropriate inversion time (TI) for the corresponding repetition time. In clinical cases, blood flow was sufficiently masked by IR-SPACE method and the plaque imaging was clearly obtained in clinical cases to the same extent as MPRAGE method. Since BBI with IR-SPACE method was derived from both IR pulse and flow void effect, this method could obtain the blood flow masking effect definitely. The present study suggested that SPACE method might be applicable to estimate properties of carotid artery plaque.

Extending CO2 cryogenic aerosol cleaning for advanced optical and EUV mask cleaning

NASA Astrophysics Data System (ADS)

Varghese, Ivin; Bowers, Charles W.; Balooch, Mehdi

2011-11-01

Cryogenic CO2 aerosol cleaning being a dry, chemically-inert and residue-free process is used in the production of optical lithography masks. It is an attractive cleaning option for the mask industry to achieve the requirement for removal of all printable soft defects and repair debris down to the 50nm printability specification. In the technique, CO2 clusters are formed by sudden expansion of liquid from high to almost atmospheric pressure through an optimally designed nozzle orifice. They are then directed on to the soft defects or debris for momentum transfer and subsequent damage free removal from the mask substrate. Unlike aggressive acid based wet cleaning, there is no degradation of the mask after processing with CO2, i.e., no critical dimension (CD) change, no transmission/phase losses, or chemical residue that leads to haze formation. Therefore no restriction on number of cleaning cycles is required to be imposed, unlike other cleaning methods. CO2 aerosol cleaning has been implemented for several years as full mask final clean in production environments at several state of the art mask shops. Over the last two years our group reported successful removal of all soft defects without damage to the fragile SRAF features, zero adders (from the cleaning and handling mechanisms) down to a 50nm printability specification. In addition, CO2 aerosol cleaning is being utilized to remove debris from Post-RAVE repair of hard defects in order to achieve the goal of no printable defects. It is expected that CO2 aerosol cleaning can be extended to extreme ultraviolet (EUV) masks. In this paper, we report advances being made in nozzle design qualification for optimum snow properties (size, velocity and flux) using Phase Doppler Anemometry (PDA) technique. In addition the two new areas of focus for CO2 aerosol cleaning i.e. pellicle glue residue removal on optical masks, and ruthenium (Ru) film on EUV masks are presented. Usually, the residue left over after the pellicle has been removed from returned masks (after long term usage/exposure in the wafer fab), requires a very aggressive SPM wet clean, that drastically reduces the available budget for mask properties (CD, phase/transmission). We show that CO2aerosol cleaning can be utilized to remove the bulk of the glue residue effectively, while preserving the mask properties. This application required a differently designed nozzle to impart the required removal force for the sticky glue residue. A new nozzle was developed and qualified that resulted in PRE in the range of 92-98%. Results also include data on a patterned mask that was exposed in a lithography stepper in a wafer production environment. On EUV mask, our group has experimentally demonstrated that 50 CO2 cleaning cycles of Ru film on the EUV Front-side resulted in no appreciable reflectivity change, implying that no degradation of the Ru film occurs.

Optimization of printing techniques for electrochemical biosensors

NASA Astrophysics Data System (ADS)

Zainuddin, Ahmad Anwar; Mansor, Ahmad Fairuzabadi Mohd; Rahim, Rosminazuin Ab; Nordin, Anis Nurashikin

2017-03-01

Electrochemical biosensors show great promise for point-of-care applications due to their low cost, portability and compatibility with microfluidics. The miniature size of these sensors provides advantages in terms of sensitivity, specificity and allows them to be mass produced in arrays. The most reliable fabrication technique for these sensors is lithography followed by metal deposition using sputtering or chemical vapor deposition techniques. This technique which is usually done in the cleanroom requires expensive masking followed by deposition. Recently, cheaper printing techniques such as screen-printing and ink-jet printing have become popular due to its low cost, ease of fabrication and mask-less method. In this paper, two different printing techniques namely inkjet and screen printing are demonstrated for an electrochemical biosensor. For ink-jet printing technique, optimization of key printing parameters, such as pulse voltages, drop spacing and waveform setting, in-house temperature and cure annealing for obtaining the high quality droplets, are discussed. These factors are compared with screen-printing parameters such as mesh size, emulsion thickness, minimum spacing of lines and curing times. The reliability and reproducibility of the sensors are evaluated using scotch tape test, resistivity and profile-meter measurements. It was found that inkjet printing is superior because it is mask-less, has minimum resolution of 100 µm compared to 200 µm for screen printing and higher reproducibility rate of 90% compared to 78% for screen printing.

Optimization of plasma etching of SiO2 as hard mask for HgCdTe dry etching

NASA Astrophysics Data System (ADS)

Chen, Yiyu; Ye, Zhenhua; Sun, Changhong; Zhang, Shan; Xin, Wen; Hu, Xiaoning; Ding, Ruijun; He, Li

2016-10-01

HgCdTe is one of the dominating materials for infrared detection. To pattern this material, our group has proven the feasibility of SiO2 as a hard mask in dry etching process. In recent years, the SiO2 mask patterned by plasma with an auto-stopping layer of ZnS sandwiched between HgCdTe and SiO2 has been developed by our group. In this article, we will report the optimization of SiO2 etching on HgCdTe. The etching of SiO2 is very mature nowadays. Multiple etching recipes with deferent gas mixtures can be used. We utilized a recipe containing Ar and CHF3. With strictly controlled photolithography, the high aspect-ratio profile of SiO2 was firstly achieved on GaAs substrate. However, the same recipe could not work well on MCT because of the low thermal conductivity of HgCdTe and CdTe, resulting in overheated and deteriorated photoresist. By decreasing the temperature, the photoresist maintained its good profile. A starting table temperature around -5°C worked well enough. And a steep profile was achieved as checked by the SEM. Further decreasing of temperature introduced profile with beveled corner. The process window of the temperature is around 10°C. Reproducibility and uniformity were also confirmed for this recipe.

Dissociable brain mechanisms underlying the conscious and unconscious control of behavior.

PubMed

van Gaal, Simon; Lamme, Victor A F; Fahrenfort, Johannes J; Ridderinkhof, K Richard

2011-01-01

Cognitive control allows humans to overrule and inhibit habitual responses to optimize performance in challenging situations. Contradicting traditional views, recent studies suggest that cognitive control processes can be initiated unconsciously. To further capture the relation between consciousness and cognitive control, we studied the dynamics of inhibitory control processes when triggered consciously versus unconsciously in a modified version of the stop task. Attempts to inhibit an imminent response were often successful after unmasked (visible) stop signals. Masked (invisible) stop signals rarely succeeded in instigating overt inhibition but did trigger slowing down of response times. Masked stop signals elicited a sequence of distinct ERP components that were also observed on unmasked stop signals. The N2 component correlated with the efficiency of inhibitory control when elicited by unmasked stop signals and with the magnitude of slowdown when elicited by masked stop signals. Thus, the N2 likely reflects the initiation of inhibitory control, irrespective of conscious awareness. The P3 component was much reduced in amplitude and duration on masked versus unmasked stop trials. These patterns of differences and similarities between conscious and unconscious cognitive control processes are discussed in a framework that differentiates between feedforward and feedback connections in yielding conscious experience.

Nuclear Export Signal Masking Regulates HIV-1 Rev Trafficking and Viral RNA Nuclear Export.

PubMed

Behrens, Ryan T; Aligeti, Mounavya; Pocock, Ginger M; Higgins, Christina A; Sherer, Nathan M

2017-02-01

HIV-1's Rev protein forms a homo-oligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study, we used a functional fluorescently tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found that Rev activity was remarkably tolerant of diverse NES sequences, including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores. Rev's ability to tolerate a SNES was both position and multimerization dependent, an observation consistent with a model wherein Rev self-association acts to transiently mask the NES peptide(s), thereby biasing Rev's trafficking into the nucleus. Combined imaging and functional assays also indicated that NES masking underpins Rev's well-known tendency to accumulate at the nucleolus, as well as Rev's capacity to activate optimal levels of late viral gene expression. We propose that Rev multimerization and NES masking regulates Rev's trafficking to and retention within the nucleus even prior to RNA binding. HIV-1 infects more than 34 million people worldwide causing >1 million deaths per year. Infectious virion production is activated by the essential viral Rev protein that mediates nuclear export of intron-bearing late-stage viral mRNAs. Rev's shuttling into and out of the nucleus is regulated by the antagonistic activities of both a peptide-encoded N-terminal nuclear localization signal and C-terminal nuclear export signal (NES). How Rev and related viral proteins balance strong import and export activities in order to achieve optimal levels of viral gene expression is incompletely understood. We provide evidence that multimerization provides a mechanism by which Rev transiently masks its NES peptide, thereby biasing its trafficking to and retention within the nucleus. Targeted pharmacological disruption of Rev-Rev interactions should perturb multiple Rev activities, both Rev-RNA binding and Rev's trafficking to the nucleus in the first place. Copyright © 2017 American Society for Microbiology.

Nuclear Export Signal Masking Regulates HIV-1 Rev Trafficking and Viral RNA Nuclear Export

PubMed Central

Behrens, Ryan T.; Aligeti, Mounavya; Pocock, Ginger M.; Higgins, Christina A.

2016-01-01

ABSTRACT HIV-1's Rev protein forms a homo-oligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study, we used a functional fluorescently tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found that Rev activity was remarkably tolerant of diverse NES sequences, including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores. Rev's ability to tolerate a SNES was both position and multimerization dependent, an observation consistent with a model wherein Rev self-association acts to transiently mask the NES peptide(s), thereby biasing Rev's trafficking into the nucleus. Combined imaging and functional assays also indicated that NES masking underpins Rev's well-known tendency to accumulate at the nucleolus, as well as Rev's capacity to activate optimal levels of late viral gene expression. We propose that Rev multimerization and NES masking regulates Rev's trafficking to and retention within the nucleus even prior to RNA binding. IMPORTANCE HIV-1 infects more than 34 million people worldwide causing >1 million deaths per year. Infectious virion production is activated by the essential viral Rev protein that mediates nuclear export of intron-bearing late-stage viral mRNAs. Rev's shuttling into and out of the nucleus is regulated by the antagonistic activities of both a peptide-encoded N-terminal nuclear localization signal and C-terminal nuclear export signal (NES). How Rev and related viral proteins balance strong import and export activities in order to achieve optimal levels of viral gene expression is incompletely understood. We provide evidence that multimerization provides a mechanism by which Rev transiently masks its NES peptide, thereby biasing its trafficking to and retention within the nucleus. Targeted pharmacological disruption of Rev-Rev interactions should perturb multiple Rev activities, both Rev-RNA binding and Rev's trafficking to the nucleus in the first place. PMID:27852860

Diurnal Cycle of Surface Flows During NAME and Comparison to Model Reanalysis

NASA Astrophysics Data System (ADS)

Ciesielski, P. E.; Johnson, R. H.

2007-05-01

During the North American Monsoon Experiment (NAME) an unprecedented surface data set of winds and thermodynamic variables was collected over the core monsoon region. The surface network included 63 automated sites with 1-30 min resolution data, 27 SMN operational sites (1-3 hourly data), and 56 US operational sites (1-3 hourly data) along the northern fringe of the monsoon region. These data, along with twice daily QuikSCAT oceanic surface winds, were quality controlled and objectively analyzed on to a uniform grid with quarter-degree, 1-h resolution for the period from 1 July - 15 August. An important application of the gridded winds is their use in diagnosing surface vertical motion due to slope flows over the Sierra Madre Occidental (SMO) terrain. With this dataset we examine the diurnal characteristics of surface fields as the monsoon evolves and compare these analyses to similar surface products from the special North American Regional Reanalysis (NARR) for NAME. Observed surface fields indicate that a robust land-sea breeze circulation is present over most of Gulf of California (GOC) region in response to the strong diurnal heating of land masses on both sides of the gulf. For reasons unclear at this time, many features of this land-sea breeze circulation are missing in the NARR. Evolution of the diurnal cycle of temperature and the land- sea breeze circulation as the monsoon progresses through the season shows a strong sensitivity to rainfall over the SMO and the coastal plains. Such a relationship likely reflects changes in land surface characteristics, such as evapotranspiration and albedo, as the forests of the SMO respond to monsoonal rains.

Dendrosomatic Sonic Hedgehog Signaling in Hippocampal Neurons Regulates Axon Elongation

PubMed Central

Petralia, Ronald S.; Ott, Carolyn; Wang, Ya-Xian; Lippincott-Schwartz, Jennifer; Mattson, Mark P.

2015-01-01

The presence of Sonic Hedgehog (Shh) and its signaling components in the neurons of the hippocampus raises a question about what role the Shh signaling pathway may play in these neurons. We show here that activation of the Shh signaling pathway stimulates axon elongation in rat hippocampal neurons. This Shh-induced effect depends on the pathway transducer Smoothened (Smo) and the transcription factor Gli1. The axon itself does not respond directly to Shh; instead, the Shh signal transduction originates from the somatodendritic region of the neurons and occurs in neurons with and without detectable primary cilia. Upon Shh stimulation, Smo localization to dendrites increases significantly. Shh pathway activation results in increased levels of profilin1 (Pfn1), an actin-binding protein. Mutations in Pfn1's actin-binding sites or reduction of Pfn1 eliminate the Shh-induced axon elongation. These findings indicate that Shh can regulate axon growth, which may be critical for development of hippocampal neurons. SIGNIFICANCE STATEMENT Although numerous signaling mechanisms have been identified that act directly on axons to regulate their outgrowth, it is not known whether signals transduced in dendrites may also affect axon outgrowth. We describe here a transcellular signaling pathway in embryonic hippocampal neurons in which activation of Sonic Hedgehog (Shh) receptors in dendrites stimulates axon growth. The pathway involves the dendritic-membrane-associated Shh signal transducer Smoothened (Smo) and the transcription factor Gli, which induces the expression of the gene encoding the actin-binding protein profilin 1. Our findings suggest scenarios in which stimulation of Shh in dendrites results in accelerated outgrowth of the axon, which therefore reaches its presumptive postsynaptic target cell more quickly. By this mechanism, Shh may play critical roles in the development of hippocampal neuronal circuits. PMID:26658865

Hedgehog-GLI signaling drives self-renewal and tumorigenicity of human melanoma-initiating cells.

PubMed

Santini, Roberta; Vinci, Maria C; Pandolfi, Silvia; Penachioni, Junia Y; Montagnani, Valentina; Olivito, Biagio; Gattai, Riccardo; Pimpinelli, Nicola; Gerlini, Gianni; Borgognoni, Lorenzo; Stecca, Barbara

2012-09-01

The question of whether cancer stem/tumor-initiating cells (CSC/TIC) exist in human melanomas has arisen in the last few years. Here, we have used nonadherent spheres and the aldehyde dehydrogenase (ALDH) enzymatic activity to enrich for CSC/TIC in a collection of human melanomas obtained from a broad spectrum of sites and stages. We find that melanomaspheres display extensive in vitro self-renewal ability and sustain tumor growth in vivo, generating human melanoma xenografts that recapitulate the phenotypic composition of the parental tumor. Melanomaspheres express high levels of Hedgehog (HH) pathway components and of embryonic pluripotent stem cell factors SOX2, NANOG, OCT4, and KLF4. We show that human melanomas contain a subset of cells expressing high ALDH activity (ALDH(high)), which is endowed with higher self-renewal and tumorigenic abilities than the ALDH(low) population. A good correlation between the number of ALDH(high) cells and sphere formation efficiency was observed. Notably, both pharmacological inhibition of HH signaling by the SMOOTHENED (SMO) antagonist cyclopamine and GLI antagonist GANT61 and stable expression of shRNA targeting either SMO or GLI1 result in a significant decrease in melanoma stem cell self-renewal in vitro and a reduction in the number of ALDH(high) melanoma stem cells. Finally, we show that interference with the HH-GLI pathway through lentiviral-mediated silencing of SMO and GLI1 drastically diminishes tumor initiation of ALDH(high) melanoma stem cells. In conclusion, our data indicate an essential role of the HH-GLI1 signaling in controlling self-renewal and tumor initiation of melanoma CSC/TIC. Targeting HH-GLI1 is thus predicted to reduce the melanoma stem cell compartment. Copyright © 2012 AlphaMed Press.

Validation of a novel wearable, wireless technology to estimate oxygen levels and lactate threshold power in the exercising muscle.

PubMed

Farzam, Parisa; Starkweather, Zack; Franceschini, Maria A

2018-04-01

There is a growing interest in monitoring muscle oxygen saturation (SmO 2 ), which is a localized measure of muscle oxidative metabolism and can be acquired continuously and noninvasively using near-infrared spectroscopy (NIRS) methods. Most NIRS systems are cumbersome, expensive, fiber coupled devices, with use limited to lab settings. A novel, low cost, wireless, wearable has been developed for use in athletic training. In this study, we evaluate the advantages and limitations of this new simple continuous-wave (CW) NIRS device with respect to a benchtop, frequency-domain near-infrared spectroscopy (FDNIRS) system. Oxygen saturation and hemoglobin/myoglobin concentration in the exercising muscles of 17 athletic individuals were measured simultaneously with the two systems, while subjects performed an incremental test on a stationary cycle ergometer. In addition, blood lactate concentration was measured at the end of each increment with a lactate analyzer. During exercise, the correlation coefficients of the SmO 2 and hemoglobin/myoglobin concentrations between the two systems were over 0.70. We also found both systems were insensitive to the presence of thin layers of varying absorption, mimicking different skin colors. Neither system was able to predict the athletes' lactate threshold power accurately by simply using SmO 2 thresholds. Instead, the proprietary software of the wearable device was able to predict the athletes' lactate threshold power within half of one power increment of the cycling test. These results indicate this novel wearable device may provide a physiological indicator of athlete's exertion. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Esmolol acutely alters oxygen supply-demand balance in exercising muscles of healthy humans.

PubMed

Proctor, David N; Luck, J Carter; Maman, Stephan R; Leuenberger, Urs A; Muller, Matthew D

2018-04-01

Beta-adrenoreceptor antagonists (β blockers) reduce systemic O 2 delivery and blood pressure (BP) during exercise, but the subsequent effects on O 2 extraction within the active limb muscles are unknown. In this study, we examined the effects of the fast-acting, β 1 selective blocker esmolol on systemic hemodynamics and leg muscle O 2 saturation (near infrared spectroscopy, NIRS) during submaximal leg ergometry. Our main hypothesis was that esmolol would augment exercise-induced reductions in leg muscle O 2 saturation. Eight healthy adults (6 men, 2 women; 23-67 year) performed light and moderate intensity bouts of recumbent leg cycling before (PRE), during (β 1 -blocked), and 45 min following (POST) intravenous infusion of esmolol. Oxygen uptake, heart rate (HR), BP, and O 2 saturation (SmO 2 ) of the vastus lateralis (VL) and medial gastrocnemius (MG) muscles were measured continuously. Esmolol attenuated the increases in HR and systolic BP during light (-12 ± 9 bpm and -26 ± 12 mmHg vs. PRE) and moderate intensity (-20 ± 10 bpm and -40 ± 18 mmHg vs. PRE) cycling (all P < 0.01). Exercise-induced reductions in SmO 2 occurred to a greater extent during the β 1 -blockade trial in both the VL (P = 0.001 vs. PRE) and MG muscles (P = 0.022 vs. PRE). HR, SBP and SmO 2 were restored during POST (all P < 0.01 vs. β 1 -blocked). In conclusion, esmolol rapidly and reversibly increases O 2 extraction within exercising muscles of healthy humans. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Contribution of proline to the pre-structuring tendency of transient helical secondary structure elements in intrinsically disordered proteins.

PubMed

Lee, Chewook; Kalmar, Lajos; Xue, Bin; Tompa, Peter; Daughdrill, Gary W; Uversky, Vladimir N; Han, Kyou-Hoon

2014-03-01

IDPs function without relying on three-dimensional structures. No clear rationale for such a behavior is available yet. PreSMos are transient secondary structures observed in the target-free IDPs and serve as the target-binding "active" motifs in IDPs. Prolines are frequently found in the flanking regions of PreSMos. Contribution of prolines to the conformational stability of the helical PreSMos in IDPs is investigated. MD simulations are performed for several IDP segments containing a helical PreSMo and the flanking prolines. To measure the influence of flanking-prolines on the structural content of a helical PreSMo calculations were done for wild type as well as for mutant segments with Pro→Asp, His, Lys, or Ala. The change in the helicity due to removal of a proline was measured both for the PreSMo region and for the flanking regions. The α-helical content in ~70% of the helical PreSMos at the early stage of simulation decreases due to replacement of an N-terminal flanking proline by other residues whereas the helix content in nearly all PreSMos increases when the same replacements occur at the C-terminal flanking region. The helix destabilizing/terminating role of the C-terminal flanking prolines is more pronounced than the helix promoting effect of the N-terminal flanking prolines. This work represents a novel example demonstrating that a proline is encoded in an IDP with a defined purpose. The helical PreSMos presage their target-bound conformations. As they most likely mediate IDP-target binding via conformational selection their helical content can be an important feature for IDP function. Copyright © 2013 Elsevier B.V. All rights reserved.

Design and Construction of a Multi-wavelength, Micromirror Total Internal Reflectance Fluorescence Microscope

PubMed Central

Larson, Joshua; Kirk, Matt; Drier, Eric A.; O’Brien, William; MacKay, James F.; Friedman, Larry; Hoskins, Aaron

2015-01-01

Colocalization Single Molecule Spectroscopy (CoSMoS) has proven to be a useful method for studying the composition, kinetics, and mechanisms of complex cellular machines. Key to the technique is the ability to simultaneously monitor multiple proteins and/or nucleic acids as they interact with one another. Here we describe a protocol for constructing a CoSMoS micromirror Total Internal Reflection Fluorescence Microscope (mmTIRFM). Design and construction of a scientific microscope often requires a number of custom components and a significant time commitment. In our protocol, we have streamlined this process by implementation of a commercially available microscopy platform designed to accommodate the optical components necessary for a mmTIRFM. The mmTIRF system eliminates the need for machining custom parts by the end-user and facilitates optical alignment. Depending on the experience-level of the microscope builder, these time-savings and the following protocol can enable mmTIRF construction to be completed within two months. PMID:25188633

Design and construction of a multiwavelength, micromirror total internal reflectance fluorescence microscope.

PubMed

Larson, Joshua; Kirk, Matt; Drier, Eric A; O'Brien, William; MacKay, James F; Friedman, Larry J; Hoskins, Aaron A

2014-10-01

Colocalization single-molecule spectroscopy (CoSMoS) has proven to be a useful method for studying the composition, kinetics and mechanisms of complex cellular machines. Key to the technique is the ability to simultaneously monitor multiple proteins and/or nucleic acids as they interact with one another. Here we describe a protocol for constructing a CoSMoS micromirror total internal reflection fluorescence microscope (mmTIRFM). Design and construction of a scientific microscope often requires a number of custom components and a substantial time commitment. In our protocol, we have streamlined this process by implementation of a commercially available microscopy platform designed to accommodate the optical components necessary for an mmTIRFM. The mmTIRF system eliminates the need for machining custom parts by the end user and facilitates optical alignment. Depending on the experience level of the microscope builder, these time savings and the following protocol can enable mmTIRF construction to be completed within 2 months.

Atom-Dependent Edge-Enhanced Second-Harmonic Generation on MoS2 Monolayers.

PubMed

Lin, Kuang-I; Ho, Yen-Hung; Liu, Shu-Bai; Ciou, Jian-Jhih; Huang, Bo-Ting; Chen, Christopher; Chang, Han-Ching; Tu, Chien-Liang; Chen, Chang-Hsiao

2018-02-14

Edge morphology and lattice orientation of single-crystal molybdenum disulfide (MoS 2 ) monolayers, a transition metal dichalcogenide (TMD), possessing a triangular shape with different edges grown by chemical vapor deposition are characterized by atomic force microscopy and transmission electron microscopy. Multiphoton laser scanning microscopy is utilized to study one-dimensional atomic edges of MoS 2 monolayers with localized midgap electronic states, which result in greatly enhanced optical second-harmonic generation (SHG). Microscopic S-zigzag edge and S-Mo Klein edge (bare Mo atoms protruding from a S-zigzag edge) terminations and the edge-atom dependent resonance energies can therefore be deduced based on SHG images. Theoretical calculations based on density functional theory clearly explain the lower energy of the S-zigzag edge states compared to the corresponding S-Mo Klein edge states. Characterization of the atomic-scale variation of edge-enhanced SHG is a step forward in this full-optical and high-yield technique of atomic-layer TMDs.

Crystal structure of a multi-domain human smoothened receptor in complex with a super stabilizing ligand

DOE PAGES

Zhang, Xianjun; Zhao, Fei; Wu, Yiran; ...

2017-05-17

Here, the Smoothened receptor (SMO) belongs to the Class Frizzled of the G protein-coupled receptor (GPCR) superfamily, constituting a key component of the Hedgehog signalling pathway. Here we report the crystal structure of the multi-domain human SMO, bound and stabilized by a designed tool ligand TC114, using an X-ray free-electron laser source at 2.9 Å. The structure reveals a precise arrangement of three distinct domains: a seven-transmembrane helices domain (TMD), a hinge domain (HD) and an intact extracellular cysteine-rich domain (CRD). This architecture enables allosteric interactions between the domains that are important for ligand recognition and receptor activation. By combiningmore » the structural data, molecular dynamics simulation, and hydrogen-deuterium-exchange analysis, we demonstrate that transmembrane helix VI, extracellular loop 3 and the HD play a central role in transmitting the signal employing a unique GPCR activation mechanism, distinct from other multi-domain GPCRs.« less

Gene expression analysis of murine cells producing amphotropic mouse leukaemia virus at a cultivation temperature of 32 and 37 degrees C.

PubMed

Beer, Christiane; Buhr, Petra; Hahn, Heidi; Laubner, Daniela; Wirth, Manfred

2003-07-01

Cultivation of retrovirus packaging cells at 32 degrees C represents a common procedure to achieve high titres in mouse retrovirus production. Gene expression profiling of mouse NIH 3T3 cells producing amphotropic mouse leukaemia virus 4070A revealed that 10 % of the 1176 cellular genes investigated were regulated by temperature shift (37/32 degrees C), while 5 % were affected by retrovirus infection. Strikingly, retrovirus production at 32 degrees C activated the cholesterol biosynthesis/transport pathway and caused an increase in plasma membrane cholesterol levels. Furthermore, these conditions resulted in transcriptional activation of smoothened (smo), patched (ptc) and gli-1; Smo, Ptc and Gli-1, as well as cholesterol, are components of the Sonic hedgehog (Shh) signalling pathway, which directs pattern formation, diversification and tumourigenesis in mammalian cells. These findings suggest a link between cultivation at 32 degrees C, production of MLV-A and the Shh signalling pathway.

Bayesian cloud detection for MERIS, AATSR, and their combination

NASA Astrophysics Data System (ADS)

Hollstein, A.; Fischer, J.; Carbajal Henken, C.; Preusker, R.

2015-04-01

A broad range of different of Bayesian cloud detection schemes is applied to measurements from the Medium Resolution Imaging Spectrometer (MERIS), the Advanced Along-Track Scanning Radiometer (AATSR), and their combination. The cloud detection schemes were designed to be numerically efficient and suited for the processing of large numbers of data. Results from the classical and naive approach to Bayesian cloud masking are discussed for MERIS and AATSR as well as for their combination. A sensitivity study on the resolution of multidimensional histograms, which were post-processed by Gaussian smoothing, shows how theoretically insufficient numbers of truth data can be used to set up accurate classical Bayesian cloud masks. Sets of exploited features from single and derived channels are numerically optimized and results for naive and classical Bayesian cloud masks are presented. The application of the Bayesian approach is discussed in terms of reproducing existing algorithms, enhancing existing algorithms, increasing the robustness of existing algorithms, and on setting up new classification schemes based on manually classified scenes.

Human observers have optimal introspective access to perceptual processes even for visually masked stimuli

PubMed Central

Peters, Megan A K; Lau, Hakwan

2015-01-01

Many believe that humans can ‘perceive unconsciously’ – that for weak stimuli, briefly presented and masked, above-chance discrimination is possible without awareness. Interestingly, an online survey reveals that most experts in the field recognize the lack of convincing evidence for this phenomenon, and yet they persist in this belief. Using a recently developed bias-free experimental procedure for measuring subjective introspection (confidence), we found no evidence for unconscious perception; participants’ behavior matched that of a Bayesian ideal observer, even though the stimuli were visually masked. This surprising finding suggests that the thresholds for subjective awareness and objective discrimination are effectively the same: if objective task performance is above chance, there is likely conscious experience. These findings shed new light on decades-old methodological issues regarding what it takes to consider a neurobiological or behavioral effect to be 'unconscious,' and provide a platform for rigorously investigating unconscious perception in future studies. DOI: http://dx.doi.org/10.7554/eLife.09651.001 PMID:26433023

How much is enough? An analysis of CD measurement amount for mask characterization

NASA Astrophysics Data System (ADS)

Ullrich, Albrecht; Richter, Jan

2009-10-01

The demands on CD (critical dimension) metrology amount in terms of both reproducibility and measurement uncertainty steadily increase from node to node. Different mask characterization requirements have to be addressed like very small features, unevenly distributed features, contacts, semi-dense structures to name only a few. Usually this enhanced need is met by an increasing number of CD measurements, where the new CD requirements are added to the well established CD characterization recipe. This leads straight forwardly to prolonged cycle times and highly complex evaluation routines. At the same time mask processes are continuously improved to become more stable. The enhanced stability offers potential to actually reduce the number of measurements. Thus, in this work we will start to address the fundamental question of how many CD measurements are needed for mask characterization for a given confidence level. We used analysis of variances (ANOVA) to distinguish various contributors like mask making process, measurement tool stability and measurement methodology. These contributions have been investigated for classical photomask CD specifications e.g. mean to target, CD uniformity, target offset tolerance and x-y bias. We found depending on specification that the importance of the contributors interchanges. Interestingly, not only short and long-term metrology contributions are dominant. Also the number of measurements and their spatial distribution on the mask layout (sampling methodology) can be the most important part of the variance. The knowledge of contributions can be used to optimize the sampling plan. As a major finding, we conclude that there is potential to reduce a significant amount of measurements without loosing confidence at all. Here, full sampling in x and y as well as full sampling for different features can be shortened substantially almost up to 50%.

Microscopic validation of whole mouse micro-metastatic tumor imaging agents using cryo-imaging and sliding organ image registration.

PubMed

Liu, Yiqiao; Zhou, Bo; Qutaish, Mohammed; Wilson, David L

2016-01-01

We created a metastasis imaging, analysis platform consisting of software and multi-spectral cryo-imaging system suitable for evaluating emerging imaging agents targeting micro-metastatic tumor. We analyzed CREKA-Gd in MRI, followed by cryo-imaging which repeatedly sectioned and tiled microscope images of the tissue block face, providing anatomical bright field and molecular fluorescence, enabling 3D microscopic imaging of the entire mouse with single metastatic cell sensitivity. To register MRI volumes to the cryo bright field reference, we used our standard mutual information, non-rigid registration which proceeded: preprocess → affine → B-spline non-rigid 3D registration. In this report, we created two modified approaches: mask where we registered locally over a smaller rectangular solid, and sliding organ . Briefly, in sliding organ , we segmented the organ, registered the organ and body volumes separately and combined results. Though s liding organ required manual annotation, it provided the best result as a standard to measure other registration methods. Regularization parameters for standard and mask methods were optimized in a grid search. Evaluations consisted of DICE, and visual scoring of a checkerboard display. Standard had accuracy of 2 voxels in all regions except near the kidney, where there were 5 voxels sliding. After mask and sliding organ correction, kidneys sliding were within 2 voxels, and Dice overlap increased 4%-10% in mask compared to standard . Mask generated comparable results with sliding organ and allowed a semi-automatic process.

Large-area soft x-ray projection lithography using multilayer mirrors structured by RIE

NASA Astrophysics Data System (ADS)

Rahn, Steffen; Kloidt, Andreas; Kleineberg, Ulf; Schmiedeskamp, Bernt; Kadel, Klaus; Schomburg, Werner K.; Hormes, F. J.; Heinzmann, Ulrich

1993-01-01

SXPL (soft X-ray projection lithography) is one of the most promising applications of X-ray reflecting optics using multilayer mirrors. Within our collaboration, such multilayer mirrors were fabricated, characterized, laterally structured and then used as reflection masks in a projecting lithography procedure. Mo/Si-multilayer mirrors were produced by electron beam evaporation in UHV under thermal treatment with an in-situ X-ray controlled thickness in the region of 2d equals 14 nm. The reflectivities measured at normal incidence reached up to 54%. Various surface analysis techniques have been applied in order to characterize and optimize the X-ray mirrors. The multilayers were patterned by reactive ion etching (RIE) with CF(subscript 4), using a photoresist as the etch mask, thus producing X-ray reflection masks. The masks were tested in the synchrotron radiation laboratory of the electron accelerator ELSA at the Physikalisches Institut of Bonn University. A double crystal X-ray monochromator was modified so as to allow about 0.5 cm(superscript 2) of the reflection mask to be illuminated by white synchrotron radiation. The reflected patterns were projected (with an energy of 100 eV) onto the resist (Hoechst AZ PF 514), which was mounted at an average distance of about 7 mm. In the first test-experiments, structure sizes down to 8 micrometers were nicely reproduced over the whole of the exposed area. Smaller structures were distorted by Fresnel-diffraction. The theoretically calculated diffraction images agree very well with the observed images.

Microscopic validation of whole mouse micro-metastatic tumor imaging agents using cryo-imaging and sliding organ image registration

NASA Astrophysics Data System (ADS)

Liu, Yiqiao; Zhou, Bo; Qutaish, Mohammed; Wilson, David L.

2016-03-01

We created a metastasis imaging, analysis platform consisting of software and multi-spectral cryo-imaging system suitable for evaluating emerging imaging agents targeting micro-metastatic tumor. We analyzed CREKA-Gd in MRI, followed by cryo-imaging which repeatedly sectioned and tiled microscope images of the tissue block face, providing anatomical bright field and molecular fluorescence, enabling 3D microscopic imaging of the entire mouse with single metastatic cell sensitivity. To register MRI volumes to the cryo bright field reference, we used our standard mutual information, non-rigid registration which proceeded: preprocess --> affine --> B-spline non-rigid 3D registration. In this report, we created two modified approaches: mask where we registered locally over a smaller rectangular solid, and sliding organ. Briefly, in sliding organ, we segmented the organ, registered the organ and body volumes separately and combined results. Though sliding organ required manual annotation, it provided the best result as a standard to measure other registration methods. Regularization parameters for standard and mask methods were optimized in a grid search. Evaluations consisted of DICE, and visual scoring of a checkerboard display. Standard had accuracy of 2 voxels in all regions except near the kidney, where there were 5 voxels sliding. After mask and sliding organ correction, kidneys sliding were within 2 voxels, and Dice overlap increased 4%-10% in mask compared to standard. Mask generated comparable results with sliding organ and allowed a semi-automatic process.

Association of lifestyle factors with abdominal subcutaneous and visceral adiposity: The Framingham Heart Study

USDA-ARS?s Scientific Manuscript database

The objective of the present study was to assess the relationship between lifestyle factors and abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in a community-based setting. Cross-sectional associations between lifestyle factors (dietary quality, physical activity, smo...

Image reconstruction through thin scattering media by simulated annealing algorithm

NASA Astrophysics Data System (ADS)

Fang, Longjie; Zuo, Haoyi; Pang, Lin; Yang, Zuogang; Zhang, Xicheng; Zhu, Jianhua

2018-07-01

An idea for reconstructing the image of an object behind thin scattering media is proposed by phase modulation. The optimized phase mask is achieved by modulating the scattered light using simulated annealing algorithm. The correlation coefficient is exploited as a fitness function to evaluate the quality of reconstructed image. The reconstructed images optimized from simulated annealing algorithm and genetic algorithm are compared in detail. The experimental results show that our proposed method has better definition and higher speed than genetic algorithm.

The role of the polyamine catabolic enzymes SSAT and SMO in the synergistic effects of standard chemotherapeutic agents with a polyamine analogue in human breast cancer cell lines

PubMed Central

Pledgie-Tracy, Allison; Billam, Madhavi; Hacker, Amy; Sobolewski, Michele D; Woster, Patrick M.; Zhang, Zhe; Casero, Robert A.; Davidson, Nancy E

2009-01-01

Polyamine analogues have demonstrated significant activity against human breast cancer cell lines as single agents as well as in combination with other cytotoxic drugs. This study evaluates the ability of a polyamine analogue N1, N11-bis(ethyl)norspermine (BENSpm) to synergize with six standard chemotherapeutic agents, 5-fluorouracil (FU), fluorodeoxyuridine, cis- diaminechloroplatinum(II) (DDP), paclitaxel, docetaxel, and vinorelbine, in four human breast cancer cell lines and one immortalized, non-tumorigenic mammary epithelial cell line. BENSpm exhibited synergistic inhibitory effect on cell proliferation in combination with 5-FU or paclitaxel in human breast cancer cell lines (MDA-MB-231 and MCF-7) and either antagonistic or less effective in the non-tumorigenic MCF-10A cell line. Synergism was highest with 120 hour concomitant treatment or pre-treatment with BENSpm for 24 hours followed by concomitant treatment for 96 additional hours. Since the cytotoxic effects of many polyamine analogues and cytotoxic agents are believed to act, in part, through induction of the polyamine catabolic enzymes SSAT and SMO, the role of these enzymes on synergistic response was evaluated in MDA-MB-231- and MCF-7-treated with BENSpm and 5-FU or paclitaxel. Combination treatments of BENSpm with 5-FU or paclitaxel resulted in induction of SSAT mRNA and activity in both cell lines compared to either drug alone, while SMO mRNA and activity were increased only in MDA-MB-231 cells. Induction was greater with BENSpm/paclitaxel combination than BENSpm/5-FU. Further, RNAi studies demonstrated that both SSAT and SMO play a significant role in the response of MDA-MB-231 cells to treatment with BENSpm and 5-FU or paclitaxel. In MCF-7 cells, only SSAT appears to be involved in the response to these treatments. In an effort to translate combination studies from in vitro to in vivo, and to form a basis for clinical setting, the in vivo therapeutic efficacy of BENSpm alone and in combination with paclitaxel on tumor regression was evaluated in xenograft mice models generated with MDA-MB-231 cells. Intraperitoneal exposure to BENSpm or taxol singly and in combination for 4 weeks resulted in significant inhibition in tumor growth These findings help elucidate the mechanisms involved in synergistic drug response and support combinations of polyamine analogues with chemotherapeutic agents which could potentially be used in the treatment of breast cancer. PMID:19727732

Role of hydrogen in the chemical vapor deposition growth of MoS2 atomic layers

NASA Astrophysics Data System (ADS)

Li, Xiao; Li, Xinming; Zang, Xiaobei; Zhu, Miao; He, Yijia; Wang, Kunlin; Xie, Dan; Zhu, Hongwei

2015-04-01

Hydrogen plays a crucial role in the chemical vapor deposition (CVD) growth of graphene. Here, we have revealed the roles of hydrogen in the two-step CVD growth of MoS2. Our study demonstrates that hydrogen acts as the following: (i) an inhibitor of the thermal-induced etching effect in the continuous film growth process; and (ii) a promoter of the desulfurization reaction by decreasing the S/Mo atomic ratio and the oxidation reaction of the obtained MoSx (0 < x < 2) films. A high hydrogen content of more than 100% in argon forms nano-sized circle-like defects and damages the continuity and uniformity of the film. Continuous MoS2 films with a high crystallinity and a nearly perfect S/Mo atomic ratio were finally obtained after sulfurization annealing with a hydrogen content in the range of 20%-80%. This insightful understanding reveals the crucial roles of hydrogen in the CVD growth of MoS2 and paves the way for the controllable synthesis of two-dimensional materials.Hydrogen plays a crucial role in the chemical vapor deposition (CVD) growth of graphene. Here, we have revealed the roles of hydrogen in the two-step CVD growth of MoS2. Our study demonstrates that hydrogen acts as the following: (i) an inhibitor of the thermal-induced etching effect in the continuous film growth process; and (ii) a promoter of the desulfurization reaction by decreasing the S/Mo atomic ratio and the oxidation reaction of the obtained MoSx (0 < x < 2) films. A high hydrogen content of more than 100% in argon forms nano-sized circle-like defects and damages the continuity and uniformity of the film. Continuous MoS2 films with a high crystallinity and a nearly perfect S/Mo atomic ratio were finally obtained after sulfurization annealing with a hydrogen content in the range of 20%-80%. This insightful understanding reveals the crucial roles of hydrogen in the CVD growth of MoS2 and paves the way for the controllable synthesis of two-dimensional materials. Electronic supplementary information (ESI) available: Low-magnification optical images; Raman spectra of 0% and 5% H2 samples; AFM characterization; Schematic of the film before and after sulfurization annealing; Schematic illustrations of two typical Raman-active phonon modes (E12g, A1g); Raman (mapping) spectra for 40% and 80% H2 samples before and after sulfurization annealing; PL spectra. See DOI: 10.1039/c5nr00904a

Identification of odor volatile compounds and deodorization of Paphia undulata enzymatic hydrolysate

NASA Astrophysics Data System (ADS)

Chen, Deke; Chen, Xin; Chen, Hua; Cai, Bingna; Wan, Peng; Zhu, Xiaolian; Sun, Han; Sun, Huili; Pan, Jianyu

2016-12-01

Unfavorable fishy odour is an inevitable problem in aquatic products. In the present study, headspace solid-phase microextraction gas chromatography mass spectrometry (HS-SPME-GC-MS) analysis of volatiles from untreated samples and three deodorized samples (under the optimal conditions) of Paphia undulata enzymatic hydrolysate revealed that the compounds contributing to the distinctive odor were 1-octen-3-ol, n-hexanal, n-heptanal, 2,4-heptadienal, and 2,4-decadienal, whereas n-pentanal, n-octanal, n-octanol, benzaldehyde, 2-ethylfuran and 2-pentylfuran were the main contributors to the aromatic flavor. The deodorizing effects of activated carbon (AC) adsorption, yeast extract (YE) masking and tea polyphenol (TP) treatment on a P. undulata enzymatic hydrolysate were investigated using orthogonal experiments with sensory evaluation as the index. The following optimized deodorization conditions were obtained: AC adsorption (35 mg mL-1, 80°C, 40 min), YE masking (7 mg mL-1, 45°C, 30 min) and TP treatment (0.4 mg mL-1, 40°C, 50 min). AC adsorption effectively removed off-flavor volatile aldehydes and ketones. YE masking modified the odor profile by increasing the relative contents of aromatic compounds and decreasing the relative contents of aldehydes and ketones. The TP treatment was not effective in reducing the odor score, but it significantly reduced the relative content of aldehydes while increasing that of alkanes. It is also notable that TP effectively suppressed trimethylamine (TMA) formation in a P. undulate hydrolysate solution for a period of 72 h.

Mask characterization for critical dimension uniformity budget breakdown in advanced extreme ultraviolet lithography

NASA Astrophysics Data System (ADS)

Nikolsky, Peter; Strolenberg, Chris; Nielsen, Rasmus; Nooitgedacht, Tjitte; Davydova, Natalia; Yang, Greg; Lee, Shawn; Park, Chang-Min; Kim, Insung; Yeo, Jeong-Ho

2013-04-01

As the International Technology Roadmap for Semiconductors critical dimension uniformity (CDU) specification shrinks, semiconductor companies need to maintain a high yield of good wafers per day and high performance (and hence market value) of finished products. This cannot be achieved without continuous analysis and improvement of on-product CDU as one of the main drivers for process control and optimization with better understanding of main contributors from the litho cluster: mask, process, metrology and scanner. We will demonstrate a study of mask CDU characterization and its impact on CDU Budget Breakdown (CDU BB) performed for advanced extreme ultraviolet (EUV) lithography with 1D (dense lines) and 2D (dense contacts) feature cases. We will show that this CDU contributor is one of the main differentiators between well-known ArFi and new EUV CDU budgeting principles. We found that reticle contribution to intrafield CDU should be characterized in a specific way: mask absorber thickness fingerprints play a role comparable with reticle CDU in the total reticle part of the CDU budget. Wafer CD fingerprints, introduced by this contributor, may or may not compensate variations of mask CDs and hence influence on total mask impact on intrafield CDU at the wafer level. This will be shown on 1D and 2D feature examples. Mask stack reflectivity variations should also be taken into account: these fingerprints have visible impact on intrafield CDs at the wafer level and should be considered as another contributor to the reticle part of EUV CDU budget. We also observed mask error enhancement factor (MEEF) through field fingerprints in the studied EUV cases. Variations of MEEF may play a role towards the total intrafield CDU and may need to be taken into account for EUV lithography. We characterized MEEF-through-field for the reviewed features, with results herein, but further analysis of this phenomenon is required. This comprehensive approach to quantifying the mask part of the overall EUV CDU contribution helps deliver an accurate and integral CDU BB per product/process and litho tool. The better understanding of the entire CDU budget for advanced EUVL nodes achieved by Samsung and ASML helps extend the limits of Moore's Law and to deliver successful implementation of smaller, faster and smarter chips in semiconductor industry.

Interleaved segment correction achieves higher improvement factors in using genetic algorithm to optimize light focusing through scattering media

NASA Astrophysics Data System (ADS)

Li, Runze; Peng, Tong; Liang, Yansheng; Yang, Yanlong; Yao, Baoli; Yu, Xianghua; Min, Junwei; Lei, Ming; Yan, Shaohui; Zhang, Chunmin; Ye, Tong

2017-10-01

Focusing and imaging through scattering media has been proved possible with high resolution wavefront shaping. A completely scrambled scattering field can be corrected by applying a correction phase mask on a phase only spatial light modulator (SLM) and thereby the focusing quality can be improved. The correction phase is often found by global searching algorithms, among which Genetic Algorithm (GA) stands out for its parallel optimization process and high performance in noisy environment. However, the convergence of GA slows down gradually with the progression of optimization, causing the improvement factor of optimization to reach a plateau eventually. In this report, we propose an interleaved segment correction (ISC) method that can significantly boost the improvement factor with the same number of iterations comparing with the conventional all segment correction method. In the ISC method, all the phase segments are divided into a number of interleaved groups; GA optimization procedures are performed individually and sequentially among each group of segments. The final correction phase mask is formed by applying correction phases of all interleaved groups together on the SLM. The ISC method has been proved significantly useful in practice because of its ability to achieve better improvement factors when noise is present in the system. We have also demonstrated that the imaging quality is improved as better correction phases are found and applied on the SLM. Additionally, the ISC method lowers the demand of dynamic ranges of detection devices. The proposed method holds potential in applications, such as high-resolution imaging in deep tissue.

Sequence Based Prediction of Antioxidant Proteins Using a Classifier Selection Strategy

PubMed Central

Zhang, Lina; Zhang, Chengjin; Gao, Rui; Yang, Runtao; Song, Qing

2016-01-01

Antioxidant proteins perform significant functions in maintaining oxidation/antioxidation balance and have potential therapies for some diseases. Accurate identification of antioxidant proteins could contribute to revealing physiological processes of oxidation/antioxidation balance and developing novel antioxidation-based drugs. In this study, an ensemble method is presented to predict antioxidant proteins with hybrid features, incorporating SSI (Secondary Structure Information), PSSM (Position Specific Scoring Matrix), RSA (Relative Solvent Accessibility), and CTD (Composition, Transition, Distribution). The prediction results of the ensemble predictor are determined by an average of prediction results of multiple base classifiers. Based on a classifier selection strategy, we obtain an optimal ensemble classifier composed of RF (Random Forest), SMO (Sequential Minimal Optimization), NNA (Nearest Neighbor Algorithm), and J48 with an accuracy of 0.925. A Relief combined with IFS (Incremental Feature Selection) method is adopted to obtain optimal features from hybrid features. With the optimal features, the ensemble method achieves improved performance with a sensitivity of 0.95, a specificity of 0.93, an accuracy of 0.94, and an MCC (Matthew’s Correlation Coefficient) of 0.880, far better than the existing method. To evaluate the prediction performance objectively, the proposed method is compared with existing methods on the same independent testing dataset. Encouragingly, our method performs better than previous studies. In addition, our method achieves more balanced performance with a sensitivity of 0.878 and a specificity of 0.860. These results suggest that the proposed ensemble method can be a potential candidate for antioxidant protein prediction. For public access, we develop a user-friendly web server for antioxidant protein identification that is freely accessible at http://antioxidant.weka.cc. PMID:27662651

It's a question of endurance - Patients with head and neck cancer experiences of 18F-FDG PET/CT in a fixation mask.

PubMed

Andersson, Camilla; Röing, Marta; Tiblom Ehrsson, Ylva; Johansson, Birgitta

2017-08-01

This study aimed to explore how patients with head and neck cancer experienced undergoing an 18 F-fluoro-deoxy-glucose positrons emissions tomography/computed tomography ( 18 F-FDG PET/CT) examination in a fixation mask. Interviews were conducted with nine patients with known or suspected head and neck cancer who were scheduled for the examination for the first time. The phenomenological method according to van Manen and his four lifeworld existentials; lived space, lived body, lived time, and lived relation was used to analyse the interviews. The thoughts and feelings of the patients during the PET/CT examination varied, some found it very difficult, while others did not. However, for all the patients, it was an experience that required some form of coping to maintain composure for example distraction. PET/CT examnation in a fixation mask may be strenuous for some patients. Patients need more detailed information, including suggestions for coping behaviours, prior to the examination, as well as higher level of support during and after the examination. The results of this study may be used to improve patient care and optimize the procedure of PET/CT examination in a fixation mask. Copyright © 2017 Elsevier Ltd. All rights reserved.

Characterization and optimization of 3D-LCD module design

NASA Astrophysics Data System (ADS)

van Berkel, Cees; Clarke, John A.

1997-05-01

Autostereoscopic displays with flat panel liquid crystal display and lenticular sheets are receiving much attention. Multiview 3D-LCD is truly autostereoscopic because no head tracking is necessary and the technology is well poised to become a mass market consumer 3D display medium as the price of liquid crystal displays continues to drop. Making the viewing experience as natural as possible is of prime importance. The main challenges are to reduce the picket fence effect of the black mask and to try to get away with as few perspective views as possible. Our solution is to 'blur' the boundaries between the views. This hides the black mask image by spreading it out and softens the transition between one view and the next, encouraging the user to perceive 'solid objects' instead of a succession of flipping views. One way to achieve this is by introducing a new pixel design in which the pixels are slanted with respect to the column direction. Another way is to place the lenticular at a small (9.46 degree) angle with respect to the LCD columns. The effect of either method is that, as the observer moves sideways in front of the display, he always 'sees' a constant amount of black mask. This renders the black mask, in effect, invisible and eliminates the picket fence effect.

An algorithm for automatic parameter adjustment for brain extraction in BrainSuite

NASA Astrophysics Data System (ADS)

Rajagopal, Gautham; Joshi, Anand A.; Leahy, Richard M.

2017-02-01

Brain Extraction (classification of brain and non-brain tissue) of MRI brain images is a crucial pre-processing step necessary for imaging-based anatomical studies of the human brain. Several automated methods and software tools are available for performing this task, but differences in MR image parameters (pulse sequence, resolution) and instrumentand subject-dependent noise and artefacts affect the performance of these automated methods. We describe and evaluate a method that automatically adapts the default parameters of the Brain Surface Extraction (BSE) algorithm to optimize a cost function chosen to reflect accurate brain extraction. BSE uses a combination of anisotropic filtering, Marr-Hildreth edge detection, and binary morphology for brain extraction. Our algorithm automatically adapts four parameters associated with these steps to maximize the brain surface area to volume ratio. We evaluate the method on a total of 109 brain volumes with ground truth brain masks generated by an expert user. A quantitative evaluation of the performance of the proposed algorithm showed an improvement in the mean (s.d.) Dice coefficient from 0.8969 (0.0376) for default parameters to 0.9509 (0.0504) for the optimized case. These results indicate that automatic parameter optimization can result in significant improvements in definition of the brain mask.

AutoCPAP initiation at home: optimal trial duration and cost-effectiveness.

PubMed

Bachour, Adel; Virkkala, Jussi T; Maasilta, Paula K

2007-11-01

The duration of automatic computer-controlled continuous positive airway pressure device (autoCPAP) initiation at home varies largely between sleep centers. Our objectives were to evaluate the cost-effectiveness and to find the optimal trial duration. Of the 206 consecutive CPAP-naive patients with obstructive sleep apnea syndrome, who were referred to our hospital, 166 received autoCPAP for a 5-day trial at home. Of the 166 patients, 89 (15 women) showed a successful 5-day autoCPAP trial (normalized oximetry and mask-on time exceeding 4 h/day for at least 4 days). For the first trial day, 88 (53%) patients had normalized oximetry and a mask-on time exceeding 4 h. A 1-day autoCPAP trial EUR 668 was less cost-effective than a 5-day trial EUR 653, with no differences in values of efficient CPAP pressure or residual apnea-hypopnea index (AHI). The systematic requirement of oximetry monitoring raised the cost considerably from EUR 481 to EUR 668. In selected patients with obstructive sleep apnea, the optimal duration for initiating CPAP therapy at home by autoCPAP is 5 days. Although a 1-day trial was sufficient to determine the CPAP pressure requirement, it was not cost-effective and had a high rate of failure.

New PSM optimized for stable resolution of fine holes in FPD

NASA Astrophysics Data System (ADS)

Imashiki, Nobuhisa; Yoshikawa, Yutaka; Hayase, Michihiko

2017-07-01

Recently, due to increases in the definition of high function panels for mobile devices such as smartphones and tablets, LCD panel TFT and OLED (organic electro luminescence display) circuits are becoming increasingly denser and more miniaturized by the year. TFT and OLED circuits are composed of several layers, such as gate, semiconductor and contact hole (C / H). It is particularly difficult to obtain a stable resolution for C/H due to the decrease in the C/H process margin (EL, DOF, MEEF) as a result of increases in the density of the circuit. Moreover, C/H productivity has also markedly decreased due to an increase in the exposure dose. In response to this, attenuated phase shift mask (Att. PSM) for large size photomasks have been proposed as a means to improve the process margin in FPD. We have developed new PSM that can further improve the process margin and the productivity of C/H via the effective positioning of a high transmittance phase shift film. Using a 1.5um sized hole as the target, we confirmed the improvement effect of the optimized PSM via a software simulation and an exposure test. Hereafter it is necessary for us to optimize the new PSM for each panel process so as to allow us to use this mask in actual processes.

Comparison of DNQ/novolac resists for e-beam exposure

NASA Astrophysics Data System (ADS)

Fedynyshyn, Theodore H.; Doran, Scott P.; Lind, Michele L.; Lyszczarz, Theodore M.; DiNatale, William F.; Lennon, Donna; Sauer, Charles A.; Meute, Jeff

1999-12-01

We have surveyed the commercial resist market with the dual purpose of identifying diazoquinone/novolac based resists that have potential for use as e-beam mask making resists and baselining these resists for comparison against future mask making resist candidates. For completeness, this survey would require that each resist be compared with an optimized developer and development process. To accomplish this task in an acceptable time period, e-beam lithography modeling was employed to quickly identify the resist and developer combinations that lead to superior resist performance. We describe the verification of a method to quickly screen commercial i-line resists with different developers, by determining modeling parameters for i-line resists from e-beam exposures, modeling the resist performance, and comparing predicted performance versus actual performance. We determined the lithographic performance of several DNQ/novolac resists whose modeled performance suggests that sensitivities of less than 40 (mu) C/cm2 coupled with less than 10-nm CD change per percent change in dose are possible for target 600-nm features. This was accomplished by performing a series of statistically designed experiments on the leading resists candidates to optimize processing variables, followed by comparing experimentally determined resist sensitivities, latitudes, and profiles of the DNQ/novolac resists a their optimized process.

Micro-optics: enabling technology for illumination shaping in optical lithography

NASA Astrophysics Data System (ADS)

Voelkel, Reinhard

2014-03-01

Optical lithography has been the engine that has empowered semiconductor industry to continually reduce the half-pitch for over 50 years. In early mask aligners a simple movie lamp was enough to illuminate the photomask. Illumination started to play a more decisive role when proximity mask aligners appeared in the mid-1970s. Off-axis illumination was introduced to reduce diffraction effects. For early projection lithography systems (wafer steppers), the only challenge was to collect the light efficiently to ensure short exposure time. When projection optics reached highest level of perfection, further improvement was achieved by optimizing illumination. Shaping the illumination light, also referred as pupil shaping, allows the optical path from reticle to wafer to be optimized and thus has a major impact on aberrations and diffraction effects. Highly-efficient micro-optical components are perfectly suited for this task. Micro-optics for illumination evolved from simple flat-top (fly's-eye) to annular, dipole, quadrupole, multipole and freeform illumination. Today, programmable micro-mirror arrays allow illumination to be changed on the fly. The impact of refractive, diffractive and reflective microoptics for photolithography will be discussed.

Automated image segmentation-assisted flattening of atomic force microscopy images.

PubMed

Wang, Yuliang; Lu, Tongda; Li, Xiaolai; Wang, Huimin

2018-01-01

Atomic force microscopy (AFM) images normally exhibit various artifacts. As a result, image flattening is required prior to image analysis. To obtain optimized flattening results, foreground features are generally manually excluded using rectangular masks in image flattening, which is time consuming and inaccurate. In this study, a two-step scheme was proposed to achieve optimized image flattening in an automated manner. In the first step, the convex and concave features in the foreground were automatically segmented with accurate boundary detection. The extracted foreground features were taken as exclusion masks. In the second step, data points in the background were fitted as polynomial curves/surfaces, which were then subtracted from raw images to get the flattened images. Moreover, sliding-window-based polynomial fitting was proposed to process images with complex background trends. The working principle of the two-step image flattening scheme were presented, followed by the investigation of the influence of a sliding-window size and polynomial fitting direction on the flattened images. Additionally, the role of image flattening on the morphological characterization and segmentation of AFM images were verified with the proposed method.

Application of Deep Learning Architectures for Accurate and Rapid Detection of Internal Mechanical Damage of Blueberry Using Hyperspectral Transmittance Data.

PubMed

Wang, Zhaodi; Hu, Menghan; Zhai, Guangtao

2018-04-07

Deep learning has become a widely used powerful tool in many research fields, although not much so yet in agriculture technologies. In this work, two deep convolutional neural networks (CNN), viz. Residual Network (ResNet) and its improved version named ResNeXt, are used to detect internal mechanical damage of blueberries using hyperspectral transmittance data. The original structure and size of hypercubes are adapted for the deep CNN training. To ensure that the models are applicable to hypercube, we adjust the number of filters in the convolutional layers. Moreover, a total of 5 traditional machine learning algorithms, viz. Sequential Minimal Optimization (SMO), Linear Regression (LR), Random Forest (RF), Bagging and Multilayer Perceptron (MLP), are performed as the comparison experiments. In terms of model assessment, k-fold cross validation is used to indicate that the model performance does not vary with the different combination of dataset. In real-world application, selling damaged berries will lead to greater interest loss than discarding the sound ones. Thus, precision, recall, and F1-score are also used as the evaluation indicators alongside accuracy to quantify the false positive rate. The first three indicators are seldom used by investigators in the agricultural engineering domain. Furthermore, ROC curves and Precision-Recall curves are plotted to visualize the performance of classifiers. The fine-tuned ResNet/ResNeXt achieve average accuracy and F1-score of 0.8844/0.8784 and 0.8952/0.8905, respectively. Classifiers SMO/ LR/RF/Bagging/MLP obtain average accuracy and F1-score of 0.8082/0.7606/0.7314/0.7113/0.7827 and 0.8268/0.7796/0.7529/0.7339/0.7971, respectively. Two deep learning models achieve better classification performance than the traditional machine learning methods. Classification for each testing sample only takes 5.2 ms and 6.5 ms respectively for ResNet and ResNeXt, indicating that the deep learning framework has great potential for online fruit sorting. The results of this study demonstrate the potential of deep CNN application on analyzing the internal mechanical damage of fruit.

Application of Deep Learning Architectures for Accurate and Rapid Detection of Internal Mechanical Damage of Blueberry Using Hyperspectral Transmittance Data

PubMed Central

Hu, Menghan; Zhai, Guangtao

2018-01-01

Deep learning has become a widely used powerful tool in many research fields, although not much so yet in agriculture technologies. In this work, two deep convolutional neural networks (CNN), viz. Residual Network (ResNet) and its improved version named ResNeXt, are used to detect internal mechanical damage of blueberries using hyperspectral transmittance data. The original structure and size of hypercubes are adapted for the deep CNN training. To ensure that the models are applicable to hypercube, we adjust the number of filters in the convolutional layers. Moreover, a total of 5 traditional machine learning algorithms, viz. Sequential Minimal Optimization (SMO), Linear Regression (LR), Random Forest (RF), Bagging and Multilayer Perceptron (MLP), are performed as the comparison experiments. In terms of model assessment, k-fold cross validation is used to indicate that the model performance does not vary with the different combination of dataset. In real-world application, selling damaged berries will lead to greater interest loss than discarding the sound ones. Thus, precision, recall, and F1-score are also used as the evaluation indicators alongside accuracy to quantify the false positive rate. The first three indicators are seldom used by investigators in the agricultural engineering domain. Furthermore, ROC curves and Precision-Recall curves are plotted to visualize the performance of classifiers. The fine-tuned ResNet/ResNeXt achieve average accuracy and F1-score of 0.8844/0.8784 and 0.8952/0.8905, respectively. Classifiers SMO/ LR/RF/Bagging/MLP obtain average accuracy and F1-score of 0.8082/0.7606/0.7314/0.7113/0.7827 and 0.8268/0.7796/0.7529/0.7339/0.7971, respectively. Two deep learning models achieve better classification performance than the traditional machine learning methods. Classification for each testing sample only takes 5.2 ms and 6.5 ms respectively for ResNet and ResNeXt, indicating that the deep learning framework has great potential for online fruit sorting. The results of this study demonstrate the potential of deep CNN application on analyzing the internal mechanical damage of fruit. PMID:29642454

Study of residue type defect formation mechanism and the effect of advanced defect reduction (ADR) rinse process

NASA Astrophysics Data System (ADS)

Arima, Hiroshi; Yoshida, Yuichi; Yoshihara, Kosuke; Shibata, Tsuyoshi; Kushida, Yuki; Nakagawa, Hiroki; Nishimura, Yukio; Yamaguchi, Yoshikazu

2009-03-01

Residue type defect is one of yield detractors in lithography process. It is known that occurrence of the residue type defect is dependent on resist development process and the defect is reduced by optimized rinsing condition. However, the defect formation is affected by resist materials and substrate conditions. Therefore, it is necessary to optimize the development process condition by each mask level. Those optimization steps require a large amount of time and effort. The formation mechanism is investigated from viewpoint of both material and process. The defect formation is affected by resist material types, substrate condition and development process condition (D.I.W. rinse step). Optimized resist formulation and new rinse technology significantly reduce the residue type defect.

Low-Angle-Incidence Microchannel Epitaxy of a-Plane GaN Grown by Ammonia-Based Metal-Organic Molecular Beam Epitaxy

NASA Astrophysics Data System (ADS)

Lin, Chia-Hung; Uchiyama, Shota; Maruyama, Takahiro; Naritsuka, Shigeya

2012-04-01

Low-angle-incidence microchannel epitaxy (LAIMCE) of a-plane GaN was performed using ammonia-based metal-organic molecular beam epitaxy to obtain wide and thin lateral overgrowth over a SiO2 mask. Trimethylgallium (TMG) was supplied perpendicular to the openings cut in the mask with a low incident angle of 5° relative to the substrate plane. The [NH3]/[TMG] ratio (R) dependence of GaN LAIMCE was optimized by varying R from 5 to 30. A wide lateral overgrowth of 3.7 µm with a dislocation density below the transmission electron microscope detection limit was obtained at R=15 for a thickness of 520 nm.

Setup calibration and optimization for comparative digital holography

NASA Astrophysics Data System (ADS)

Baumbach, Torsten; Osten, Wolfgang; Kebbel, Volker; von Kopylow, Christoph; Jueptner, Werner

2004-08-01

With increasing globalization many enterprises decide to produce the components of their products at different locations all over the world. Consequently, new technologies and strategies for quality control are required. In this context the remote comparison of objects with regard to their shape or response on certain loads is getting more and more important for a variety of applications. For such a task the novel method of comparative digital holography is a suitable tool with interferometric sensitivity. With this technique the comparison in shape or deformation of two objects does not require the presence of both objects at the same place. In contrast to the well known incoherent techniques based on inverse fringe projection this new approach uses a coherent mask for the illumination of the sample object. The coherent mask is created by digital holography to enable the instant access to the complete optical information of the master object at any wanted place. The reconstruction of the mask is done by a spatial light modulator (SLM). The transmission of the digital master hologram to the place of comparison can be done via digital telecommunication networks. Contrary to other interferometric techniques this method enables the comparison of objects with different microstructure. In continuation of earlier reports our investigations are focused here on the analysis of the constraints of the setup with respect to the quality of the hologram reconstruction with a spatial light modulator. For successful measurements the selection of the appropriate reconstruction method and the adequate optical set-up is mandatory. In addition, the use of a SLM for the reconstruction requires the knowledge of its properties for the accomplishment of this method. The investigation results for the display properties such as display curvature, phase shift and the consequences for the technique will be presented. The optimization and the calibration of the set-up and its components lead to improved results in comparative digital holography with respect to the resolution. Examples of measurements before and after the optimization and calibration will be presented.

A Human Activity Recognition System Based on Dynamic Clustering of Skeleton Data.

PubMed

Manzi, Alessandro; Dario, Paolo; Cavallo, Filippo

2017-05-11

Human activity recognition is an important area in computer vision, with its wide range of applications including ambient assisted living. In this paper, an activity recognition system based on skeleton data extracted from a depth camera is presented. The system makes use of machine learning techniques to classify the actions that are described with a set of a few basic postures. The training phase creates several models related to the number of clustered postures by means of a multiclass Support Vector Machine (SVM), trained with Sequential Minimal Optimization (SMO). The classification phase adopts the X-means algorithm to find the optimal number of clusters dynamically. The contribution of the paper is twofold. The first aim is to perform activity recognition employing features based on a small number of informative postures, extracted independently from each activity instance; secondly, it aims to assess the minimum number of frames needed for an adequate classification. The system is evaluated on two publicly available datasets, the Cornell Activity Dataset (CAD-60) and the Telecommunication Systems Team (TST) Fall detection dataset. The number of clusters needed to model each instance ranges from two to four elements. The proposed approach reaches excellent performances using only about 4 s of input data (~100 frames) and outperforms the state of the art when it uses approximately 500 frames on the CAD-60 dataset. The results are promising for the test in real context.

Public Health Impact of Wildfire Emissions: Up-date on the Wildfire Smoke Guide, Public Health Information and Communications Research

EPA Science Inventory

EPA Tools and Resources Webinar: Public Health Impact of Wildfire Smoke Emissions Specific strategies to reduce smoke exposure and the Smoke Sense App As the start of the summer wildfire season approaches, public officials, communities and individuals need up-to-date wildfire smo...

Ecosystems and diversity of the Sierra Madre Occidental

Treesearch

M. S. Gonzalez-Elizondo; M. Gonzalez-Elizondo; L. Ruacho Gonzalez; I. L. Lopez Enriquez; F. I . Retana Renteria; J. A. Tena Flores

2013-01-01

The Sierra Madre Occidental (SMO) is the largest continuous ignimbrite plate on Earth. Despite its high biological and cultural diversity and enormous environmental and economical importance, it is yet not well known. We describe the vegetation and present a preliminary regionalization based on physiographic, climatic, and floristic criteria. A confluence of three main...

Serbo-Croatian. SC-15A. Part 3. Advanced Grammar and Syntax,

DTIC Science & Technology

1983-09-01

mislili smo, (mi) The second person designates the person whom the speaker is addressing. Sg. govoris, pevas , pises, pevao si (ti) PI. govorite, pevate...one who is addressed. Sg. govori (on or ona), peva , pise, je pevao (la) PI. govore, pevau, pisu, su pevali(le) (one, oni) II. Aspect Predicates: There

Targeting human respiratory syncytial virus transcription anti-termination factor M2-1 to inhibit in vivo viral replication

PubMed Central

Bailly, B.; Richard, C.-A.; Sharma, G.; Wang, L.; Johansen, L.; Cao, J.; Pendharkar, V.; Sharma, D.-C.; Galloux, M.; Wang, Y.; Cui, R.; Zou, G.; Guillon, P.; von Itzstein, M.; Eléouët, J.-F.; Altmeyer, R.

2016-01-01

Human respiratory syncytial virus (hRSV) is a leading cause of acute lower respiratory tract infection in infants, elderly and immunocompromised individuals. To date, no specific antiviral drug is available to treat or prevent this disease. Here, we report that the Smoothened receptor (Smo) antagonist cyclopamine acts as a potent and selective inhibitor of in vitro and in vivo hRSV replication. Cyclopamine inhibits hRSV through a novel, Smo-independent mechanism. It specifically impairs the function of the hRSV RNA-dependent RNA polymerase complex notably by reducing expression levels of the viral anti-termination factor M2-1. The relevance of these findings is corroborated by the demonstration that a single R151K mutation in M2-1 is sufficient to confer virus resistance to cyclopamine in vitro and that cyclopamine is able to reduce virus titers in a mouse model of hRSV infection. The results of our study open a novel avenue for the development of future therapies against hRSV infection. PMID:27194388

mTORC1-Mediated Inhibition of 4EBP1 Is Essential for Hedgehog Signaling-Driven Translation and Medulloblastoma.

PubMed

Wu, Chang-Chih; Hou, Shirui; Orr, Brent A; Kuo, Bryan R; Youn, Yong Ha; Ong, Taren; Roth, Fanny; Eberhart, Charles G; Robinson, Giles W; Solecki, David J; Taketo, Makoto M; Gilbertson, Richard J; Roussel, Martine F; Han, Young-Goo

2017-12-18

Mechanistic target of rapamycin (MTOR) cooperates with Hedgehog (HH) signaling, but the underlying mechanisms are incompletely understood. Here we provide genetic, biochemical, and pharmacologic evidence that MTOR complex 1 (mTORC1)-dependent translation is a prerequisite for HH signaling. The genetic loss of mTORC1 function inhibited HH signaling-driven growth of the cerebellum and medulloblastoma. Inhibiting translation or mTORC1 blocked HH signaling. Depleting 4EBP1, an mTORC1 target that inhibits translation, alleviated the dependence of HH signaling on mTORC1. Consistent with this, phosphorylated 4EBP1 levels were elevated in HH signaling-driven medulloblastomas in mice and humans. In mice, an mTORC1 inhibitor suppressed medulloblastoma driven by a mutant SMO that is inherently resistant to existing SMO inhibitors, prolonging the survival of the mice. Our study reveals that mTORC1-mediated translation is a key component of HH signaling and an important target for treating medulloblastoma and other cancers driven by HH signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

Sliding Mode Observer-Based Current Sensor Fault Reconstruction and Unknown Load Disturbance Estimation for PMSM Driven System.

PubMed

Zhao, Kaihui; Li, Peng; Zhang, Changfan; Li, Xiangfei; He, Jing; Lin, Yuliang

2017-12-06

This paper proposes a new scheme of reconstructing current sensor faults and estimating unknown load disturbance for a permanent magnet synchronous motor (PMSM)-driven system. First, the original PMSM system is transformed into two subsystems; the first subsystem has unknown system load disturbances, which are unrelated to sensor faults, and the second subsystem has sensor faults, but is free from unknown load disturbances. Introducing a new state variable, the augmented subsystem that has sensor faults can be transformed into having actuator faults. Second, two sliding mode observers (SMOs) are designed: the unknown load disturbance is estimated by the first SMO in the subsystem, which has unknown load disturbance, and the sensor faults can be reconstructed using the second SMO in the augmented subsystem, which has sensor faults. The gains of the proposed SMOs and their stability analysis are developed via the solution of linear matrix inequality (LMI). Finally, the effectiveness of the proposed scheme was verified by simulations and experiments. The results demonstrate that the proposed scheme can reconstruct current sensor faults and estimate unknown load disturbance for the PMSM-driven system.

Treatment of oily waters using vermiculite.

PubMed

Mysore, Deepa; Viraraghavan, Thiruvenkatachari; Jin, Yee-Chung

2005-07-01

The main objective of this study was to examine the removal of oil from water by expanded and hydrophobized vermiculite. A pH of 9 showed a higher removal efficiency of oil by vermiculite. Oil removal efficiencies at pH 9 were found to be 79%, 93%, 90%, 57% for standard mineral oil (SMO), Canola oil (CO), Kutwell oil (KUT45), refinery effluent (RE), respectively, in the case of expanded vermiculite, and 56%, 58%, 47%, 43% for SMO, CO, KUT45 and RE, respectively, for hydrophobized vermiculite. Kinetic data satisfied both the Lagergren and Ho models. Equilibrium studies showed that the Langmuir isotherm was the best-fit isotherm for oil removal by both expanded and hydrophobized vermiculite. The data showed a higher adsorptive capacity by the expanded vermiculite compared to the hydrophobized vermiculite. Desorption studies showed that the expanded vermiculite did not desorb oil to the same extent compared to hydrophobized vermiculite. The Freundlich isotherm was the best-fit model for desorption. Expanded vermiculite showed better retention than hydrophobic vermiculite. The results showed that the expanded vermiculite had a greater affinity for oil than hydrophobized vermiculite.

Metal-ion interactions with carbohydrates. Crystal structure and FT-IR study of the SmCl3-ribose complex.

PubMed

Lu, Yan; Guo, Jianyu

2006-04-10

A single-crystal of SmCl3.C5H10O5.5H2O was obtained from methanol-water solution and its structure determined by X-ray. Two forms of the complex as a pair of anomers and related conformers were found in the single-crystal in a disordered state. One ligand is alpha-D-ribopyranose in the 4C1 conformation and the other one is beta-D-ribopyranose. The anomeric ratio is 1:1. Both ligands provide three hydroxyl groups in ax-eq-ax orientation for coordination. The Sm3+ ion is nine-coordinated with five Sm-O bonds from water molecules, three Sm-O bonds from hydroxyl groups of the D-ribopyranose and one Sm-Cl bond. The hydroxyl groups, water molecules and chloride ions form an extensive hydrogen-bond network. The IR spectral C-C, O-H, C-O, and C-O-H vibrations were observed to be shifted in the complex and the IR results are in accord with those of X-ray diffraction.

A study and simulation of the impact of high-order aberrations to overlay error distribution

NASA Astrophysics Data System (ADS)

Sun, G.; Wang, F.; Zhou, C.

2011-03-01

With reduction of design rules, a number of corresponding new technologies, such as i-HOPC, HOWA and DBO have been proposed and applied to eliminate overlay error. When these technologies are in use, any high-order error distribution needs to be clearly distinguished in order to remove the underlying causes. Lens aberrations are normally thought to mainly impact the Matching Machine Overlay (MMO). However, when using Image-Based overlay (IBO) measurement tools, aberrations become the dominant influence on single machine overlay (SMO) and even on stage repeatability performance. In this paper, several measurements of the error distributions of the lens of SMEE SSB600/10 prototype exposure tool are presented. Models that characterize the primary influence from lens magnification, high order distortion, coma aberration and telecentricity are shown. The contribution to stage repeatability (as measured with IBO tools) from the above errors was predicted with simulator and compared to experiments. Finally, the drift of every lens distortion that impact to SMO over several days was monitored and matched with the result of measurements.

Edge detection - Image-plane versus digital processing

NASA Technical Reports Server (NTRS)

Huck, Friedrich O.; Fales, Carl L.; Park, Stephen K.; Triplett, Judith A.

1987-01-01

To optimize edge detection with the familiar Laplacian-of-Gaussian operator, it has become common to implement this operator with a large digital convolution mask followed by some interpolation of the processed data to determine the zero crossings that locate edges. It is generally recognized that this large mask causes substantial blurring of fine detail. It is shown that the spatial detail can be improved by a factor of about four with either the Wiener-Laplacian-of-Gaussian filter or an image-plane processor. The Wiener-Laplacian-of-Gaussian filter minimizes the image-gathering degradations if the scene statistics are at least approximately known and also serves as an interpolator to determine the desired zero crossings directly. The image-plane processor forms the Laplacian-of-Gaussian response by properly combining the optical design of the image-gathering system with a minimal three-by-three lateral-inhibitory processing mask. This approach, which is suggested by Marr's model of early processing in human vision, also reduces data processing by about two orders of magnitude and data transmission by up to an order of magnitude.

Estimation of Orbital Neutron Detector Spatial Resolution by Systematic Shifting of Differential Topographic Masks

NASA Technical Reports Server (NTRS)

McClanahan, T. P.; Mitrofanov, I. G.; Boynton, W. V.; Chin, G.; Livengood, T.; Starr, R. D.; Evans, L. G.; Mazarico, E.; Smith, D. E.

2012-01-01

We present a method and preliminary results related to determining the spatial resolution of orbital neutron detectors using epithermal maps and differential topographic masks. Our technique is similar to coded aperture imaging methods for optimizing photonic signals in telescopes [I]. In that approach photon masks with known spatial patterns in a telescope aperature are used to systematically restrict incoming photons which minimizes interference and enhances photon signal to noise. Three orbital neutron detector systems with different stated spatial resolutions are evaluated. The differing spatial resolutions arise due different orbital altitudes and the use of neutron collimation techniques. 1) The uncollimated Lunar Prospector Neutron Spectrometer (LPNS) system has spatial resolution of 45km FWHM from approx. 30km altitude mission phase [2]. The Lunar Rennaissance Orbiter (LRO) Lunar Exploration Neutron Detector (LEND) with two detectors at 50km altitude evaluated here: 2) the collimated 10km FWHM spatial resolution detector CSETN and 3) LEND's collimated Sensor for Epithermal Neutrons (SETN). Thus providing two orbital altitudes to study factors of: uncollimated vs collimated and two average altitudes for their effect on fields-of-view.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barnard, John J.; Schenkel, Thomas

Intense, pulsed ion beams locally heat materials and deliver dense electronic excitations that can induce material modifications and phase transitions. Material properties can potentially be stabilized by rapid quenching. Pulsed ion beams with pulse lengths of order ns have recently become available for materials processing. Here, we optimize mask geometries for local modification of materials by intense ion pulses. The goal is to rapidly excite targets volumetrically to the point where a phase transition or local lattice reconstruction is induced followed by rapid cooling that stabilizes desired material's properties fast enough before the target is altered or damaged by, e.g.,more » hydrodynamic expansion. By using a mask, the longitudinal dimension can be large compared to the transverse dimension, allowing the possibility of rapid transverse cooling. We performed HYDRA simulations that calculate peak temperatures for a series of excitation conditions and cooling rates of silicon targets with micro-structured masks and compare these to a simple analytical model. In conclusion, the model gives scaling laws that can guide the design of targets over a wide range of pulsed ion beam parameters.« less

Genetic Algorithms Applied to Multi-Objective Aerodynamic Shape Optimization

NASA Technical Reports Server (NTRS)

Holst, Terry L.

2004-01-01

A genetic algorithm approach suitable for solving multi-objective optimization problems is described and evaluated using a series of aerodynamic shape optimization problems. Several new features including two variations of a binning selection algorithm and a gene-space transformation procedure are included. The genetic algorithm is suitable for finding pareto optimal solutions in search spaces that are defined by any number of genes and that contain any number of local extrema. A new masking array capability is included allowing any gene or gene subset to be eliminated as decision variables from the design space. This allows determination of the effect of a single gene or gene subset on the pareto optimal solution. Results indicate that the genetic algorithm optimization approach is flexible in application and reliable. The binning selection algorithms generally provide pareto front quality enhancements and moderate convergence efficiency improvements for most of the problems solved.

Automated annotation of functional imaging experiments via multi-label classification

PubMed Central

Turner, Matthew D.; Chakrabarti, Chayan; Jones, Thomas B.; Xu, Jiawei F.; Fox, Peter T.; Luger, George F.; Laird, Angela R.; Turner, Jessica A.

2013-01-01

Identifying the experimental methods in human neuroimaging papers is important for grouping meaningfully similar experiments for meta-analyses. Currently, this can only be done by human readers. We present the performance of common machine learning (text mining) methods applied to the problem of automatically classifying or labeling this literature. Labeling terms are from the Cognitive Paradigm Ontology (CogPO), the text corpora are abstracts of published functional neuroimaging papers, and the methods use the performance of a human expert as training data. We aim to replicate the expert's annotation of multiple labels per abstract identifying the experimental stimuli, cognitive paradigms, response types, and other relevant dimensions of the experiments. We use several standard machine learning methods: naive Bayes (NB), k-nearest neighbor, and support vector machines (specifically SMO or sequential minimal optimization). Exact match performance ranged from only 15% in the worst cases to 78% in the best cases. NB methods combined with binary relevance transformations performed strongly and were robust to overfitting. This collection of results demonstrates what can be achieved with off-the-shelf software components and little to no pre-processing of raw text. PMID:24409112

Multivariate Time Series Forecasting of Crude Palm Oil Price Using Machine Learning Techniques

NASA Astrophysics Data System (ADS)

Kanchymalay, Kasturi; Salim, N.; Sukprasert, Anupong; Krishnan, Ramesh; Raba'ah Hashim, Ummi

2017-08-01

The aim of this paper was to study the correlation between crude palm oil (CPO) price, selected vegetable oil prices (such as soybean oil, coconut oil, and olive oil, rapeseed oil and sunflower oil), crude oil and the monthly exchange rate. Comparative analysis was then performed on CPO price forecasting results using the machine learning techniques. Monthly CPO prices, selected vegetable oil prices, crude oil prices and monthly exchange rate data from January 1987 to February 2017 were utilized. Preliminary analysis showed a positive and high correlation between the CPO price and soy bean oil price and also between CPO price and crude oil price. Experiments were conducted using multi-layer perception, support vector regression and Holt Winter exponential smoothing techniques. The results were assessed by using criteria of root mean square error (RMSE), means absolute error (MAE), means absolute percentage error (MAPE) and Direction of accuracy (DA). Among these three techniques, support vector regression(SVR) with Sequential minimal optimization (SMO) algorithm showed relatively better results compared to multi-layer perceptron and Holt Winters exponential smoothing method.

Thermoelectric properties of FeAs based superconductors, with thick perovskite- and Sm-O fluorite-type blocking layers

NASA Astrophysics Data System (ADS)

Singh, S. J.; Shimoyama, J.; Ogino, H.; Kishio, K.

2015-11-01

The transport properties (electrical resistivity, Hall and Seebeck coefficient, and thermal conductivity) of iron based superconductors with thick perovskite-type oxide blocking layers and fluorine-doped SmFeAsO were studied to explore their possible potential for thermoelectric applications. The thermal conductivity of former compounds depicts the dominated role of phonon and its value decreases rapidly below the Tc, suggesting the addition of scattering of phonons. Both the Seebeck coefficient (S) and Hall coefficient (RH) of all samples were negative in the whole temperature region below 300 K, indicating that the major contribution to the normal state conductivity is by electrons. In addition, the profile of S(T) and RH(T) of all samples have similar behaviours as would be expected for a multi-band superconductors. Although the estimated thermoelectric figure of merit (ZT) of these compounds was much lower than that of practically applicable thermoelectric materials, however its improvement can be expected by optimizing microstructure of the polycrystalline materials, such as densification and grain orientation.

Mask characterization for CDU budget breakdown in advanced EUV lithography

NASA Astrophysics Data System (ADS)

Nikolsky, Peter; Strolenberg, Chris; Nielsen, Rasmus; Nooitgedacht, Tjitte; Davydova, Natalia; Yang, Greg; Lee, Shawn; Park, Chang-Min; Kim, Insung; Yeo, Jeong-Ho

2012-11-01

As the ITRS Critical Dimension Uniformity (CDU) specification shrinks, semiconductor companies need to maintain a high yield of good wafers per day and a high performance (and hence market value) of finished products. This cannot be achieved without continuous analysis and improvement of on-product CDU as one of the main drivers for process control and optimization with better understanding of main contributors from the litho cluster: mask, process, metrology and scanner. In this paper we will demonstrate a study of mask CDU characterization and its impact on CDU Budget Breakdown (CDU BB) performed for an advanced EUV lithography with 1D and 2D feature cases. We will show that this CDU contributor is one of the main differentiators between well-known ArFi and new EUV CDU budgeting principles. We found that reticle contribution to intrafield CDU should be characterized in a specific way: mask absorber thickness fingerprints play a role comparable with reticle CDU in the total reticle part of the CDU budget. Wafer CD fingerprints, introduced by this contributor, may or may not compensate variations of mask CD's and hence influence on total mask impact on intrafield CDU at the wafer level. This will be shown on 1D and 2D feature examples in this paper. Also mask stack reflectivity variations should be taken into account: these fingerprints have visible impact on intrafield CDs at the wafer level and should be considered as another contributor to the reticle part of EUV CDU budget. We observed also MEEF-through-field fingerprints in the studied EUV cases. Variations of MEEF may also play a role for the total intrafield CDU and may be taken into account for EUV Lithography. We characterized MEEF-through-field for the reviewed features, the results to be discussed in our paper, but further analysis of this phenomenon is required. This comprehensive approach to characterization of the mask part of EUV CDU characterization delivers an accurate and integral CDU Budget Breakdown per product/process and Litho tool. The better understanding of the entire CDU budget for advanced EUVL nodes achieved by Samsung and ASML helps to extend the limits of Moore's Law and to deliver successful implementation of smaller, faster and smarter chips in semiconductor industry.

Slit device for FOCCoS-PFS-Subaru

NASA Astrophysics Data System (ADS)

de Oliveira, Antonio Cesar; Gunn, James E.; de Oliveira, Ligia Souza; Vital de Arruda, Marcio; Souza Marrara, Lucas; dos Santos, Leandro Henrique; Ferreira, Décio; dos Santos, Jesulino Bispo; Rosa, Josimar Aparecido; Ribeiro, Flavio Felipe; Vilaça, Rodrigo de Paiva; Verducci, Orlando; Sodré, Laerte; Oliveira, Claudia Mendes

2014-07-01

The Fiber Optical Cable and Connector System, "FOCCoS", subsystem of the Prime Focus Spectrograph, "PFS", for Subaru telescope, is responsible to feed four spectrographs with a set of optical fibers cables. The light injection for each spectrograph is assured by a convex curved slit with a linear array of 616 optical fibers. In this paper we present a design of a slit that ensures the right direction of the fibers by using masks of micro holes. This kind of mask is made by a technique called electroforming, which is able to produce a nickel plate with holes in a linear sequence. The precision error is around 1-μm in the diameter and 1-μm in the positions of the holes. This nickel plate may be produced with a thickness between 50 and 200 microns, so it may be very flexible. This flexibility allows the mask to be bent into the shape necessary for a curved slit. The concept requires two masks, which we call Front Mask, and Rear Mask, separated by a gap that defines the thickness of the slit. The pitch and the diameter of the holes define the linear geometry of the slit; the curvature of each mask defines the angular geometry of the slit. Obviously, this assembly must be mounted inside a structure rigid and strong enough to be supported inside the spectrograph. This structure must have a CTE optimized to avoid displacement of the fibers or increased FRD of the fibers when the device is submitted to temperatures around 3 degrees Celsius, the temperature of operation of the spectrograph. We have produced two models. Both are mounted inside a very compact Invar case, and both have their front surfaces covered by a dark composite, to reduce stray light. Furthermore, we have conducted experiments with two different internal structures to minimize effects caused by temperature gradients. This concept has several advantages relative to a design based on Vgrooves, which is the classical option. It is much easier and quicker to assemble, much cheaper, more accurate, easier to adjust; and it also offers the possibility of making a device much more strong, robust and completely miniaturized.

Analysis of channel confined selective area growth in evolutionary growth of GaN on SiO 2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leung, Benjamin; Tsai, Miao-Chan; Song, Jie

2015-09-01

Here, we analyze the chemical vapor deposition of semiconductor crystals by selective area growth in a non-planar geometry. Specifically, the growth process in laterally and vertically confined masks forming single-crystal GaN on SiO2 by metal-organic chemical vapor deposition is considered in detail. A textured AlN seed is used to initiate growth of oriented GaN selectively through the mask, allowing the reduction of degrees of freedom by the evolutionary grain selection process. As shown by measurements of growth rates within the mask, the sub micron length scale of the channel opening is comparable to the mean free path of precursors inmore » the gas phase, resulting in transport characteristics that can be described by an intermediate flow regime between continuum and free-molecular. Mass transport is modeled through kinetic theory to explain the growth rate enhancements of more than a factor of two by changes in reactor pressure. The growth conditions that enable the modification of nucleation density within the channel are then discussed, and are measured by electron-back scatter diffraction of the nucleated grains on the AlN seed. Finally, the selectivity behavior using the low fill factor masks needed in these configurations has been optimized by control of precursor flow rates and the H2 enhanced etching of the polycrystalline GaN nuclei.« less

Design of a multistep phase mask for high-energy THz pulse generation in ZnTe crystal

NASA Astrophysics Data System (ADS)

Avetisyan, Yuri H.; Makaryan, Armen; Tadevosyan, Vahe

2017-08-01

A new scheme for generating high-energy terahertz (THz) pulses by optical rectification of tilted pulse front (TPF) femtosecond laser pulses in ZnTe crystal is proposed and analyzed. The TPF laser pulses are originated due to propagation through a multistep phase mask (MSPM) attached to the entrance surface of the nonlinear crystal. Similar to the case of contacting optical grating the necessity of the imaging optics is avoided. In addition, introduction of large amounts of angular dispersion is also eliminated. The operation principle is based on the fact that the MSPM splits a single input beam into many smaller time-delayed "beamlets", which together form a discretely TPF in the nonlinear crystal. The dimensions of the mask's steps required for high-energy THz-pulse generation in ZnTe and widely used lithium niobate (LN) crystals are calculated. The optimal number of steps is estimated taking into account individual beamlet's spatial broadening and problems related to the mask fabrication. The THz field in no pump depletion approximation is analytically calculated using radiating antenna model. The analysis shows that application of ZnTe crystal allows obtaining higher THz-pulse energy than that of LN crystal, especially when long-wavelength pump sources are used. The proposed method is a promising way to develop high-energy, monolithic, and alignment-free THzpulse source.

[Effectiveness of the HighFO novel oxygen nebulizer for respiratory failure patients with severe hypoxia].

PubMed

Takamatsu, Kazufumi; Sakuramoto, Minoru; Inoue, Daiki; Ishitoko, Manabu; Itotani, Ryo; Suzuki, Shinko; Matsumoto, Masataka; Takemura, Masaya; Fukui, Motonari

2011-04-01

Optimal oxygen delivery is an essential component of therapy for patients with respiratory failure. Reservoir masks or air entrainment nebulizers have often been used for patients who require highly concentrated oxygen, but these may not actually deliver a sufficient fraction of inspired oxygen if there is a marked increase in the patient's ventilatory demands, or if oxygen flow becomes limited due to high resistance in the nebulizer nozzles. The HighFO nebulizer is a novel air entrainment nebulizer equipped with unique structures which reduce nozzle resistance, and as a result, it is possible to supply a sufficient flow of highly concentrated-oxygen. The purpose of this study was to evaluate the effectiveness and usefulness of the HighFO nebulizer in 10 respiratory failure patients with severe hypoxemia who used a reservoir mask and required more than 10 L/min of oxygen supply. In each case, the reservoir mask was replaced with the HighFO nebulizer, and changes in percutaneous oxygen saturation (SpO2) were monitored using pulse oximetry. Oxygenation improved promptly after the reservoir mask was substituted for the HighFO nebulizer (SpO2 : 83.7% +/- 8.5%-94.2% +/- 3.2%, p = 0.007). This finding suggests that the HighFO nebulizer was reasonably effective in delivering highly concentrated oxygen, sufficient for patient demands. The HighFO nebulizer may be the beginning of a new strategy for oxygen therapy.

Genomic identification and biochemical characterization of the mammalian polyamine oxidase involved in polyamine back-conversion.

PubMed Central

Vujcic, Slavoljub; Liang, Ping; Diegelman, Paula; Kramer, Debora L; Porter, Carl W

2003-01-01

In the polyamine back-conversion pathway, spermine and spermidine are first acetylated by spermidine/spermine N1 -acetyltransferase (SSAT) and then oxidized by polyamine oxidase (PAO) to produce spermidine and putrescine respectively. Although PAO was first purified more than two decades ago, the protein has not yet been linked to genomic sequences. In the present study, we apply a BLAST search strategy to identify novel oxidase sequences located on human chromosome 10 and mouse chromosome 7. Homologous mammalian cDNAs derived from human brain and mouse mammary tumour were deduced to encode proteins of approx. 55 kDa having 82% sequence identity. When either cDNA was transiently transfected into HEK-293 cells, intracellular spermine pools decreased by approx. 30%, whereas spermidine increased 2-4-fold. Lysates of human PAO cDNA-transfected HEK-293 cells, but not vector-transfected cells, rapidly oxidized N1-acetylspermine to spermidine. Substrate specificity determinations with the lysate assay revealed a preference ranking of N1-acetylspermine= N1-acetylspermidine> N1,N12-diacetylspermine>>spermine; spermidine was not acted upon. This ranking is identical to that reported for purified PAO and distinctly different from the recently identified spermine oxidase (SMO), which prefers spermine over N1-acetylspermine. Monoethyl- and diethylspermine analogues also served as substrates for PAO, and were internally cleaved adjacent to a secondary amine. We deduce that the present oxidase sequences are those of the FAD-dependent PAO involved in the polyamine back-conversion pathway. In Northern blot analysis, PAO mRNA was much less abundant in HEK-293 cells than SMO or SSAT mRNA, and all three were differentially induced in a similar manner by selected polyamine analogues. The identification of PAO sequences, together with the recently identified SMO sequences, provides new opportunities for understanding the dynamics of polyamine homoeostasis and for interpreting metabolic and cellular responses to clinically-relevant polyamine analogues and inhibitors. PMID:12477380

Polyamine catabolism is enhanced after traumatic brain injury.

PubMed

Zahedi, Kamyar; Huttinger, Francis; Morrison, Ryan; Murray-Stewart, Tracy; Casero, Robert A; Strauss, Kenneth I

2010-03-01

Polyamines spermine and spermidine are highly regulated, ubiquitous aliphatic cations that maintain DNA structure and function as immunomodulators and as antioxidants. Polyamine homeostasis is disrupted after brain injuries, with concomitant generation of toxic metabolites that may contribute to secondary injuries. To test the hypothesis of increased brain polyamine catabolism after traumatic brain injury (TBI), we determined changes in catabolic enzymes and polyamine levels in the rat brain after lateral controlled cortical impact TBI. Spermine oxidase (SMO) catalyzes the degradation of spermine to spermidine, generating H2O2 and aminoaldehydes. Spermidine/spermine-N(1)-acetyltransferase (SSAT) catalyzes acetylation of these polyamines, and both are further oxidized in a reaction that generates putrescine, H2O2, and aminoaldehydes. In a rat cortical impact model of TBI, SSAT mRNA increased subacutely (6-24 h) after TBI in ipsilateral cortex and hippocampus. SMO mRNA levels were elevated late, from 3 to 7 days post-injury. Polyamine catabolism increased as well. Spermine levels were normal at 6 h and decreased slightly at 24 h, but were normal again by 72 h post-injury. Spermidine levels also decreased slightly (6-24 h), then increased by approximately 50% at 72 h post-injury. By contrast, normally low putrescine levels increased up to sixfold (6-72 h) after TBI. Moreover, N-acetylspermidine (but not N-acetylspermine) was detectable (24-72 h) near the site of injury, consistent with increased SSAT activity. None of these changes were seen in the contralateral hemisphere. Immunohistochemical confirmation indicated that SSAT and SMO were expressed throughout the brain. SSAT-immunoreactivity (SSAT-ir) increased in both neuronal and nonneuronal (likely glial) populations ipsilateral to injury. Interestingly, bilateral increases in cortical SSAT-ir neurons occurred at 72 h post-injury, whereas hippocampal changes occurred only ipsilaterally. Prolonged increases in brain polyamine catabolism are the likely cause of loss of homeostasis in this pathway. The potential for simple therapeutic interventions (e.g., polyamine supplementation or inhibition of polyamine oxidation) is an exciting implication of these studies.

Parcel-scale urban coastal flood mapping: Leveraging the multi-scale CoSMoS model for coastal flood forecasting

NASA Astrophysics Data System (ADS)

Gallien, T.; Barnard, P. L.; Sanders, B. F.

2011-12-01

California coastal sea levels are projected to rise 1-1.4 meters in the next century and evidence suggests mean tidal range, and consequently, mean high water (MHW) is increasing along portions of Southern California Bight. Furthermore, emerging research indicates wind stress patterns associated with the Pacific Decadal Oscillation (PDO) have suppressed sea level rise rates along the West Coast since 1980, and a reversal in this pattern would result in the resumption of regional sea level rise rates equivalent to or exceeding global mean sea level rise rates, thereby enhancing coastal flooding. Newport Beach is a highly developed, densely populated lowland along the Southern California coast currently subject to episodic flooding from coincident high tides and waves, and the frequency and intensity of flooding is expected to increase with projected future sea levels. Adaptation to elevated sea levels will require flood mapping and forecasting tools that are sensitive to the dominant factors affecting flooding including extreme high tides, waves and flood control infrastructure. Considerable effort has been focused on the development of nowcast and forecast systems including Scripps Institute of Oceanography's Coastal Data Information Program (CDIP) and the USGS Multi-hazard model, the Southern California Coastal Storm Modeling System (CoSMoS). However, fine scale local embayment dynamics and overtopping flows are needed to map unsteady flooding effects in coastal lowlands protected by dunes, levees and seawalls. Here, a recently developed two dimensional Godunov non-linear shallow water solver is coupled to water level and wave forecasts from the CoSMoS model to investigate the roles of tides, waves, sea level changes and flood control infrastructure in accurate flood mapping and forecasting. The results of this study highlight the important roles of topographic data, embayment hydrodynamics, water level uncertainties and critical flood processes required for meaningful prediction of sea level rise impacts and coastal flood forecasting.

Coupling Fluvial and Oceanic Drivers in Flooding Forecasts for San Francisco Bay

NASA Astrophysics Data System (ADS)

Herdman, L.; Kim, J.; Cifelli, R.; Barnard, P.; Erikson, L. H.; Johnson, L. E.; Chandrasekar, V.

2016-12-01

San Francisco Bay is a highly urbanized estuary and the surrounding communities are susceptible to flooding along the bay shoreline and inland rivers and creeks that drain to the Bay. A forecast model that integrates fluvial and oceanic drivers is necessary for predicting flooding in this complex urban environment. This study introduces the state-of-the-art coupling of the USGS Coastal Storm Modeling System (CoSMoS) with the NWS Research Distributed Hydrologic Model (RDHM) for San Francisco Bay. For this application, we utilize Delft3D-FM, a hydrodynamic model based on a flexible mesh grid, to calculate water levels that account for tidal forcing, seasonal water level anomalies, surge and in-Bay generated wind waves from the wind and pressure fields of a NWS forecast model. The tributary discharges from RDHM are dynamic, meteorologically driven allowing for operational use of CoSMoS which has previously relied on statistical estimates of river discharge. The flooding extent is determined by overlaying the resulting maximum water levels onto a recently updated 2-m digital elevation model of the study area which best resolves the extensive levee and tidal marsh systems in the region. The results we present here are focused on the interaction of the Bay and the Napa River watershed. This study demonstrates the interoperability of the CoSMoS and RDHM prediction models. We also use this pilot region to examine storm flooding impacts in a series of storm scenarios that simulate 5-100yr return period events in terms of either coastal or fluvial events. These scenarios demonstrate the wide range of possible flooding outcomes considering rainfall recurrence intervals, soil moisture conditions, storm surge, wind speed, and tides (spring and neap). With a simulated set of over 25 storm scenarios we show how the extent, level, and duration of flooding is dependent on these atmospheric and hydrologic parameters and we also determine a range of likely flood events.

Deriving sulfamethoxazole dissipation endpoints in pasture soils using first order and biphasic kinetic models.

PubMed

Srinivasan, Prakash; Sarmah, Ajit K; Rohan, Maheswaran

2014-08-01

Single first-order (SFO) kinetic model is often used to derive the dissipation endpoints of an organic chemical in soil. This model is used due to its simplicity and requirement by regulatory agencies. However, using the SFO model for all types of decay pattern could lead to under- or overestimation of dissipation endpoints when the deviation from first-order is significant. In this study the performance of three biphasic kinetic models - bi-exponential decay (BEXP), first-order double exponential decay (FODED), and first-order two-compartment (FOTC) models was evaluated using dissipation datasets of sulfamethoxazole (SMO) antibiotic in three different soils under varying concentration, depth, temperature, and sterile conditions. Corresponding 50% (DT50) and 90% (DT90) dissipation times for the antibiotics were numerically obtained and compared against those obtained using the SFO model. The fit of each model to the measured values was evaluated based on an array of statistical measures such as coefficient of determination (R(2)adj), root mean square error (RMSE), chi-square (χ(2)) test at 1% significance, Bayesian Information Criteria (BIC) and % model error. Box-whisker residual plots were also used to compare the performance of each model to the measured datasets. The antibiotic dissipation was successfully predicted by all four models. However, the nonlinear biphasic models improved the goodness-of-fit parameters for all datasets. Deviations from datasets were also often less evident with the biphasic models. The fits of FOTC and FODED models for SMO dissipation datasets were identical in most cases, and were found to be superior to the BEXP model. Among the biphasic models, the FOTC model was found to be the most suitable for obtaining the endpoints and could provide a mechanistic explanation for SMO dissipation in the soils. Copyright © 2014 Elsevier B.V. All rights reserved.

A system for optimal edging and trimming of rough hardwood lumber

Treesearch

Sang-Mook Lee; A. Lynn Abbott; Daniel L. Schmoldt; Philip A. Araman

2003-01-01

Despite the importance of improving lumber processing early in manufacturing, scanning of unplaned, green hardwood lumber has received relatively little attention in the research community. This has been due in part to the difficulty of clearly imaging fresh-cut boards whose fibrous surfaces mask many wood features. This paper describes a prototype system that scans...

UDOF direct improvement by modulating mask absorber thickness

NASA Astrophysics Data System (ADS)

Yu, Tuan-Yen; Lio, En Chuan; Chen, Po Tsang; Wei, Chih I.; Chen, Yi Ting; Peng, Ming Chun; Chou, William; Yu, Chun Chi

2016-10-01

As the process generation migrate to advanced and smaller dimension or pitch, the mask and resist 3D effects will impact the lithography focus common window severely because of both individual depth-of-focus (iDOF) range decrease and center mismatch. Furthermore, some chemical or thermal factors, such as PEB (Post Exposure Bake) also worsen the usable depth-of-focus (uDOF) performance. So the mismatch of thru-pitch iDOF center should be considered as a lithography process integration issue, and more complicated to partition the 3D effects induced by optical or chemical factors. In order to reduce the impact of 3D effects induced by both optical and chemical issues, and improve iDOF center mismatch, we would like to propose a mask absorber thickness offset approach, which is directly to compensate the iDOF center bias by adjusting mask absorber thickness, for iso, semi-iso or dense characteristics in line, space or via patterns to enlarge common process window, i.e uDOF, which intends to provide similar application as Flexwave[1] (ASML trademark). By the way, since mask absorber thickness offset approach is similar to focus tuning or change on wafer lithography process, it could be acted as the process tuning method of photoresist (PR) profile optimization locally, PR scum improvement in specific patterns or to modulate etching bias to meet process integration request. For mass production consideration, and available material, current att-PSM blank, quartz, MoSi with chrome layer as hard-mask in reticle process, will be implemented in this experiment, i.e. chrome will be kept remaining above partial thru-pitch patterns, and act as the absorber thickness bias in different patterns. And then, from the best focus offset of thru-pitch patterns, the iDOF center shifts could be directly corrected and to enlarge uDOF by increasing the overlap of iDOF. Finally, some negative tone development (NTD) result in line patterns will be demonstrated as well.

Alternative method for variable aspect ratio vias using a vortex mask

NASA Astrophysics Data System (ADS)

Schepis, Anthony R.; Levinson, Zac; Burbine, Andrew; Smith, Bruce W.

2014-03-01

Historically IC (integrated circuit) device scaling has bridged the gap between technology nodes. Device size reduction is enabled by increased pattern density, enhancing functionality and effectively reducing cost per chip. Exemplifying this trend are aggressive reductions in memory cell sizes that have resulted in systems with diminishing area between bit/word lines. This affords an even greater challenge in the patterning of contact level features that are inherently difficult to resolve because of their relatively small area and complex aerial image. To accommodate these trends, semiconductor device design has shifted toward the implementation of elliptical contact features. This empowers designers to maximize the use of free device space, preserving contact area and effectively reducing the via dimension just along a single axis. It is therefore critical to provide methods that enhance the resolving capacity of varying aspect ratio vias for implementation in electronic design systems. Vortex masks, characterized by their helically induced propagation of light and consequent dark core, afford great potential for the patterning of such features when coupled with a high resolution negative tone resist system. This study investigates the integration of a vortex mask in a 193nm immersion (193i) lithography system and qualifies its ability to augment aspect ratio through feature density using aerial image vector simulation. It was found that vortex fabricated vias provide a distinct resolution advantage over traditionally patterned contact features employing a 6% attenuated phase shift mask (APM). 1:1 features were resolvable at 110nm pitch with a 38nm critical dimension (CD) and 110nm depth of focus (DOF) at 10% exposure latitude (EL). Furthermore, iterative source-mask optimization was executed as means to augment aspect ratio. By employing mask asymmetries and directionally biased sources aspect ratios ranging between 1:1 and 2:1 were achievable, however, this range is ultimately dictated by pitch employed.

Graben calderas of the Sierra Madre Occidental: The case of Guanajuato, central Mexico

NASA Astrophysics Data System (ADS)

Aguirre-Diaz, G. J.; Tristán-González, M.; Labarthe-Hernández, G.; Marti, J.

2013-12-01

The Sierra Madre Occidental (SMO) volcanic province is characterized by voluminous silicic ignimbrites that reach an accumulated thickness of 500 to 1500 m. A single ignimbrite can reach up to 350 m thick in its outflow facies. This ignimbrite sequence formed mostly within 38-23 Ma, building up a total estimated volume of ca. 580,000 km3 making the SMO the largest ignimbrite province of the world. We have showed that several and probably most of the SMO ignimbrites were erupted from fissures associated to Basin and Range fault systems or grabens (Geology, 2003), thus naming these volcano-tectonic structures as graben calderas (Caldera Volcanism book, Elsevier, 2008). Generally, the sequence observed in graben calderas include, from oldest to youngest, alluvial fan deposits combined with lacustrine deposits, pyroclastic surge deposits and minor volume ignimbrites, a large-volume ignimbrite that could be massive or made of successive layers, and sometimes silicic lava domes and/or mafic fissural lavas both with vents aligned with the graben trend. Fallout deposits, plinian or non-plinian, are not observed in the sequence. Thus, onset of caldera collapse represented by the major ignimbrite must occur just after deposition of continental sediments within the graben domain. A similar volcano-tectonic development is observed in pull-apart grabens. Therefore, extensional or transtensional tectonics, before and during caldera collapse, and the emplacement of a subgraben shallow silicic magma chamber are the necessary conditions for the development of graben calderas. We describe here the case of the Guanajuato graben caldera, located in the central part of Mexico and in the southeastern portion of the SMO volcanic province. The caldera is part of the economically important mining district of Guanajuato, with 28 silver mines, some active since the 16th century. The caldera structure, a rectangle of 10 x 16 km, was controlled by NW and NE regional fault systems. Most ore deposits occur along this orthogonal faulting network, but mainly along the NW fault of Veta Madre that crosses through the center of the caldera. The mid-Tertiary stratigraphy in Guanajuato follows the general sequence observed in graben calderas; i.e., from oldest to youngest includes 1) at least 1,500 m of alluvial fan deposits within a tectonic basin (Guanajuato Red Conglomerate), 2) pyroclastic flow deposits, consisting of surge deposits (Loseros Formation) that are concordant with a massive, large volume, rhyolitic ignimbrite (Bufa Rhyolite), which is covered by a layered series of pyroclastic flow deposits (Calderones Formation), and 3) effusive volcanism in the form of rhyolitic lava domes (Chichíndaro Rhyolite) and basaltic-andesite dikes and lavas (Cedros Andesite). The Guanajuato graben caldera formed at about 33 Ma, based on our new U-Pb zr age of the main ignimbrite, Bufa Rhyolite.

Patterning optimization for 55nm design rule DRAM/flash memory using production-ready customized illuminations

NASA Astrophysics Data System (ADS)

Chen, Ting; Van Den Broeke, Doug; Hsu, Stephen; Hsu, Michael; Park, Sangbong; Berger, Gabriel; Coskun, Tamer; de Vocht, Joep; Chen, Fung; Socha, Robert; Park, JungChul; Gronlund, Keith

2005-11-01

Illumination optimization, often combined with optical proximity corrections (OPC) to the mask, is becoming one of the critical components for a production-worthy lithography process for 55nm-node DRAM/Flash memory devices and beyond. At low-k1, e.g. k1<0.31, both resolution and imaging contrast can be severely limited by the current imaging tools while using the standard illumination sources. Illumination optimization is a process where the source shape is varied, in both profile and intensity distribution, to achieve enhancement in the final image contrast as compared to using the non-optimized sources. The optimization can be done efficiently for repetitive patterns such as DRAM/Flash memory cores. However, illumination optimization often produces source shapes that are "free-form" like and they can be too complex to be directly applicable for production and lack the necessary radial and annular symmetries desirable for the diffractive optical element (DOE) based illumination systems in today's leading lithography tools. As a result, post-optimization rendering and verification of the optimized source shape are often necessary to meet the production-ready or manufacturability requirements and ensure optimal performance gains. In this work, we describe our approach to the illumination optimization for k1<0.31 DRAM/Flash memory patterns, using an ASML XT:1400i at NA 0.93, where the all necessary manufacturability requirements are fully accounted for during the optimization. The imaging contrast in the resist is optimized in a reduced solution space constrained by the manufacturability requirements, which include minimum distance between poles, minimum opening pole angles, minimum ring width and minimum source filling factor in the sigma space. For additional performance gains, the intensity within the optimized source can vary in a gray-tone fashion (eight shades used in this work). Although this new optimization approach can sometimes produce closely spaced solutions as gauged by the NILS based metrics, we show that the optimal and production-ready source shape solution can be easily determined by comparing the best solutions to the "free-form" solution and more importantly, by their respective imaging fidelity and process latitude ranking. Imaging fidelity and process latitude simulations are performed to analyze the impact and sensitivity of the manufacturability requirements on pattern specific illumination optimizations using ASML XT:1400i and other latest imaging systems. Mask model based OPC (MOPC) is applied and optimized sequentially to ensure that the CD uniformity requirements are met.

In-die photomask registration and overlay metrology with PROVE using 2D correlation methods

NASA Astrophysics Data System (ADS)

Seidel, D.; Arnz, M.; Beyer, D.

2011-11-01

According to the ITRS roadmap, semiconductor industry drives the 193nm lithography to its limits, using techniques like double exposure, double patterning, mask-source optimization and inverse lithography. For photomask metrology this translates to full in-die measurement capability for registration and critical dimension together with challenging specifications for repeatability and accuracy. Especially, overlay becomes more and more critical and must be ensured on every die. For this, Carl Zeiss SMS has developed the next generation photomask registration and overlay metrology tool PROVE® which serves the 32nm node and below and which is already well established in the market. PROVE® features highly stable hardware components for the stage and environmental control. To ensure in-die measurement capability, sophisticated image analysis methods based on 2D correlations have been developed. In this paper we demonstrate the in-die capability of PROVE® and present corresponding measurement results for shortterm and long-term measurements as well as the attainable accuracy for feature sizes down to 85nm using different illumination modes and mask types. Standard measurement methods based on threshold criteria are compared with the new 2D correlation methods to demonstrate the performance gain of the latter. In addition, mask-to-mask overlay results of typical box-in-frame structures down to 200nm feature size are presented. It is shown, that from overlay measurements a reproducibility budget can be derived that takes into account stage, image analysis and global effects like mask loading and environmental control. The parts of the budget are quantified from measurement results to identify critical error contributions and to focus on the corresponding improvement strategies.

Wildfire smoke exposure and cardiopulmonary hospitalizations among those over age 65 in the United States

EPA Science Inventory

Background: The health implications of excess PM2.5 due to wildland fire smoke are not well understood. Very few studies have assessed the effect of wildland fire smoke from multiple fires across the US. Methods: We estimated daily concentrations of PM2.5 due to wildland fire smo...

Transcript Profiling of Common Bean (Phaseolus vulgaris) Using the GeneChip Soybean Genome Array: Optimizing Analysis by Masking Biased Probes

USDA-ARS?s Scientific Manuscript database

Common bean (Phaseolus vulgaris) and soybean (Glycine max) both belong to the Phaseoleae tribe and share significant coding sequence homology. To evaluate the utility of the soybean GeneChip for transcript profiling of common bean, we hybridized cRNAs purified from nodule, leaf, and root of common b...

Transcript Profiling of Common Bean (Phaseolus vulgaris L.) Using the GeneChip(R) Soybean Genome Array: Optimizing Analysis by Masking Biased Probes

USDA-ARS?s Scientific Manuscript database

Common bean (Phaseolus vulgaris) and soybean (Glycine max) both belong to the Phaseoleae tribe and share significant coding sequence homology. This suggests that the GeneChip(R) Soybean Genome Array (soybean GeneChip) may be used for gene expression studies using common bean. To evaluate the utility...

Transcript Profiling of Two Alfalfa Genotypes with Contrasting Cell Wall Composition in Stems Using a Cross-Species Platform: Optimizing Analysis by Masking Biased Probes

USDA-ARS?s Scientific Manuscript database

The stem cell walls of alfalfa [Medicago sativa (L.) ssp. sativa] genotype 252 have high cellulose and lignin concentrations, while stem cell walls of genotype 1283 have low cellulose and lignin concentrations. The GeneChip® Medicago Genome Array, developed for Medicago truncatula, is a suitable pla...

Optimal Mixtures of Test Types in Paired-Associate Learning (Sensory Information Processing). Final Report.

ERIC Educational Resources Information Center

Wolford, George

Seven experiments were run to determine the precise nature of some of the variables which affect the processing of short-term visual information. In particular, retinal location, report order, processing order, lateral masking, and redundancy were studied along with the nature of the confusion errors which are made in the full report procedure.…

Isolation strategy of a two-strain avian influenza model using optimal control

NASA Astrophysics Data System (ADS)

Mardlijah, Ariani, Tika Desi; Asfihani, Tahiyatul

2017-08-01

Avian influenza has killed many victims of both birds and humans. Most cases of avian influenza infection in humans have resulted transmission from poultry to humans. To prevent or minimize the patients of avian influenza can be done by pharmaceutical and non-pharmaceutical measures such as the use of masks, isolation, etc. We will be analyzed two strains of avian influenza models that focus on treatment of symptoms with insulation, then investigate the stability of the equilibrium point by using Routh-Hurwitz criteria. We also used optimal control to reduce the number of humans infected by making the isolation level as the control then proceeds optimal control will be simulated. The completion of optimal control used in this study is the Pontryagin Minimum Principle and for simulation we are using Runge Kutta method. The results obtained showed that the application of two control is more optimal compared to apply one control only.

Genetic Algorithms Applied to Multi-Objective Aerodynamic Shape Optimization

NASA Technical Reports Server (NTRS)

Holst, Terry L.

2005-01-01

A genetic algorithm approach suitable for solving multi-objective problems is described and evaluated using a series of aerodynamic shape optimization problems. Several new features including two variations of a binning selection algorithm and a gene-space transformation procedure are included. The genetic algorithm is suitable for finding Pareto optimal solutions in search spaces that are defined by any number of genes and that contain any number of local extrema. A new masking array capability is included allowing any gene or gene subset to be eliminated as decision variables from the design space. This allows determination of the effect of a single gene or gene subset on the Pareto optimal solution. Results indicate that the genetic algorithm optimization approach is flexible in application and reliable. The binning selection algorithms generally provide Pareto front quality enhancements and moderate convergence efficiency improvements for most of the problems solved.

Take a byte out of MEEF: VAMPIRE: Vehicle for Advanced Mask Pattern Inspection Readiness Evaluations

NASA Astrophysics Data System (ADS)

Badger, Karen D.; Rankin, Jed; Turley, Christina; Seki, Kazunori; Dechene, Dan J.; Abdelghany, Hesham

2016-09-01

MEEF, or Mask Error Enhancement Factor, is simply defined as the ratio of the change in printed wafer feature width to the change in mask feature width scaled to wafer level. It is important in chip manufacturing that leads to the amplification of mask errors, creating challenges with both achieving dimensional control tolerances and ensuring defect free masks, as measured by on-wafer image quality. As lithographic imaging continues to be stressed, using lower and lower k1 factor resolution enhancement techniques, the high MEEF areas present on advanced optical masks creates an environment where the need for increased mask defect sensitivity in high-MEEF areas becomes more and more critical. There are multiple approaches to mask inspection that may or may not provide enough sensitivity to detect all wafer-printable defects; the challenge in the application of these techniques is simultaneously maintaining an acceptable level of mask inspectability. The higher the MEEF, the harder the challenge will be to achieve and appropriate level of sensitivity while maintaining inspectability…and to do so on the geometries that matter. The predominant photomask fabrication inspection approach in use today compares the features on the reticle directly with the design database using high-NA optics. This approach has the ability to detect small defects, however, when inspecting aggressive OPC, it can lead to the over-detection of inconsequential, or nuisance defects. To minimize these nuisance detections, changing the sensitivity of the inspection can improve the inspectability of a mask inspected in high-NA mode, however, it leads to the inability to detect subtle, yet wafer-printable defects in High-MEEF geometry, due to the fact that this `desense' must be applied globally. There are also `lithography-emulating' approaches to inspection that use various means to provide high defect sensitivity and the ability to tolerate inconsequential, non-printing defects by using scanner-like conditions to determine which defects are wafer printable. This inspection technique is commonly referred to as being `lithography plane' or `litho plane,' since it's assessing the mask quality based on how the mask appears to the imaging optics during use, as proposed to traditional `reticle plane' inspection which is comparing the mask only with its target design. Regardless of how the defects are detected, the real question is when should they be detected? For larger technology nodes, defects are considered `statistical risks'…i.e., first they have to occur, and then they have to fall in high-MEEF areas in order to be of concern, and be below the detection limits of traditional reticle-plane inspection. In short, the `perfect storm' has to happen in order to miss printable defects using well-optimized traditional inspection approaches. The introduction of lithographic inspection techniques has revealed this statistical game is a much higher risk than originally estimated, in that very subtle waferprintable CD errors typically fall into the desense band for traditional reticle plane inspection. Because printability is largely influenced by MEEF, designs with high-MEEF values are at greater risk of traditional inspection missing printable CD errors. The question is… how high is high… and at what MEEF is optical inspection at the reticle plane sufficient? This paper will provide evaluation results for both reticle-plane and litho-plane inspections as they pertain to varying degrees of MEEF. A newly designed high-MEEF programmed defect test mask, named VAMPIRE, will be introduced. This test mask is based on 7 nm node technology and contains intentionally varying degrees of MEEF as well as a variety of programmed defects in high-MEEF environments…all of which have been verified for defect lithographic significance on a Zeiss AIMS system.

Masked Proportional Routing

NASA Technical Reports Server (NTRS)

Wolpert, David

2004-01-01

Masked proportional routing is an improved procedure for choosing links between adjacent nodes of a network for the purpose of transporting an entity from a source node ("A") to a destination node ("B"). The entity could be, for example, a physical object to be shipped, in which case the nodes would represent waypoints and the links would represent roads or other paths between waypoints. For another example, the entity could be a message or packet of data to be transmitted from A to B, in which case the nodes could be computer-controlled switching stations and the links could be communication channels between the stations. In yet another example, an entity could represent a workpiece while links and nodes could represent, respectively, manufacturing processes and stages in the progress of the workpiece towards a finished product. More generally, the nodes could represent states of an entity and the links could represent allowed transitions of the entity. The purpose of masked proportional routing and of related prior routing procedures is to schedule transitions of entities from their initial states ("A") to their final states ("B") in such a manner as to minimize a cost or to attain some other measure of optimality or efficiency. Masked proportional routing follows a distributed (in the sense of decentralized) approach to probabilistically or deterministically choosing the links. It was developed to satisfy a need for a routing procedure that 1. Does not always choose the same link(s), even for two instances characterized by identical estimated values of associated cost functions; 2. Enables a graceful transition from one set of links to another set of links as the circumstances of operation of the network change over time; 3. Is preferably amenable to separate optimization of different portions of the network; 4. Is preferably usable in a network in which some of the routing decisions are made by one or more other procedure(s); 5. Preferably does not cause an entity to visit the same node twice; and 6. Preferably can be modified so that separate entities moving from A to B do not arrive out of order.

Quantifying noise in optical tweezers by allan variance.

PubMed

Czerwinski, Fabian; Richardson, Andrew C; Oddershede, Lene B

2009-07-20

Much effort is put into minimizing noise in optical tweezers experiments because noise and drift can mask fundamental behaviours of, e.g., single molecule assays. Various initiatives have been taken to reduce or eliminate noise but it has been difficult to quantify their effect. We propose to use Allan variance as a simple and efficient method to quantify noise in optical tweezers setups.We apply the method to determine the optimal measurement time, frequency, and detection scheme, and quantify the effect of acoustic noise in the lab. The method can also be used on-the-fly for determining optimal parameters of running experiments.

Max-margin weight learning for medical knowledge network.

PubMed

Jiang, Jingchi; Xie, Jing; Zhao, Chao; Su, Jia; Guan, Yi; Yu, Qiubin

2018-03-01

The application of medical knowledge strongly affects the performance of intelligent diagnosis, and method of learning the weights of medical knowledge plays a substantial role in probabilistic graphical models (PGMs). The purpose of this study is to investigate a discriminative weight-learning method based on a medical knowledge network (MKN). We propose a training model called the maximum margin medical knowledge network (M 3 KN), which is strictly derived for calculating the weight of medical knowledge. Using the definition of a reasonable margin, the weight learning can be transformed into a margin optimization problem. To solve the optimization problem, we adopt a sequential minimal optimization (SMO) algorithm and the clique property of a Markov network. Ultimately, M 3 KN not only incorporates the inference ability of PGMs but also deals with high-dimensional logic knowledge. The experimental results indicate that M 3 KN obtains a higher F-measure score than the maximum likelihood learning algorithm of MKN for both Chinese Electronic Medical Records (CEMRs) and Blood Examination Records (BERs). Furthermore, the proposed approach is obviously superior to some classical machine learning algorithms for medical diagnosis. To adequately manifest the importance of domain knowledge, we numerically verify that the diagnostic accuracy of M 3 KN is gradually improved as the number of learned CEMRs increase, which contain important medical knowledge. Our experimental results show that the proposed method performs reliably for learning the weights of medical knowledge. M 3 KN outperforms other existing methods by achieving an F-measure of 0.731 for CEMRs and 0.4538 for BERs. This further illustrates that M 3 KN can facilitate the investigations of intelligent healthcare. Copyright © 2018 Elsevier B.V. All rights reserved.

MACVIA-ARIA Sentinel NetworK for allergic rhinitis (MASK-rhinitis): the new generation guideline implementation.

PubMed

Bousquet, J; Schunemann, H J; Fonseca, J; Samolinski, B; Bachert, C; Canonica, G W; Casale, T; Cruz, A A; Demoly, P; Hellings, P; Valiulis, A; Wickman, M; Zuberbier, T; Bosnic-Anticevitch, S; Bedbrook, A; Bergmann, K C; Caimmi, D; Dahl, R; Fokkens, W J; Grisle, I; Lodrup Carlsen, K; Mullol, J; Muraro, A; Palkonen, S; Papadopoulos, N; Passalacqua, G; Ryan, D; Valovirta, E; Yorgancioglu, A; Aberer, W; Agache, I; Adachi, M; Akdis, C A; Akdis, M; Annesi-Maesano, I; Ansotegui, I J; Anto, J M; Arnavielhe, S; Arshad, H; Baiardini, I; Baigenzhin, A K; Barbara, C; Bateman, E D; Beghé, B; Bel, E H; Ben Kheder, A; Bennoor, K S; Benson, M; Bewick, M; Bieber, T; Bindslev-Jensen, C; Bjermer, L; Blain, H; Boner, A L; Boulet, L P; Bonini, M; Bonini, S; Bosse, I; Bourret, R; Bousquet, P J; Braido, F; Briggs, A H; Brightling, C E; Brozek, J; Buhl, R; Burney, P G; Bush, A; Caballero-Fonseca, F; Calderon, M A; Camargos, P A M; Camuzat, T; Carlsen, K H; Carr, W; Cepeda Sarabia, A M; Chavannes, N H; Chatzi, L; Chen, Y Z; Chiron, R; Chkhartishvili, E; Chuchalin, A G; Ciprandi, G; Cirule, I; Correia de Sousa, J; Cox, L; Crooks, G; Costa, D J; Custovic, A; Dahlen, S E; Darsow, U; De Carlo, G; De Blay, F; Dedeu, T; Deleanu, D; Denburg, J A; Devillier, P; Didier, A; Dinh-Xuan, A T; Dokic, D; Douagui, H; Dray, G; Dubakiene, R; Durham, S R; Dykewicz, M S; El-Gamal, Y; Emuzyte, R; Fink Wagner, A; Fletcher, M; Fiocchi, A; Forastiere, F; Gamkrelidze, A; Gemicioğlu, B; Gereda, J E; González Diaz, S; Gotua, M; Grouse, L; Guzmán, M A; Haahtela, T; Hellquist-Dahl, B; Heinrich, J; Horak, F; Hourihane, J O 'b; Howarth, P; Humbert, M; Hyland, M E; Ivancevich, J C; Jares, E J; Johnston, S L; Joos, G; Jonquet, O; Jung, K S; Just, J; Kaidashev, I; Kalayci, O; Kalyoncu, A F; Keil, T; Keith, P K; Khaltaev, N; Klimek, L; Koffi N'Goran, B; Kolek, V; Koppelman, G H; Kowalski, M L; Kull, I; Kuna, P; Kvedariene, V; Lambrecht, B; Lau, S; Larenas-Linnemann, D; Laune, D; Le, L T T; Lieberman, P; Lipworth, B; Li, J; Louis, R; Magard, Y; Magnan, A; Mahboub, B; Majer, I; Makela, M J; Manning, P; De Manuel Keenoy, E; Marshall, G D; Masjedi, M R; Maurer, M; Mavale-Manuel, S; Melén, E; Melo-Gomes, E; Meltzer, E O; Merk, H; Miculinic, N; Mihaltan, F; Milenkovic, B; Mohammad, Y; Molimard, M; Momas, I; Montilla-Santana, A; Morais-Almeida, M; Mösges, R; Namazova-Baranova, L; Naclerio, R; Neou, A; Neffen, H; Nekam, K; Niggemann, B; Nyembue, T D; O'Hehir, R E; Ohta, K; Okamoto, Y; Okubo, K; Ouedraogo, S; Paggiaro, P; Pali-Schöll, I; Palmer, S; Panzner, P; Papi, A; Park, H S; Pavord, I; Pawankar, R; Pfaar, O; Picard, R; Pigearias, B; Pin, I; Plavec, D; Pohl, W; Popov, T A; Portejoie, F; Postma, D; Potter, P; Price, D; Rabe, K F; Raciborski, F; Radier Pontal, F; Repka-Ramirez, S; Robalo-Cordeiro, C; Rolland, C; Rosado-Pinto, J; Reitamo, S; Rodenas, F; Roman Rodriguez, M; Romano, A; Rosario, N; Rosenwasser, L; Rottem, M; Sanchez-Borges, M; Scadding, G K; Serrano, E; Schmid-Grendelmeier, P; Sheikh, A; Simons, F E R; Sisul, J C; Skrindo, I; Smit, H A; Solé, D; Sooronbaev, T; Spranger, O; Stelmach, R; Strandberg, T; Sunyer, J; Thijs, C; Todo-Bom, A; Triggiani, M; Valenta, R; Valero, A L; van Hage, M; Vandenplas, O; Vezzani, G; Vichyanond, P; Viegi, G; Wagenmann, M; Walker, S; Wang, D Y; Wahn, U; Williams, D M; Wright, J; Yawn, B P; Yiallouros, P K; Yusuf, O M; Zar, H J; Zernotti, M E; Zhang, L; Zhong, N; Zidarn, M; Mercier, J

2015-11-01

Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

150-nm DR contact holes die-to-database inspection

NASA Astrophysics Data System (ADS)

Kuo, Shen C.; Wu, Clare; Eran, Yair; Staud, Wolfgang; Hemar, Shirley; Lindman, Ofer

2000-07-01

Using a failure analysis-driven yield enhancements concept, based on an optimization of the mask manufacturing process and UV reticle inspection is studied and shown to improve the contact layer quality. This is achieved by relating various manufacturing processes to very fine tuned contact defect detection. In this way, selecting an optimized manufacturing process with fine-tuned inspection setup is achieved in a controlled manner. This paper presents a study, performed on a specially designed test reticle, which simulates production contact layers of design rule 250nm, 180nm and 150nm. This paper focuses on the use of advanced UV reticle inspection techniques as part of the process optimization cycle. Current inspection equipment uses traditional and insufficient methods of small contact-hole inspection and review.

Zernike Wavefront Sensor Modeling Development for LOWFS on WFIRST-AFTA

NASA Technical Reports Server (NTRS)

Wang, Xu; Wallace, J. Kent; Shi, Fang

2015-01-01

WFIRST-AFTA design makes use of an existing 2.4m telescope for direct imaging of exoplanets. To maintain the high contrast needed for the coronagraph, wavefront error (WFE) of the optical system needs to be continuously sensed and controlled. Low Order Wavefront Sensing (LOWFS) uses the rejected starlight from an immediate focal plane to sense wavefront changes (mostly thermally induced low order WFE) by combining the LOWFS mask (a phase plate located at the small center region with reflective layer) with the starlight rejection masks, i.e. Hybrid Lyot Coronagraph (HLC)'s occulter or Shaped Pupil Coronagraph (SPC)'s field stop. Zernike wavefront sensor (ZWFS) measures phase via the phase-contrast method and is known to be photon noise optimal for measuring low order aberrations. Recently, ZWFS was selected as the baseline LOWFS technology on WFIST/AFTA for its good sensitivity, accuracy, and its easy integration with the starlight rejection mask. In this paper, we review the theory of ZWFS operation, describe the ZWFS algorithm development, and summarize various numerical sensitivity studies on the sensor performance. In the end, the predicted sensor performance on SPC and HLC configurations are presented.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Naulleau, Patrick; Mochi, Iacopo; Goldberg, Kenneth A.

Defect free masks remain one of the most significant challenges facing the commercialization of extreme ultraviolet (EUV) lithography. Progress on this front requires high-performance wavelength-specific metrology of EUV masks, including high-resolution and aerial-image microscopy performed near the 13.5 nm wavelength. Arguably the most cost-effective and rapid path to proliferating this capability is through the development of Fresnel zoneplate-based microscopes. Given the relative obscurity of such systems, however, modeling tools are not necessarily optimized to deal with them and their imaging properties are poorly understood. Here we present a modeling methodology to analyze zoneplate microscopes based on commercially available optical modelingmore » software and use the technique to investigate the imaging performance of an off-axis EUV microscope design. The modeling predicts that superior performance can be achieved by tilting the zoneplate, making it perpendicular to the chief ray at the center of the field, while designing the zoneplate to explicitly work in that tilted plane. Although the examples presented here are in the realm of EUV mask inspection, the methods described and analysis results are broadly applicable to zoneplate microscopes in general, including full-field soft-x-ray microscopes rou tinely used in the synchrotron community.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Naulleau, Patrick P.; Mochi, Iacopo; Goldberg, Kenneth A.

Defect free masks remain one of the most significant challenges facing the commercialization of extreme ultraviolet (EUV) lithography. Progress on this front requires high-performance wavelength-specific metrology of EUV masks, including high-resolution and aerial-image microscopy performed near the 13.5 nm wavelength. Arguably the most cost-effective and rapid path to proliferating this capability is through the development of Fresnel zoneplate-based microscopes. Given the relative obscurity of such systems, however, modeling tools are not necessarily optimized to deal with them and their imaging properties are poorly understood. Here we present a modeling methodology to analyze zoneplate microscopes based on commercially available optical modelingmore » software and use the technique to investigate the imaging performance of an off-axis EUV microscope design. The modeling predicts that superior performance can be achieved by tilting the zoneplate, making it perpendicular to the chief ray at the center of the field, while designing the zoneplate to explicitly work in that tilted plane. Although the examples presented here are in the realm of EUV mask inspection, the methods described and analysis results are broadly applicable to zoneplate microscopes in general, including full-field soft-x-ray microscopes routinely used in the synchrotron community.« less

Revisiting adoption of high transmission PSM: pros, cons and path forward

NASA Astrophysics Data System (ADS)

Ma, Z. Mark; McDonald, Steve; Progler, Chris

2009-12-01

High transmission attenuated phase shift masks (Hi-T PSM) have been successfully applied in volume manufacturing for certain memory devices. Moreover, numerous studies have shown the potential benefits of Hi-T PSM for specific lithography applications. In this paper, the potential for extending Hi-T PSM to logic devices, is revisited with an emphasis on understanding layout, transmission, and manufacturing of Hi-T PSM versus traditional 6% embedded attenuated phase shift mask (EAPSM). Simulations on various layouts show Hi-T PSM has advantage over EAPSM in low duty cycle line patterns and high duty cycle space patterns. The overall process window can be enhanced when Hi- T PSM is combined with optimized optical proximity correction (OPC), sub-resolution assist features (SRAF), and source illumination. Therefore, Hi-T PSM may be a viable and lower cost alternative to other complex resolution enhancement technology (RET) approaches. Aerial image measurement system (AIMS) results on test masks, based on an inverse lithography technology (ILT) generated layout, confirm the simulation results. New advancement in high transmission blanks also make low topography Hi-T PSM a reality, which can minimize scattering effects in high NA lithography.

Targeting the Hedgehog pathway in cancer: can the spines be smoothened?

PubMed

Ailles, Laurie; Siu, Lillian L

2011-04-15

Aberrant Hedgehog (Hh) pathway signaling has been suggested to play a role in the development of multiple solid tumors and hematologic malignancies. GDC-0449 is a novel first-in-human, first-in-class smoothened (SMO) inhibitor, which has completed its phase I evaluation and achieved proof of concept in tumors with Hh pathway mutations. ©2011 AACR.

Hedgehog Signaling Regulates Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem-Like Cells

PubMed Central

Wang, Feng; Ma, Ling; Zhang, Zhengkui; Liu, Xiaoran; Gao, Hongqiao; Zhuang, Yan; Yang, Pei; Kornmann, Marko; Tian, Xiaodong; Yang, Yinmo

2016-01-01

Hedgehog (Hh) signaling is crucially involved in tumorigenesis. This study aimed to assess the role of Hh signaling in the regulation of epithelial-mesenchymal transition (EMT), stemness properties and chemoresistance of human pancreatic Panc-1 cancer stem cells (CSCs). Panc-1 cells were transfected with recombinant lentiviral vectors to silence SMO and serum-free floating-culture system was used to isolate Panc-1 tumorspheres. The expression of CSC and EMT markers was detected by flow cytometry, real-time RT-PCR and Western blot analysis. Malignant behaviors of Panc-1 CSC were evaluated by tumorigenicity assays and nude mouse lung metastasis model. We found that tumorspheres derived from pancreatic cancer cell line Panc-1 possessed self-renewal, differentiation and stemness properties. Hh pathway and EMT were active in Panc-1 tumorspheres. Inhibition of Hh signaling by SMO knockdown inhibited self-renewal, EMT, invasion, chemoresistance, pulmonary metastasis, tumorigenesis of pancreatic CSCs. In conclusion, Hh signaling contributes to the maintenance of stem-like properties and chemoresistance of pancreatic CSC and promotes the tumorigenesis and metastasis of pancreatic cancer. Hh pathway is a potential molecular target for the development of therapeutic strategies for pancreatic CSCs. PMID:26918054

Instantaneous power control of a high speed permanent magnet synchronous generator based on a sliding mode observer and a phase locked loop

NASA Astrophysics Data System (ADS)

Duan, Jiandong; Fan, Shaogui; Wu, Fengjiang; Sun, Li; Wang, Guanglin

2018-06-01

This paper proposes an instantaneous power control method for high speed permanent magnet synchronous generators (PMSG), to realize the decoupled control of active power and reactive power, through vector control based on a sliding mode observer (SMO), and a phase locked loop (PLL). Consequently, the high speed PMSG has a high internal power factor, to ensure efficient operation. Vector control and accurate estimation of the instantaneous power require an accurate estimate of the rotor position. The SMO is able to estimate the back electromotive force (EMF). The rotor position and speed can be obtained using a combination of the PLL technique and the phase compensation method. This method has the advantages of robust operation, and being resistant to noise when estimating the position of the rotor. Using instantaneous power theory, the relationship between the output active power, reactive power, and stator current of the PMSG is deduced, and the power constraint condition is analysed for operation at the unit internal power factor. Finally, the accuracy of the rotor position detection, the instantaneous power detection, and the control methods are verified using simulations and experiments.

Sliding Mode Observer-Based Current Sensor Fault Reconstruction and Unknown Load Disturbance Estimation for PMSM Driven System

PubMed Central

Li, Xiangfei; Lin, Yuliang

2017-01-01

This paper proposes a new scheme of reconstructing current sensor faults and estimating unknown load disturbance for a permanent magnet synchronous motor (PMSM)-driven system. First, the original PMSM system is transformed into two subsystems; the first subsystem has unknown system load disturbances, which are unrelated to sensor faults, and the second subsystem has sensor faults, but is free from unknown load disturbances. Introducing a new state variable, the augmented subsystem that has sensor faults can be transformed into having actuator faults. Second, two sliding mode observers (SMOs) are designed: the unknown load disturbance is estimated by the first SMO in the subsystem, which has unknown load disturbance, and the sensor faults can be reconstructed using the second SMO in the augmented subsystem, which has sensor faults. The gains of the proposed SMOs and their stability analysis are developed via the solution of linear matrix inequality (LMI). Finally, the effectiveness of the proposed scheme was verified by simulations and experiments. The results demonstrate that the proposed scheme can reconstruct current sensor faults and estimate unknown load disturbance for the PMSM-driven system. PMID:29211017

The Hedgehog Signal Transduction Network

PubMed Central

Robbins, David J.; Fei, Dennis Liang; Riobo, Natalia A.

2013-01-01

Hedgehog (Hh) proteins regulate the development of a wide range of metazoan embryonic and adult structures, and disruption of Hh signaling pathways results in various human diseases. Here, we provide a comprehensive review of the signaling pathways regulated by Hh, consolidating data from a diverse array of organisms in a variety of scientific disciplines. Similar to the elucidation of many other signaling pathways, our knowledge of Hh signaling developed in a sequential manner centered on its earliest discoveries. Thus, our knowledge of Hh signaling has for the most part focused on elucidating the mechanism by which Hh regulates the Gli family of transcription factors, the so-called “canonical” Hh signaling pathway. However, in the past few years, numerous studies have shown that Hh proteins can also signal through Gli-independent mechanisms collectively referred to as “noncanonical” signaling pathways. Noncanonical Hh signaling is itself subdivided into two distinct signaling modules: (i) those not requiring Smoothened (Smo) and (ii) those downstream of Smo that do not require Gli transcription factors. Thus, Hh signaling is now proposed to occur through a variety of distinct context-dependent signaling modules that have the ability to crosstalk with one another to form an interacting, dynamic Hh signaling network. PMID:23074268

Low Volume Aerobic Training Heightens Muscle Deoxygenation in Early Post-Angina Pectoris Patients.

PubMed

Takagi, Shun; Murase, Norio; Kime, Ryotaro; Niwayama, Masatsugu; Osada, Takuya; Katsumura, Toshihito

2016-01-01

The aim of this study was to investigate the effect of low volume aerobic exercise training on muscle O2 dynamics during exercise in early post-angina pectoris (AP) patients, as a pilot study. Seven AP patients (age: 72 ± 6 years) participated in aerobic exercise training for 12 weeks. Training consisted of continuous cycling exercise for 30 min at the individual's estimated lactate threshold, and the subjects trained for 15 ± 5 exercise sessions over 12 weeks. Before and after training, the subjects performed ramp cycling exercise until exhaustion. Muscle O2 saturation (SmO2) and relative changes from rest in deoxygenated hemoglobin concentration (∆Deoxy-Hb) and total hemoglobin concentration (∆Total-Hb) were monitored at the vastus lateralis by near infrared spatial resolved spectroscopy during exercise. The SmO2 was significantly lower and ∆Deoxy-Hb was significantly higher after training than before training, while there were no significant changes in ∆Total-Hb. These results indicated that muscle deoxygenation and muscle O2 extraction were potentially heightened by aerobic exercise training in AP patients, even though the exercise training volume was low.

Hedgehog Signaling Regulates Epithelial-Mesenchymal Transition in Pancreatic Cancer Stem-Like Cells.

PubMed

Wang, Feng; Ma, Ling; Zhang, Zhengkui; Liu, Xiaoran; Gao, Hongqiao; Zhuang, Yan; Yang, Pei; Kornmann, Marko; Tian, Xiaodong; Yang, Yinmo

2016-01-01

Hedgehog (Hh) signaling is crucially involved in tumorigenesis. This study aimed to assess the role of Hh signaling in the regulation of epithelial-mesenchymal transition (EMT), stemness properties and chemoresistance of human pancreatic Panc-1 cancer stem cells (CSCs). Panc-1 cells were transfected with recombinant lentiviral vectors to silence SMO and serum-free floating-culture system was used to isolate Panc-1 tumorspheres. The expression of CSC and EMT markers was detected by flow cytometry, real-time RT-PCR and Western blot analysis. Malignant behaviors of Panc-1 CSC were evaluated by tumorigenicity assays and nude mouse lung metastasis model. We found that tumorspheres derived from pancreatic cancer cell line Panc-1 possessed self-renewal, differentiation and stemness properties. Hh pathway and EMT were active in Panc-1 tumorspheres. Inhibition of Hh signaling by SMO knockdown inhibited self-renewal, EMT, invasion, chemoresistance, pulmonary metastasis, tumorigenesis of pancreatic CSCs. In conclusion, Hh signaling contributes to the maintenance of stem-like properties and chemoresistance of pancreatic CSC and promotes the tumorigenesis and metastasis of pancreatic cancer. Hh pathway is a potential molecular target for the development of therapeutic strategies for pancreatic CSCs.

The Dark Matter Crisis: Falsification of the Current Standard Model of Cosmology

NASA Astrophysics Data System (ADS)

Kroupa, P.

2012-06-01

The current standard model of cosmology (SMoC) requires The Dual Dwarf Galaxy Theorem to be true according to which two types of dwarf galaxies must exist: primordial dark-matter (DM) dominated (type A) dwarf galaxies, and tidal-dwarf and ram-pressure-dwarf (type B) galaxies void of DM. Type A dwarfs surround the host approximately spherically, while type B dwarfs are typically correlated in phase-space. Type B dwarfs must exist in any cosmological theory in which galaxies interact. Only one type of dwarf galaxy is observed to exist on the baryonic Tully-Fisher plot and in the radius-mass plane. The Milky Way satellite system forms a vast phase-space-correlated structure that includes globular clusters and stellar and gaseous streams. Other galaxies also have phase-space correlated satellite systems. Therefore, The Dual Dwarf Galaxy Theorem is falsified by observation and dynamically relevant cold or warm DM cannot exist. It is shown that the SMoC is incompatible with a large set of other extragalactic observations. Other theoretical solutions to cosmological observations exist. In particular, alone the empirical mass-discrepancy-acceleration correlation constitutes convincing evidence that galactic-scale dynamics must be Milgromian. Major problems with inflationary big bang cosmologies remain unresolved.

Identification of protein-interacting nucleotides in a RNA sequence using composition profile of tri-nucleotides.

PubMed

Panwar, Bharat; Raghava, Gajendra P S

2015-04-01

The RNA-protein interactions play a diverse role in the cells, thus identification of RNA-protein interface is essential for the biologist to understand their function. In the past, several methods have been developed for predicting RNA interacting residues in proteins, but limited efforts have been made for the identification of protein-interacting nucleotides in RNAs. In order to discriminate protein-interacting and non-interacting nucleotides, we used various classifiers (NaiveBayes, NaiveBayesMultinomial, BayesNet, ComplementNaiveBayes, MultilayerPerceptron, J48, SMO, RandomForest, SMO and SVM(light)) for prediction model development using various features and achieved highest 83.92% sensitivity, 84.82 specificity, 84.62% accuracy and 0.62 Matthew's correlation coefficient by SVM(light) based models. We observed that certain tri-nucleotides like ACA, ACC, AGA, CAC, CCA, GAG, UGA, and UUU preferred in protein-interaction. All the models have been developed using a non-redundant dataset and are evaluated using five-fold cross validation technique. A web-server called RNApin has been developed for the scientific community (http://crdd.osdd.net/raghava/rnapin/). Copyright © 2015 Elsevier Inc. All rights reserved.

Measurement of EUV lithography pupil amplitude and phase variation via image-based methodology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levinson, Zachary; Verduijn, Erik; Wood, Obert R.

2016-04-01

Here, an approach to image-based EUV aberration metrology using binary mask targets and iterative model-based solutions to extract both the amplitude and phase components of the aberrated pupil function is presented. The approach is enabled through previously developed modeling, fitting, and extraction algorithms. We seek to examine the behavior of pupil amplitude variation in real-optical systems. Optimized target images were captured under several conditions to fit the resulting pupil responses. Both the amplitude and phase components of the pupil function were extracted from a zone-plate-based EUV mask microscope. The pupil amplitude variation was expanded in three different bases: Zernike polynomials,more » Legendre polynomials, and Hermite polynomials. It was found that the Zernike polynomials describe pupil amplitude variation most effectively of the three.« less

Reducing Line Edge Roughness in Si and SiN through plasma etch chemistry optimization for photonic waveguide applications

NASA Astrophysics Data System (ADS)

Marchack, Nathan; Khater, Marwan; Orcutt, Jason; Chang, Josephine; Holmes, Steven; Barwicz, Tymon; Kamlapurkar, Swetha; Green, William; Engelmann, Sebastian

2017-03-01

The LER and LWR of subtractively patterned Si and SiN waveguides was calculated after each step in the process. It was found for Si waveguides that adjusting the ratio of CF4:CHF3 during the hard mask open step produced reductions in LER of 26 and 43% from the initial lithography for isolated waveguides patterned with partial and full etches, respectively. However for final LER values of 3.0 and 2.5 nm on fully etched Si waveguides, the corresponding optical loss measurements were indistinguishable. For SiN waveguides, introduction of C4H9F to the conventional CF4/CHF3 measurement was able to reduce the mask height budget by a factor of 5, while reducing LER from the initial lithography by 26%.

Process research on non-CZ silicon material

NASA Technical Reports Server (NTRS)

1982-01-01

High risk, high payoff research areas associated with he process for producing photovoltaic modules using non-CZ sheet material are investigated. All investigations are being performed using dendritic web silicon, but all processes are directly applicable to other ribbon forms of sheet material. The technical feasibility of forming front and back junctions in non-CZ silicon using liquid dopant techniques was determined. Numerous commercially available liquid phosphorus and boron dopant solutions are investigated. Temperature-time profiles to achieve N(+) and P(+) sheet resistivities of 60 + or - 10 and 40 + or - s10 ohms per square centimeter respectively are established. A study of the optimal method of liquid dopant application is performed. The technical feasibility of forming a liquid applied diffusion mask to replace the more costly chemical vapor deposited SiO2 diffusion mask was also determined.

Optimization of coronagraph design for segmented aperture telescopes

NASA Astrophysics Data System (ADS)

Jewell, Jeffrey; Ruane, Garreth; Shaklan, Stuart; Mawet, Dimitri; Redding, Dave

2017-09-01

The goal of directly imaging Earth-like planets in the habitable zone of other stars has motivated the design of coronagraphs for use with large segmented aperture space telescopes. In order to achieve an optimal trade-off between planet light throughput and diffracted starlight suppression, we consider coronagraphs comprised of a stage of phase control implemented with deformable mirrors (or other optical elements), pupil plane apodization masks (gray scale or complex valued), and focal plane masks (either amplitude only or complex-valued, including phase only such as the vector vortex coronagraph). The optimization of these optical elements, with the goal of achieving 10 or more orders of magnitude in the suppression of on-axis (starlight) diffracted light, represents a challenging non-convex optimization problem with a nonlinear dependence on control degrees of freedom. We develop a new algorithmic approach to the design optimization problem, which we call the "Auxiliary Field Optimization" (AFO) algorithm. The central idea of the algorithm is to embed the original optimization problem, for either phase or amplitude (apodization) in various planes of the coronagraph, into a problem containing additional degrees of freedom, specifically fictitious "auxiliary" electric fields which serve as targets to inform the variation of our phase or amplitude parameters leading to good feasible designs. We present the algorithm, discuss details of its numerical implementation, and prove convergence to local minima of the objective function (here taken to be the intensity of the on-axis source in a "dark hole" region in the science focal plane). Finally, we present results showing application of the algorithm to both unobscured off-axis and obscured on-axis segmented telescope aperture designs. The application of the AFO algorithm to the coronagraph design problem has produced solutions which are capable of directly imaging planets in the habitable zone, provided end-to-end telescope system stability requirements can be met. Ongoing work includes advances of the AFO algorithm reported here to design in additional robustness to a resolved star, and other phase or amplitude aberrations to be encountered in a real segmented aperture space telescope.

Thermochemistry and Reactivity of Metals Engaged in Chemiionization

DTIC Science & Technology

2015-12-03

SUPPLEMENTARY NOTES 14. ABSTRACT The exothermicity of the chemi-ionization reaction Sm + O -> SmO+ + e– has been re evaluated. Guided ion beam tandem mass ...tandem mass spectrometer (GIBMS). Such reactions are of direct interest in understanding the chemistry that might occur when such lanthanides are...complete loss of communication. Scintillation can be caused by natural irregularities in the ionosphere. In critical applications, it may be desirable

The Race Relations Advisory Group: An Intergroup Intervention.

DTIC Science & Technology

1985-03-01

Washington, DC 20548 National Institute of Education EOLC/SMO 1200 19th Street, N.W. Washington, DC 20208 National Inntitute of Mental Health Division...of Extramural Research Programs 5600 Fishers Lane Rockville, HD 20852 National Institute of Mental Health Minority Group Mental Health Programs Room 7...organization members, balances membership by nender within race, and reflects a repre- sentative cross-section of hierarchical levels and functional

Preliminary flora of the Sierra Bacadehuachi, Sonora, Mexico

Treesearch

Thomas R. Van Devender; Ana Lilia Reina-Guerrero; George M. Ferguson; George Yatskievych; Beatriz E. Loyola-Reina; Gertrudis Yanes-Arvayo; Maria de la Paz Montanez-Armenta; John L. Anderson; Stephen F. Hale; Sky Jacobs

2013-01-01

The Sierra Bacadéhuachi in east-central Sonora is the westernmost mountain range in the Sierra Madre Occidental (SMO), located east of Bacadéhuachi, Municipio de Bacadéhuachi, 34 km east of the Chihuahua border, and 165 km south of the Arizona border. The vegetation ranges from lowland foothills thornscrub up through desert grassland to oak woodland and pine-oak forest...

Polyamine Catabolism Is Enhanced after Traumatic Brain Injury

PubMed Central

Zahedi, Kamyar; Huttinger, Francis; Morrison, Ryan; Murray-Stewart, Tracy; Casero, Robert A.

2010-01-01

Abstract Polyamines spermine and spermidine are highly regulated, ubiquitous aliphatic cations that maintain DNA structure and function as immunomodulators and as antioxidants. Polyamine homeostasis is disrupted after brain injuries, with concomitant generation of toxic metabolites that may contribute to secondary injuries. To test the hypothesis of increased brain polyamine catabolism after traumatic brain injury (TBI), we determined changes in catabolic enzymes and polyamine levels in the rat brain after lateral controlled cortical impact TBI. Spermine oxidase (SMO) catalyzes the degradation of spermine to spermidine, generating H2O2 and aminoaldehydes. Spermidine/spermine-N1-acetyltransferase (SSAT) catalyzes acetylation of these polyamines, and both are further oxidized in a reaction that generates putrescine, H2O2, and aminoaldehydes. In a rat cortical impact model of TBI, SSAT mRNA increased subacutely (6–24 h) after TBI in ipsilateral cortex and hippocampus. SMO mRNA levels were elevated late, from 3 to 7 days post-injury. Polyamine catabolism increased as well. Spermine levels were normal at 6 h and decreased slightly at 24 h, but were normal again by 72 h post-injury. Spermidine levels also decreased slightly (6–24 h), then increased by ∼50% at 72 h post-injury. By contrast, normally low putrescine levels increased up to sixfold (6–72 h) after TBI. Moreover, N-acetylspermidine (but not N-acetylspermine) was detectable (24–72 h) near the site of injury, consistent with increased SSAT activity. None of these changes were seen in the contralateral hemisphere. Immunohistochemical confirmation indicated that SSAT and SMO were expressed throughout the brain. SSAT-immunoreactivity (SSAT-ir) increased in both neuronal and nonneuronal (likely glial) populations ipsilateral to injury. Interestingly, bilateral increases in cortical SSAT-ir neurons occurred at 72 h post-injury, whereas hippocampal changes occurred only ipsilaterally. Prolonged increases in brain polyamine catabolism are the likely cause of loss of homeostasis in this pathway. The potential for simple therapeutic interventions (e.g., polyamine supplementation or inhibition of polyamine oxidation) is an exciting implication of these studies. PMID:19968558

A Role for Smoothened during Murine Lens and Cornea Development

PubMed Central

Trogrlic, Lidia; Milevski, Stefan V.; Familari, Mary; Martinez, Gemma; de Iongh, Robb U

2014-01-01

Various studies suggest that Hedgehog (Hh) signalling plays roles in human and zebrafish ocular development. Recent studies (Kerr et al., Invest Ophthalmol Vis Sci. 2012; 53, 3316–30) showed that conditionally activating Hh signals promotes murine lens epithelial cell proliferation and disrupts fibre differentiation. In this study we examined the expression of the Hh pathway and the requirement for the Smoothened gene in murine lens development. Expression of Hh pathway components in developing lens was examined by RT-PCR, immunofluorescence and in situ hybridisation. The requirement of Smo in lens development was determined by conditional loss-of-function mutations, using LeCre and MLR10 Cre transgenic mice. The phenotype of mutant mice was examined by immunofluorescence for various markers of cell cycle, lens and cornea differentiation. Hh pathway components (Ptch1, Smo, Gli2, Gli3) were detected in lens epithelium from E12.5. Gli2 was particularly localised to mitotic nuclei and, at E13.5, Gli3 exhibited a shift from cytosol to nucleus, suggesting distinct roles for these transcription factors. Conditional deletion of Smo, from ∼E12.5 (MLR10 Cre) did not affect ocular development, whereas deletion from ∼E9.5 (LeCre) resulted in lens and corneal defects from E14.5. Mutant lenses were smaller and showed normal expression of p57Kip2, c-Maf, E-cadherin and Pax6, reduced expression of FoxE3 and Ptch1 and decreased nuclear Hes1. There was normal G1-S phase but decreased G2-M phase transition at E16.5 and epithelial cell death from E14.5-E16.5. Mutant corneas were thicker due to aberrant migration of Nrp2+ cells from the extraocular mesenchyme, resulting in delayed corneal endothelial but normal epithelial differentiation. These results indicate the Hh pathway is required during a discrete period (E9.5–E12.5) in lens development to regulate lens epithelial cell proliferation, survival and FoxE3 expression. Defective corneal development occurs secondary to defects in lens and appears to be due to defective migration of peri-ocular Nrp2+ neural crest/mesenchymal cells. PMID:25268479

Tracking the mutual shaping of the technical and social dimensions of solar-powered mosquito trapping systems (SMoTS) for malaria control on Rusinga Island, western Kenya.

PubMed

Oria, Prisca A; Hiscox, Alexandra; Alaii, Jane; Ayugi, Margaret; Mukabana, Wolfgang Richard; Takken, Willem; Leeuwis, Cees

2014-11-18

There has been increasing effort in recent years to incorporate user needs in technology design and re-design. This project employed a bottom-up approach that engaged end users from the outset. Bottom-up approaches have the potential to bolster novel interventions and move them towards adaptive and evidence-based strategies. The present study concerns an innovative use of solar-powered mosquito trapping systems (SMoTS) to control malaria in western Kenya. Our paper highlights the co-dependence of research associated with the development of the SMoTS technology on one hand and research for enhancing the sustainable uptake of that very same intervention within the community on the other. During the pre-intervention year, we examined the design, re-design and piloting of a novel technology to generate lessons for malaria elimination on Rusinga Island. Initial ideas about many technological necessities were evaluated and re-designed following feedback from various sources, including technical and social research as well as broader interactions with the social environment. We documented the interlocking of the multiple processes and activities that took place through process observation and document reviews. We analysed the data within the conceptual framework of system innovation by identifying mutual shaping between technical and social factors. Our findings illustrate how various project stakeholders including project staff, collaborators, donor, and community members simultaneously pursued interdependent technological transformations and social interests. In the ongoing process, we observed how partial outcomes in the technological domain influenced social events at a later phase and vice versa. Looking at malaria intervention projects employing novel technologies as niches that may evolve towards system innovation, helps to reveal interrelations between the various technical and social aspects. Revealing these interrelations requires a different role for research and different perspective on innovation where innovation is more than the technical aspects. This approach therefore requires that research is designed in a way that enables obtaining feedback from both aspects.

Effects of cold water immersion and active recovery on hemodynamics and recovery of muscle strength following resistance exercise.

PubMed

Roberts, Llion A; Muthalib, Makii; Stanley, Jamie; Lichtwark, Glen; Nosaka, Kazunori; Coombes, Jeff S; Peake, Jonathan M

2015-08-15

Cold water immersion (CWI) and active recovery (ACT) are frequently used as postexercise recovery strategies. However, the physiological effects of CWI and ACT after resistance exercise are not well characterized. We examined the effects of CWI and ACT on cardiac output (Q̇), muscle oxygenation (SmO2), blood volume (tHb), muscle temperature (Tmuscle), and isometric strength after resistance exercise. On separate days, 10 men performed resistance exercise, followed by 10 min CWI at 10°C or 10 min ACT (low-intensity cycling). Q̇ (7.9 ± 2.7 l) and Tmuscle (2.2 ± 0.8°C) increased, whereas SmO2 (-21.5 ± 8.8%) and tHb (-10.1 ± 7.7 μM) decreased after exercise (P < 0.05). During CWI, Q̇ (-1.1 ± 0.7 l) and Tmuscle (-6.6 ± 5.3°C) decreased, while tHb (121 ± 77 μM) increased (P < 0.05). In the hour after CWI, Q̇ and Tmuscle remained low, while tHb also decreased (P < 0.05). By contrast, during ACT, Q̇ (3.9 ± 2.3 l), Tmuscle (2.2 ± 0.5°C), SmO2 (17.1 ± 5.7%), and tHb (91 ± 66 μM) all increased (P < 0.05). In the hour after ACT, Tmuscle, and tHb remained high (P < 0.05). Peak isometric strength during 10-s maximum voluntary contractions (MVCs) did not change significantly after CWI, whereas it decreased after ACT (-30 to -45 Nm; P < 0.05). Muscle deoxygenation time during MVCs increased after ACT (P < 0.05), but not after CWI. Muscle reoxygenation time after MVCs tended to increase after CWI (P = 0.052). These findings suggest first that hemodynamics and muscle temperature after resistance exercise are dependent on ambient temperature and metabolic demands with skeletal muscle, and second, that recovery of strength after resistance exercise is independent of changes in hemodynamics and muscle temperature. Copyright © 2015 the American Physiological Society.

On Optimizing H. 264/AVC Rate Control by Improving R-D Model and Incorporating HVS Characteristics

NASA Astrophysics Data System (ADS)

Zhu, Zhongjie; Wang, Yuer; Bai, Yongqiang; Jiang, Gangyi

2010-12-01

The state-of-the-art JVT-G012 rate control algorithm of H.264 is improved from two aspects. First, the quadratic rate-distortion (R-D) model is modified based on both empirical observations and theoretical analysis. Second, based on the existing physiological and psychological research findings of human vision, the rate control algorithm is optimized by incorporating the main characteristics of the human visual system (HVS) such as contrast sensitivity, multichannel theory, and masking effect. Experiments are conducted, and experimental results show that the improved algorithm can simultaneously enhance the overall subjective visual quality and improve the rate control precision effectively.

Library-based illumination synthesis for critical CMOS patterning.

PubMed

Yu, Jue-Chin; Yu, Peichen; Chao, Hsueh-Yung

2013-07-01

In optical microlithography, the illumination source for critical complementary metal-oxide-semiconductor layers needs to be determined in the early stage of a technology node with very limited design information, leading to simple binary shapes. Recently, the availability of freeform sources permits us to increase pattern fidelity and relax mask complexities with minimal insertion risks to the current manufacturing flow. However, source optimization across many patterns is often treated as a design-of-experiments problem, which may not fully exploit the benefits of a freeform source. In this paper, a rigorous source-optimization algorithm is presented via linear superposition of optimal sources for pre-selected patterns. We show that analytical solutions are made possible by using Hopkins formulation and quadratic programming. The algorithm allows synthesized illumination to be linked with assorted pattern libraries, which has a direct impact on design rule studies for early planning and design automation for full wafer optimization.

Computer-Aided Diagnosis of Anterior Segment Eye Abnormalities using Visible Wavelength Image Analysis Based Machine Learning.

PubMed

S V, Mahesh Kumar; R, Gunasundari

2018-06-02

Eye disease is a major health problem among the elderly people. Cataract and corneal arcus are the major abnormalities that exist in the anterior segment eye region of aged people. Hence, computer-aided diagnosis of anterior segment eye abnormalities will be helpful for mass screening and grading in ophthalmology. In this paper, we propose a multiclass computer-aided diagnosis (CAD) system using visible wavelength (VW) eye images to diagnose anterior segment eye abnormalities. In the proposed method, the input VW eye images are pre-processed for specular reflection removal and the iris circle region is segmented using a circular Hough Transform (CHT)-based approach. The first-order statistical features and wavelet-based features are extracted from the segmented iris circle and used for classification. The Support Vector Machine (SVM) by Sequential Minimal Optimization (SMO) algorithm was used for the classification. In experiments, we used 228 VW eye images that belong to three different classes of anterior segment eye abnormalities. The proposed method achieved a predictive accuracy of 96.96% with 97% sensitivity and 99% specificity. The experimental results show that the proposed method has significant potential for use in clinical applications.

Optimization of reactive-ion etching (RIE) parameters for fabrication of tantalum pentoxide (Ta2O5) waveguide using Taguchi method

NASA Astrophysics Data System (ADS)

Muttalib, M. Firdaus A.; Chen, Ruiqi Y.; Pearce, S. J.; Charlton, Martin D. B.

2017-11-01

In this paper, we demonstrate the optimization of reactive-ion etching (RIE) parameters for the fabrication of tantalum pentoxide (Ta2O5) waveguide with chromium (Cr) hard mask in a commercial OIPT Plasmalab 80 RIE etcher. A design of experiment (DOE) using Taguchi method was implemented to find optimum RF power, mixture of CHF3 and Ar gas ratio, and chamber pressure for a high etch rate, good selectivity, and smooth waveguide sidewall. It was found that the optimized etch condition obtained in this work were RF power = 200 W, gas ratio = 80 %, and chamber pressure = 30 mTorr with an etch rate of 21.6 nm/min, Ta2O5/Cr selectivity ratio of 28, and smooth waveguide sidewall.

Wavelet-Smoothed Interpolation of Masked Scientific Data for JPEG 2000 Compression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brislawn, Christopher M.

2012-08-13

How should we manage scientific data with 'holes'? Some applications, like JPEG 2000, expect logically rectangular data, but some sources, like the Parallel Ocean Program (POP), generate data that isn't defined on certain subsets. We refer to grid points that lack well-defined, scientifically meaningful sample values as 'masked' samples. Wavelet-smoothing is a highly scalable interpolation scheme for regions with complex boundaries on logically rectangular grids. Computation is based on forward/inverse discrete wavelet transforms, so runtime complexity and memory scale linearly with respect to sample count. Efficient state-of-the-art minimal realizations yield small constants (O(10)) for arithmetic complexity scaling, and in-situ implementationmore » techniques make optimal use of memory. Implementation in two dimensions using tensor product filter banks is straighsorward and should generalize routinely to higher dimensions. No hand-tuning required when the interpolation mask changes, making the method aeractive for problems with time-varying masks. Well-suited for interpolating undefined samples prior to JPEG 2000 encoding. The method outperforms global mean interpolation, as judged by both SNR rate-distortion performance and low-rate artifact mitigation, for data distributions whose histograms do not take the form of sharply peaked, symmetric, unimodal probability density functions. These performance advantages can hold even for data whose distribution differs only moderately from the peaked unimodal case, as demonstrated by POP salinity data. The interpolation method is very general and is not tied to any particular class of applications, could be used for more generic smooth interpolation.« less

Deformably registering and annotating whole CLARITY brains to an atlas via masked LDDMM

NASA Astrophysics Data System (ADS)

Kutten, Kwame S.; Vogelstein, Joshua T.; Charon, Nicolas; Ye, Li; Deisseroth, Karl; Miller, Michael I.

2016-04-01

The CLARITY method renders brains optically transparent to enable high-resolution imaging in the structurally intact brain. Anatomically annotating CLARITY brains is necessary for discovering which regions contain signals of interest. Manually annotating whole-brain, terabyte CLARITY images is difficult, time-consuming, subjective, and error-prone. Automatically registering CLARITY images to a pre-annotated brain atlas offers a solution, but is difficult for several reasons. Removal of the brain from the skull and subsequent storage and processing cause variable non-rigid deformations, thus compounding inter-subject anatomical variability. Additionally, the signal in CLARITY images arises from various biochemical contrast agents which only sparsely label brain structures. This sparse labeling challenges the most commonly used registration algorithms that need to match image histogram statistics to the more densely labeled histological brain atlases. The standard method is a multiscale Mutual Information B-spline algorithm that dynamically generates an average template as an intermediate registration target. We determined that this method performs poorly when registering CLARITY brains to the Allen Institute's Mouse Reference Atlas (ARA), because the image histogram statistics are poorly matched. Therefore, we developed a method (Mask-LDDMM) for registering CLARITY images, that automatically finds the brain boundary and learns the optimal deformation between the brain and atlas masks. Using Mask-LDDMM without an average template provided better results than the standard approach when registering CLARITY brains to the ARA. The LDDMM pipelines developed here provide a fast automated way to anatomically annotate CLARITY images; our code is available as open source software at http://NeuroData.io.

Improving global CD uniformity by optimizing post-exposure bake and develop sequences

NASA Astrophysics Data System (ADS)

Osborne, Stephen P.; Mueller, Mark; Lem, Homer; Reyland, David; Baik, KiHo

2003-12-01

Improvements in the final uniformity of masks can be shrouded by error contributions from many sources. The final Global CD Uniformity (GCDU) of a mask is degraded by individual contributions of the writing tool, the Post Applied Bake (PAB), the Post Exposure Bake (PEB), the Develop sequence and the Etch step. Final global uniformity will improve by isolating and minimizing the variability of the PEB and Develop. We achieved this de-coupling of the PEB and Develop process from the whole process stream by using "dark loss" which is the loss of unexposed resist during the develop process. We confirmed a correspondence between Angstroms of dark loss and nanometer sized deviations in the chrome CD. A plate with a distinctive dark loss pattern was related to a nearly identical pattern in the chrome CD. This pattern was verified to have originated during the PEB process and displayed a [Δ(Final CD)/Δ(Dark Loss)] ratio of 6 for TOK REAP200 resist. Previous papers have reported a sensitive linkage between Angstroms of dark loss and nanometers in the final uniformity of the written plate. These initial studies reported using this method to improve the PAB of resists for greater uniformity of sensitivity and contrast. Similarly, this paper demonstrates an outstanding optimization of PEB and Develop processes.

A Genetic Algorithm for the Generation of Packetization Masks for Robust Image Communication

PubMed Central

Zapata-Quiñones, Katherine; Duran-Faundez, Cristian; Gutiérrez, Gilberto; Lecuire, Vincent; Arredondo-Flores, Christopher; Jara-Lipán, Hugo

2017-01-01

Image interleaving has proven to be an effective solution to provide the robustness of image communication systems when resource limitations make reliable protocols unsuitable (e.g., in wireless camera sensor networks); however, the search for optimal interleaving patterns is scarcely tackled in the literature. In 2008, Rombaut et al. presented an interesting approach introducing a packetization mask generator based in Simulated Annealing (SA), including a cost function, which allows assessing the suitability of a packetization pattern, avoiding extensive simulations. In this work, we present a complementary study about the non-trivial problem of generating optimal packetization patterns. We propose a genetic algorithm, as an alternative to the cited work, adopting the mentioned cost function, then comparing it to the SA approach and a torus automorphism interleaver. In addition, we engage the validation of the cost function and provide results attempting to conclude about its implication in the quality of reconstructed images. Several scenarios based on visual sensor networks applications were tested in a computer application. Results in terms of the selected cost function and image quality metric PSNR show that our algorithm presents similar results to the other approaches. Finally, we discuss the obtained results and comment about open research challenges. PMID:28452934

Design and Implementation of a Video-Zoom Driven Digital Audio-Zoom System for Portable Digital Imaging Devices

NASA Astrophysics Data System (ADS)

Park, Nam In; Kim, Seon Man; Kim, Hong Kook; Kim, Ji Woon; Kim, Myeong Bo; Yun, Su Won

In this paper, we propose a video-zoom driven audio-zoom algorithm in order to provide audio zooming effects in accordance with the degree of video-zoom. The proposed algorithm is designed based on a super-directive beamformer operating with a 4-channel microphone system, in conjunction with a soft masking process that considers the phase differences between microphones. Thus, the audio-zoom processed signal is obtained by multiplying an audio gain derived from a video-zoom level by the masked signal. After all, a real-time audio-zoom system is implemented on an ARM-CORETEX-A8 having a clock speed of 600 MHz after different levels of optimization are performed such as algorithmic level, C-code, and memory optimizations. To evaluate the complexity of the proposed real-time audio-zoom system, test data whose length is 21.3 seconds long is sampled at 48 kHz. As a result, it is shown from the experiments that the processing time for the proposed audio-zoom system occupies 14.6% or less of the ARM clock cycles. It is also shown from the experimental results performed in a semi-anechoic chamber that the signal with the front direction can be amplified by approximately 10 dB compared to the other directions.

[Affine transformation-based automatic registration for peripheral digital subtraction angiography (DSA)].

PubMed

Kong, Gang; Dai, Dao-Qing; Zou, Lu-Min

2008-07-01

In order to remove the artifacts of peripheral digital subtraction angiography (DSA), an affine transformation-based automatic image registration algorithm is introduced here. The whole process is described as follows: First, rectangle feature templates are constructed with their centers of the extracted Harris corners in the mask, and motion vectors of the central feature points are estimated using template matching technology with the similarity measure of maximum histogram energy. And then the optimal parameters of the affine transformation are calculated with the matrix singular value decomposition (SVD) method. Finally, bilinear intensity interpolation is taken to the mask according to the specific affine transformation. More than 30 peripheral DSA registrations are performed with the presented algorithm, and as the result, moving artifacts of the images are removed with sub-pixel precision, and the time consumption is less enough to satisfy the clinical requirements. Experimental results show the efficiency and robustness of the algorithm.

Advantages of isofocal printing in maskmaking with the ALTA 3500

NASA Astrophysics Data System (ADS)

Fuller, Scott E.; Pochkowski, Mike

1999-04-01

The ALTA 3500, an advanced scanned-laser mask lithography tool produced by Etec, was introduced to the marketplace in 1997. The system architecture was described and an initial performance evaluation was presented. This system, based on the ALTA 3000 system, uses a new 33.3X, 0.8 NA final reduction lens to reduce the spot size to 0.27 micrometers FWHM, thereby affording improved resolution and pattern acuity on the mask. An anisotropic chrome etch process was developed and introduced along with a TOK iP3600 resist to take advantage of the improved resolution. In this paper we will more extensively describe the performance of the ALTA 3500 scanned laser system and the performance of these new processes. In addition, an investigation of the benefits of operating in the optimal isofocal print region is examined and compared to printing at the nominal process conditions.

Perceptually-Based Adaptive JPEG Coding

NASA Technical Reports Server (NTRS)

Watson, Andrew B.; Rosenholtz, Ruth; Null, Cynthia H. (Technical Monitor)

1996-01-01

An extension to the JPEG standard (ISO/IEC DIS 10918-3) allows spatial adaptive coding of still images. As with baseline JPEG coding, one quantization matrix applies to an entire image channel, but in addition the user may specify a multiplier for each 8 x 8 block, which multiplies the quantization matrix, yielding the new matrix for the block. MPEG 1 and 2 use much the same scheme, except there the multiplier changes only on macroblock boundaries. We propose a method for perceptual optimization of the set of multipliers. We compute the perceptual error for each block based upon DCT quantization error adjusted according to contrast sensitivity, light adaptation, and contrast masking, and pick the set of multipliers which yield maximally flat perceptual error over the blocks of the image. We investigate the bitrate savings due to this adaptive coding scheme and the relative importance of the different sorts of masking on adaptive coding.

Detection of pigment network in dermatoscopy images using texture analysis

PubMed Central

Anantha, Murali; Moss, Randy H.; Stoecker, William V.

2011-01-01

Dermatoscopy, also known as dermoscopy or epiluminescence microscopy (ELM), is a non-invasive, in vivo technique, which permits visualization of features of pigmented melanocytic neoplasms that are not discernable by examination with the naked eye. ELM offers a completely new range of visual features. One such prominent feature is the pigment network. Two texture-based algorithms are developed for the detection of pigment network. These methods are applicable to various texture patterns in dermatoscopy images, including patterns that lack fine lines such as cobblestone, follicular, or thickened network patterns. Two texture algorithms, Laws energy masks and the neighborhood gray-level dependence matrix (NGLDM) large number emphasis, were optimized on a set of 155 dermatoscopy images and compared. Results suggest superiority of Laws energy masks for pigment network detection in dermatoscopy images. For both methods, a texel width of 10 pixels or approximately 0.22 mm is found for dermatoscopy images. PMID:15249068

Effects of ramp reset pulses on the address discharge in a shadow mask plasma display panel

NASA Astrophysics Data System (ADS)

Yang, Lanlan; Tu, Yan; Zhang, Xiong; Jiang, Youyan; Zhang, Jian; Wang, Baoping

2007-05-01

A two-dimensional self-consistent numerical simulation model is used to analyse the effects of the ramp reset pulses on the address discharge in a shadow mask plasma display panel (SM-PDP). Some basic parameters such as the slope of the ramp pulse and the terminal voltage of the ramp reset period are varied to investigate their effects. The simulation results illustrate that the wall voltage is mainly decided by the terminal voltage and the firing voltage at the end of the ramp reset period. Moreover, the variation of the ramp slope will also bring a few modifications to the wall voltage. The priming particles in the beginning of the addressing period are related to the slope of the ramping down voltage pulse. The simulation results can help us optimize the driving scheme of the SM-PDP.

Overlay degradation induced by film stress

NASA Astrophysics Data System (ADS)

Huang, Chi-hao; Liu, Yu-Lin; Luo, Shing-Ann; Yang, Mars; Yang, Elvis; Hung, Yung-Tai; Luoh, Tuung; Yang, T. H.; Chen, K. C.

2017-03-01

The semiconductor industry has continually sought the approaches to produce memory devices with increased memory cells per memory die. One way to meet the increasing storage capacity demand and reduce bit cost of NAND flash memories is 3D stacked flash cell array. In constructing 3D NAND flash memories, increasing the number of stacked layers to build more memory cell number per unit area necessitates many high-aspect-ratio etching processes accordingly the incorporation of thick and unique etching hard-mask scheme has been indispensable. However, the ever increasingly thick requirement on etching hard-mask has made the hard-mask film stress control extremely important for maintaining good process qualities. The residual film stress alters the wafer shape consequently several process impacts have been readily observed across wafer, such as wafer chucking error on scanner, film peeling, materials coating and baking defects, critical dimension (CD) non-uniformity and overlay degradation. This work investigates the overlay and residual order performance indicator (ROPI) degradation coupling with increasingly thick advanced patterning film (APF) etching hard-mask. Various APF films deposited by plasma enhanced chemical vapor deposition (PECVD) method under different deposition temperatures, chemicals combinations, radio frequency powers and chamber pressures were carried out. And -342MPa to +80MPa film stress with different film thicknesses were generated for the overlay performance study. The results revealed the overlay degradation doesn't directly correlate with convex or concave wafer shapes but the magnitude of residual APF film stress, while increasing the APF thickness will worsen the overlay performance and ROPI strongly. High-stress APF film was also observed to enhance the scanner chucking difference and lead to more serious wafer to wafer overlay variation. To reduce the overlay degradation from ever increasingly thick APF etching hard-mask, optimizing the film stress of APF is the most effective way and high order overlay compensation is also helpful.

Splendidly blended: a machine learning set up for CDU control

NASA Astrophysics Data System (ADS)

Utzny, Clemens

2017-06-01

As the concepts of machine learning and artificial intelligence continue to grow in importance in the context of internet related applications it is still in its infancy when it comes to process control within the semiconductor industry. Especially the branch of mask manufacturing presents a challenge to the concepts of machine learning since the business process intrinsically induces pronounced product variability on the background of small plate numbers. In this paper we present the architectural set up of a machine learning algorithm which successfully deals with the demands and pitfalls of mask manufacturing. A detailed motivation of this basic set up followed by an analysis of its statistical properties is given. The machine learning set up for mask manufacturing involves two learning steps: an initial step which identifies and classifies the basic global CD patterns of a process. These results form the basis for the extraction of an optimized training set via balanced sampling. A second learning step uses this training set to obtain the local as well as global CD relationships induced by the manufacturing process. Using two production motivated examples we show how this approach is flexible and powerful enough to deal with the exacting demands of mask manufacturing. In one example we show how dedicated covariates can be used in conjunction with increased spatial resolution of the CD map model in order to deal with pathological CD effects at the mask boundary. The other example shows how the model set up enables strategies for dealing tool specific CD signature differences. In this case the balanced sampling enables a process control scheme which allows usage of the full tool park within the specified tight tolerance budget. Overall, this paper shows that the current rapid developments off the machine learning algorithms can be successfully used within the context of semiconductor manufacturing.

In vitro and in vivo correlation of disintegration and bitter taste masking using orally disintegrating tablet containing ion exchange resin-drug complex.

PubMed

Kim, Jong-Il; Cho, Sang-Min; Cui, Jing-Hao; Cao, Qing-Ri; Oh, Euichaul; Lee, Beom-Jin

2013-10-15

Although the taste-masking of bitter drug using ion exchange resin has been recognized, in vitro testing using an electronic tongue (e-Tongue) and in vivo bitterness test by human panel test was not fully understood. In case of orally disintegrating tablet (ODT) containing bitter medicine, in vitro and in vivo disintegration is also importance for dosage performance. Donepezil hydrochloride was chosen as a model drug due to its bitterness and requires rapid disintegration for the preparation of ODT. In this study, ion exchange resin drug complex (IRDC) at three different ratios (1:2, 1:1, 2:1) was prepared using a spray-drying method and then IRDC-loaded ODT containing superdisintegrants (crospovidone, croscarmellose sodium, and sodium starch glycolate) were prepared by the direct compression method. The physical properties and morphologies were then characterized by scanning electron microscopy (SEM), X-ray powder diffraction (PXRD) and electrophoretic laser scattering (ELS), respectively. The in vitro taste-masking efficiency was measured with an electronic tongue (e-Tongue). In vivo bitterness scale was also evaluated by human volunteers and then we defined new term, "bitterness index (BI)" to link in vitro e-Tongue. There was a good correlation of IRDC between in vitro e-Tongue values and in vivo BI. Furthermore, IRDC-loaded ODT showed good in vitro/in vivo correlation in the disintegration time. The optimal IRDC-loaded ODTs displayed similar drug release profiles to the reference tablet (Aricept(®) ODT) in release media of pH 1.2, pH 4.0, pH 6.8 and distilled water but had significantly better palatability in vivo taste-masking evaluation. The current IRDC-loaded ODT according to the in vitro and in vivo correlation of disintegration and bitter taste masking could provide platforms in ODT dosage formulations of donepezil hydrochloride for improved patient compliances. Copyright © 2013 Elsevier B.V. All rights reserved.

Placement-aware decomposition of a digital standard cells library for double patterning lithography

NASA Astrophysics Data System (ADS)

Wassal, Amr G.; Sharaf, Heba; Hammouda, Sherif

2012-11-01

To continue scaling the circuit features down, Double Patterning (DP) technology is needed in 22nm technologies and lower. DP requires decomposing the layout features into two masks for pitch relaxation, such that the spacing between any two features on each mask is greater than the minimum allowed mask spacing. The relaxed pitches of each mask are then processed on two separate exposure steps. In many cases, post-layout decomposition fails to decompose the layout into two masks due to the presence of conflicts. Post-layout decomposition of a standard cells block can result in native conflicts inside the cells (internal conflict), or native conflicts on the boundary between two cells (boundary conflict). Resolving native conflicts requires a redesign and/or multiple iterations for the placement and routing phases to get a clean decomposition. Therefore, DP compliance must be considered in earlier phases, before getting the final placed cell block. The main focus of this paper is generating a library of decomposed standard cells to be used in a DP-aware placer. This library should contain all possible decompositions for each standard cell, i.e., these decompositions consider all possible combinations of boundary conditions. However, the large number of combinations of boundary conditions for each standard cell will significantly increase the processing time and effort required to obtain all possible decompositions. Therefore, an efficient methodology is required to reduce this large number of combinations. In this paper, three different reduction methodologies are proposed to reduce the number of different combinations processed to get the decomposed library. Experimental results show a significant reduction in the number of combinations and decompositions needed for the library processing. To generate and verify the proposed flow and methodologies, a prototype for a placement-aware DP-ready cell-library is developed with an optimized number of cell views.

Variations in backward masking with different masking stimuli: II. The effects of spatially quantised masks in the light of local contour interaction, interchannel inhibition, perceptual retouch, and substitution theories.

PubMed

Bachmann, Talis; Luiga, Iiris; Põder, Endel

2005-01-01

In part I we showed that with spatially non-overlapping targets and masks both local metacontrast-like interactions and attentional processes are involved in backward masking. In this second part we extend the strategy of varying the contents of masks to pattern masking where targets and masks overlap in space, in order to compare different masking theories. Images of human faces were backward-masked by three types of spatially quantised masks (the same faces as targets, faces different from targets, and Gaussian noise with power spectra typical for faces). Configural characteristics, rather than the spectral content of the mask, predicted the extent of masking at relatively long stimulus onset asynchronies (SOAs). This poses difficulties for the theory of transient-on-sustained inhibition as the principal mechanism of masking and also for local contour interaction being a decisive factor in pattern masking. The scale of quantisation had no effect on the masking capacity of noise masks and a strong effect on the capacity of different-face masks. Also, the decrease of configural masking with an increase in the coarseness of the quantisation of the mask highlights ambiguities inherent in the re-entrance-based substitution theory of masking. Different masking theories cannot solve the problems of masking separately. They should be combined in order to create a complex, yet comprehensible mode of interaction for the different mechanisms involved in visual backward masking.

What's in a mask? Information masking with forward and backward visual masks.

PubMed

Davis, Chris; Kim, Jeesun

2011-10-01

Three experiments tested how the physical format and information content of forward and backward masks affected the extent of visual pattern masking. This involved using different types of forward and backward masks with target discrimination measured by percentage correct in the first experiment (with a fixed target duration) and by an adaptive threshold procedure in the last two. The rationale behind the manipulation of the content of the masks stemmed from masking theories emphasizing attentional and/or conceptual factors rather than visual ones. Experiment 1 used word masks and showed that masking was reduced (a masking reduction effect) when the forward and backward masks were the same word (although in different case) compared to when the masks were different words. Experiment 2 tested the extent to which a reduction in masking might occur due to the physical similarity between the forward and backward masks by comparing the effect of the same content of the masks in the same versus different case. The result showed a significant reduction in masking for same content masks but no significant effect of case. The last experiment examined whether the reduction in masking effect would be observed with nonword masks--that is, having no high-level representation. No reduction in masking was found from same compared to different nonword masks (Experiment 3). These results support the view that the conscious perception of a rapidly displayed target stimulus is in part determined by high-level perceptual/cognitive factors concerned with masking stimulus grouping and attention.

Freeze drying of orally disintegrating tablets containing taste masked naproxen sodium granules in blisters.

PubMed

Stange, Ulrike; Führling, Christian; Gieseler, Henning

2014-09-15

Abstract Orally disintegrating tablets (ODTs) were freeze dried in blisters using the Lyostar® II SMART™ Freeze Dryer Technology. ODT formulations either without non-water soluble particles (placebo) or containing large fractions (717 mg) of taste-masked naproxen sodium (NaS) granules were freeze dried. The process data revealed differences between ODTs with and without embedded granules in the pressure rise curves as well as in the shelf (inlet) temperature adjustments during freeze-drying. Pressure rise curves of the placebo ODTs from eight hours process time showed no distinct temperature-dominated part, and the last optimization step of the shelf temperature to achieve -24.4 °C might be prone to errors. The final shelf temperature of ODTs containing granules was -23.3 °C. The detection of primary drying endpoints using SMART™ Technology or comparative pressure measurements was reliable for both ODT formulations, whereas the application of thermocouples resulted in premature endpoint indication. Product resistance of ODTs containing granules was generally elevated in comparison to ODTs without granules, but increased only slightly over the course of the drying process. In summary, the developed freeze-drying cycle was found applicable for production of elegant ODTs with incorporated taste masked NaS granules.

The influence of viewing conditions on radiological diagnosis of periapical inflammation.

PubMed

Patel, N; Rushton, V E; Macfarlane, T V; Horner, K

2000-07-08

To determine the effect of viewing conditions upon diagnosis of early periapical inflammatory pathosis on intra-oral radiographs, and to examine the effect of observer experience upon diagnostic performance in this task. 50 observers examined 18 periapical radiographs using three different viewing conditions (room lighting; viewing box; viewing box with x2 magnification and masking). Their diagnoses were compared with an 'expert' diagnosis provided by repeated viewings of the films by two dental radiologists. Sensitivities and specificities were determined. When 'ideal' viewing conditions were used, optimal sensitivity (78%) and specificity (78%) were obtained. Use of a viewing box was associated with significantly higher specificity than the use of room lighting (P = 0.0016). Use of masking and x2 magnification was associated with significantly higher sensitivity than a viewing box alone (P = 0.004). There were few significant differences in diagnostic performance between observers, but qualified dental staff had significantly higher specificities than 4th year (P = 0.01) and 5th year (P = 0.01) students when a viewing box was used alone. This study on early periapical inflammatory pathosis gives support to guidelines which recommend the use of a viewing box, x2 magnification and masking for interpreting intra-oral radiographs. It also suggests that observer experience may influence interpretation of early periapical pathosis.

Risk Stratification by Self-Measured Home Blood Pressure across Categories of Conventional Blood Pressure: A Participant-Level Meta-Analysis

PubMed Central

Asayama, Kei; Thijs, Lutgarde; Brguljan-Hitij, Jana; Niiranen, Teemu J.; Hozawa, Atsushi; Boggia, José; Aparicio, Lucas S.; Hara, Azusa; Johansson, Jouni K.; Ohkubo, Takayoshi; Tzourio, Christophe; Stergiou, George S.; Sandoya, Edgardo; Tsuji, Ichiro; Jula, Antti M.; Imai, Yutaka; Staessen, Jan A.

2014-01-01

Background The Global Burden of Diseases Study 2010 reported that hypertension is worldwide the leading risk factor for cardiovascular disease, causing 9.4 million deaths annually. We examined to what extent self-measurement of home blood pressure (HBP) refines risk stratification across increasing categories of conventional blood pressure (CBP). Methods and Findings This meta-analysis included 5,008 individuals randomly recruited from five populations (56.6% women; mean age, 57.1 y). All were not treated with antihypertensive drugs. In multivariable analyses, hazard ratios (HRs) associated with 10-mm Hg increases in systolic HBP were computed across CBP categories, using the following systolic/diastolic CBP thresholds (in mm Hg): optimal, <120/<80; normal, 120–129/80–84; high-normal, 130–139/85–89; mild hypertension, 140–159/90–99; and severe hypertension, ≥160/≥100. Over 8.3 y, 522 participants died, and 414, 225, and 194 had cardiovascular, cardiac, and cerebrovascular events, respectively. In participants with optimal or normal CBP, HRs for a composite cardiovascular end point associated with a 10-mm Hg higher systolic HBP were 1.28 (1.01–1.62) and 1.22 (1.00–1.49), respectively. At high-normal CBP and in mild hypertension, the HRs were 1.24 (1.03–1.49) and 1.20 (1.06–1.37), respectively, for all cardiovascular events and 1.33 (1.07–1.65) and 1.30 (1.09–1.56), respectively, for stroke. In severe hypertension, the HRs were not significant (p≥0.20). Among people with optimal, normal, and high-normal CBP, 67 (5.0%), 187 (18.4%), and 315 (30.3%), respectively, had masked hypertension (HBP≥130 mm Hg systolic or ≥85 mm Hg diastolic). Compared to true optimal CBP, masked hypertension was associated with a 2.3-fold (1.5–3.5) higher cardiovascular risk. A limitation was few data from low- and middle-income countries. Conclusions HBP substantially refines risk stratification at CBP levels assumed to carry no or only mildly increased risk, in particular in the presence of masked hypertension. Randomized trials could help determine the best use of CBP vs. HBP in guiding BP management. Our study identified a novel indication for HBP, which, in view of its low cost and the increased availability of electronic communication, might be globally applicable, even in remote areas or in low-resource settings. Please see later in the article for the Editors' Summary PMID:24465187

Clinical practice guidelines for the management of metastatic colorectal cancer: a consensus statement of the Hellenic Society of Medical Oncologists (HeSMO)

PubMed Central

Dervenis, Christos; Xynos, Evaghelos; Sotiropoulos, George; Gouvas, Nikolaos; Boukovinas, Ioannis; Agalianos, Christos; Androulakis, Nikolaos; Athanasiadis, Athanasios; Christodoulou, Christos; Chrysou, Evangelia; Emmanouilidis, Christos; Georgiou, Panagiotis; Karachaliou, Niki; Katopodi, Ourania; Kountourakis, Panteleimon; Kyriazanos, Ioannis; Makatsoris, Thomas; Papakostas, Pavlos; Papamichael, Demetris; Pechlivanides, George; Pentheroudakis, Georgios; Pilpilidis, Ioannis; Sgouros, Joseph; Tekkis, Paris; Triantopoulou, Charina; Tzardi, Maria; Vassiliou, Vassilis; Vini, Louiza; Xynogalos, Spyridon; Ziras, Nikolaos; Souglakos, John

2016-01-01

There is discrepancy and failure to adhere to current international guidelines for the management of metastatic colorectal cancer (CRC) in hospitals in Greece and Cyprus. The aim of the present document is to provide a consensus on the multidisciplinary management of metastastic CRC, considering both special characteristics of our Healthcare System and international guidelines. Following discussion and online communication among the members of an executive team chosen by the Hellenic Society of Medical Oncology (HeSMO), a consensus for metastastic CRC disease was developed. Statements were subjected to the Delphi methodology on two voting rounds by invited multidisciplinary international experts on CRC. Statements reaching level of agreement by ≥80% were considered as having achieved large consensus, whereas statements reaching 60-80% moderate consensus. One hundred and nine statements were developed. Ninety experts voted for those statements. The median rate of abstain per statement was 18.5% (range: 0-54%). In the end of the process, all statements achieved a large consensus. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized. R0 resection is the only intervention that may offer substantial improvement in the oncological outcomes. PMID:27708505

Guided ion beam and theoretical studies of the bond energy of SmS+

NASA Astrophysics Data System (ADS)

Armentrout, P. B.; Demireva, Maria; Peterson, Kirk A.

2017-12-01

Previous work has shown that atomic samarium cations react with carbonyl sulfide to form SmS+ + CO in an exothermic and barrierless process. To characterize this reaction further, the bond energy of SmS+ is determined in the present study using guided ion beam tandem mass spectrometry. Reactions of SmS+ with Xe, CO, and O2 are examined. Results for collision-induced dissociation processes with all three molecules along with the endothermicity of the SmS+ + CO → Sm+ + COS exchange reaction are combined to yield D0(Sm+-S) = 3.37 ± 0.20 eV. The CO and O2 reactions also yield a SmSO+ product, with measured endothermicities that indicate D0(SSm+-O) = 3.73 ± 0.16 eV and D0(OSm+-S) = 1.38 ± 0.27 eV. The SmS+ bond energy is compared with theoretical values characterized at several levels of theory, including CCSD(T) complete basis set extrapolations using all-electron basis sets. Multireference configuration interaction calculations with explicit spin-orbit calculations along with composite thermochemistry using the Feller-Peterson-Dixon method and all-electron basis sets were also explored for SmS+, and for comparison, SmO, SmO+, and EuO.

Guided ion beam and theoretical studies of the bond energy of SmS.

PubMed

Armentrout, P B; Demireva, Maria; Peterson, Kirk A

2017-12-07

Previous work has shown that atomic samarium cations react with carbonyl sulfide to form SmS + + CO in an exothermic and barrierless process. To characterize this reaction further, the bond energy of SmS + is determined in the present study using guided ion beam tandem mass spectrometry. Reactions of SmS + with Xe, CO, and O 2 are examined. Results for collision-induced dissociation processes with all three molecules along with the endothermicity of the SmS + + CO → Sm + + COS exchange reaction are combined to yield D 0 (Sm + -S) = 3.37 ± 0.20 eV. The CO and O 2 reactions also yield a SmSO + product, with measured endothermicities that indicate D 0 (SSm + -O) = 3.73 ± 0.16 eV and D 0 (OSm + -S) = 1.38 ± 0.27 eV. The SmS + bond energy is compared with theoretical values characterized at several levels of theory, including CCSD(T) complete basis set extrapolations using all-electron basis sets. Multireference configuration interaction calculations with explicit spin-orbit calculations along with composite thermochemistry using the Feller-Peterson-Dixon method and all-electron basis sets were also explored for SmS + , and for comparison, SmO, SmO + , and EuO.

Enhanced kinetics of polysulfide redox reactions on Mo2C/CNT in lithium-sulfur batteries.

PubMed

Razaq, Rameez; Sun, Dan; Xin, Ying; Li, Qian; Huang, Taizhong; Zheng, Lei; Zhang, Zhaoliang; Huang, Yunhui

2018-07-20

Among different energy storage devices, the lithium-sulfur (Li-S) battery is the subject of recent attention. However, the capacity decay caused by polysulfide shuttle leading to sluggish kinetics of polysulfide redox reactions is the main hindrance for its practical application in Li-S batteries. Herein, molybdenum carbide nanoparticles anchored on carbon nanotubes (Mo 2 C/CNT) are reported to serve as an efficient cathode material to enhance the electrochemical kinetics of polysulfide conversion in Li-S batteries. Mo 2 C/CNT shows strong adsorption and activation of polar polysulfides and therefore accelerates the redox kinetics of polysulfides, reduces the energy barrier, effectively mitigates the polarization and polysulfide shuttle, thus improving the electrochemical performance. The S-Mo 2 C/CNT composite with 70 wt% sulfur loading exhibits high specific discharge capacity (1206 mA h g -1 at 0.5 C), excellent high-rate performance, long cycle life (900 cycles), and outstanding Coulombic efficiency (∼100%) at a high rate (2 C) corresponding to a capacity decay of only 0.05%. Remarkably, the S-Mo 2 C/CNT cathode with high areal sulfur loading of 2.5 mg cm -2 exhibits high-rate capacities and stable cycling performance over 100 cycles, offering the potential for use in high energy Li-S batteries.

Enhanced kinetics of polysulfide redox reactions on Mo2C/CNT in lithium–sulfur batteries

NASA Astrophysics Data System (ADS)

Razaq, Rameez; Sun, Dan; Xin, Ying; Li, Qian; Huang, Taizhong; Zheng, Lei; Zhang, Zhaoliang; Huang, Yunhui

2018-07-01

Among different energy storage devices, the lithium–sulfur (Li–S) battery is the subject of recent attention. However, the capacity decay caused by polysulfide shuttle leading to sluggish kinetics of polysulfide redox reactions is the main hindrance for its practical application in Li–S batteries. Herein, molybdenum carbide nanoparticles anchored on carbon nanotubes (Mo2C/CNT) are reported to serve as an efficient cathode material to enhance the electrochemical kinetics of polysulfide conversion in Li–S batteries. Mo2C/CNT shows strong adsorption and activation of polar polysulfides and therefore accelerates the redox kinetics of polysulfides, reduces the energy barrier, effectively mitigates the polarization and polysulfide shuttle, thus improving the electrochemical performance. The S-Mo2C/CNT composite with 70 wt% sulfur loading exhibits high specific discharge capacity (1206 mA h g‑1 at 0.5 C), excellent high-rate performance, long cycle life (900 cycles), and outstanding Coulombic efficiency (∼100%) at a high rate (2 C) corresponding to a capacity decay of only 0.05%. Remarkably, the S-Mo2C/CNT cathode with high areal sulfur loading of 2.5 mg cm‑2 exhibits high-rate capacities and stable cycling performance over 100 cycles, offering the potential for use in high energy Li–S batteries.

Electrochemical Evaluation of Stainless Steels in Acidified Sodium Chloride Solutions

NASA Technical Reports Server (NTRS)

Calle, L. M.; MacDowell, L. G.; Vinje, R. D.

2004-01-01

This paper presents the results of an investigation in which several 300-series stainless steels (SS): AISI S30403 SS (UNS S30403), AISI 316L SS (UNS S31603), and AISI 317L SS (LINS S31703), as well as highly-alloyed: SS 254-SMO (UNS S32154), AL-6XN (N08367) and AL29-4C (UNS S44735), were evaluated using DC electrochemical techniques in three different electrolyte solutions. The solutions consisted of neutral 3.55% NaCl, 3.55% NaCl in 0.1N HCl, and 3.55% NaCl in 1.0N HCl. These solutions were chosen to simulate environments that are less, similar, and more aggressive, respectively, than the conditions at the Space Shuttle launch pads. The electrochemical test results were compared to atmospheric exposure data and evaluated for their ability to predict the long-term corrosion performance of the subject alloys. The electrochemical measurements for the six alloys indicated that the higher-alloyed SS 254-SMO, AL29-4C, and AL-6XN exhibited significantly higher resistance to localized corrosion than the 300-series SS. There was a correlation between the corrosion performance of the alloys during a two-year atmospheric exposure and the corrosion rates calculated from electrochemical (polarization resistance) measurements.

Single continuous lumen formation in the zebrafish gut is mediated by smoothened-dependent tissue remodeling

PubMed Central

Alvers, Ashley L.; Ryan, Sean; Scherz, Paul J.; Huisken, Jan; Bagnat, Michel

2014-01-01

The formation of a single lumen during tubulogenesis is crucial for the development and function of many organs. Although 3D cell culture models have identified molecular mechanisms controlling lumen formation in vitro, their function during vertebrate organogenesis is poorly understood. Using light sheet microscopy and genetic approaches we have investigated single lumen formation in the zebrafish gut. Here we show that during gut development multiple lumens open and enlarge to generate a distinct intermediate, which consists of two adjacent unfused lumens separated by basolateral contacts. We observed that these lumens arise independently from each other along the length of the gut and do not share a continuous apical surface. Resolution of this intermediate into a single, continuous lumen requires the remodeling of contacts between adjacent lumens and subsequent lumen fusion. We show that lumen resolution, but not lumen opening, is impaired in smoothened (smo) mutants, indicating that fluid-driven lumen enlargement and resolution are two distinct processes. Furthermore, we show that smo mutants exhibit perturbations in the Rab11 trafficking pathway and demonstrate that Rab11-mediated trafficking is necessary for single lumen formation. Thus, lumen resolution is a distinct genetically controlled process crucial for single, continuous lumen formation in the zebrafish gut. PMID:24504339

Efficient full-chip SRAF placement using machine learning for best accuracy and improved consistency

NASA Astrophysics Data System (ADS)

Wang, Shibing; Baron, Stanislas; Kachwala, Nishrin; Kallingal, Chidam; Sun, Dezheng; Shu, Vincent; Fong, Weichun; Li, Zero; Elsaid, Ahmad; Gao, Jin-Wei; Su, Jing; Ser, Jung-Hoon; Zhang, Quan; Chen, Been-Der; Howell, Rafael; Hsu, Stephen; Luo, Larry; Zou, Yi; Zhang, Gary; Lu, Yen-Wen; Cao, Yu

2018-03-01

Various computational approaches from rule-based to model-based methods exist to place Sub-Resolution Assist Features (SRAF) in order to increase process window for lithography. Each method has its advantages and drawbacks, and typically requires the user to make a trade-off between time of development, accuracy, consistency and cycle time. Rule-based methods, used since the 90 nm node, require long development time and struggle to achieve good process window performance for complex patterns. Heuristically driven, their development is often iterative and involves significant engineering time from multiple disciplines (Litho, OPC and DTCO). Model-based approaches have been widely adopted since the 20 nm node. While the development of model-driven placement methods is relatively straightforward, they often become computationally expensive when high accuracy is required. Furthermore these methods tend to yield less consistent SRAFs due to the nature of the approach: they rely on a model which is sensitive to the pattern placement on the native simulation grid, and can be impacted by such related grid dependency effects. Those undesirable effects tend to become stronger when more iterations or complexity are needed in the algorithm to achieve required accuracy. ASML Brion has developed a new SRAF placement technique on the Tachyon platform that is assisted by machine learning and significantly improves the accuracy of full chip SRAF placement while keeping consistency and runtime under control. A Deep Convolutional Neural Network (DCNN) is trained using the target wafer layout and corresponding Continuous Transmission Mask (CTM) images. These CTM images have been fully optimized using the Tachyon inverse mask optimization engine. The neural network generated SRAF guidance map is then used to place SRAF on full-chip. This is different from our existing full-chip MB-SRAF approach which utilizes a SRAF guidance map (SGM) of mask sensitivity to improve the contrast of optical image at the target pattern edges. In this paper, we demonstrate that machine learning assisted SRAF placement can achieve a superior process window compared to the SGM model-based SRAF method, while keeping the full-chip runtime affordable, and maintain consistency of SRAF placement . We describe the current status of this machine learning assisted SRAF technique and demonstrate its application to full chip mask synthesis and discuss how it can extend the computational lithography roadmap.

Retention of pediatric bag-mask ventilation efficacy skill by inexperienced medical student resuscitators using standard bag-mask ventilation masks, pocket masks, and blob masks.

PubMed

Kitagawa, Kory H; Nakamura, Nina M; Yamamoto, Loren

2006-03-01

To measure the ventilation efficacy with three single-sized mask types on infant and child manikin models. Medical students were recruited as study subjects inasmuch as they are inexperienced resuscitators. They were taught proper bag-mask ventilation (BMV) according to the American Heart Association guidelines on an infant and a child manikin. Subjects completed a BMV attempt successfully using the adult standard mask (to simulate the uncertainty of mask selection), pocket mask, and blob mask. Each attempt consisted of 5 ventilations assessed by chest rise of the manikin. Study subjects were asked which mask was easiest to use. Four to six weeks later, subjects repeated the procedure with no instructions (to simulate an emergency BMV encounter without immediate pre-encounter teaching). Forty-six volunteer subjects were studied. During the first attempt, subjects preferred the standard and blob masks over the pocket mask. For the second attempt, the blob mask was preferred over the standard mask, and few liked the pocket mask. Using the standard, blob, and pocket masks on the child manikin, 39, 42, and 20 subjects, respectively, were able to achieve adequate ventilation. Using the standard, blob, and pocket masks on the infant manikin, 45, 45, and 11 subjects, respectively, were able to achieve adequate ventilation. Both the standard and blob masks are more effective than the pocket mask at achieving adequate ventilation on infant and child manikins in this group of inexperienced medical student resuscitators, who most often preferred the blob mask.

Rates of initial acceptance of PAP masks and outcomes of mask switching.

PubMed

Bachour, Adel; Vitikainen, Pirjo; Maasilta, Paula

2016-05-01

Recently, we noticed a considerable development in alleviating problems related to positive airway pressure (PAP) masks. In this study, we report on the initial PAP mask acceptance rates and the effects of mask switching on mask-related symptoms. We prospectively collected all cases of mask switching in our sleep unit for a period of 14 months. At the time of the study, we used ResMed™ CPAP devices and masks. Mask switching was defined as replacing a mask used for at least 1 day with another type of mask. Changing to a different size but keeping the same type of mask did not count as mask switching. Switching outcomes were considered failed if the initial problem persisted or reappeared during the year that followed switching. Our patient pool was 2768. We recorded 343 cases of mask switching among 267 patients. Of the 566 patients who began new PAP therapy, 108 (39 women) had switched masks, yielding an initial mask acceptance rate of 81 %. The reason for switching was poor-fit/uncomfortable mask in 39 %, leak-related in 30 %, outdated model in 25 %, and nasal stuffiness in 6 % of cases; mask switching resolved these problems in 61 %. Mask switching occurred significantly (p = 0.037) more often in women and in new PAP users. The odds ratio for abandoning PAP therapy within 1 year after mask switching was 7.2 times higher (interval 4.7-11.1) than not switching masks. The initial PAP mask acceptance rate was high. Patients who switched their masks are at greater risk for abandoning PAP therapy.

Testing the efficacy of homemade masks: would they protect in an influenza pandemic?

PubMed

Davies, Anna; Thompson, Katy-Anne; Giri, Karthika; Kafatos, George; Walker, Jimmy; Bennett, Allan

2013-08-01

This study examined homemade masks as an alternative to commercial face masks. Several household materials were evaluated for the capacity to block bacterial and viral aerosols. Twenty-one healthy volunteers made their own face masks from cotton t-shirts; the masks were then tested for fit. The number of microorganisms isolated from coughs of healthy volunteers wearing their homemade mask, a surgical mask, or no mask was compared using several air-sampling techniques. The median-fit factor of the homemade masks was one-half that of the surgical masks. Both masks significantly reduced the number of microorganisms expelled by volunteers, although the surgical mask was 3 times more effective in blocking transmission than the homemade mask. Our findings suggest that a homemade mask should only be considered as a last resort to prevent droplet transmission from infected individuals, but it would be better than no protection.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Webb, Aaron P.; Carlson, Charles T.; Weaver, William T.

A mask alignment system for providing precise and repeatable alignment between ion implantation masks and workpieces. The system includes a mask frame having a plurality of ion implantation masks loosely connected thereto. The mask frame is provided with a plurality of frame alignment cavities, and each mask is provided with a plurality of mask alignment cavities. The system further includes a platen for holding workpieces. The platen may be provided with a plurality of mask alignment pins and frame alignment pins configured to engage the mask alignment cavities and frame alignment cavities, respectively. The mask frame can be lowered ontomore » the platen, with the frame alignment cavities moving into registration with the frame alignment pins to provide rough alignment between the masks and workpieces. The mask alignment cavities are then moved into registration with the mask alignment pins, thereby shifting each individual mask into precise alignment with a respective workpiece.« less

A cluster randomised trial of cloth masks compared with medical masks in healthcare workers

PubMed Central

MacIntyre, C Raina; Seale, Holly; Dung, Tham Chi; Hien, Nguyen Tran; Nga, Phan Thi; Chughtai, Abrar Ahmad; Rahman, Bayzidur; Dwyer, Dominic E; Wang, Quanyi

2015-01-01

Objective The aim of this study was to compare the efficacy of cloth masks to medical masks in hospital healthcare workers (HCWs). The null hypothesis is that there is no difference between medical masks and cloth masks. Setting 14 secondary-level/tertiary-level hospitals in Hanoi, Vietnam. Participants 1607 hospital HCWs aged ≥18 years working full-time in selected high-risk wards. Intervention Hospital wards were randomised to: medical masks, cloth masks or a control group (usual practice, which included mask wearing). Participants used the mask on every shift for 4 consecutive weeks. Main outcome measure Clinical respiratory illness (CRI), influenza-like illness (ILI) and laboratory-confirmed respiratory virus infection. Results The rates of all infection outcomes were highest in the cloth mask arm, with the rate of ILI statistically significantly higher in the cloth mask arm (relative risk (RR)=13.00, 95% CI 1.69 to 100.07) compared with the medical mask arm. Cloth masks also had significantly higher rates of ILI compared with the control arm. An analysis by mask use showed ILI (RR=6.64, 95% CI 1.45 to 28.65) and laboratory-confirmed virus (RR=1.72, 95% CI 1.01 to 2.94) were significantly higher in the cloth masks group compared with the medical masks group. Penetration of cloth masks by particles was almost 97% and medical masks 44%. Conclusions This study is the first RCT of cloth masks, and the results caution against the use of cloth masks. This is an important finding to inform occupational health and safety. Moisture retention, reuse of cloth masks and poor filtration may result in increased risk of infection. Further research is needed to inform the widespread use of cloth masks globally. However, as a precautionary measure, cloth masks should not be recommended for HCWs, particularly in high-risk situations, and guidelines need to be updated. Trial registration number Australian New Zealand Clinical Trials Registry: ACTRN12610000887077. PMID:25903751

Optimizing a machine learning based glioma grading system using multi-parametric MRI histogram and texture features

PubMed Central

Hu, Yu-Chuan; Li, Gang; Yang, Yang; Han, Yu; Sun, Ying-Zhi; Liu, Zhi-Cheng; Tian, Qiang; Han, Zi-Yang; Liu, Le-De; Hu, Bin-Quan; Qiu, Zi-Yu; Wang, Wen; Cui, Guang-Bin

2017-01-01

Current machine learning techniques provide the opportunity to develop noninvasive and automated glioma grading tools, by utilizing quantitative parameters derived from multi-modal magnetic resonance imaging (MRI) data. However, the efficacies of different machine learning methods in glioma grading have not been investigated.A comprehensive comparison of varied machine learning methods in differentiating low-grade gliomas (LGGs) and high-grade gliomas (HGGs) as well as WHO grade II, III and IV gliomas based on multi-parametric MRI images was proposed in the current study. The parametric histogram and image texture attributes of 120 glioma patients were extracted from the perfusion, diffusion and permeability parametric maps of preoperative MRI. Then, 25 commonly used machine learning classifiers combined with 8 independent attribute selection methods were applied and evaluated using leave-one-out cross validation (LOOCV) strategy. Besides, the influences of parameter selection on the classifying performances were investigated. We found that support vector machine (SVM) exhibited superior performance to other classifiers. By combining all tumor attributes with synthetic minority over-sampling technique (SMOTE), the highest classifying accuracy of 0.945 or 0.961 for LGG and HGG or grade II, III and IV gliomas was achieved. Application of Recursive Feature Elimination (RFE) attribute selection strategy further improved the classifying accuracies. Besides, the performances of LibSVM, SMO, IBk classifiers were influenced by some key parameters such as kernel type, c, gama, K, etc. SVM is a promising tool in developing automated preoperative glioma grading system, especially when being combined with RFE strategy. Model parameters should be considered in glioma grading model optimization. PMID:28599282

Optimizing a machine learning based glioma grading system using multi-parametric MRI histogram and texture features.

PubMed

Zhang, Xin; Yan, Lin-Feng; Hu, Yu-Chuan; Li, Gang; Yang, Yang; Han, Yu; Sun, Ying-Zhi; Liu, Zhi-Cheng; Tian, Qiang; Han, Zi-Yang; Liu, Le-De; Hu, Bin-Quan; Qiu, Zi-Yu; Wang, Wen; Cui, Guang-Bin

2017-07-18

Current machine learning techniques provide the opportunity to develop noninvasive and automated glioma grading tools, by utilizing quantitative parameters derived from multi-modal magnetic resonance imaging (MRI) data. However, the efficacies of different machine learning methods in glioma grading have not been investigated.A comprehensive comparison of varied machine learning methods in differentiating low-grade gliomas (LGGs) and high-grade gliomas (HGGs) as well as WHO grade II, III and IV gliomas based on multi-parametric MRI images was proposed in the current study. The parametric histogram and image texture attributes of 120 glioma patients were extracted from the perfusion, diffusion and permeability parametric maps of preoperative MRI. Then, 25 commonly used machine learning classifiers combined with 8 independent attribute selection methods were applied and evaluated using leave-one-out cross validation (LOOCV) strategy. Besides, the influences of parameter selection on the classifying performances were investigated. We found that support vector machine (SVM) exhibited superior performance to other classifiers. By combining all tumor attributes with synthetic minority over-sampling technique (SMOTE), the highest classifying accuracy of 0.945 or 0.961 for LGG and HGG or grade II, III and IV gliomas was achieved. Application of Recursive Feature Elimination (RFE) attribute selection strategy further improved the classifying accuracies. Besides, the performances of LibSVM, SMO, IBk classifiers were influenced by some key parameters such as kernel type, c, gama, K, etc. SVM is a promising tool in developing automated preoperative glioma grading system, especially when being combined with RFE strategy. Model parameters should be considered in glioma grading model optimization.

A closer look at four-dot masking of a foveated target

PubMed Central

Wilson, Hugh R.

2016-01-01

Four-dot masking with a common onset mask was recently demonstrated in a fully attended and foveated target (Filmer, Mattingley & Dux, 2015). Here, we replicate and extend this finding by directly comparing a four-dot mask with an annulus mask while probing masking as a function of mask duration, and target-mask separation. Our results suggest that while an annulus mask operates via spatially local contour interactions, a four-dot mask operates through spatially global mechanisms. We also measure how the visual system’s representation of an oriented bar is impacted by a four-dot mask, and find that masking here does not degrade the precision of perceived targets, but instead appears to be driven exclusively by rendering the target completely invisible. PMID:27280073

Force-dependent static dead space of face masks used with holding chambers.

PubMed

Shah, Samir A; Berlinski, Ariel B; Rubin, Bruce K

2006-02-01

Pressurized metered-dose inhalers with valved holding chambers and masks are commonly used for aerosol delivery in children. Drug delivery can decrease when the dead-space volume (DSV) of the valved holding chamber is increased, but there are no published data evaluating force-dependent DSV among different masks. Seven masks were studied. Masks were sealed at the valved holding chamber end and filled with water to measure mask volume. To measure mask DSV we used a mannequin of 2-year-old-size face and we applied the mask with forces of 1.5, 3.5, and 7 pounds. Mask seal was determined by direct observation. Intra-brand analysis was done via analysis of variance. At 3.5 pounds of force, the DSV ranged from 29 mL to 100 mL, with 3 masks having DSV of < 50 mL. The remaining masks all had DSV > 60 mL. At 3.5 pounds of force, DSV percent of mask volume ranged from 33.7% (Aerochamber, p < 0.01 compared with other masks) to 100% (Pocket Chamber). DSV decreased with increasing force with most of the masks, and the slope of this line was inversely proportional to mask flexibility. Mask fit was 100% at 1.5 pounds of force only with the Aerochamber and Optichamber. Mask fit was poorest with the Vortex, Pocket Chamber, and BreatheRite masks. Rigid masks with large DSV might not be not suitable for use in children, especially if discomfort from the stiff mask makes its use less acceptable to the child.