ERDC MSRC Resource. High Performance Computing for the Warfighter. Spring 2006

DTIC Science & Technology

2006-01-01

named Ruby, and the HP/Compaq SC45, named Emerald , continue to add their unique sparkle to the ERDC MSRC computer infrastructure. ERDC invited the...configuration on B-52H purchased additional memory for the login nodes so that this part of the solution process could be done as a preprocessing step. On...application and system services. Of the service nodes, 10 are login nodes and 23 are input/output (I/O) server nodes for the Lustre file system (i.e., the

[Characterization of microstructure of ibuprofen-hydroxypropyl-beta-cyclodextrin and ibuprofen-beta-cyclodextrin by atomic force microscope].

PubMed

Wang, Li-juan; Zhu, Zhao-jing; Che, Ke-ke; Ju, Feng-ge

2008-09-01

The microstructures of ibuprofen-hydroxypropyl-bets-cyclodextrin (IBU-HP-beta-CyD) and ibuprofen-beta-cyclodextrin (IBU-beta-CyD) were observed by atomic force microscope (AFM). The high resolving capability of AFM has the tungsten filament probe with the spring constant of 0.06 N x m(-1). Samples were observed in a small scale scanning area of 10.5 nm x 10.5 nm and 800 x 800 pixels. The original scanning images were gained by tapping mode at room temperature. Their three-dimensional reconstruction of microstructure was performed by G3DR software. The outer diameters of HP-beta-CyD and beta-CyD are 1.53 nm. The benzene diameter of IBU is 0.62 nm, fitting to the inner diameters of HP-beta-CyD and beta-CyD. The benzene and hydrophobic chain of IBU enter into the hole of cyclodextrin at 1:1 ratio. The results were evidenced by IR, X-ray diffraction and the phase solubility.

Parallel studies of His-DTrp-Ala-Trp-DPhe-Lys-NH2 and human pancreatic growth hormone-releasing factor-44-NH2 in rat primary pituitary cell monolayer culture.

PubMed

Sartor, O; Bowers, C Y; Chang, D

1985-03-01

His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GH-RP-6) is a synthetic hexapeptide that specifically releases GH both in vivo and in vitro in pituitary incubates. In this study, for the first time, GH-RP-6 was studied in primary pituitary cell monolayer culture. Parallel studies were performed with human pancreatic GH-releasing factor-44 (hpGRF-44). Culture conditions optimal for GH-RP-6 were not optimal for hpGRF-44. Both peptides released GH in a dose- and time-dependent manner. In this assay system, the ED50 for GH-RP-6 was 9 nM, and the ED50 for hp-GRF-44 was 1.6 nM. Calcium-blocking agents inhibited the GH responses of both peptides as well as basal GH release. Pretreatment with GH-RP-6 decreased the subsequent response to both GH-RP-6 and hpGRF-44. hpGRF-44 down regulated itself but not GH-RP-6. Rat sera potentiated the GH response of hpGRF-44 but not that of GH-RP-6. GH-RP-6 and hpGRF-44 GH responses were additive. These results suggest that GH-RP-6 and hpGRF-44 stimulate GH release via different somatotroph receptors.

Challenges of image placement and overlay at the 90-nm and 65-nm nodes

NASA Astrophysics Data System (ADS)

Trybula, Walter J.

2003-05-01

The technology acceleration of the ITRS Roadmap has many implications on both the semiconductor supplier community and the manufacturers. INTERNATIONAL SE-MATECH has been leading and supporting efforts to investigate the impact of the tech-nology introduction. This paper examines the issue of manufacturing tolerances available for image placement on adjacent critical levels (overlay) at the 90nm and 65nm technol-ogy nodes. The allowable values from the 2001 release of the ITRS Roadmap are 32nm for the 90nm node, and 23nm for the 65nm node. Even the 130nm node has overlay requirements of only 46nm. Employing tolerances that can be predicted, the impact of existing production/processing tolerance accumulation can provide an indication of the challenges facing the manufacturer in the production of 90nm and 65nm Node devices.

Photodynamic Cell Killing Effects and Acute Skin Photosensitivity of Aluminum‐chloro‐tetrasulfonated Phthalocyanine and Hematoporphyrin Derivative

PubMed Central

Komatsu, Kazuto

1991-01-01

Aluminum‐chloro‐tetrasulfonated phthalocyanine (PC) showing an absorption peak at 678 nm was compared to hematoporphyrin derivative (MpD), a photosensitizer commonly used in the photodynamic therapy (PDT) of cancers. In vitro studies: KK‐47 cells were exposed to long‐wavelength ultraviolet (UVA) or red light (>600 nm, >640 nm and >660 nm) after drug sensitization. With UVA irradiation, a higher photodynamic cell killing effect was observed in the cells treated with HpD than with PC. However, with red light irradiation (both > 640 nm and >660 nm) PC resulted in greater cell damage. PC was less toxic to KK‐47 cells in the dark. In vivo studies: Using a gold vapor laser (GVL: 627.8 nm, 200 mW/cm2, 200 J/cm2), the photodynamic tumor response was determined in C3H/He mice bearing transplantable squamous cell carcinoma. No significant difference was observed in the tumor volume between the PC and HpD groups, except that the PC group (10.0 mg/kg body weight) showed a significantly higher remission rate (3/6) than the control group (0/10, P<0.05). Skin Photosensitivity test: Skin photosensitivity was estimated by measuring changes in back skin thickness due to photosensitization. With UVA irradiation, a stronger skin reaction was observed in the HpD group, while with visible light irradiation there was no significant difference between the HpD and PC groups. Based on the superior cell killing effect with red light, reduced toxicity to the cells in the dark and mild skin reaction with UVA, PC may be a more promising photosensitizer for PDT. PMID:1905706

Effect of seawater salinity on pore-size distribution on a poly(styrene)-based HP20 resin and its adsorption of diarrhetic shellfish toxins.

PubMed

Fan, Lin; Sun, Geng; Qiu, Jiangbing; Ma, Qimin; Hess, Philipp; Li, Aifeng

2014-12-19

In the present study, okadaic acid (OA) and dinophysistoxin-1 (DTX1) were spiked into artificial seawater at low, medium and high estuarine salinities (9‰, 13.5‰ and 27‰). Passive samplers (HP20 resin) used for solid phase adsorption toxin tracking (SPATT) technology were exposed in these seawaters for 12-h periods. Adsorption curves well fitted a pseudo-secondary kinetics model. The highest initial sorption rates of both toxins occurred in the seawater of medium salinity, followed by seawater of low and high estuarine salinity. Pore volumes of micropores (<2 nm) and small mesopores (2 nm

Effect of laser activated bleaching on the chemical stability and morphology of intracoronal dentin.

PubMed

Lopes, Fabiane Carneiro; Roperto, Renato; Akkus, Anna; Akkus, Ozan; Palma-Dibb, Regina Guenka; de Sousa-Neto, Manoel Damião

2018-02-01

To evaluate the effect of the bleaching with 35% hydrogen peroxide either activated or not by a 970nm diode laser on the chemical stability and dentin surface morphology of intracoronary dentin. Twenty-seven slabs of intracoronary dentin specimens (3×3mm) were distributed into three groups (n=9), according to surface treatment: HP - 35% hydrogen peroxide (1×4'), DL - 970nm diode laser (1×30"/0,8W/10Hz), HP+DL - 35% HP activated with 970nm diode laser (1×30"/0,8W/10Hz leaving the gel in contact to the surface for 4' after activation). Three Raman spectra from each fragment were obtained to calculate the mean intensity of peaks of inorganic component (a.u.), organic collagen content (a.u.), and the ratio of inorganic/organic content, before and after treatment. Analyses of the samples by confocal laser microscopy were performed to evaluate the surface roughness, percentage of tubules, perimeter and area percentage of tubules, before and after treatment. Data were analyzed by Kruskal-Wallis, Dunn's, and Wilcoxon test (P<0.05). Data analysis showed that HP+DL did not change the inorganic content peaks 8.31 [29.78] or the inorganic/organic ratio 3.37 [14.67] (P>0.05). Similarly, DL did not affect the chemical stability of the dentin surface (P>0.05). However, HP significantly increased inorganic content peaks 10.87 [22.62], as well as the inorganic/organic ratio 6.25 [27.78] (P<0.05). Regarding the morphological alterations, all surface treatments increase tubules exposure; HP treatment significantly increases perimeter and area percentage; and HP+DL increases surface roughness. Bleaching HP combined with DL offers an improvement in terms of intracoronal dentin surface protection, yielding better maintenance of dentin chemical stability and morphology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Protection efficiency of a standard compliant EUV reticle handling solution

NASA Astrophysics Data System (ADS)

He, Long; Lystad, John; Wurm, Stefan; Orvek, Kevin; Sohn, Jaewoong; Ma, Andy; Kearney, Patrick; Kolbow, Steve; Halbmaier, David

2009-03-01

For successful implementation of extreme ultraviolet lithography (EUVL) technology for late cycle insertion at 32 nm half-pitch (hp) and full introduction for 22 nm hp high volume production, the mask development infrastructure must be in place by 2010. The central element of the mask infrastructure is contamination-free reticle handling and protection. Today, the industry has already developed and balloted an EUV pod standard for shipping, transporting, transferring, and storing EUV masks. We have previously demonstrated that the EUV pod reticle handling method represents the best approach in meeting EUVL high volume production requirements, based on then state-of-the-art inspection capability at ~53nm polystyrene latex (PSL) equivalent sensitivity. In this paper, we will present our latest data to show defect-free reticle handling is achievable down to 40 nm particle sizes, using the same EUV pod carriers as in the previous study and the recently established world's most advanced defect inspection capability of ~40 nm SiO2 equivalent sensitivity. The EUV pod is a worthy solution to meet EUVL pilot line and pre-production exposure tool development requirements. We will also discuss the technical challenges facing the industry in refining the EUV pod solution to meet 22 nm hp EUVL production requirements and beyond.

Long Periodic Structure of a Room-Temperature Ionic Liquid by High-Pressure Small-Angle X-Ray Scattering and Wide-Angle X-Ray Scattering: 1-Decyl-3-Methylimidazolium Chloride.

PubMed

Abe, Hiroshi; Hamaya, Nozomu; Koyama, Yoshihiro; Kishimura, Hiroaki; Takekiyo, Takahiro; Yoshimura, Yukihiro; Wakabayashi, Daisuke; Funamori, Nobumasa; Matsuishi, Kiyoto

2018-04-23

The Bragg reflections of 1-decyl-3-methylimidazolium chloride ([C 10 mim][Cl]), a room-temperature ionic liquid, are observed in a lowly scattered wavevector (q) region using high-pressure (HP) small-angle X-ray scattering methods. The HP crystal of [C 10 mim][Cl] was characterized by an extremely long periodic structure. The peak position at the lowest q (1.4 nm -1 ) was different from that of the prepeak observed in the liquid state (2.3 nm -1 ). Simultaneously, Bragg reflections at high-q were detected using HP wide-angle X-ray scattering. The longest lattice constant was estimated to be 4.3 nm using structural analysis. The crystal structure of HP differed from that of the low-temperature (LT) crystal and the LT liquid crystal. With increasing pressure, Bragg reflections in the high-q component became much broader, and were accompanied by phase transition, although those in the low-q component were observed to be relatively sharp. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Individual dose monitoring of the nuclear medicine departments staff controlled by Central Laboratory for Radiological Protection.

PubMed

Szewczak, Kamil; Jednoróg, Sławomir; Krajewski, Paweł

2013-01-01

Presented paper describes the results of the individual doses measurements for ionizing radiation, carried out by the Laboratory of Individual and Environmental Doses Monitoring (PDIS) of the Central Laboratory for Radiological Protection in Warsaw (CLOR) for the medical staff employees in several nuclear medicine (NM) departments across Poland. In total there are48 NM departments in operation in Poland [1] (consultation in Nuclear Atomic Agency). Presented results were collected over the period from January 2011 to December 2011 at eight NM departments located in Krakow, Warszawa (two departments), Rzeszow (two departments), Opole, Przemysl and Gorzow Wielkopolski. For radiation monitoring three kinds of thermo luminescence dosimeters (TLD) were used. The first TLD h collected information about whole body (C) effective dose, the second dosimeter was mounted in the ring (P) meanwhile the third on the wrist (N) of the tested person. Reading of TLDs was performed in quarterly periods. As a good approximation of effective and equivalent dose assessment of operational quantities both the individual dose equivalent Hp(10) and the Hp(0.07) were used. The analysis of the data was performed using two methods The first method was based on quarterly estimations of Hp(10)q and Hp(0.07)q while the second measured cumulative annual doses Hp(10)a and Hp(0.07)a. The highest recorded value of the radiation dose for quarterly assessments reached 24.4 mSv and was recorded by the wrist type dosimeter worn by a worker involved in source preparation procedure. The mean values of Hp(10)q(C type dosimeter) and Hp(0.07)q (P and N type dosimeter) for all monitored departments were respectively 0.46 mSv and 3.29 mSv. There was a strong correlation between the performed job and the value of the received dose. The highest doses always were absorbed by those staff members who were involved in sources preparation. The highest annual cumulative dose for a particular worker in the considered time period was 4.22 mSv for Hp(10)a and 67.7 mSv for Hp(0.07)a. In 2011 no case of exceeding the allowed dose limits was noted.

A catalytic and dual recycling amplification ATP sensor based on target-driven allosteric structure switching of aptamer beacons.

PubMed

Peng, Ying; Li, Daxiu; Yuan, Ruo; Xiang, Yun

2018-05-15

Abnormal concentrations of ATP are associated with many diseases and cancers, and quantitative detection of ATP is thus of great importance for disease diagnosis and prognosis. In the present work, we report a new dual recycling amplification sensor integrated with catalytic hairpin assembly (CHA) to achieve high sensitivity for fluorescent detection of ATP. The association of the target ATP with the aptamer beacons causes the allosteric structure switching of the aptamer beacons to expose the toehold regions, which hybridize with and unfold the fluorescently quenched hairpin signal probes (HP1) to recycle the target ATP and to trigger CHA between HP1 and the secondary hairpin probes (HP2) to form HP1/HP2 duplexes. Due to the recycling amplification, the presence of ATP leads to the formation of many HP1/HP2 duplexes, generating dramatically amplified fluorescent signals for sensitive detection of ATP. Under optimal experimental conditions, our sensor linearly responds to ATP in the range from 25 to 600nM with a calculated detection limit of 8.2nM. Furthermore, the sensor shows a high selectivity and can also be used to detect ATP in human serums to realize its application for real samples. With the distinct advantage of significant signal amplification without the involvement of any nanomaterial and enzyme, the developed sensor thus holds great potential for simple and sensitive detection of different small molecules and proteins. Copyright © 2018 Elsevier B.V. All rights reserved.

Sensitivity enhancement of the high-resolution xMT multi-trigger resist for EUV lithography

NASA Astrophysics Data System (ADS)

Popescu, Carmen; Frommhold, Andreas; McClelland, Alexandra; Roth, John; Ekinci, Yasin; Robinson, Alex P. G.

2017-03-01

Irresistible Materials is developing a new molecular resist system that demonstrates high-resolution capability based on the multi-trigger concept. A series of studies such as resist purification, developer choice,and enhanced resist crosslinking were conducted in order to optimize the performance of this material. The optimized conditions allowed patterning 14 nm half-pitch (hp) lines with a line width roughness (LWR) of 2.7 nm at the XIL beamline of the Swiss Light source. Furthermore it was possible to pattern 14 nm hp features with dose of 14 mJ/cm2 with an LWR of 4.9 nm. We have also begun to investigate the addition of high-Z additives to EUV photoresist as a means to increase sensitivity and modify secondary electron blur.

Irradiation of amelanotic melanoma cells with 532 nm high peak power pulsed laser radiation in the presence of the photothermal sensitizer Cu(II)-hematoporphyrin: a new approach to cell photoinactivation.

PubMed

Soncin, M; Busetti, A; Fusi, F; Jori, G; Rodgers, M A

1999-06-01

Cu(II)-hematoporphyrin (CuHp) was efficiently accumulated by B78H1 amelanotic melanoma cells upon incubation with porphyrin concentrations up to 52 microM. When the cells incubated for 18 h with 13 microM CuHp were irradiated with 532 nm light from a Q-switched Nd: YAG laser operated in a pulsed mode (10 ns pulses, 10 Hz) a significant decrease in cell survival was observed. The cell photoinactivation was not the consequence of a photodynamic process, as CuHp gave no detectable triplet signal upon laser flash photolysis excitation and no decrease in cell survival was observed upon continuous wave irradiation. Thus, it is likely that CuHp sensitization takes place by photothermal pathways. The efficiency of the photoprocess was modulated by different parameters; thus, while varying the amount of added CuHp in the 3.25-26 microM range had little effect, pulse energies larger than 50 mJ and irradiation times of at least 120 s were necessary to induce a cell inactivation of about 50%. The porphyrin-cell incubation time prior to irradiation had a major influence on cell survival, suggesting that the nature of the CuHp microenvironment can control the efficiency of photothermal sensitization.

Patterned mask inspection technology with Projection Electron Microscope (PEM) technique for 11 nm half-pitch (hp) generation EUV masks

NASA Astrophysics Data System (ADS)

Hirano, Ryoichi; Iida, Susumu; Amano, Tsuyoshi; Watanabe, Hidehiro; Hatakeyama, Masahiro; Murakami, Takeshi; Yoshikawa, Shoji; Suematsu, Kenichi; Terao, Kenji

2015-07-01

High-sensitivity EUV mask pattern defect detection is one of the major issues in order to realize the device fabrication by using the EUV lithography. We have already designed a novel Projection Electron Microscope (PEM) optics that has been integrated into a new inspection system named EBEYE-V30 ("Model EBEYE" is an EBARA's model code), and which seems to be quite promising for 16 nm hp generation EUVL Patterned mask Inspection (PI). Defect inspection sensitivity was evaluated by capturing an electron image generated at the mask by focusing onto an image sensor. The progress of the novel PEM optics performance is not only about making an image sensor with higher resolution but also about doing a better image processing to enhance the defect signal. In this paper, we describe the experimental results of EUV patterned mask inspection using the above-mentioned system. The performance of the system is measured in terms of defect detectability for 11 nm hp generation EUV mask. To improve the inspection throughput for 11 nm hp generation defect detection, it would require a data processing rate of greater than 1.5 Giga- Pixel-Per-Second (GPPS) that would realize less than eight hours of inspection time including the step-and-scan motion associated with the process. The aims of the development program are to attain a higher throughput, and enhance the defect detection sensitivity by using an adequate pixel size with sophisticated image processing resulting in a higher processing rate.

Replica-exchange molecular dynamics simulation of basic fibroblast growth factor adsorption on hydroxyapatite.

PubMed

Liao, Chenyi; Zhou, Jian

2014-06-05

The adsorption of basic fibroblast growth factor (bFGF) on the hydroxyapatite (001) surface was investigated by a combination of replica-exchange molecular dynamics (REMD) and conventional molecular dynamics (CMD) methods. In CMD, the protein cannot readily cross the surface water layer, whereas in REMD, the protein can cross the adsorption barrier from the surface water layer and go through weak, medium, then strong adsorption states with three energetically preferred configurations: heparin-binding-up (HP-up), heparin-binding-middle (HP-middle), and heparin-binding-down (HP-down). The HP-middle orientation, with the strongest adsorption energy (-1149 ± 40 kJ·mol(-1)), has the largest adsorption population (52.1-52.6%) and exhibits the largest conformational charge (RMSD of 0.26 ± 0.01 nm) among the three orientations. The HP-down and HP-up orientations, with smaller adsorption energies of -1022 ± 55 and -894 ± 70 kJ·mol(-1), respectively, have smaller adsorption populations of 27.4-27.7% and 19.7-20.5% and present smaller RMSD values of 0.21 ± 0.01 and 0.19 ± 0.01 nm, respectively. The convergent distribution indicates that nearly half of the population (in the HP-middle orientation) will support both FGF/FGFR and DGR-integrin signaling and another half (in the HP-up and HP-down orientations) will support DGR-integrin signaling. The major population (~80%) has the protein dipole directed outward. In the strong adsorption state, there are usually 2 to 3 basic residues that form the anchoring interactions of 210-332 kJ·mol(-1) per residue or that are accompanied by an acidic residue with an adsorption energy of ~207 kJ·mol(-1). Together, the major bound residues form a triangle or a quadrilateral on the surface and stabilize the adsorption geometrically, which indicates topologic matching between the protein and HAP surfaces.

Normal and frictional interactions of purified human statherin adsorbed on molecularly-smooth solid substrata.

PubMed

Harvey, Neale M; Carpenter, Guy H; Proctor, Gordon B; Klein, Jacob

2011-09-01

Human salivary statherin was purified from parotid saliva and adsorbed to bare hydrophilic (HP) mica and STAI-coated hydrophobic (HB) mica in a series of Surface Force Balance experiments that measured the normal (F(n)) and friction forces (F(s)*) between statherin-coated mica substrata. Readings were taken both in the presence of statherin solution (HP and HB mica) and after rinsing (HP mica). F(n) measurements showed, for both substrata, monotonic steric repulsion that set on at a surface separation D ~20 nm, indicating an adsorbed layer whose unperturbed thickness was ca 10 nm. An additional longer-ranged repulsion, probably of electrostatic double-layer origin, was observed for rinsed surfaces under pure water. Under applied pressures of ~1 MPa, each surface layer was compressed to a thickness of ca 2 nm on both types of substratum, comparable with earlier estimates of the size of the statherin molecule. Friction measurements, in contrast with F(n) observations, were markedly different on the two different substrata: friction coefficients, μ ≡ ∂F(s)*/∂F(n), on the HB substratum (μ ≈ 0.88) were almost an order of magnitude higher than on the HP substratum (μ ≈ 0.09 and 0.12 for unrinsed and rinsed, respectively), and on the HB mica there was a lower dependence of friction on sliding speed than on the HP mica. The observations were attributed to statherin adsorbing to the mica in multimer aggregates, with internal re-arrangement of the protein molecules within the aggregate dependent on the substratum to which the aggregate adsorbed. This internal re-arrangement permitted aggregates to be of similar size on HP and HB mica but to have different internal molecular orientations, thus exposing different moieties to the solution in each case and accounting for the very different friction behaviour.

Immunoreactivities of human nonmetastatic clone 23 and p53 products are disassociated and not good predictors of lymph node metastases in early-stage cervical cancer patients.

PubMed

Tee, Y T; Wang, P H; Ko, J L; Chen, G D; Chang, H; Lin, L Y

2007-01-01

To assess the relation between expressions of human nonmetastatic clone 23 (nm23-H1) and p53 in cervical cancer, their relationships with lymph node metastasis, and further to examine their predictive of lymph node metastases. nm23-H1 and p53 expression profiles were visualized by immunohistochemistry in early-stage cervical cancer specimens. Immunoreactivities of nm23-H1 and p53 were disassociated. The independent variables related with lymph node metastases were grade of cancer cell differentiation (p < 0.029) and stromal invasion (p < 0.039). Sensitivity, specificity, positive and negative predictive values, and accuracy for lymph node metastasis were calculated to be 91.7%, 13.5%, 25.6%, 83.3%, and 32.7% for nm23-H1 and 66.7%, 51.4%, 30.8%, 82.6%, and 55.1% for p53. Nm23-H1 and p53 are disassociated and not good predictors of lymph node metastases in early-stage cervical cancer patients. However, stromal invasion and cell differentiation can predict lymph node metastasis.

Results from a new die-to-database reticle inspection platform

NASA Astrophysics Data System (ADS)

Broadbent, William; Xiong, Yalin; Giusti, Michael; Walsh, Robert; Dayal, Aditya

2007-03-01

A new die-to-database high-resolution reticle defect inspection system has been developed for the 45nm logic node and extendable to the 32nm node (also the comparable memory nodes). These nodes will use predominantly 193nm immersion lithography although EUV may also be used. According to recent surveys, the predominant reticle types for the 45nm node are 6% simple tri-tone and COG. Other advanced reticle types may also be used for these nodes including: dark field alternating, Mask Enhancer, complex tri-tone, high transmission, CPL, EUV, etc. Finally, aggressive model based OPC will typically be used which will include many small structures such as jogs, serifs, and SRAF (sub-resolution assist features) with accompanying very small gaps between adjacent structures. The current generation of inspection systems is inadequate to meet these requirements. The architecture and performance of a new die-to-database inspection system is described. This new system is designed to inspect the aforementioned reticle types in die-to-database and die-to-die modes. Recent results from internal testing of the prototype systems are shown. The results include standard programmed defect test reticles and advanced 45nm and 32nm node reticles from industry sources. The results show high sensitivity and low false detections being achieved.

Single-nm resolution approach by applying DDRP and DDRM

NASA Astrophysics Data System (ADS)

Shibayama, Wataru; Shigaki, Shuhei; Takeda, Satoshi; Nakajima, Makoto; Sakamoto, Rikimaru

2017-03-01

EUV lithography has been desired as the leading technology for 1x or single nm half-pitch patterning. However, the source power, masks and resist materials still have critical issues for mass production. Especially in resist materials, RLS trade-off has been the key issue. To overcome this issue, we are suggesting Dry Development Rinse Process (DDRP) and Materials (DDRM) as the pattern collapse mitigation approach. This DDRM can perform not only as pattern collapse free materials for fine pitch, but also as the etching hard mask against bottom layer (spin on carbon : SOC). In this paper, we especially propose new approaches to achieve high resolution around hp1X nm L/S and single nm line patterning. Especially, semi iso 8nm line was successfully achieved with good LWR (2.5nm) and around 3 times aspect ratio. This single nm patterning technique also helped to enhance sensitivity about 33%. On the other hand, pillar patterning thorough CH pattern by applying DDRP also showed high resolution below 20nm pillar CD with good LCDU and high sensitivity. This new DDRP technology can be the promising approach not only for hp1Xnm level patterning but also single nm patterning in N7/N5 and beyond.

Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Induces Prostaglandin E2 Production through Cyclooxygenase 1, Which Is Dependent on the ERK1/2-p-C/EBP-β Pathway

PubMed Central

Bi, Yanmin; Guo, Xue-kun; Zhao, Haiyan; Gao, Li; Wang, Lianghai; Tang, Jun

2014-01-01

ABSTRACT Atypical porcine reproductive and respiratory syndrome (PRRS) caused by highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) is characterized by high fever and high mortality. However, the mechanism underlying the fever induction is still unknown. Prostaglandin E2 (PGE2), synthesized by cyclooxygenase type 1/2 (COX-1/2) enzymes, is essential for inducing fever. In this study, we found that PGE2, together with COX-1, was significantly elevated by HP-PRRSV. We subsequently demonstrated that extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphorylated ERK (p-ERK) were the key nodes to trigger COX-1 expression after HP-PRRSV infection. Furthermore, we proved the direct binding of p-C/EBP-β to the COX-1 promoter by luciferase reporter and chromatin immunoprecipitation assays. In addition, silencing of C/EBP-β remarkably impaired the enhancement of COX-1 production induced by HP-PRRSV infection. Taken together, our results indicate that HP-PPRSV elicits the expression of COX-1 through the ERK1/2-p-C/EBP-β signaling pathway, resulting in the increase of PGE2, which might be the cause of high fever in infected pigs. Our findings might provide new insights into the molecular mechanisms underlying the pathogenesis of HP-PRRSV infection. IMPORTANCE The atypical PRRS caused by HP-PRRSV was characterized by high fever, high morbidity, and high mortality in pigs of all ages, yet how HP-PRRSV induces high fever in pigs remains unknown. In the present study, we found out that HP-PRRSV infection could increase PGE2 production by upregulation of COX-1, and we subsequently characterized the underlying mechanisms about how HP-PRRSV enhances COX-1 production. PGE2 plays a critical role in inducing high temperature in hosts during pathogen infections. Thus, our findings here could help us have a better understanding of HP-PRRSV pathogenesis. PMID:24352469

A novel dicyanoisophorone based red-emitting fluorescent probe with a large Stokes shift for detection of hydrazine in solution and living cells

NASA Astrophysics Data System (ADS)

Lv, Hongshui; Sun, Haiyan; Wang, Shoujuan; Kong, Fangong

2018-05-01

A novel dicyanoisophorone based fluorescent probe HP was developed to detect hydrazine. Upon the addition of hydrazine, probe HP displayed turn-on fluorescence in the red region with a large Stokes shift (180 nm). This probe exhibited high selectivity and high sensitivity to hydrazine in solution. The detection limit of HP was found to be 3.26 ppb, which was lower than the threshold limit value set by USEPA (10 ppb). Moreover, the probe was successfully applied to detect hydrazine in different water samples and living cells.

Analysis method to determine and characterize the mask mean-to-target and uniformity specification

NASA Astrophysics Data System (ADS)

Lee, Sung-Woo; Leunissen, Leonardus H. A.; Van de Kerkhove, Jeroen; Philipsen, Vicky; Jonckheere, Rik; Lee, Suk-Joo; Woo, Sang-Gyun; Cho, Han-Ku; Moon, Joo-Tae

2006-06-01

The specification of the mask mean-to-target (MTT) and uniformity is related to functions as: mask error enhancement factor, dose sensitivity and critical dimension (CD) tolerances. The mask MTT shows a trade-off relationship with the uniformity. Simulations for the mask MTT and uniformity (M-U) are performed for LOGIC devices of 45 and 37 nm nodes according to mask type, illumination condition and illuminator polarization state. CD tolerances and after develop inspection (ADI) target CD's in the simulation are taken from the 2004 ITRS roadmap. The simulation results allow for much smaller tolerances in the uniformity and larger offsets in the MTT than the values as given in the ITRS table. Using the parameters in the ITRS table, the mask uniformity contributes to nearly 95% of total CDU budget for the 45 nm node, and is even larger than the CDU specification of the ITRS for the 37 nm node. We also compared the simulation requirements with the current mask making capabilities. The current mask manufacturing status of the mask uniformity is barely acceptable for the 45 nm node, but requires process improvements towards future nodes. In particular, for the 37 nm node, polarized illumination is necessary to meet the ITRS requirements. The current mask linearity deviates for pitches smaller than 300 nm, which is not acceptable even for the 45 nm node. More efforts on the proximity correction method are required to improve the linearity behavior.

Locally advanced pancreatic cancer: association between prolonged preoperative treatment and lymph-node negativity and overall survival.

PubMed

Kadera, Brian E; Sunjaya, Dharma B; Isacoff, William H; Li, Luyi; Hines, O Joe; Tomlinson, James S; Dawson, David W; Rochefort, Matthew M; Donald, Graham W; Clerkin, Barbara M; Reber, Howard A; Donahue, Timothy R

2014-02-01

Treatment of patients with locally advanced/borderline resectable (LA/BR) pancreatic ductal adenocarcinoma (PDAC) is not standardized. To (1) perform a detailed survival analysis of our institution's experience with patients with LA/BR PDAC who were downstaged and underwent surgical resection and (2) identify prognostic biomarkers that may help to guide a decision for the use of adjuvant therapy in this patient subgroup. Retrospective observational study of 49 consecutive patients from a single institution during 1992-2011 with American Joint Committee on Cancer stage III LA/BR PDAC who were initially unresectable, as determined by staging computed tomography and/or surgical exploration, and who were treated and then surgically resected. Clinicopathologic variables and prognostic biomarkers SMAD4, S100A2, and microRNA-21 were correlated with survival by univariate and multivariate Cox proportional hazard modeling. All 49 patients were deemed initially unresectable owing to vascular involvement. After completing preoperative chemotherapy for a median of 7.1 months (range, 5.4-9.6 months), most (75.5%) underwent a pylorus-preserving Whipple operation; 3 patients (6.1%) had a vascular resection. Strikingly, 37 of 49 patients were lymph-node (LN) negative (75.5%) and 42 (85.7%) had negative margins; 45.8% of evaluable patients achieved a complete histopathologic (HP) response. The median overall survival (OS) was 40.1 months (range, 22.7-65.9 months). A univariate analysis of HP prognostic biomarkers revealed that perineural invasion (hazard ratio, 5.5; P=.007) and HP treatment response (hazard ratio, 9.0; P=.009) were most significant. Lymph-node involvement, as a marker of systemic disease, was also significant on univariate analysis (P=.05). Patients with no LN involvement had longer OS (44.4 vs 23.2 months, P=.04) than LN-positive patients. The candidate prognostic biomarkers, SMAD4 protein loss (P=.01) in tumor cells and microRNA-21 expression in the stroma (P=.05), also correlated with OS. On multivariate Cox proportional hazard modeling of HP and prognostic biomarkers, only SMAD4 protein loss was significant (hazard ratio, 9.3; P=.004). Our approach to patients with LA/BR PDAC, which includes prolonged preoperative chemotherapy, is associated with a high incidence of LN-negative disease and excellent OS. After surgical resection, HP treatment response, perineural invasion, and SMAD4 status should help determine who should receive adjuvant therapy in this select subset of patients.

Field results from a new die-to-database reticle inspection platform

NASA Astrophysics Data System (ADS)

Broadbent, William; Yokoyama, Ichiro; Yu, Paul; Seki, Kazunori; Nomura, Ryohei; Schmalfuss, Heiko; Heumann, Jan; Sier, Jean-Paul

2007-05-01

A new die-to-database high-resolution reticle defect inspection platform, TeraScanHR, has been developed for advanced production use with the 45nm logic node, and extendable for development use with the 32nm node (also the comparable memory nodes). These nodes will use predominantly ArF immersion lithography although EUV may also be used. According to recent surveys, the predominant reticle types for the 45nm node are 6% simple tri-tone and COG. Other advanced reticle types may also be used for these nodes including: dark field alternating, Mask Enhancer, complex tri-tone, high transmission, CPL, etc. Finally, aggressive model based OPC will typically be used which will include many small structures such as jogs, serifs, and SRAF (sub-resolution assist features) with accompanying very small gaps between adjacent structures. The current generation of inspection systems is inadequate to meet these requirements. The architecture and performance of the new TeraScanHR reticle inspection platform is described. This new platform is designed to inspect the aforementioned reticle types in die-to-database and die-to-die modes using both transmitted and reflected illumination. Recent results from field testing at two of the three beta sites are shown (Toppan Printing in Japan and the Advanced Mask Technology Center in Germany). The results include applicable programmed defect test reticles and advanced 45nm product reticles (also comparable memory reticles). The results show high sensitivity and low false detections being achieved. The platform can also be configured for the current 65nm, 90nm, and 130nm nodes.

Negative-tone imaging with EUV exposure toward 13nm hp

NASA Astrophysics Data System (ADS)

Tsubaki, Hideaki; Nihashi, Wataru; Tsuchihashi, Toru; Yamamoto, Kei; Goto, Takahiro

2016-03-01

Negative-tone imaging (NTI) with EUV exposure has major advantages with respect to line-width roughness (LWR) and resolution due in part to polymer swelling and favorable dissolution mechanics. In NTI process, both resist and organic solvents play important roles in determining lithography performances. The present study describes novel chemically amplified resist materials based on NTI technology with EUV using a specific organic solvents. Lithographic performances of NTI process were described in this paper under exposures using ASML NXE:3300 EUV scanner at imec. It is emphasized that 14 nm hp was nicely resolved under exposure dose of 37 mJ/cm2 without any bridge and collapse, which are attributed to the low swelling character of NTI process. Although 13 nm hp resolution was potentially obtained, a pattern collapse still restricts its resolution in case coating resist film thickness is 40 nm. Dark mask limitation due mainly to mask defectivity issue makes NTI with EUV favorable approach for printing block mask to produce logic circuit. A good resolution of CD-X 21 nm/CD-Y 32 nm was obtained for block mask pattern using NTI with usable process window and dose of 49 mJ/cm2. Minimum resolution now reaches CD-X 17 nm / CD-Y 23 nm for the block. A 21 nm block mask resolution was not affected by exposure dose and explored toward low dose down to 18 mJ/cm2 by reducing quencher loading. In addition, there was a negligible amount of increase in LCDU for isolated dot pattern when decreasing exposure dose from 66 mJ/cm2 to 24 mJ/cm2. On the other hand, there appeared tradeoff relationship between LCDU and dose for dense dot pattern, indicating photon-shot noise restriction, but strong dependency on patterning features. Design to improve acid generation efficiency was described based on acid generation mechanism in traditional chemically amplified materials which contains photo-acid generator (PAG) and polymer. Conventional EUV absorber comprises of organic compounds is expected to have 1.6 times higher EUV absorption than polyhydroxystyrene based on calculation. However, observed value of acid amount was comparable or significantly worse than polyhydroxystyrene.

Analysis of shade, temperature and hydrogen peroxide concentration during dental bleaching: in vitro study with the KTP and diode lasers.

PubMed

Fornaini, C; Lagori, G; Merigo, E; Meleti, M; Manfredi, M; Guidotti, R; Serraj, A; Vescovi, P

2013-01-01

Many dental bleaching techniques are now available, several of them using a laser source. However, the literature on the exact role of coherent light in the biochemical reaction of the whitening process is very discordant. The aims of this in vitro study were: (1) to compare two different laser sources, a KTP laser with a wavelength of 532 nm and a diode laser with a wavelength of 808 nm, during dental bleaching, and (2) to investigate the relationships among changes in gel temperature, tooth shade and hydrogen peroxide (HP) concentration during laser irradiation. Altogether, 116 bovine teeth were bleached using a 30% HP gel, some of them with gel only and others with gel plus one of the two lasers (532 or 808 nm) at two different powers (2 and 4 W). The KTP laser produced a significant shade variation with a minimal temperature increase. The diode laser led to a higher temperature increase with a greater reduction in HP concentration, but the change in shade was only statistically significant with a power of 4 W. At a power of 2 W, the KTP laser caused a greater change in shade than the diode laser. No significant correlations were found among temperature, HP concentration and shade variation. The KTP laser appears to provide better results with less dangerous thermal increases than the diode laser. This might call into question most of the literature affirming that the action of laser bleaching is by increasing the gel temperature and, consequently, the speed of the redox reaction. Further study is required to investigate the correlations between the parameters investigated and efficacy of the bleaching process.

Evaluation of Gallium as a Tracer of Exogenous Hemoglobin-Haptoglobin Complexes for Targeted Drug Delivery Applications

NASA Astrophysics Data System (ADS)

Xu, Shengsheng; Kaltashov, Igor A.

2016-12-01

Haptoglobin (Hp) is a plasma glycoprotein that generates significant interest in the drug delivery community because of its potential for delivery of antiretroviral medicines with high selectivity to macrophages and monocytes, the latent reservoirs of human immunodeficiency virus. As is the case with other therapies that exploit transport networks for targeted drug delivery, the success of the design and optimization of Hp-based therapies will critically depend on the ability to accurately localize and quantitate Hp-drug conjugates on the varying and unpredictable background of endogenous proteins having identical structure. In this work, we introduce a new strategy for detecting and quantitating exogenous Hp and Hp-based drugs with high sensitivity in complex biological samples using gallium as a tracer of this protein and inductively coupled plasma mass spectrometry (ICP MS) as a method of detection. Metal label is introduced by reconstituting hemoglobin (Hb) with gallium(III)-protoporphyrin IX followed by its complexation with Hp. Formation of the Hp/Hb assembly and its stability are evaluated with native electrospray ionization mass spectrometry. Both stable isotopes of Ga give rise to an abundant signal in ICP MS of a human plasma sample spiked with the metal-labeled Hp/Hb complex. The metal label signal exceeds the spectral interferences' contributions by more than an order of magnitude even with the concentration of the exogenous protein below 10 nM, the level that is more than adequate for the planned pharmacokinetic studies of Hp-based therapeutics.

Effect of sodium metabisulfite on hydrogen peroxide production in light-exposed pediatric parenteral amino acid solutions.

PubMed

Brawley, V; Bhatia, J; Karp, W B

1998-06-15

The effect of sodium metabisulfite (MBS) on hydrogen peroxide (HP) production in model and commercial amino acid solutions exposed to phototherapy light was studied. Model and commercial pediatric amino acid solutions were prepared such that the amino acid concentration was 1%. MBS concentration, riboflavin concentration, and duration of exposure to phototherapy light were varied to determine the effect on HP production. Control solutions were kept in the dark. HP production was assayed in the model amino acid solutions by using potassium iodide in the presence of ammonium molybdate. In all experiments, HP production was measured at 360 nm in the presence and absence of catalase. In light-exposed solutions, HP production increased linearly for several hours and reached a plateau by eight hours. A mean maximum of 940 microM was produced (data pooled for all solutions). No detectable HP was generated in the solutions kept in the dark. After two hours of light exposure, it was necessary to add at least 10 times more MBS than is typically found in commercial total parenteral nutrient solutions to scavenge all the HP produced. An average of up to 940 microM of HP was produced in model and commercial pediatric parenteral 1% amino acid solutions in the presence of phototherapy light and clinically relevant concentrations of riboflavin and MBS. Light exposure decreased the antioxidant effect of MBS.

Printability and inspectability of programmed pit defects on teh masks in EUV lithography

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

Kang, I.-Y.; Seo, H.-S.; Ahn, B.-S.

2010-03-12

Printability and inspectability of phase defects in ELlVL mask originated from substrate pit were investigated. For this purpose, PDMs with programmed pits on substrate were fabricated using different ML sources from several suppliers. Simulations with 32-nm HP L/S show that substrate pits with below {approx}20 nm in depth would not be printed on the wafer if they could be smoothed by ML process down to {approx}1 nm in depth on ML surface. Through the investigation of inspectability for programmed pits, minimum pit sizes detected by KLA6xx, AIT, and M7360 depend on ML smoothing performance. Furthermore, printability results for pit defectsmore » also correlate with smoothed pit sizes. AIT results for pattemed mask with 32-nm HP L/S represents that minimum printable size of pits could be {approx}28.3 nm of SEVD. In addition, printability of pits became more printable as defocus moves to (-) directions. Consequently, printability of phase defects strongly depends on their locations with respect to those of absorber patterns. This indicates that defect compensation by pattern shift could be a key technique to realize zero printable phase defects in EUVL masks.« less

[Expression of hnRNPK in gastric carcinoma and its relationship with Helicobacter pylori L-form infection].

PubMed

Zhao, Yan; Jin, Xin; Tian, Tian; Yu, Dong-hong

2011-10-01

To investigate the expression feature of heterogeneous nuclear ribonucleoprotein K in gastric carcinoma and its clinical significance, and to explore the relationship between hnRNPK expression and Helicobacter pylori L-form infection. The expression of hnRNPK protein was examined in 100 cases of gastric carcinoma, 50 paracancerous gastric tissues and 30 matched normal gastric mucosa by Elivision immunohistochemistry and hnRNPK-mRNA by in situ hybridization. Hp-L was detected with Gram staining and immunohistochemical staining. The positive rates of hnRNPK protein and mRNA in gastric carcinoma were 82.0% and 86.0%, respectively, significantly higher than those in the paracancerous gastric tissues and normal controls (P < 0.05). The expression of hnRNPK protein was significantly correlated with histological differentiation, TNM stage and lymph node metastasis (P < 0.05). The positive rates of Hp-L in the three groups were 67.0%, 58.0% and 23.3%, respectively. The positive rate of Hp-L in gastric carcinoma had no significant correlation with it in the paracancerous gastric tissues, but was significantly higher than it in the normal controls (P < 0.05). In gastric carcinoma, the expression of hnRNPK protein was higher in cases of Hp-L positive patients than those of Hp-L negative cases (P < 0.05). Positive correlation existed between the expression of hnRNPK protein and Hp-L infection (r = 0.391, P < 0.01). There is a higher expression of hnRNPK in gastric carcinoma. Hp-L infection may be associated with the up-regulated hnRNPK expression. The two factors may play a synergetic role in gastric carcinogenesis.

Imaging performance and challenges of 10nm and 7nm logic nodes with 0.33 NA EUV

NASA Astrophysics Data System (ADS)

van Setten, Eelco; Schiffelers, Guido; Psara, Eleni; Oorschot, Dorothe; Davydova, Natalia; Finders, Jo; Depre, Laurent; Farys, Vincent

2014-10-01

The NXE:3300B is ASML's third generation EUV system and has an NA of 0.33 and is positioned at a resolution of 22nm, which can be extended down to 18nm and below with off-axis illumination at full transmission. Multiple systems have been qualified and installed at customers. The NXE:3300B succeeds the NXE:3100 system (NA of 0.25), which has allowed customers to gain valuable EUV experience. It is expected that EUV will be adopted first for critical Logic layers at 10nm and 7nm nodes, such as Metal-1, to avoid the complexity of triple patterning schemes using ArF immersion. In this paper we will evaluate the imaging performance of (sub-)10nm node Logic M1 on the NXE:3300B EUV scanner. We will show the line-end performance of tip-to-tip and tip-to-space test features for various pitches and illumination settings and the performance enhancement obtained by means of a 1st round of OPC. We will also show the magnitude of local variations. The Logic M1 cell is evaluated at various critical features to identify hot spots. A 2nd round OPC model was calibrated of which we will show the model accuracy and ability to predict hot spots in the Logic M1 cell. The calibrated OPC model is used to predict the expected performance at 7nm node Logic using off-axis illumination at 16nm minimum half pitch. Initial results of L/S exposed on the NXE:3300B at 7nm node resolutions will be shown. An outlook is given to future 0.33 NA systems on the ASML roadmap with enhanced illuminator capabilities to further improve performance and process window.

A methodology for double patterning compliant split and design

NASA Astrophysics Data System (ADS)

Wiaux, Vincent; Verhaegen, Staf; Iwamoto, Fumio; Maenhoudt, Mireille; Matsuda, Takashi; Postnikov, Sergei; Vandenberghe, Geert

2008-11-01

Double Patterning allows to further extend the use of water immersion lithography at its maximum numerical aperture NA=1.35. Splitting of design layers to recombine through Double Patterning (DP) enables an effective resolution enhancement. Single polygons may need to be split up (cut) depending on the pattern density and its 2D content. The split polygons recombine at the so-called 'stitching points'. These stitching points may affect the yield due to the sensitivity to process variations. We describe a methodology to ensure a robust double patterning by identifying proper split- and design- guidelines. Using simulations and experimental data, we discuss in particular metal1 first interconnect layers of random LOGIC and DRAM applications at 45nm half-pitch (hp) and 32nm hp where DP may become the only timely patterning solution.

The novel solution for negative impact of out-of-band and outgassing by top coat materials in EUVL

NASA Astrophysics Data System (ADS)

Fujitani, Noriaki; Sakamoto, Rikimaru; Endo, Takafumi; Onishi, Ryuji; Nishita, Tokio; Yaguchi, Hiroaki; Ho, Bang-Ching

2013-03-01

EUV lithography (EUVL) is the most promising candidate of next generation technology for hp20nm node device manufacturing and beyond. However, the power of light source, masks and photo resists are the most critical issues for driving the EUVL. Especially, concerning about deterioration of the patterning performance by Out-of-Band (OoB) light existing in the EUV light, and contamination problem of exposure tool due to the resist outgassing are the key issues which have to be resolved in the material view point toward the high volume manufacturing by EUVL. This paper proposes the solution for these critical issues by applying the top coat material. The key characteristics for top coat material are the protection of the OoB effect, the prevention of the outgassing from resist as a barrier layer and enhancement of photo resist performance, like resist profile and process window. This paper describes the material design and performance. The optical property needs having the high absorbance of DUV light in OoB range and high transmittance for 13.5nm wavelength. Outgassing barrier property needs high broking property against non contamination chemical species from photo resist outgassing. The study of TOF-SIMS analysis indicates how much the polymer chemistry can impact for outgassing barrier property. The dependency of material design and lithography performance is also discussed.

Hydroxypropyl-β-Cyclodextrin Spikes Local Inflammation That Induces Th2 Cell and T Follicular Helper Cell Responses to the Coadministered Antigen

PubMed Central

Onishi, Motoyasu; Ozasa, Koji; Kobiyama, Kouji; Ohata, Keiichi; Kitano, Mitsutaka; Taniguchi, Keiichi; Homma, Tomoyuki; Kobayashi, Masanori; Sato, Akihiko; Katakai, Yuko; Yasutomi, Yasuhiro; Wijaya, Edward; Igarashi, Yoshinobu; Nakatsu, Noriyuki; Ise, Wataru; Inoue, Takeshi; Yamada, Hiroshi; Vandenbon, Alexis; Standley, Daron M.; Kurosaki, Tomohiro; Coban, Cevayir; Aoshi, Taiki; Kuroda, Etsushi

2015-01-01

Cyclodextrins are commonly used as a safe excipient to enhance the solubility and bioavailability of hydrophobic pharmaceutical agents. Their efficacies and mechanisms as drug-delivery systems have been investigated for decades, but their immunological properties have not been examined. In this study, we reprofiled hydroxypropyl-β-cyclodextrin (HP-β-CD) as a vaccine adjuvant and found that it acts as a potent and unique adjuvant. HP-β-CD triggered the innate immune response at the injection site, was trapped by MARCO+ macrophages, increased Ag uptake by dendritic cells, and facilitated the generation of T follicular helper cells in the draining lymph nodes. It significantly enhanced Ag-specific Th2 and IgG Ab responses as potently as did the conventional adjuvant, aluminum salt (alum), whereas its ability to induce Ag-specific IgE was less than that of alum. At the injection site, HP-β-CD induced the temporary release of host dsDNA, a damage-associated molecular pattern. DNase-treated mice, MyD88-deficient mice, and TBK1-deficient mice showed significantly reduced Ab responses after immunization with this adjuvant. Finally, we demonstrated that HP-β-CD–adjuvanted influenza hemagglutinin split vaccine protected against a lethal challenge with a clinically isolated pandemic H1N1 influenza virus, and the adjuvant effect of HP-β-CD was demonstrated in cynomolgus macaques. Our results suggest that HP-β-CD acts as a potent MyD88- and TBK1-dependent T follicular helper cell adjuvant and is readily applicable to various vaccines. PMID:25681338

New approach to calculate the true-coincidence effect of HpGe detector

NASA Astrophysics Data System (ADS)

Alnour, I. A.; Wagiran, H.; Ibrahim, N.; Hamzah, S.; Siong, W. B.; Elias, M. S.

2016-01-01

The corrections for true-coincidence effects in HpGe detector are important, especially at low source-to-detector distances. This work established an approach to calculate the true-coincidence effects experimentally for HpGe detectors of type Canberra GC3018 and Ortec GEM25-76-XLB-C, which are in operation at neutron activation analysis lab in Malaysian Nuclear Agency (NM). The correction for true-coincidence effects was performed close to detector at distances 2 and 5 cm using 57Co, 60Co, 133Ba and 137Cs as standard point sources. The correction factors were ranged between 0.93-1.10 at 2 cm and 0.97-1.00 at 5 cm for Canberra HpGe detector; whereas for Ortec HpGe detector ranged between 0.92-1.13 and 0.95-100 at 2 and 5 cm respectively. The change in efficiency calibration curve of the detector at 2 and 5 cm after correction was found to be less than 1%. Moreover, the polynomial parameters functions were simulated through a computer program, MATLAB in order to find an accurate fit to the experimental data points.

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.

Hematoporphyrin-Augmented Phototherapy: Dosimetric Studies In Experimental Liver Cancer In The Rat

NASA Astrophysics Data System (ADS)

Pimstone, N. R.; Horner, I. J.; Shaylor-Billings, J.; Gandhi, S. N.

1982-12-01

Liver cancer is an aggressively malignant tumor refractory to known therapy. This study investigated the potential of hematoporphyrin (HP) and light energy to selectively photo-necrose experimental hepatoma in rats. Hepatoma cells (106) when inoculated directly into the liver of recipient Wistar rats developed into a rapidly growing neoplasm which simulated human liver cancer. Seventy-two hours following intravenous HP (5-25 mg/kg), the tumor exhibited patchy porphyrin fluorescence on gross examination and on U.V. microscopy. Fluorescence was maximal in areas furthest from blood vessels, and was within cells which morphologically appeared least viable. Liver tissue did not fluoresce but contained HP concentrations 60% of that in fluorescent tumor and 3 times greater than that in non-fluorescent viable tumor. Tumor necrosis produced by light (Tungsten, 600-640 nm, 200 mW/ sq cm, 240 joules) and HP appeared macroscopically complete to a depth of 1.5 cm. Histologically, in necrotic areas, there were islands of surviving tumor enveloping blood vessels. Three weeks after irradiation, tumor volume averaged 2 mm3 compared to 250 mm3 in control operated animals where HP containing neoplasm was exposed to diffuse room light only. Neighboring liver tissue also was necrosed reflecting HP uptake. As the liver behaved in vivo as a tumor, this provided an ideal solid tissue model to study the biology of the photodynamic action of porphyrins. The clearly visible line of demarcation between photonecrosed and living tissue allowed measurement of the depth of necrosis with an accuracy of a fraction of a millimeter. We observed the following: 1) blue light (Xenon, bandwidth 60 nm, 30 mW/sq cm, 360 joules) produced 1/10 depth of necrosis when compared to red light of the same bandwidth and energy. This may relate in part to demonstrated preferential absorption of shorter wavelength (<590 nm) light energy by liver tissue pigments and hemoglobin. 2) The depth of necrosis related to the log of incident light energy (joules/sq cm). 3) The photodynamic effect of red coherent light (545-625 nm) from a tunable dye pulse laser system was no different from that of red light from a continuous noncoherent (Tungsten) source. 4) There was a logarithmic relationship between the dose of HP administered and the depth of liver necrosis. 5) If one interposed a photoopaque shield between the incident laser light and the liver, a considerable back scattering of light caused tissue necrosis behind the shield. However, when the diameter of the shield was greater than 1.3 mm, there always was a surviving island of tissue which escaped destruction. 6) The depth of necrosis in liver (mms) was significantly less than adjacent non-pigment tumor (cms) which suggests that the optical density of the tissue is a major factor in determining effective light penetration. We conclude that measurement of tissue porphyrin, and optical density with reference to the liver, will allow precise calculation potentially of major clinical importance in the treatment of skin and mucosal cancers.

Unified Hall-Petch description of nano-grain nickel hardness, flow stress and strain rate sensitivity measurements

NASA Astrophysics Data System (ADS)

Armstrong, R. W.; Balasubramanian, N.

2017-08-01

It is shown that: (i) nano-grain nickel flow stress and hardness data at ambient temperature follow a Hall-Petch (H-P) relation over a wide range of grain size; and (ii) accompanying flow stress and strain rate sensitivity measurements follow an analogous H-P relationship for the reciprocal "activation volume", (1/v*) = (1/A*b) where A* is activation area. Higher temperature flow stress measurements show a greater than expected reduction both in the H-P kɛ and in v*. The results are connected with smaller nano-grain size (< ˜20 nm) measurements exhibiting grain size weakening behavior that extends to larger grain size when tested at very low imposed strain rates.

Connected component analysis of review-SEM images for sub-10nm node process verification

NASA Astrophysics Data System (ADS)

Halder, Sandip; Leray, Philippe; Sah, Kaushik; Cross, Andrew; Parisi, Paolo

2017-03-01

Analysis of hotspots is becoming more and more critical as we scale from node to node. To define true process windows at sub-14 nm technology nodes, often defect inspections are being included to weed out design weak spots (often referred to as hotspots). Defect inspection sub 28 nm nodes is a two pass process. Defect locations identified by optical inspection tools need to be reviewed by review-SEM's to understand exactly which feature is failing in the region flagged by the optical tool. The images grabbed by the review-SEM tool are used for classification but rarely for quantification. The goal of this paper is to see if the thousands of review-SEM images which are existing can be used for quantification and further analysis. More specifically we address the SEM quantification problem with connected component analysis.

REBL: design progress toward 16 nm half-pitch maskless projection electron beam lithography

NASA Astrophysics Data System (ADS)

McCord, Mark A.; Petric, Paul; Ummethala, Upendra; Carroll, Allen; Kojima, Shinichi; Grella, Luca; Shriyan, Sameet; Rettner, Charles T.; Bevis, Chris F.

2012-03-01

REBL (Reflective Electron Beam Lithography) is a novel concept for high speed maskless projection electron beam lithography. Originally targeting 45 nm HP (half pitch) under a DARPA funded contract, we are now working on optimizing the optics and architecture for the commercial silicon integrated circuit fabrication market at the equivalent of 16 nm HP. The shift to smaller features requires innovation in most major subsystems of the tool, including optics, stage, and metrology. We also require better simulation and understanding of the exposure process. In order to meet blur requirements for 16 nm lithography, we are both shrinking the pixel size and reducing the beam current. Throughput will be maintained by increasing the number of columns as well as other design optimizations. In consequence, the maximum stage speed required to meet wafer throughput targets at 16 nm will be much less than originally planned for at 45 nm. As a result, we are changing the stage architecture from a rotary design to a linear design that can still meet the throughput requirements but with more conventional technology that entails less technical risk. The linear concept also allows for simplifications in the datapath, primarily from being able to reuse pattern data across dies and columns. Finally, we are now able to demonstrate working dynamic pattern generator (DPG) chips, CMOS chips with microfabricated lenslets on top to prevent crosstalk between pixels.

Defect inspection and printability study for 14 nm node and beyond photomask

NASA Astrophysics Data System (ADS)

Seki, Kazunori; Yonetani, Masashi; Badger, Karen; Dechene, Dan J.; Akima, Shinji

2016-10-01

Two different mask inspection techniques are developed and compared for 14 nm node and beyond photomasks, High resolution and Litho-based inspection. High resolution inspection is the general inspection method in which a 19x nm wavelength laser is used with the High NA inspection optics. Litho-based inspection is a new inspection technology. This inspection uses the wafer lithography information, and as such, this method has automatic defect classification capability which is based on wafer printability. Both High resolution and Litho-based inspection methods are compared using 14 nm and 7 nm node programmed defect and production design masks. The defect sensitivity and mask inspectability is compared, in addition to comparing the defect classification and throughput. Additionally, the Cost / Infrastructure comparison is analyzed and the impact of each inspection method is discussed.

Radiation Performance of 1 Gbit DDR SDRAMs Fabricated in the 90 nm CMOS Technology Node

NASA Technical Reports Server (NTRS)

Ladbury, Raymond L.; Gorelick, Jerry L.; Berg, M. D.; Kim, H.; LaBel, K.; Friendlich, M.; Koga, R.; George, J.; Crain, S.; Yu, P.;

One-Step Production of Amphiphilic Nanofibrillated Cellulose Using a Cellulose-Producing Bacterium.

PubMed

Tajima, Kenji; Kusumoto, Ryo; Kose, Ryota; Kono, Hiroyuki; Matsushima, Tokuo; Isono, Takuya; Yamamoto, Takuya; Satoh, Toshifumi

2017-10-09

Nanofibrillated bacterial cellulose (NFBC) is produced by culturing a cellulose-producing bacterium (Gluconacetobacter intermedius NEDO-01) with rotation or agitation in medium supplemented with carboxymethylcellulose (CMC). Despite a high yield and dispersibility in water, the product immediately aggregates in organic solvents. To broaden its applicability, we prepared amphiphilic NFBC by culturing strain NEDO-01 in medium supplemented with hydroxyethylcellulose or hydroxypropylcellulose instead of CMC. Transmission electron microscopy analysis revealed that the resultant materials (HE-NFBC and HP-NFBC, respectively) comprised relatively uniform fibers with diameters of 33 ± 7 and 42 ± 8 nm, respectively. HP-NFBC was dispersible in polar organic solvents such as methanol, acetone, isopropyl alcohol, acetonitrile, tetrahydrofuran (THF), and dimethylformamide, and was also dispersible in poly(methyl methacrylate) (PMMA) by solvent mixing using THF. HP-NFBC/PMMA composite films were highly transparent and had a higher tensile strength than neat PMMA film. Thus, HP-NFBC has a broad range of applications, including as a filler material.

Effect of Toothpaste Application Prior to Dental Bleaching on Whitening Effectiveness and Enamel Properties.

PubMed

Vieira-Junior, W F; Lima, D A N L; Tabchoury, C P M; Ambrosano, G M B; Aguiar, F H B; Lovadino, J R

2016-01-01

The purpose of this study was to investigate the effects on the enamel properties and effectiveness of bleaching using 35% hydrogen peroxide (HP) when applying toothpastes with different active agents prior to dental bleaching. Seventy enamel blocks (4 × 4 × 2 mm) were submitted to in vitro treatment protocols in a tooth-brushing machine (n=10): with distilled water and exposure to placebo gel (negative control [NC]) or HP bleaching (positive control [PC]); and brushing with differing toothpastes prior to HP bleaching, including potassium nitrate toothpaste (PN) containing NaF, conventional sodium monofluorophosphate toothpaste (FT), arginine-based toothpastes (PA and SAN), or a toothpaste containing bioactive glass (NM). Color changes were determined using the CIE L*a*b* system (ΔE, ΔL, Δa, and Δb), and a roughness (Ra) analysis was performed before and after treatments. Surface microhardness (SMH) and cross-sectional microhardness (CSMH) were analyzed after treatment. Data were analyzed with repeated measures ANOVA for Ra, one-way ANOVA (SMH, ΔE, ΔL, Δa, and Δb), split-plot ANOVA (CSMH), and Tukey post hoc test (α<0.05). The relationship between the physical surface properties and color properties was evaluated using a multivariate Canonical correlation analysis. Color changes were statistically similar in the bleached groups. After treatments, SMH and CSMH decreased in PC. SMH increased significantly in the toothpaste groups vs the negative and positive control (NM > PA = SAN > all other groups) or decreased HP effects (CSMH). Ra increased in all bleached groups, with the exception of NM, which did not differ from the NC. The variation in the color variables (ΔL, Δa, and Δb) explained 21% of the variation in the physical surface variables (Ra and SMH). The application of toothpaste prior to dental bleaching did not interfere with the effectiveness of treatment. The bioactive glass based toothpaste protected the enamel against the deleterious effects of dental bleaching.

High-protein diet differently modifies intestinal goblet cell characteristics and mucosal cytokine expression in ileum and colon.

PubMed

Lan, Annaïg; Andriamihaja, Mireille; Blouin, Jean-Marc; Liu, Xinxin; Descatoire, Véronique; Desclée de Maredsous, Caroline; Davila, Anne-Marie; Walker, Francine; Tomé, Daniel; Blachier, François

2015-01-01

We have previously shown that high-protein (HP) diet ingestion causes marked changes in the luminal environment of the colonic epithelium. This study aimed to evaluate the impact of such modifications on small intestinal and colonic mucosa, two segments with different transit time and physiological functions. Rats were fed with either normal protein (NP; 14% protein) or HP (53% protein) isocaloric diet for 2 weeks, and parameters related to intestinal mucous-secreting cells and to several innate/adaptive immune characteristics (myeloperoxidase activity, cytokine and epithelial TLR expression, proportion of immune cells in gut-associated lymphoid tissues) were measured in the ileum and colon. In ileum from HP animals, we observed hyperplasia of mucus-producing cells concomitant with an increased expression of Muc2 at both gene and protein levels, reduction of mucosal myeloperoxidase activity, down-regulation of Tlr4 gene expression in enterocytes and down-regulation of mucosal Th cytokines associated with CD4+ lymphocyte reduction in mesenteric lymph nodes. These changes coincided with an increased amount of acetate in the ileal luminal content. In colon, HP diet ingestion resulted in a lower number of goblet cells at the epithelial surface but increased goblet cell number in colonic crypts together with an increased Muc3 and a slight reduction of Il-6 gene expression. Our data suggest that HP diet modifies the goblet cell distribution in colon and, in ileum, increases goblet cell activity and decreases parameters related to basal gut inflammatory status. The impact of HP diet on intestinal mucosa in terms of beneficial or deleterious effects is discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Haemophilus ducreyi Partially Activates Human Myeloid Dendritic Cells▿

PubMed Central

Banks, Keith E.; Humphreys, Tricia L.; Li, Wei; Katz, Barry P.; Wilkes, David S.; Spinola, Stanley M.

2007-01-01

Dendritic cells (DC) orchestrate innate and adaptive immune responses to bacteria. How Haemophilus ducreyi, which causes genital ulcers and regional lymphadenitis, interacts with DC is unknown. H. ducreyi evades uptake by polymorphonuclear leukocyte and macrophage-like cell lines by secreting LspA1 and LspA2. Many H. ducreyi strains express cytolethal distending toxin (CDT), and recombinant CDT causes apoptosis of DC in vitro. Here, we examined interactions between DC and H. ducreyi 35000HP, which produces LspA1, LspA2, and CDT. In human volunteers infected with 35000HP, the ratio of myeloid DC to plasmacytoid DC was 2.8:1 in lesions, compared to a ratio of 1:1 in peripheral blood. Using myeloid DC derived from monocytes as surrogates for lesional DC, we found that DC infected with 35000HP remained as viable as uninfected DC for up to 48 h. Gentamicin protection and confocal microscopy assays demonstrated that DC ingested and killed 35000HP, but killing was incomplete at 48 h. The expression of LspA1 and LspA2 did not inhibit the uptake of H. ducreyi, despite inactivating Src kinases. Infection of DC with live 35000HP caused less cell surface marker activation than infection with heat-killed 35000HP and lipopolysaccharide (LPS) and inhibited maturation by LPS. However, infection of DC with live bacteria caused the secretion of significantly higher levels of interleukin-6 and tumor necrosis factor alpha than infection with heat-killed bacteria and LPS. The survival of H. ducreyi in DC may provide a mechanism by which the organism traffics to lymph nodes. Partial activation of DC may abrogate the establishment of a full Th1 response and an environment that promotes phagocytosis. PMID:17923525

Surface characterization of stainless HP-40 steel using laser induced μ-breakdown spectroscopy (μ -LIBS)

NASA Astrophysics Data System (ADS)

Pinto, M.; Calderón, X.; Mejía Ospino, E.; Cabanzo, R.; Poveda, Juan C.

2016-02-01

In the present study, optical microscopy in stereoscopic mode coupled to laser- induced p-breakdown spectroscopy (μ-LIBS) was applied for analysing HP-40 steel samples. microLIBS (μ-LIBS) is a new growing area that employs low energy laser pulses for the generation of plasma emission, which allow the realization of localized microanalysis [1]. This new LIBS instrument was used for the surface characterization of the steel samples in the spectral range from 356 to 401nm. Elements such as Cr, Ni, Fe, Nb, Pb, Mo, C, Mn and Si in the steel samples were investigated. The results allowed the construction of elemental distribution profiles of the samples. Complementary the HP-40 steel samples were superficially characterized by Scanning Electron Microscope (SEM).

New approach to calculate the true-coincidence effect of HpGe detector

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

Alnour, I. A., E-mail: aaibrahim3@live.utm.my, E-mail: ibrahim.elnour@yahoo.com; Wagiran, H.; Ibrahim, N.

The corrections for true-coincidence effects in HpGe detector are important, especially at low source-to-detector distances. This work established an approach to calculate the true-coincidence effects experimentally for HpGe detectors of type Canberra GC3018 and Ortec GEM25-76-XLB-C, which are in operation at neutron activation analysis lab in Malaysian Nuclear Agency (NM). The correction for true-coincidence effects was performed close to detector at distances 2 and 5 cm using {sup 57}Co, {sup 60}Co, {sup 133}Ba and {sup 137}Cs as standard point sources. The correction factors were ranged between 0.93-1.10 at 2 cm and 0.97-1.00 at 5 cm for Canberra HpGe detector; whereas for Ortec HpGemore » detector ranged between 0.92-1.13 and 0.95-100 at 2 and 5 cm respectively. The change in efficiency calibration curve of the detector at 2 and 5 cm after correction was found to be less than 1%. Moreover, the polynomial parameters functions were simulated through a computer program, MATLAB in order to find an accurate fit to the experimental data points.« less

The application of phase grating to CLM technology for the sub-65nm node optical lithography

NASA Astrophysics Data System (ADS)

Yoon, Gi-Sung; Kim, Sung-Hyuck; Park, Ji-Soong; Choi, Sun-Young; Jeon, Chan-Uk; Shin, In-Kyun; Choi, Sung-Woon; Han, Woo-Sung

2005-06-01

As a promising technology for sub-65nm node optical lithography, CLM(Chrome-Less Mask) technology among RETs(Resolution Enhancement Techniques) for low k1 has been researched worldwide in recent years. CLM has several advantages, such as relatively simple manufacturing process and competitive performance compared to phase-edge PSM's. For the low-k1 lithography, we have researched CLM technique as a good solution especially for sub-65nm node. As a step for developing the sub-65nm node optical lithography, we have applied CLM technology in 80nm-node lithography with mesa and trench method. From the analysis of the CLM technology in the 80nm lithography, we found that there is the optimal shutter size for best performance in the technique, the increment of wafer ADI CD varied with pattern's pitch, and a limitation in patterning various shapes and size by OPC dead-zone - OPC dead-zone in CLM technique is the specific region of shutter size that dose not make the wafer CD increased more than a specific size. And also small patterns are easily broken, while fabricating the CLM mask in mesa method. Generally, trench method has better optical performance than mesa. These issues have so far restricted the application of CLM technology to a small field. We approached these issues with 3-D topographic simulation tool and found that the issues could be overcome by applying phase grating in trench-type CLM. With the simulation data, we made some test masks which had many kinds of patterns with many different conditions and analyzed their performance through AIMS fab 193 and exposure on wafer. Finally, we have developed the CLM technology which is free of OPC dead-zone and pattern broken in fabrication process. Therefore, we can apply the CLM technique into sub-65nm node optical lithography including logic devices.

Imaging Prostate Cancer Microenvironment by collagen Hybridization

DTIC Science & Technology

2014-10-01

from enlarged lymph nodes. Figure 3. Ex vivo NIRF imaging of PC-3 PIP xenograft. AI = androgen independent, AR = androgen receptor negative, PSMA ...center O.D. rim/focal ROI PC-3 rapid 0.25 ± .09 1.21 ± 0.40 PC-3 ( PSMA +) PIP rapid 0.26 ± .12 NA DU-145 slow 0.01 ± 0.01 0.06 ± 0.02 HP LNCaP

Hematoporphyrin derivative and laser photoradiation in the treatment of lung cancer.

PubMed

Hayata, Y; Kato, H; Konaka, C; Ono, J; Takizawa, N

1982-03-01

Photoradiation therapy (PRT) was performed in 13 lung cancer cases and in one case of severely atypical squamous metaplasia following administration of hematoporphyrin derivative (HpD). The HpD is activated by visible red light (630 nm, 90 to 400 mW) from an argon dye laser. The cytocidal effects were due to the activation of the HpD, since 400 mW of power has in itself no effect on normal epithelium, even with long-term exposure. HpD is retained longer by malignant tissue than by normal tissue. Therefore, the lesions were irradiated with the red laser beam, delivered by a quartz fiber inserted through the instrumentation channel of the fiberoptic bronchoscope, 48 hours or more after intravenous injection of 2.5 to 4.0 mg/kg of HpD. A total of 14 cases received PRT. In one, two small, smooth-surfaced, squamous cell carcinoma tumors in the right B2b of a 74-year-old man who had refused surgery disappeared three days after HpD-photoradiation, and the patient remained disease-free 16 months after the treatment. In 12 cases of centrally located lung cancer local effects were obtained in all. However, there was no significant improvement in survival, attributable to the fact that all were advanced-stage cases. One patient with severely atypical squamous metaplasia requested treatment, and complete disappearance of metaplastic atypic was obtained.

Nanoliposome-Encapsulated Brinzolamide-hydropropyl-β-cyclodextrin Inclusion Complex: A Potential Therapeutic Ocular Drug-Delivery System

PubMed Central

Wang, Fazhan; Bao, Xingting; Fang, Aiping; Li, Huili; Zhou, Yang; Liu, Yongmei; Jiang, Chunling; Wu, Jinhui; Song, Xiangrong

2018-01-01

Novel ocular drug delivery systems (NODDSs) remain to be explored to overcome the anatomical and physiological barriers of the eyes. This study was to encapsulate brinzolamide (BRZ)-hydropropyl-β-cyclodextrin (HP-β-CD) inclusion complex (HP-β-CD/BRZ) into nanoliposomes and investigate its potential as one of NODDS to improve BRZ local glaucomatous therapeutic effect. HP-β-CD/BRZ was firstly prepared to enhance the solubility of poorly water-soluble BRZ. The HP-β-CD/BRZ loaded nanoliposomes (BCL) were subsequently constructed by thin-film dispersion method. After the optimization of the ratio of BRZ to HP-β-CD, the optimal BCL showed an average size of 82.29 ± 6.20 nm, ζ potential of -3.57 ± 0.46 mV and entrapment efficiency (EE) of 92.50 ± 2.10% with nearly spherical in shape. The X-ray diffraction (XRD) confirmed the formation of HP-β-CD/BRZ and BCL. The in vitro release study of BCL was evaluated using the dialysis technique, and BCL showed moderate sustained release. BCL (1 mg/mL BRZ) showed a 9.36-fold increase in the apparent permeability coefficient and had a sustained and enhanced intraocular pressure reduction efficacy when compared with the commercially available formulation (BRZ-Sus) (10 mg/mL BRZ). In conclusion, BCL might have a promising future as a NODDS for glaucoma treatment. PMID:29487529

Diffusion and localization of hematoporphyrin derivative in the normal bladder wall of a pig and a rat after local administration

NASA Astrophysics Data System (ADS)

Bisson, Jean F.; Notter, Dominique; Labrude, P.; Vigneron, C.; Guillemin, Francois H.

1996-04-01

Photochemotherapy using I.V. administered porphyrin photosensitizers has been used to treat superficial bladder cancers. In order to avoid cutaneous photosensitivity, lasting 6 - 8 weeks, we instilled the photosensitizer intravesically. After first studying the diffusion and localization of HpD in aqueous phase (5 mg/ml) in vitro through the bladder wall of pig by spectrofluorimetry ((lambda) ex equals 392 nm and (lambda) em equals 612.8 nm) and fluorescence microscopy, we determined the biodistribution of HpD in vivo in the rat bladder wall, 2 and 4 hours after bladder instillation of 0.4 ml of HpD: (1) the controls show only a weak autofluorescence restricted to the urothelium after 2 hours (24 micrometers plus or minus 5 micrometers, n equals 3) as well as after 4 hours (29.5 micrometers plus or minus 5 micrometers, n equals 3); (2) on the test preparation a higher fluorescence was observed: after 2 hours, HpD was localized in the urothelium and a very small part of the chorion (55 micrometers plus or minus 9 micrometers, n equals 9) whereas after 4 hours, it penetrated almost completely in the bladder wall (960 micrometers plus or minus 118 micrometers, n equals 9). In conclusion, a bladder instillation of 2 hours seems to be the optimal time of application in the rat since superficial bladder cancers, like carcinoma in situ, particularly occur in the urothelium (stage 0, pTa) or in the chorion (stage 1, pT1).

In vitro studies of chlorin e6-assisted photodynamic inactivation of Helicobacter pylori

NASA Astrophysics Data System (ADS)

Simon, C.; Mohrbacher, C.; Hüttenberger, D.; Bauer-Marschall, Ina; Krickhahn, C.; Stachon, A.; Foth, H.-J.

2014-03-01

Helicobacter pylori (HP), a gram-negative microaerophilic bacterium located in gastric mucosa, plays an im- portant role in gastro carcinogenesis. Due to the increasing emergence of antibiotic resistance, photodynamic inactivation of bacteria presents a new approach to treat bacterial infections, like HP. In vitro experiments were performed to determine the irradiation conditions for a complete inactivation of HP with the photosensitizer Chlorin e6 (Ce6). The HP strain CCUG 38770 (Culture Collection, University of Gothenburg, Sweden) was routinely cultured under microaerophilic conditions, suspended in sodium chloride, incubated with Ce6 and irradiated briefly with red light of the appropriate wavelength of λ = 660 nm. Series of measurements of different Ce6-concentrations (0.1 μM - 100 μM) were carried out, whereby the incubation time was kept constant at 1 min. The absorbed energy dose has been selected in varying the irradiation time (1 s - 300 s) and the power density (4.5 mW/cm2 - 31 mW/cm2 ). Quantification of inactivation was performed by enumeration of the grown colonies. In addition, the accumulation of Ce6 in HP cells was studied more precisely by uorescence spectroscopy. With a Ce6 concentration of 100 μM and a power density of 9 mW cm2 , a 6-log10 reduction in the survival rate of HP was achieved within 30 seconds of irradiation. In conclusion the most relevant factor for the inactivation of HP is the exposure time of irradiation, followed by the concentration of Ce6 and the light intensity. Further studies with HP strains obtained from patient specimens are under current investigation.

Multispectral Emissions of Lanthanide-Doped Gadolinium Oxide Nanophosphors for Cathodoluminescence and Near-Infrared Upconversion/Downconversion Imaging

PubMed Central

Thi Kim Dung, Doan; Fukushima, Shoichiro; Furukawa, Taichi; Niioka, Hirohiko; Sannomiya, Takumi; Kobayashi, Kaori; Yukawa, Hiroshi; Baba, Yoshinobu; Hashimoto, Mamoru; Miyake, Jun

2016-01-01

Comprehensive imaging of a biological individual can be achieved by utilizing the variation in spatial resolution, the scale of cathodoluminescence (CL), and near-infrared (NIR), as favored by imaging probe Gd2O3 co-doped lanthanide nanophosphors (NPPs). A series of Gd2O3:Ln3+/Yb3+ (Ln3+: Tm3+, Ho3+, Er3+) NPPs with multispectral emission are prepared by the sol-gel method. The NPPs show a wide range of emissions spanning from the visible to the NIR region under 980 nm excitation. The dependence of the upconverting (UC)/downconverting (DC) emission intensity on the dopant ratio is investigated. The optimum ratios of dopants obtained for emissions in the NIR regions at 810 nm, 1200 nm, and 1530 nm are applied to produce nanoparticles by the homogeneous precipitation (HP) method. The nanoparticles produced from the HP method are used to investigate the dual NIR and CL imaging modalities. The results indicate the possibility of using Gd2O3 co-doped Ln3+/Yb3+ (Ln3+: Tm3+, Ho3+, Er3+) in correlation with NIR and CL imaging. The use of Gd2O3 promises an extension of the object dimension to the whole-body level by employing magnetic resonance imaging (MRI). PMID:28335291

Multispectral Emissions of Lanthanide-Doped Gadolinium Oxide Nanophosphors for Cathodoluminescence and Near-Infrared Upconversion/Downconversion Imaging.

PubMed

Thi Kim Dung, Doan; Fukushima, Shoichiro; Furukawa, Taichi; Niioka, Hirohiko; Sannomiya, Takumi; Kobayashi, Kaori; Yukawa, Hiroshi; Baba, Yoshinobu; Hashimoto, Mamoru; Miyake, Jun

2016-09-06

Comprehensive imaging of a biological individual can be achieved by utilizing the variation in spatial resolution, the scale of cathodoluminescence (CL), and near-infrared (NIR), as favored by imaging probe Gd₂O₃ co-doped lanthanide nanophosphors (NPPs). A series of Gd₂O₃:Ln 3+ /Yb 3+ (Ln 3+ : Tm 3+ , Ho 3+ , Er 3+ ) NPPs with multispectral emission are prepared by the sol-gel method. The NPPs show a wide range of emissions spanning from the visible to the NIR region under 980 nm excitation. The dependence of the upconverting (UC)/downconverting (DC) emission intensity on the dopant ratio is investigated. The optimum ratios of dopants obtained for emissions in the NIR regions at 810 nm, 1200 nm, and 1530 nm are applied to produce nanoparticles by the homogeneous precipitation (HP) method. The nanoparticles produced from the HP method are used to investigate the dual NIR and CL imaging modalities. The results indicate the possibility of using Gd₂O₃ co-doped Ln 3+ /Yb 3+ (Ln 3+ : Tm 3+ , Ho 3+ , Er 3+ ) in correlation with NIR and CL imaging. The use of Gd₂O₃ promises an extension of the object dimension to the whole-body level by employing magnetic resonance imaging (MRI).

NAS Parallel Benchmark Results 11-96. 1.0

NASA Technical Reports Server (NTRS)

Bailey, David H.; Bailey, David; Chancellor, Marisa K. (Technical Monitor)

1997-01-01

The NAS Parallel Benchmarks have been developed at NASA Ames Research Center to study the performance of parallel supercomputers. The eight benchmark problems are specified in a "pencil and paper" fashion. In other words, the complete details of the problem to be solved are given in a technical document, and except for a few restrictions, benchmarkers are free to select the language constructs and implementation techniques best suited for a particular system. These results represent the best results that have been reported to us by the vendors for the specific 3 systems listed. In this report, we present new NPB (Version 1.0) performance results for the following systems: DEC Alpha Server 8400 5/440, Fujitsu VPP Series (VX, VPP300, and VPP700), HP/Convex Exemplar SPP2000, IBM RS/6000 SP P2SC node (120 MHz), NEC SX-4/32, SGI/CRAY T3E, SGI Origin200, and SGI Origin2000. We also report High Performance Fortran (HPF) based NPB results for IBM SP2 Wide Nodes, HP/Convex Exemplar SPP2000, and SGI/CRAY T3D. These results have been submitted by Applied Parallel Research (APR) and Portland Group Inc. (PGI). We also present sustained performance per dollar for Class B LU, SP and BT benchmarks.

Preparation and evaluation of poly(2-hydroxyethyl aspartamide)-hexadecylamine-iron oxide for MR imaging of lymph nodes

PubMed Central

2014-01-01

The purpose of this study was to synthesize biocompatible poly(2-hydroxyethyl aspartamide)–C16-iron oxide (PHEA-C16-iron oxide) nanoparticles and to evaluate their efficacy as a contrast agent for magnetic resonance imaging of lymph nodes. The PHEA-C16-iron oxide nanoparticles were synthesized by coprecipitation method. The core size of the PHEA-C16-iron oxide nanoparticles was about 5 to 7 nm, and the overall size of the nanoparticles was around 20, 60, and 150 nm in aqueous solution. The size of the nanoparticles was controlled by the amount of C16. The 3.0-T MRI signal intensity of a rabbit lymph node was effectively reduced after intravenous administration of PHEA-C16-iron oxide with the size of 20 nm. The in vitro and in vivo toxicity tests revealed the high biocompatibility of PHEA-C16-iron oxide nanoparticles. Therefore, PHEA-C16-iron oxide nanoparticles with 20-nm size can be potentially useful as T2-weighted MR imaging contrast agents for the detection of lymph nodes. PMID:24438671

N7 logic via patterning using templated DSA: implementation aspects

NASA Astrophysics Data System (ADS)

Bekaert, J.; Doise, J.; Gronheid, R.; Ryckaert, J.; Vandenberghe, G.; Fenger, G.; Her, Y. J.; Cao, Y.

2015-07-01

In recent years, major advancements have been made in the directed self-assembly (DSA) of block copolymers (BCP). Insertion of DSA for IC fabrication is seriously considered for the 7 nm node. At this node the DSA technology could alleviate costs for multiple patterning and limit the number of masks that would be required per layer. At imec, multiple approaches for inserting DSA into the 7 nm node are considered. One of the most straightforward approaches for implementation would be for via patterning through templated DSA; a grapho-epitaxy flow using cylindrical phase BCP material resulting in contact hole multiplication within a litho-defined pre-pattern. To be implemented for 7 nm node via patterning, not only the appropriate process flow needs to be available, but also DSA-aware mask decomposition is required. In this paper, several aspects of the imec approach for implementing templated DSA will be discussed, including experimental demonstration of density effect mitigation, DSA hole pattern transfer and double DSA patterning, creation of a compact DSA model. Using an actual 7 nm node logic layout, we derive DSA-friendly design rules in a logical way from a lithographer's view point. A concrete assessment is provided on how DSA-friendly design could potentially reduce the number of Via masks for a place-and-routed N7 logic pattern.

Photomask quality assessment solution for 90-nm technology node

NASA Astrophysics Data System (ADS)

Ohira, Katsumi; Chung, Dong Hoon P.; Nobuyuki, Yoshioka; Tateno, Motonari; Matsumura, Kenichi; Chen, Jiunn-Hung; Luk-Pat, Gerard T.; Fukui, Norio; Tanaka, Yoshio

2004-08-01

As 90 nm LSI devices are about to enter pre-production, the cost and turn-around time of photomasks for such devices will be key factors for success in device production. Such devices will be manufactured with state-of-the-art 193nm photolithography systems. Photomasks for these devices are being produced with the most advanced equipment, material and processing technologies and yet, quality assurance still remains an issue for volume production. These issues include defect classification and disposition due to the insufficient resolution of the defect inspection system at conventional review and classification processes and to aggressive RETs, uncertainty of the impact the defects have on the printed feature as well as inconsistencies of classical defect specifications as applied in the sub-wavelength era are becoming a serious problem. Simulation-based photomask qualification using the Virtual Stepper System is widely accepted today as a reliable mask quality assessment tool of mask defects for both the 180 nm and 130 nm technology nodes. This study examines the extendibility of the Virtual Stepper System to 90nm technology node. The proposed method of simulation-based mask qualification uses aerial image defect simulation in combination with a next generation DUV inspection system with shorter wavelength (266nm) and small pixel size combined with DUV high-resolution microscope for some defect cases. This paper will present experimental results that prove the applicability for enabling 90nm technology nodes. Both contact and line/space patterns with varies programmed defects on ArF Attenuated PSM will be used. This paper will also address how to make the strategy production-worthy.

pHP-Tethered N-Acyl Carbamate: A Photocage for Nicotinamide.

PubMed

Salahi, Farbod; Purohit, Vatsal; Ferraudi, Guillermo; Stauffacher, Cynthia; Wiest, Olaf; Helquist, Paul

2018-05-04

The synthesis of a new photocaged nicotinamide having an N-acyl carbamate linker and a p-hydroxyphenacyl (pHP) chromophore is described. The photophysical and photochemical studies showed an absorption maximum at λ = 330 nm and a quantum yield for release of 11% that are dependent upon both pH and solvent. While the acyl carbamate releases nicotinamide efficiently, a simpler amide linker was inert to photocleavage. This photocaged nicotinamide has significant advantages with respect to quantum yield, absorbance wavelength, rate of release, and solubility that make it the first practical example of a photocaged amide.

Simultaneous mapping of pan and sentinel lymph nodes for real-time image-guided surgery.

PubMed

Ashitate, Yoshitomo; Hyun, Hoon; Kim, Soon Hee; Lee, Jeong Heon; Henary, Maged; Frangioni, John V; Choi, Hak Soo

2014-01-01

The resection of regional lymph nodes in the basin of a primary tumor is of paramount importance in surgical oncology. Although sentinel lymph node mapping is now the standard of care in breast cancer and melanoma, over 20% of patients require a completion lymphadenectomy. Yet, there is currently no technology available that can image all lymph nodes in the body in real time, or assess both the sentinel node and all nodes simultaneously. In this study, we report an optical fluorescence technology that is capable of simultaneous mapping of pan lymph nodes (PLNs) and sentinel lymph nodes (SLNs) in the same subject. We developed near-infrared fluorophores, which have fluorescence emission maxima either at 700 nm or at 800 nm. One was injected intravenously for identification of all regional lymph nodes in a basin, and the other was injected locally for identification of the SLN. Using the dual-channel FLARE intraoperative imaging system, we could identify and resect all PLNs and SLNs simultaneously. The technology we describe enables simultaneous, real-time visualization of both PLNs and SLNs in the same subject.

Exogenous ROS-induced cell sheet transfer based on hematoporphyrin-polyketone film via a one-step process.

PubMed

Koo, Min-Ah; Lee, Mi Hee; Kwon, Byeong-Ju; Seon, Gyeung Mi; Kim, Min Sung; Kim, Dohyun; Nam, Ki Chang; Park, Jong-Chul

2018-04-01

To date, most of invasive cell sheet harvesting methods have used culture surface property variations, such as wettability, pH, electricity, and magnetism, to induce cell detachment. These methods that rely on surface property changes are effective when cell detachment prior to application is necessary, but of limited use when used for cell sheet transfer to target regions. The study reports a new reactive oxygen species (ROS)-induced strategy based on hematoporphyrin-incorporated polyketone film (Hp-PK film) to transfer cell sheets directly to target areas without an intermediate harvesting process. After green LED (510 nm) irradiation, production of exogenous ROS from the Hp-PK films induces cell sheet detachment and transfer. The study suggests that ROS-induced cell detachment property of the Hp-PK film is closely related to conformational changes of extracellular matrix (ECM) proteins. Also, this strategy with the Hp-PK film can be applied by regulating production rate of exogenous ROS in various types of cells, including fibroblasts, mesenchymal stem cells and keratinocytes. In conclusion, ROS-induced method using the Hp-PK film can be used for one-step cell sheet transplantation and has potential in biomedical applications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Early events in photodynamic therapy: chemical and physical changes in a POPC:cholesterol bilayer due to hematoporphyrin IX-mediated photosensitization.

PubMed

Santos, António; Rodrigues, António M; Sobral, Abílio J F N; Monsanto, Paula V; Vaz, Winchil L C; Moreno, Maria João

2009-01-01

We studied the interaction of hematoporphyrin IX (HpIX) with bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) containing cholesterol at a molar fraction between 0 and 0.5. The membrane-associated fraction of HpIX decreases significantly over a period of hours, for porphyrin concentrations in the aqueous phase above 50 nM. This was attributed to self-aggregation of HpIX and was well described by a dimerization process. A model was developed to correct for aggregation and obtain the true partition coefficient which is dependent on the molar fraction of cholesterol with a maximum at 20 mol%. The chemical and physical effects on the lipid bilayer upon irradiation of HpIX were studied for lipid bilayers with POPC:Chol 1:1. Exposure of these bilayers to visible light in the presence of HpIX leads to several cholesterol oxidation products that were identified using GC-MS. A dramatic increase in the membrane leakiness was also observed, even for short irradiation times and small light intensities, as evaluated from the rate of pH equilibration and dithionite permeability. The relevance of these results for the mechanism of photodynamic therapy is discussed.

Double exposure technique for 45nm node and beyond

NASA Astrophysics Data System (ADS)

Hsu, Stephen; Park, Jungchul; Van Den Broeke, Douglas; Chen, J. Fung

2005-11-01

The technical challenges in using F2 lithography for the 45nm node, along with the insurmountable difficulties in EUV lithography, has driven the semiconductor chipmaker into the low k1 lithography era under the pressure of ever decreasing feature sizes. Extending lithography towards lower k1 puts heavy demand on the resolution enhancement technique (RET), exposure tool, and the need for litho friendly design. Hyper numerical aperture (NA) exposure tools, immersion, and double exposure techniques (DET's) are the promising methods to extend lithography manufacturing to the 45nm node at k1 factors below 0.3. Scattering bars (SB's) have become an integral part of the lithography process as chipmakers move to production at ever lower k1 factors. To achieve better critical dimension (CD) control, polarization is applied to enhance the image contrast in the preferential imaging orientation, which increases the risk of SB printability. The optimum SB width is approximately (0.20 ~ 0.25)*(λ/NA). When the SB width becomes less than the exposure wavelength on the 4X mask, Kirchhoff's scalar theory under predicts the SB intensity. The optical weighting factor of the SB increases (Figure 1b) and the SB's become more susceptible to printing. Meanwhile, under hyper NA conditions, the effectiveness of "subresolution" SB's is significantly diminished. A full-sized scattering bars (FSB) scheme becomes necessary. Double exposure methods, such as using ternary 6% attenuated PSM (attPSM) for DDL, are good imaging solutions that can reach and likely go beyond the 45nm node. Today DDL, using binary chrome masks, is capable of printing 65 nm device patterns. In this work, we investigate the use of DET with 6% attPSM masks to target 45nm node device. The SB scalability and printability issues can be taken cared of by using "mutual trimming", i.e., with the combined energy from the two exposures. In this study, we share our findings of using DET to pattern a 45nm node device design with polarization and immersion. We also explore other double patterning methods which in addition to having two exposures, incorporates double coat/developing/etch processing to break the 0.25 k1 barrier.

Carbon nanotube circuit integration up to sub-20 nm channel lengths.

PubMed

Shulaker, Max Marcel; Van Rethy, Jelle; Wu, Tony F; Liyanage, Luckshitha Suriyasena; Wei, Hai; Li, Zuanyi; Pop, Eric; Gielen, Georges; Wong, H-S Philip; Mitra, Subhasish

2014-04-22

Carbon nanotube (CNT) field-effect transistors (CNFETs) are a promising emerging technology projected to achieve over an order of magnitude improvement in energy-delay product, a metric of performance and energy efficiency, compared to silicon-based circuits. However, due to substantial imperfections inherent with CNTs, the promise of CNFETs has yet to be fully realized. Techniques to overcome these imperfections have yielded promising results, but thus far only at large technology nodes (1 μm device size). Here we demonstrate the first very large scale integration (VLSI)-compatible approach to realizing CNFET digital circuits at highly scaled technology nodes, with devices ranging from 90 nm to sub-20 nm channel lengths. We demonstrate inverters functioning at 1 MHz and a fully integrated CNFET infrared light sensor and interface circuit at 32 nm channel length. This demonstrates the feasibility of realizing more complex CNFET circuits at highly scaled technology nodes.

Considerations for fine hole patterning for the 7nm node

NASA Astrophysics Data System (ADS)

Yaegashi, Hidetami; Oyama, Kenichi; Hara, Arisa; Natori, Sakurako; Yamauchi, Shohei; Yamato, Masatoshi; Koike, Kyohei

2016-03-01

One of the practical candidates to produce 7nm node logic devices is to use the multiple patterning with 193-immersion exposure. For the multiple patterning, it is important to evaluate the relation between the number of mask layer and the minimum pitch systematically to judge the device manufacturability. Although the number of the time of patterning, namely LE(Litho-Etch) ^ x-time, and overlay steps have to be reduced, there are some challenges in miniaturization of hole size below 20nm. Various process fluctuations on contact hole have a direct impact on device performance. According to the technical trend, 12nm diameter hole on 30nm-pitch hole will be needed on 7nm node. Extreme ultraviolet lithography (EUV) and Directed self-assembly (DSA) are attracting considerable attention to obtain small feature size pattern, however, 193-immersion still has the potential to extend optical lithography cost-effectively for sub-7nm node. The objective of this work is to study the process variation challenges and resolution in post-processing for the CD-bias control to meet sub-20nm diameter contact hole. Another pattern modulation is also demonstrated during post-processing step for hole shrink. With the realization that pattern fidelity and pattern placement management will limit scaling long before devices and interconnects fail to perform intrinsically, the talk will also outline how circle edge roughness (CER) and Local-CD uniformity can correct efficiency. On the other hand, 1D Gridded-Design-Rules layout (1D layout) has simple rectangular shapes. Also, we have demonstrated CD-bias modification on short trench pattern to cut grating line for its fabrication.

Pathway to Cryogen Free Production of Hyperpolarized Krypton-83 and Xenon-129

PubMed Central

Six, Joseph S.; Hughes-Riley, Theodore; Stupic, Karl F.; Pavlovskaya, Galina E.; Meersmann, Thomas

2012-01-01

Hyperpolarized (hp) 129Xe and hp 83Kr for magnetic resonance imaging (MRI) are typically obtained through spin-exchange optical pumping (SEOP) in gas mixtures with dilute concentrations of the respective noble gas. The usage of dilute noble gases mixtures requires cryogenic gas separation after SEOP, a step that makes clinical and preclinical applications of hp 129Xe MRI cumbersome. For hp 83Kr MRI, cryogenic concentration is not practical due to depolarization that is caused by quadrupolar relaxation in the condensed phase. In this work, the concept of stopped flow SEOP with concentrated noble gas mixtures at low pressures was explored using a laser with 23.3 W of output power and 0.25 nm linewidth. For 129Xe SEOP without cryogenic separation, the highest obtained MR signal intensity from the hp xenon-nitrogen gas mixture was equivalent to that arising from 15.5±1.9% spin polarized 129Xe in pure xenon gas. The production rate of the hp gas mixture, measured at 298 K, was 1.8 cm3/min. For hp 83Kr, the equivalent of 4.4±0.5% spin polarization in pure krypton at a production rate of 2 cm3/min was produced. The general dependency of spin polarization upon gas pressure obtained in stopped flow SEOP is reported for various noble gas concentrations. Aspects of SEOP specific to the two noble gas isotopes are discussed and compared with current theoretical opinions. A non-linear pressure broadening of the Rb D1 transition was observed and taken into account for the qualitative description of the SEOP process. PMID:23209620

Development of new FIB technology for EUVL mask repair

NASA Astrophysics Data System (ADS)

Aramaki, Fumio; Ogawa, Takashi; Matsuda, Osamu; Kozakai, Tomokazu; Sugiyama, Yasuhiko; Oba, Hiroshi; Yasaka, Anto; Amano, Tsuyoshi; Shigemura, Hiroyuki; Suga, Osamu

2011-04-01

The next generation EUVL masks beyond hp15nm are difficult to repair for the current repair technologies including focused ion beam (FIB) and electron beam (EB) in view of the minimum repairable size. We developed a new FIB technology to repair EUVL masks. Conventional FIB use gallium ions (Ga+) generated by a liquid metal ion source (LMIS), but the new FIB uses hydrogen ions (H2+) generated by a gas field ion source (GFIS). The minimum reaction area of H2+ FIB is theoretically much smaller than that of EB. We investigated the repair performance of H2+ FIB. In the concrete, we evaluated image resolution, scan damage, etching rate, material selectivity of etching and actinic image of repaired area. The most important result is that there was no difference between the repaired area and the non-repaired one on actinic images. That result suggests that the H2+ GFIS technology is a promising candidate for the solution to repair the next generation EUVL masks beyond hp15nm.

Immersion and dry scanner extensions for sub-10nm production nodes

NASA Astrophysics Data System (ADS)

Weichselbaum, Stefan; Bornebroek, Frank; de Kort, Toine; Droste, Richard; de Graaf, Roelof F.; van Ballegoij, Rob; Botter, Herman; McLaren, Matthew G.; de Boeij, Wim P.

2015-03-01

Progressing towards the 10nm and 7nm imaging node, pattern-placement and layer-to-layer overlay requirements keep on scaling down and drives system improvements in immersion (ArFi) and dry (ArF/KrF) scanners. A series of module enhancements in the NXT platform have been introduced; among others, the scanner is equipped with exposure stages with better dynamics and thermal control. Grid accuracy improvements with respect to calibration, setup, stability, and layout dependency tighten MMO performance and enable mix and match scanner operation. The same platform improvements also benefit focus control. Improvements in detectability and reproducibility of low contrast alignment marks enhance the alignment solution window for 10nm logic processes and beyond. The system's architecture allows dynamic use of high-order scanner optimization based on advanced actuators of projection lens and scanning stages. This enables a holistic optimization approach for the scanner, the mask, and the patterning process. Productivity scanner design modifications esp. stage speeds and optimization in metrology schemes provide lower layer costs for customers using immersion lithography as well as conventional dry technology. Imaging, overlay, focus, and productivity data is presented, that demonstrates 10nm and 7nm node litho-capability for both (immersion & dry) platforms.

Clinical significance of nm23 gene expression in gastric cancer.

PubMed

Mönig, Stefan P; Nolden, Brit; Lübke, Thomas; Pohl, Alexandra; Grass, Guido; Schneider, Paul M; Dienes, Hans P; Hölscher, Arnulf H; Baldus, Stephan E

2007-01-01

The expression of the nm23 gene has been associated with the development of metastasis. Numerous studies have shown down-regulation of nm23 expression in metastatic breast and colon cancer. The expression of the putative metastasis-suppressor gene nm23 in gastric carcinoma is controversial. The aim of this study was the analysis of nm23 expression in a large series of gastric cancer patients. In a retrospective immunohistochemical study specimens obtained from 116 gastric cancer patients (mean age 64 years; range: 33-85) who had undergone gastrectomy with extended lymphadenectomy were analyzed. Nm23 expression in the tumor epithelium was studied by immunohistochemistry followed by a semi-quantitative (score 0-3) evaluation. Statistical analysis including Chi-square test, uni- and multivariate survival analyses were performed. The nm23 staining pattern was positive (score 2-3) in 100 (86.2%) specimens and negative (score 0-1) in 16 (13.8%) samples. Lymph node metastasis was found in 65% of the patients. No significant correlations could be determined between nm23 expression and other variables such as gender, age, tumor differentiation, WHO-, Laurén-, Goseki-, or Ming-classification. The intensity of nm23 staining in the tumor cells was not significantly correlated with depth of tumor infiltration (T-stage), lymph node metastasis (N-stage), distant metastasis (M-stage), UICC-stage, or prognosis. Our series did not show a correlation of nm23 expression in terms of lymph node and distant metastasis or prognosis in gastric cancer patients.

Impact of a narrative medicine programme on healthcare providers' empathy scores over time.

PubMed

Chen, Po-Jui; Huang, Chien-Da; Yeh, San-Jou

2017-07-05

The cultivation of empathy for healthcare providers is an important issue in medical education. Narrative medicine (NM) has been shown to foster empathy. To our knowledge, there has been no research that examines whether a NM programme affects multi-professional healthcare providers' empathy. Our study aims to fill this gap by investigating whether a NM programme effects multi-professional healthcare providers' empathy. A pre-post questionnaire method was used.142 participants (n = 122 females) who attended the NM programme were divided into single (n = 58) and team groups (n = 84) on the basis of inter-professional education during a period of 2 months. Perceptions of the NM programme were collected using our developed questionnaire. Empathy levels were measured using the Chinese version of Jefferson Scale of Empathy - Healthcare Providers Version (JSE-HP) - at three time points: prior to (Time 1), immediately after (T2), and 1.5 years (T3) after the programme. Participants' perceptions about the NM programme (n = 116; n = 96 females) suggested an in enhancement of empathy (90.5%). Empathy scores via the JSE-HP increased after the NM programme (T1 mean 111.05, T2 mean 116.19) and were sustainable for 1.5 years (T3 mean 116.04) for all participants (F(2297) = 3.74, p < .025). A main effect of gender on empathy scores was found (F(1298) = 5.33, p < .022). No significant effect of gender over time was found but there was a trend that showed females increasing empathy scores at T2, sustaining at T3, but males demonstrating a slow rise in empathy scores over time. NM programme as an educational tool for empathy is feasible. However, further research is needed to examine gender difference as it might be that males and females respond differently to a NM programme intervention.

Electron-induced single event upsets in 28 nm and 45 nm bulk SRAMs

DOE PAGES

Trippe, J. M.; Reed, R. A.; Austin, R. A.; ...

2015-12-01

In this study, we present experimental evidence of single electron-induced upsets in commercial 28 nm and 45 nm CMOS SRAMs from a monoenergetic electron beam. Upsets were observed in both technology nodes when the SRAM was operated in a low power state. The experimental cross section depends strongly on both bias and technology node feature size, consistent with previous work in which SRAMs were irradiated with low energy muons and protons. Accompanying simulations demonstrate that δ-rays produced by the primary electrons are responsible for the observed upsets. Additional simulations predict the on-orbit event rates for various Earth and Jovian environmentsmore » for a set of sensitive volumes representative of current technology nodes. The electron contribution to the total upset rate for Earth environments is significant for critical charges as high as 0.2 fC. This value is comparable to that of sub-22 nm bulk SRAMs. Similarly, for the Jovian environment, the electron-induced upset rate is larger than the proton-induced upset rate for critical charges as high as 0.3 fC.« less

Pharmacological characterization of recombinant human and rat P2X receptor subtypes.

PubMed

Bianchi, B R; Lynch, K J; Touma, E; Niforatos, W; Burgard, E C; Alexander, K M; Park, H S; Yu, H; Metzger, R; Kowaluk, E; Jarvis, M F; van Biesen, T

1999-07-02

ATP functions as a fast neurotransmitter through the specific activation of a family of ligand-gated ion channels termed P2X receptors. In this report, six distinct recombinant P2X receptor subtypes were pharmacologically characterized in a heterologous expression system devoid of endogenous P2 receptor activity. cDNAs encoding four human P2X receptor subtypes (hP2X1, hP2X3, hP2X4, and hP2X7), and two rat P2X receptor subtypes (rP2X2 and rP2X3), were stably expressed in 1321N1 human astrocytoma cells. Furthermore, the rP2X2 and rP2X3 receptor subtypes were co-expressed in these same cells to form heteromultimeric receptors. Pharmacological profiles were determined for each receptor subtype, based on the activity of putative P2 ligands to stimulate Ca2+ influx. The observed potency and kinetics of each response was receptor subtype-specific and correlated with their respective electrophysiological properties. Each receptor subtype exhibited a distinct pharmacological profile, based on its respective sensitivity to nucleotide analogs, diadenosine polyphosphates and putative P2 receptor antagonists. Alphabeta-methylene ATP (alphabeta-meATP), a putative P2X receptor-selective agonist, was found to exhibit potent agonist activity only at the hP2X1, hP2X3 and rP2X3 receptor subtypes. Benzoylbenzoic ATP (BzATP, 2' and 3' mixed isomers), which has been reported to act as a P2X7 receptor-selective agonist, was least active at the rat and human P2X7 receptors, but was a potent (nM) agonist at hP2X1, rP2X3 and hP2X3 receptors. These data comprise a systematic examination of the functional pharmacology of P2X receptor activation.

1D design style implications for mask making and CEBL

NASA Astrophysics Data System (ADS)

Smayling, Michael C.

2013-09-01

At advanced nodes, CMOS logic is being designed in a highly regular design style because of the resolution limitations of optical lithography equipment. Logic and memory layouts using 1D Gridded Design Rules (GDR) have been demonstrated to nodes beyond 12nm.[1-4] Smaller nodes will require the same regular layout style but with multiple patterning for critical layers. One of the significant advantages of 1D GDR is the ease of splitting layouts into lines and cuts. A lines and cuts approach has been used to achieve good pattern fidelity and process margin to below 12nm.[4] Line scaling with excellent line-edge roughness (LER) has been demonstrated with self-aligned spacer processing.[5] This change in design style has important implications for mask making: • The complexity of the masks will be greatly reduced from what would be required for 2D designs with very complex OPC or inverse lithography corrections. • The number of masks will initially increase, as for conventional multiple patterning. But in the case of 1D design, there are future options for mask count reduction. • The line masks will remain simple, with little or no OPC, at pitches (1x) above 80nm. This provides an excellent opportunity for continual improvement of line CD and LER. The line pattern will be processed through a self-aligned pitch division sequence to divide pitch by 2 or by 4. • The cut masks can be done with "simple OPC" as demonstrated to beyond 12nm.[6] Multiple simple cut masks may be required at advanced nodes. "Coloring" has been demonstrated to below 12nm for two colors and to 8nm for three colors. • Cut/hole masks will eventually be replaced by e-beam direct write using complementary e-beam lithography (CEBL).[7-11] This transition is gated by the availability of multiple column e-beam systems with throughput adequate for high- volume manufacturing. A brief description of 1D and 2D design styles will be presented, followed by examples of 1D layouts. Mask complexity for 1D layouts patterned directly will be compared to mask complexity for lines and cuts at nodes larger than 20nm. No such comparison is possible below 20nm since single-patterning does not work below ~80nm pitch using optical exposure tools. Also discussed will be recently published wafer results for line patterns with pitch division by-2 and by-4 at sub-12nm nodes, plus examples of post-etch results for 1D patterns done with cut masks and compared to cuts exposed by a single-column e-beam direct write system.

Novel method for in vitro depletion of T cells by monoclonal antibody-targeted photosensitization.

PubMed

Berki, T; Németh, P

1998-02-01

An immunotargeting method (called photo-immunotargeting) has been developed for selective in vitro cell destruction. The procedure combines the photosensitizing (toxic) effect of light-induced dye-molecules, e.g., hematoporphyrin (HP) and the selective binding ability of monoclonal antibodies (mAb) to cell surface molecules. The photosensitizer HP molecules were covalently attached to monoclonal antibodies (a-Thy-1) recognizing an antigen on the surface of T lymphocytes, and used for T cell destruction. To increase the selectivity of the conventional targeting methods, a physical activation step (local light irradiation) as a second degree of specificity was employed. The HP in conjugated form was sufficient to induce T cell (thymocytes, EL-4 cell line) death after irradiation at 400 nm, at tenfold lower concentration compared to the photosensitizing effect of unbound HP. The selective killing of T lymphocytes (bearing the Thy-1 antigen) in a mixed cell population was demonstrated after a treatment with the phototoxic conjugate and light irradiation. This method can be useful for selective destruction of one population (target cell) in an in vitro heterogeneous cell mixture, e.g., in bone marrow transplants for T cell depletion to avoid graft vs. host reaction.

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.

Hairpin DNA-Templated Silver Nanoclusters as Novel Beacons in Strand Displacement Amplification for MicroRNA Detection.

PubMed

Zhang, Jingpu; Li, Chao; Zhi, Xiao; Ramón, Gabriel Alfranca; Liu, Yanlei; Zhang, Chunlei; Pan, Fei; Cui, Daxiang

2016-01-19

MicroRNA (miRNA) biomarkers display great potential for cancer diagnosis and prognosis. The development of rapid and specific methods for miRNA detection has become a hotspot. Herein, hairpin DNA-templated silver nanoclusters (AgNCs/HpDNA) were prepared and integrated into strand-displacement amplification (SDA) as a novel beacon for miRNA detection. The light-up platform was established based on guanine (G)-rich fluorescence enhancement that essentially converted the excitation/emission pair of AgNCs/HpDNAs from a shorter wavelength to a longer wavelength, and then achieved fluorescent enhancement at longer wavelength. On the basis of the validation of the method, the single and duplex detection were conducted in two plasma biomarkers (miR-16-5p and miR-19b-3p) for the diagnosis of gastric cancer. The probe (AgNCs/RED 16(7s)C) utilized for miR-16-5p detection adopted a better conformation with high specificity to recognize single-base mismatches by producing dramatically opposite signals (increase or decrease at 580 nm ex/640 nm em) while the probe (AgNCs/GRE 19b(5s)C) for miR-19b-3p generated dual signals (increase at 490 nm ex/570 nm em and decrease at 430 nm ex/530 nm em) with bright fluorescence in one reaction during the amplification, but unexpectedly was partially digested. This is for the first time to allow the generation of enhanced fluorescent AgNCs and the target recognition integrated into a single process, which offers great opportunity for specific miRNA detection in an easy and rapid way.

Applications of p-hydroxyphenacyl (pHP) and coumarin-4-ylmethyl photoremovable protecting groups.

PubMed

Givens, Richard S; Rubina, Marina; Wirz, Jakob

2012-03-01

Most applications of photoremovable protecting groups have used o-nitrobenzyl compounds and their (often commercially available) derivatives that, however, have several disadvantages. The focus of this review is on applications of the more recently developed title compounds, which are especially well suited for time-resolved biochemical and physiological investigations, because they release the caged substrates in high yield within a few nanoseconds or less. Together, these two chromophores cover the action spectrum for photorelease from >700 nm to 250 nm.

Heterodyne common-path grating interferometer with Littrow configuration.

PubMed

Wu, Chyan-Chyi; Hsu, Cheng-Chih; Lee, Ju-Yi; Chen, Yan-Zou

2013-06-03

This paper presents a heterodyne common-path grating interferometer with Littrow configuration (HCGIL). The HCGIL can effectively overcome environmental disturbance effect and the DC offset and the amplitude variation of the measurement signals. Experimental results match well with the HP5529A results for long-range measurements. Results also show that the estimated measurement resolution is 0.15 ± 0.027 nm. The stability of the HCGIL is -0.41 ± 0.23 nm. Therefore, the HCGIL has potential for subnanometer resolution and long-range applications.

Elastic scattering spectroscopy findings in formalin-fixed oral squamous cell carcinoma specimens

NASA Astrophysics Data System (ADS)

Swinson, B.; Elmaaytah, M.; Jerjes, W.; Hopper, C.

2005-11-01

Oral squamous cell carcinoma (OSCC) has been shown to spread locally and infiltrate adjacent bone or via the lymphatic system to the cervical lymph nodes. This usually necessitates a surgical neck dissection and either a local or segmental resection for bone clearance. While histopathology remains the gold standard for tissue diagnosis, several new diagnostic techniques are being developed that rely on physical and biochemical changes that mirror or precede malignant changes within tissue. The aim of this study was to compare findings of Elastic Scattering Spectroscopy (ESS) with histopathology on formalin-fixed specimens of both neck lymph node dissections and de-calcified archival bone from patients with OSCC. We wished to see if this technique could be used as an adjunct or alternative to histopathology in defining cervical nodal involvement and if it could be used to identify bone resection margins positive for tumour. 130 lymph nodes were examined from 13 patients. The nodes were formalin-fixed, bivalved and examined by ESS. The intensity of the spectrum at 4 points was considered for comparison; at 360nm, 450nm, 630nm and 690nm. 341 spectra were taken from the mandibular specimens of 21 patients, of which 231 spectra were taken from histologically positive sites and the rest were normal. The nodes and bone specimens were then routinely processed with haematoxylin and eosin-stained sections, examined histopathologically, and the results compared. Using Linear Discriminant Analysis (LDA) as a statistical method, a sensitivity of 98% and a specificity of 68% was obtained for the neck nodes and a sensitivity of 87% and a specificity of 80% for the bone margins.

28nm node process optimization: a lithography centric view

NASA Astrophysics Data System (ADS)

Seltmann, Rolf

2014-10-01

Many experts claim that the 28nm technology node will be the most cost effective technology node forever. This results from primarily from the cost of manufacturing due to the fact that 28nm is the last true Single Patterning (SP) node. It is also affected by the dramatic increase of design costs and the limited shrink factor of the next following nodes. Thus, it is assumed that this technology still will be alive still for many years. To be cost competitive, high yields are mandatory. Meanwhile, leading edge foundries have optimized the yield of the 28nm node to such a level that that it is nearly exclusively defined by random defectivity. However, it was a long way to go to come to that level. In my talk I will concentrate on the contribution of lithography to this yield learning curve. I will choose a critical metal patterning application. I will show what was needed to optimize the process window to a level beyond the usual OPC model work that was common on previous nodes. Reducing the process (in particular focus) variability is a complementary need. It will be shown which improvements were needed in tooling, process control and design-mask-wafer interaction to remove all systematic yield detractors. Over the last couple of years new scanner platforms were introduced that were targeted for both better productivity and better parametric performance. But this was not a clear run-path. It needed some extra affords of the tool suppliers together with the Fab to bring the tool variability down to the necessary level. Another important topic to reduce variability is the interaction of wafer none-planarity and lithography optimization. Having an accurate knowledge of within die topography is essential for optimum patterning. By completing both the variability reduction work and the process window enhancement work we were able to transfer the original marginal process budget to a robust positive budget and thus ensuring high yield and low costs.

Design strategy for integrating DSA via patterning in sub-7 nm interconnects

NASA Astrophysics Data System (ADS)

Karageorgos, Ioannis; Ryckaert, Julien; Tung, Maryann C.; Wong, H.-S. P.; Gronheid, Roel; Bekaert, Joost; Karageorgos, Evangelos; Croes, Kris; Vandenberghe, Geert; Stucchi, Michele; Dehaene, Wim

2016-03-01

In recent years, major advancements have been made in the directed self-assembly (DSA) of block copolymers (BCPs). As a result, the insertion of DSA for IC fabrication is being actively considered for the sub-7nm nodes. At these nodes the DSA technology could alleviate costs for multiple patterning and limit the number of litho masks that would be required per metal layer. One of the most straightforward approaches for DSA implementation would be for via patterning through templated DSA, where hole patterns are readily accessible through templated confinement of cylindrical phase BCP materials. Our in-house studies show that decomposition of via layers in realistic circuits below the 7nm node would require at least many multi-patterning steps (or colors), using 193nm immersion lithography. Even the use of EUV might require double patterning in these dimensions, since the minimum via distance would be smaller than EUV resolution. The grouping of vias through templated DSA can resolve local conflicts in high density areas. This way, the number of required colors can be significantly reduced. For the implementation of this approach, a DSA-aware mask decomposition is required. In this paper, our design approach for DSA via patterning in sub-7nm nodes is discussed. We propose options to expand the list of DSA-compatible via patterns (DSA letters) and we define matching cost formulas for the optimal DSA-aware layout decomposition. The flowchart of our proposed approach tool is presented.

Simultaneous determination of triple therapy for Helicobacter pylori in human plasma by reversed phase chromatography with online wavelength switching

NASA Astrophysics Data System (ADS)

Ahmed, Sameh; Atia, Noha N.

2015-02-01

The infection of gastric mucosa by Helicobacter pylori (HP) is an essential cofactor in the aetiology of gastroduodenal ulcer and gastric carcinoma. Because of the bacterial resistance, combination therapy containing omeprazole (OME), tinidazole (TNZ) and clarithromycin (CLA) is commonly used for eradication of HP. However, the simultaneous determination of the triple therapy in human plasma was not reported. A simple, reproducible, and selective HPLC method was developed for the simultaneous determination of the triple therapy mixture used for management of HP infections in human plasma. An HPLC procedure based on a liquid-liquid extraction, enrichment of the analytes and subsequent reversed-phase chromatography with UV detection was used. To enable sensitive and selective detection, the method involved the use of online wavelength switching detection, with two different detection wavelengths; 280 nm for detection of OME and TNZ and 210 nm for detection of CLA. Separations were performed on C18 analytical column with acetonitrile-10 mM phosphate buffer of pH = 3.0 at flow rate of 1.0 mL min-1. The linear ranges in human plasma were 0.05-10 μg mL-1 with correlation coefficients >0.9990. The detection limits in human plasma were 0.02-0.07 μg mL-1. Validation parameters were assessed in compliance with US-FDA guidelines. The method proved to be valuable for the therapeutic drug monitoring after oral administration of triple therapy tablets.

Drug-in-cyclodextrin-in-liposomes: A novel drug delivery system for flurbiprofen.

PubMed

Zhang, Lina; Zhang, Qi; Wang, Xin; Zhang, Wenji; Lin, Congcong; Chen, Fen; Yang, Xinggang; Pan, Weisan

2015-08-15

A novel delivery system based on drug-cyclodextrin (CD) complexation and liposomes has been developed to improve therapeutic effect. Three different means, i.e., co-evaporation (COE), co-ground (GR) and co-lyophilization (COL) and three different CDs (β-CD, HP-β-CD and SBE-β-CD) were contrasted to investigate the characteristics of the end products. FP/FP-CD loaded liposomes were obtained by thin layer evaporation technique. Size, zeta potential and encapsulation efficiency were investigated by light scattering analysis and minicolumn centrifugation. Differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) showed the amorphous form of complexes and spherical morphology of FP-HP-β-CD COE loaded liposomes. The pH 7.4 phosphate buffer solution (PBS) was selected as the medium for the in vitro release. Wistar rats were put into use to study the pharmacokinetic behavior in vivo. FP-HP-β-CD COE loaded liposomes showed the better physicochemical characters that followed the average particle size, polydispersity index, zeta potential and mean encapsulation efficiency 158±10 nm, 0.19±0.1, -12.4±0.1 mW and 56.1±0.5%, separately. The relative bioavailability of FP-HP-β-CD COE loaded liposomes was 420%, 201% and 402% compared with FP solution, FP-HP-β-CD and FP-liposomes, respectively. In conclusion, the novel delivery system improved the relative bioavailability of FP significantly and provided a perspective way for delivery of insoluble drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

PMJ 2007 panel discussion overview: double exposure and double patterning for 32-nm half-pitch design node

NASA Astrophysics Data System (ADS)

Nagaoka, Yoshinori; Watanabe, Hidehiro

2007-10-01

As part of the technical program in Photomask Japan 2007, we held a panel discussion to discuss challenges and solutions for the double exposure and double patterning lithography technique for 32nm half-pitch design node. 4 panelists, Rik Jonckheere of IMEC, Belgium), Tsann-Binn Chiou of ASML Taiwan Ltd., Taiwan), Judy Huckabay of Cadence Design Systems Inc. (USA) and Yoshimitsu Okuda of Toppan Printing Co., Ltd., Japan) were invited to represent each key technical area. We also took a survey from the PMJ attendees prior to the panel discussion, to vote which key technical area they think the challenge exists for the 32nm half-pitch DE/DP lithography. The result of the survey was also presented during the panel discussion. One would intuitively think that by using a DE/DP technique you're relaxing the design rule by 2x, thus for 32nm node it's essentially the 65nm process- you're just repeating it 2 times. Well, not exactly, as identified by the panelists and the participants in the discussion. We recognized the difficulties in the LSI fabrication process steps, the lithography tool overlay, photomask CD and registration, and the issue of data splitting conflict. These difficulties are big challenge for both LSI and photomask manufactures; however, we have confirmed some solutions are already examined by the theoretical and experimental works of the people in research. Despite these difficulties, we are convinced that the immersion lithography with double exposure and double patterning techniques is one of the most promising candidates of the lithography for 32nm half pitch design node.

Investigating the intrinsic cleanliness of automated handling designed for EUV mask pod-in-pod systems

NASA Astrophysics Data System (ADS)

Brux, O.; van der Walle, P.; van der Donck, J. C. J.; Dress, P.

2011-11-01

Extreme Ultraviolet Lithography (EUVL) is the most promising solution for technology nodes 16nm (hp) and below. However, several unique EUV mask challenges must be resolved for a successful launch of the technology into the market. Uncontrolled introduction of particles and/or contamination into the EUV scanner significantly increases the risk for device yield loss and potentially scanner down-time. With the absence of a pellicle to protect the surface of the EUV mask, a zero particle adder regime between final clean and the point-of-exposure is critical for the active areas of the mask. A Dual Pod concept for handling EUV masks had been proposed by the industry as means to minimize the risk of mask contamination during transport and storage. SuSS-HamaTech introduces MaskTrackPro InSync as a fully automated solution for the handling of EUV masks in and out of this Dual Pod System and therefore constitutes an interface between various tools inside the Fab. The intrinsic cleanliness of each individual handling and storage step of the inner shell (EIP) of this Dual Pod and the EUV mask inside the InSync Tool has been investigated to confirm the capability for minimizing the risk of cross-contamination. An Entegris Dual Pod EUV-1000A-A110 has been used for the qualification. The particle detection for the qualification procedure was executed with the TNO's RapidNano Particle Scanner, qualified for particle sizes down to 50nm (PSL equivalent). It has been shown that the target specification of < 2 particles @ 60nm per 25 cycles has been achieved. In case where added particles were measured, the EIP has been identified as a potential root cause for Ni particle generation. Any direct Ni-Al contact has to be avoided to mitigate the risk of material abrasion.

Design technology co-optimization for 14/10nm metal1 double patterning layer

NASA Astrophysics Data System (ADS)

Duan, Yingli; Su, Xiaojing; Chen, Ying; Su, Yajuan; Shao, Feng; Zhang, Recco; Lei, Junjiang; Wei, Yayi

2016-03-01

Design and technology co-optimization (DTCO) can satisfy the needs of the design, generate robust design rule, and avoid unfriendly patterns at the early stage of design to ensure a high level of manufacturability of the product by the technical capability of the present process. The DTCO methodology in this paper includes design rule translation, layout analysis, model validation, hotspots classification and design rule optimization mainly. The correlation of the DTCO and double patterning (DPT) can optimize the related design rule and generate friendlier layout which meets the requirement of the 14/10nm technology node. The experiment demonstrates the methodology of DPT-compliant DTCO which is applied to a metal1 layer from the 14/10nm node. The DTCO workflow proposed in our job is an efficient solution for optimizing the design rules for 14/10 nm tech node Metal1 layer. And the paper also discussed and did the verification about how to tune the design rule of the U-shape and L-shape structures in a DPT-aware metal layer.

Functional Analysis in Long-Term Operation of High Power UV-LEDs in Continuous Fluoro-Sensing Systems for Hydrocarbon Pollution

PubMed Central

Arques-Orobon, Francisco Jose; Nuñez, Neftali; Vazquez, Manuel; Gonzalez-Posadas, Vicente

2016-01-01

This work analyzes the long-term functionality of HP (High-power) UV-LEDs (Ultraviolet Light Emitting Diodes) as the exciting light source in non-contact, continuous 24/7 real-time fluoro-sensing pollutant identification in inland water. Fluorescence is an effective alternative in the detection and identification of hydrocarbons. The HP UV-LEDs are more advantageous than classical light sources (xenon and mercury lamps) and helps in the development of a low cost, non-contact, and compact system for continuous real-time fieldwork. This work analyzes the wavelength, output optical power, and the effects of viscosity, temperature of the water pollutants, and the functional consistency for long-term HP UV-LED working operation. To accomplish the latter, an analysis of the influence of two types 365 nm HP UV-LEDs degradation under two continuous real-system working mode conditions was done, by temperature Accelerated Life Tests (ALTs). These tests estimate the mean life under continuous working conditions of 6200 h and for cycled working conditions (30 s ON & 30 s OFF) of 66,000 h, over 7 years of 24/7 operating life of hydrocarbon pollution monitoring. In addition, the durability in the face of the internal and external parameter system variations is evaluated. PMID:26927113

Functional Analysis in Long-Term Operation of High Power UV-LEDs in Continuous Fluoro-Sensing Systems for Hydrocarbon Pollution.

PubMed

Arques-Orobon, Francisco Jose; Nuñez, Neftali; Vazquez, Manuel; Gonzalez-Posadas, Vicente

2016-02-26

This work analyzes the long-term functionality of HP (High-power) UV-LEDs (Ultraviolet Light Emitting Diodes) as the exciting light source in non-contact, continuous 24/7 real-time fluoro-sensing pollutant identification in inland water. Fluorescence is an effective alternative in the detection and identification of hydrocarbons. The HP UV-LEDs are more advantageous than classical light sources (xenon and mercury lamps) and helps in the development of a low cost, non-contact, and compact system for continuous real-time fieldwork. This work analyzes the wavelength, output optical power, and the effects of viscosity, temperature of the water pollutants, and the functional consistency for long-term HP UV-LED working operation. To accomplish the latter, an analysis of the influence of two types 365 nm HP UV-LEDs degradation under two continuous real-system working mode conditions was done, by temperature Accelerated Life Tests (ALTs). These tests estimate the mean life under continuous working conditions of 6200 h and for cycled working conditions (30 s ON & 30 s OFF) of 66,000 h, over 7 years of 24/7 operating life of hydrocarbon pollution monitoring. In addition, the durability in the face of the internal and external parameter system variations is evaluated.

The verification of printability about marginal defects and the detectability at the inspection tool in sub 50nm node

NASA Astrophysics Data System (ADS)

Lee, Hyemi; Jeong, Goomin; Seo, Kangjun; Kim, Sangchul; kim, changreol

2008-05-01

Since mask design rule is smaller and smaller, Defects become one of the issues dropping the mask yield. Furthermore controlled defect size become smaller while masks are manufactured. According to ITRS roadmap on 2007, controlled defect size is 46nm in 57nm node and 36nm in 45nm node on a mask. However the machine development is delayed in contrast with the speed of the photolithography development. Generally mask manufacturing process is divided into 3 parts. First part is patterning on a mask and second part is inspecting the pattern and repairing the defect on the mask. At that time, inspection tools of transmitted light type are normally used and are the most trustful as progressive type in the developed inspection tools until now. Final part is shipping the mask after the qualifying the issue points and weak points. Issue points on a mask are qualified by using the AIMS (Aerial image measurement system). But this system is including the inherent error possibility, which is AIMS measures the issue points based on the inspection results. It means defects printed on a wafer are over the specific size detected by inspection tools and the inspection tool detects the almost defects. Even though there are no tools to detect the 46nm and 36nm defects suggested by ITRS roadmap, this assumption is applied to manufacturing the 57nm and 45nm device. So we make the programmed defect mask consisted with various defect type such as spot, clear extension, dark extension and CD variation on L/S(line and space), C/H(contact hole) and Active pattern in 55nm and 45nm node. And the programmed defect mask was inspected by using the inspection tool of transmitted light type and was measured by using AIMS 45-193i. Then the marginal defects were compared between the inspection tool and AIMS. Accordingly we could verify whether defect size is proper or not, which was suggested to be controlled on a mask by ITRS roadmap. Also this result could suggest appropriate inspection tools for next generation device among the inspection tools of transmitted light type, reflected light type and aerial image type.

Via patterning in the 7-nm node using immersion lithography and graphoepitaxy directed self-assembly

NASA Astrophysics Data System (ADS)

Doise, Jan; Bekaert, Joost; Chan, Boon Teik; Hori, Masafumi; Gronheid, Roel

2017-04-01

Insertion of a graphoepitaxy directed self-assembly process as a via patterning technology into integrated circuit fabrication is seriously considered for the 7-nm node and beyond. At these dimensions, a graphoepitaxy process using a cylindrical block copolymer that enables hole multiplication can alleviate costs by extending 193-nm immersion-based lithography and significantly reducing the number of masks that would be required per layer. To be considered for implementation, it needs to be proved that this approach can achieve the required pattern quality in terms of defects and variability using a representative, aperiodic design. The patterning of a via layer from an actual 7-nm node logic layout is demonstrated using immersion lithography and graphoepitaxy directed self-assembly in a fab-like environment. The performance of the process is characterized in detail on a full 300-mm wafer scale. The local variability in an edge placement error of the obtained patterns (4.0 nm 3σ for singlets) is in line with the recent results in the field and significantly less than of the prepattern (4.9 nm 3σ for singlets). In addition, it is expected that pattern quality can be further improved through an improved mask design and optical proximity correction. No major complications for insertion of the graphoepitaxy directed self-assembly into device manufacturing were observed.

Accuracy of CT parameters for assessment of tumour size and aggressiveness in lung adenocarcinoma with bronchoalveolar elements.

PubMed

Bhure, U N; Lardinois, D; Kalff, V; Hany, T F; Soltermann, A; Seifert, B; Steinert, H C

2010-10-01

Accurate determination of tumour size in lung adenocarcinoma with bronchoalveolar features (BAC) is important for the determination of TNM (tumour, nodes, metastasis) scores used in staging, prognosis and therapy response assessment. However, tumour sizes derived using lung window (LW) CT or soft-tissue/mediastinal window (MW) CT often give different results. This study examines which measurement correlates best with actual tumour size and which best identifies advanced disease. This retrospective study included 43 BAC patients who underwent surgical resection with mediastinal lymphadenectomy <4 weeks post CT scan. The largest unidimensional tumour diameter on each CT window was compared with actual histopathological tumour size (HP). LW, MW and HP size measurements and a recently described CT parameter - the modified tumour shadow disappearance rate (mTDR) = (1 - [MW/LW]) - were then used to determine which parameter best discriminated between the presence or absence of advanced disease. There was no difference between HP and LW sizes, but MW significantly underestimated HP size (p<0.0001). Unlike MW (p = 0.01) and mTDR (p = 0.001), neither HP (p = 0.14) nor LW (p = 0.10) distinguished between patients with or without advanced disease. On receiver operating characteristic (ROC) analysis at a cut-off of ≤0.13, the sensitivity and specificity of mTDR for detecting advanced disease were 69% and 89%, respectively. In patients with tumours ≤3 cm, only mTDR remained a significant predictor of advanced disease (p = 0.017), with best cut-off at ≤0.20, giving a sensitivity and specificity of 71% and 94%, respectively. MW better predicts advanced disease than LW and might also need to be recorded for RECIST (response evaluation criteria in solid tumours) assessment for T staging of BAC; however, mTDR appears to be an even better predictor and should also be used.

Evaluation of serum haptoglobin and C-reactive protein in dogs with mammary tumors.

PubMed

Planellas, Marta; Bassols, Anna; Siracusa, Carlo; Saco, Yolanda; Giménez, Mercè; Pato, Raquel; Pastor, Josep

2009-09-01

In veterinary medicine, there is increasing interest in measuring acute phase proteins as a tool in the diagnosis and monitoring of neoplastic diseases. Although mammary neoplasms are the most common type of cancer in dogs, acute phase proteins have not been extensively evaluated in dogs with mammary tumors. The aim of this study was to evaluate serum haptoglobin (Hp) and C-reactive protein (CRP) concentrations in the dogs with mammary tumors and assess their potential association with malignancy. A retrospective study of dogs with mammary tumors was performed. Serum concentrations of CRP and Hp were determined in healthy control dogs (n=20) and dogs with mammary tumors before surgery (n=41). Mammary tumors were grouped as carcinomas (n=24), fibrosarcoma (n=1), malignant mixed tumors (n=7), benign mixed tumors (n=6), and adenomas (n=3). CRP and Hp concentrations were compared in dogs with different tumor types and were also compared based on tumor size, lymph node infiltration, skin ulceration, fixation to underlying tissue, and time between tumor identification and removal. Hp concentration was significantly (P<.043) higher in dogs with mammary tumors (median 2.03 g/L, range 0.09-2.94 g/L) compared with controls (1.38 g/L, range 0.08-3.00 g/L), but the range of values overlapped considerably. CRP concentration was higher in dogs with carcinomas (4.70 mg/L, range 0.63-128.96 mg/L) vs controls (2.11 mg/L, range 0.25-6.57 mg/L) (P=.0008) and in dogs with ulcerated skin (14.8 mg/L, range 5.7-128.9 mg/L, n=3) compared with those without ulceration (2.4 mg/L, range 0.11-30.3 mg/L, n=38) (P=.048). Serum Hp and CRP do not appear to have value in diagnosing or predicting malignancy of mammary tumors in dogs. Higher CRP concentrations in dogs with mammary carcinoma suggest a role for inflammation in this tumor type.

A dual-modal magnetic nanoparticle probe for preoperative and intraoperative mapping of sentinel lymph nodes by magnetic resonance and near infrared fluorescence imaging

PubMed Central

Zhou, Zhengyang; Chen, Hongwei; Lipowska, Malgorzata; Wang, Liya; Yu, Qiqi; Yang, Xiaofeng; Tiwari, Diana; Yang, Lily; Mao, Hui

2016-01-01

The ability to reliably detect sentinel lymph nodes for sentinel lymph node biopsy and lymphadenectomy is important in clinical management of patients with metastatic cancers. However, the traditional sentinel lymph node mapping with visible dyes is limited by the penetration depth of light and fast clearance of the dyes. On the other hand, sentinel lymph node mapping with radionucleotide technique has intrinsically low spatial resolution and does not provide anatomic details in the sentinel lymph node mapping procedure. This work reports the development of a dual modality imaging probe with magnetic resonance and near infrared imaging capabilities for sentinel lymph node mapping using magnetic iron oxide nanoparticles (10 nm core size) conjugated with a near infrared molecule with emission at 830 nm. Accumulation of magnetic iron oxide nanoparticles in sentinel lymph nodes leads to strong T2 weighted magnetic resonance imaging contrast that can be potentially used for preoperative localization of sentinel lymph nodes, while conjugated near infrared molecules provide optical imaging tracking of lymph nodes with a high signal to background ratio. The new magnetic nanoparticle based dual imaging probe exhibits a significant longer lymph node retention time. Near infrared signals from nanoparticle conjugated near infrared dyes last up to 60 min in sentinel lymph node compared to that of 25 min for the free near infrared dyes in a mouse model. Furthermore, axillary lymph nodes, in addition to sentinel lymph nodes, can be also visualized with this probe, given its slow clearance and sufficient sensitivity. Therefore, this new dual modality imaging probe with the tissue penetration and sensitive detection of sentinel lymph nodes can be applied for preoperative survey of lymph nodes with magnetic resonance imaging and allows intraoperative sentinel lymph node mapping using near infrared optical devices. PMID:23812946

Perpendicular STT_RAM cell in 8 nm technology node using Co1/Ni3(1 1 1)||Gr2||Co1/Ni3(1 1 1) structure as magnetic tunnel junction

NASA Astrophysics Data System (ADS)

Varghani, Ali; Peiravi, Ali; Moradi, Farshad

2018-04-01

The perpendicular anisotropy Spin-Transfer Torque Random Access Memory (P-STT-RAM) is considered to be a promising candidate for high-density memories. Many distinct advantages of Perpendicular Magnetic Tunnel Junction (P-MTJ) compared to the conventional in-plane MTJ (I-MTJ) such as lower switching current, circular cell shape that facilitates manufacturability in smaller technology nodes, large thermal stability, smaller cell size, and lower dipole field interaction between adjacent cells make it a promising candidate as a universal memory. However, for small MTJ cell sizes, the perpendicular technology requires new materials with high polarization and low damping factor as well as low resistance area product of a P-MTJ in order to avoid a high write voltage as technology is scaled down. A new graphene-based STT-RAM cell for 8 nm technology node that uses high perpendicular magnetic anisotropy cobalt/nickel (Co/Ni) multilayer as magnetic layers is proposed in this paper. The proposed junction benefits from enough Tunneling Magnetoresistance Ratio (TMR), low resistance area product, low write voltage, and low power consumption that make it suitable for 8 nm technology node.

Advanced Technology for Ultra-Low Power System-on-Chip (SoC)

DTIC Science & Technology

2017-06-01

design at IDS=1mA/μm compared with that in experimental 14nm-node FinFET. The redistributed electric field along the channel length direction can... design can result in more uniform electron density and electron velocity distributions compared to a homojunction device. This uniform electron... design at IDS=1mA/μm compared with that in experimental 14nm-node FinFET. 14 Approved for public release, distribution is unlimited. 0 5 10 15 20

Integrated scatterometry for tight overlay and CD control to enable 20-nm node wafer manufacturing.

NASA Astrophysics Data System (ADS)

Benschop, Jos; Engelen, Andre; Cramer, Hugo; Kubis, Michael; Hinnen, Paul; van der Laan, Hans; Bhattacharyya, Kaustuve; Mulkens, Jan

2013-04-01

The overlay, CDU and focus requirements for the 20nm node can only be met using a holistic lithography approach whereby full use is made of high-order, field-by-field, scanner correction capabilities. An essential element in this approach is a fast, precise and accurate in-line metrology sensor, capable to measure on product. The capabilities of the metrology sensor as well as the impact on overlay, CD and focus will be shared in this paper.

Potential of desensitizing toothpastes to reduce the hydrogen peroxide diffusion in teeth with cervical lesions.

PubMed

Dávila-Sánchez, Andrés; Montenegro, Andrés Fernando; Alfonso, Arana-Gordillo; Farago, Paulo Vitor; Loguercio, Alessandro D; Reis, Alessandra

2016-06-01

To evaluate the occlusive potential of four toothpastes by atomic force microscopy (AFM) before and after bleaching and quantify the hydrogen peroxide (HP) diffusion into the pulp chamber after application of desensitizing toothpastes in teeth with cervical lesions. In 52 human extracted premolars, 2-mm deep artificial cervical lesions (ACL) were prepared and rinsed with EDTA for 10 seconds. Then teeth were adapted in a brushing machine and brushed with one of the following toothpastes [Regular toothpaste with no occlusive compounds Colgate Cavity Protection (CP), Oral-B Pro Health (OB), Colgate ProRelief (PR) and Sensodyne Rapid Relief (RR)] under constant loading (250 g; 4.5 cycles/seconds; 3 minutes). In 13 teeth (control group), no artificial cervical lesion was prepared. After that, the teeth were bleached with 35% HP with three 15-minute applications. The HP diffusion was measured spectrophotometrically as a stable red product based on HP reaction with 4-aminoanthipyrine and phenol in presence of peroxidase, at a wavelength of 510 nm and the dentin surfaces of ACL were evaluated before and after bleaching by AFM. Data was statistically analyzed by one-way ANOVA and Tukey's test (alpha = 0.05). In the AFM images, some modifications of the dentin surface were observed after application of OB and RR. However, only for RR the formation of a surface deposit was produced, which occluded the majority of the dentin tubules. Also, only for RR, this deposit was not modified/removed by bleaching. Despite this, all groups with ACL showed higher HP penetration than sound teeth, regardless of the toothpaste used (P < 0.001).

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

Trippe, J. M.; Reed, R. A.; Austin, R. A.

In this study, we present experimental evidence of single electron-induced upsets in commercial 28 nm and 45 nm CMOS SRAMs from a monoenergetic electron beam. Upsets were observed in both technology nodes when the SRAM was operated in a low power state. The experimental cross section depends strongly on both bias and technology node feature size, consistent with previous work in which SRAMs were irradiated with low energy muons and protons. Accompanying simulations demonstrate that δ-rays produced by the primary electrons are responsible for the observed upsets. Additional simulations predict the on-orbit event rates for various Earth and Jovian environmentsmore » for a set of sensitive volumes representative of current technology nodes. The electron contribution to the total upset rate for Earth environments is significant for critical charges as high as 0.2 fC. This value is comparable to that of sub-22 nm bulk SRAMs. Similarly, for the Jovian environment, the electron-induced upset rate is larger than the proton-induced upset rate for critical charges as high as 0.3 fC.« less

Ultimate patterning limits for EUV at 5nm node and beyond

NASA Astrophysics Data System (ADS)

Ali, Rehab Kotb; Hamed Fatehy, Ahmed; Lafferty, Neal; Word, James

2018-03-01

The 5nm technology node introduces more aggressive geometries than previous nodes. In this paper, we are introducing a comprehensive study to examine the pattering limits of EUV at 0.33NA. The study is divided into two main approaches: (A) Exploring pattering limits of Single Exposure EUV Cut/Block mask in Self-Aligned-Multi-Patterning (SAMP) process, and (B) Exploring the pattering limits of a Single Exposure EUV printing of metal Layers. The printability of the resulted OPC masks is checked through a model based manufacturing flow for the two pattering approaches. The final manufactured patterns are quantified by Edge Placement Error (EPE), Process Variation Band (PVBand), soft/hard bridging and pinching, Image Log Slope (ILS) and Common Depth of Focus (CDOF)

Size-dependent lymphatic uptake of nanoscale-tailored particles as tumor mass increases.

PubMed

Kjellman, Pontus; Fredriksson, Sarah; Kjellman, Christian; Strand, Sven-Erik; Zandt, René In 't

2015-11-01

To investigate the size-dependent lymphatic uptake of nanoparticles in mice with rapidly growing syngeneic tumors. Mice were inoculated subcutaneously with EL4 lymphoma cells and on day 5 or day 6 of tumor growth, injected peritumorally with either 29 nm or 58 nm of ultra-small superparamagnetic iron oxide nanoparticles. Twenty-four hours later the animals were imaged using MRI. The larger of the two particles can only be detected in the lymph node when injected in animals with 6-day-old tumors while the 29 nm ultra-small superparamagnetic iron oxide nanoparticle is observed on both time points. Tumor mass greatly impacts the size of particles that are transported to the lymph nodes.

Low-energy electron beam proximity projection lithography (LEEPL): the world's first e-beam production tool, LEEPL 3000

NASA Astrophysics Data System (ADS)

Behringer, Uwe F. W.

2004-06-01

In June 2000 ago the company Accretech and LEEPL corporation decided to develop an E-beam lithography tool for high throughput wafer exposure, called LEEPL. In an amazing short time the alpha tool was built. In 2002 the beta tool was installed at Accretech. Today the first production tool the LEEPL 3000 is ready to be shipped. The 2keV E-beam tool will be used in the first lithography strategy to expose (in mix and match mode with optical exposure tools) critical levels like gate structures, contact holes (CH), and via pattern of the 90 nm and 65 nm node. At the SEMATECH EPL workshop on September 22nd in Cambridge, England it was mentioned that the amount of these levels will increase very rapidly (8 in 2007; 13 in 2010 and 17 in 2013). The schedule of the production tool for 45 nm node is mid 2005 and for the 32 nm node 2008. The Figure 1 shows from left to right α-tool, the β-tool and the production tool LEEPL 3000. Figure 1 also shows the timetable of the 4 LEEPL forum all held in Japan.

Progress and process improvements for multiple electron-beam direct write

NASA Astrophysics Data System (ADS)

Servin, Isabelle; Pourteau, Marie-Line; Pradelles, Jonathan; Essomba, Philippe; Lattard, Ludovic; Brandt, Pieter; Wieland, Marco

2017-06-01

Massively parallel electron beam direct write (MP-EBDW) lithography is a cost-effective patterning solution, complementary to optical lithography, for a variety of applications ranging from 200 to 14 nm. This paper will present last process/integration results to achieve targets for both 28 and 45 nm nodes. For 28 nm node, we mainly focus on line-width roughness (LWR) mitigation by playing with stack, new resist platform and bias design strategy. The lines roughness was reduced by using thicker spin-on-carbon (SOC) hardmask (-14%) or non-chemically amplified (non-CAR) resist with bias writing strategy implementation (-20%). Etch transfer into trilayer has been demonstrated by preserving pattern fidelity and profiles for both CAR and non-CAR resists. For 45 nm node, we demonstrate the electron-beam process integration within optical CMOS flows. Resists based on KrF platform show a full compatibility with multiple stacks to fit with conventional optical flow used for critical layers. Electron-beam resist performances have been optimized to fit the specifications in terms of resolution, energy latitude, LWR and stack compatibility. The patterning process overview showing the latest achievements is mature enough to enable starting the multi-beam technology pre-production mode.

Photodynamic therapy of endometriosis with HpD (Photosan III) in a new in vitro model

NASA Astrophysics Data System (ADS)

Viereck, Volker; Werter, Wiebke; Rueck, Angelika C.; Steiner, Rudolf W.; Keckstein, J.

1994-07-01

As a new treatment model for endometriosis, photodynamic therapy was applied to endometriotic and endometrial cultures. It could be demonstrated that both endometrial components (epithelium and stroma) were present in the cultures, proved by immunocytology and electron microscopy. No major differences were seen between endometriotic and endometrial cells. The cultures were treated by HpD-sensitized PDT. Incubation time was 24 h and concentrations of 5 and 10 (mu) g/ml were used. Irradiation was performed by an argon-pumped dye laser at 630 nm with a power density of 80 mW/cm2. Evaluation both morphologically and by trypan blue exclusion test, was effected 24 h after irradiation. Toxicity in endometriotic and endometrial cultures was practically identical. Stroma cells were more sensitive to photodynamic treatment than epithelial cells. Complete stromal cell destruction was reached at 15 J/cm2, whereas epithelial cells showed 100 lethality at 40 J/cm2 (10(mu) g/ml HpD). These and subsequent results demonstrate that the sensitivity of stromal cells was about seven times higher than that of epithelial cells.

Integration of e-beam direct write in BEOL processes of 28nm SRAM technology node using mix and match

NASA Astrophysics Data System (ADS)

Gutsch, Manuela; Choi, Kang-Hoon; Hanisch, Norbert; Hohle, Christoph; Seidel, Robert; Steidel, Katja; Thrun, Xaver; Werner, Thomas

2014-10-01

Many efforts were spent in the development of EUV technologies, but from a customer point of view EUV is still behind expectations. In parallel since years maskless lithography is included in the ITRS roadmap wherein multi electron beam direct patterning is considered as an alternative or complementary approach for patterning of advanced technology nodes. The process of multi beam exposures can be emulated by single beam technologies available in the field. While variable shape-beam direct writers are already used for niche applications, the integration capability of e-beam direct write at advanced nodes has not been proven, yet. In this study the e-beam lithography was implemented in the BEoL processes of the 28nm SRAM technology. Integrated 300mm wafers with a 28nm back-end of line (BEoL) stack from GLOBALFOUNDRIES, Dresden, were used for the experiments. For the patterning of the Metal layer a Mix and Match concept based on the sequence litho - etch - litho - etch (LELE) was developed and evaluated wherein several exposure fields were blanked out during the optical exposure. E-beam patterning results of BEoL Metal and Via layers are presented using a 50kV VISTEC SB3050DW variable shaped electron beam direct writer at Fraunhofer IPMS-CNT. Etch results are shown and compared to the POR. In summary we demonstrate the integration capability of EBDW into a productive CMOS process flow at the example of the 28nm SRAM technology node.

A hybrid optic-fiber sensor network with the function of self-diagnosis and self-healing

NASA Astrophysics Data System (ADS)

Xu, Shibo; Liu, Tiegen; Ge, Chunfeng; Chen, Cheng; Zhang, Hongxia

2014-11-01

We develop a hybrid wavelength division multiplexing optical fiber network with distributed fiber-optic sensors and quasi-distributed FBG sensor arrays which detect vibrations, temperatures and strains at the same time. The network has the ability to locate the failure sites automatically designated as self-diagnosis and make protective switching to reestablish sensing service designated as self-healing by cooperative work of software and hardware. The processes above are accomplished by master-slave processors with the help of optical and wireless telemetry signals. All the sensing and optical telemetry signals transmit in the same fiber either working fiber or backup fiber. We take wavelength 1450nm as downstream signal and wavelength 1350nm as upstream signal to control the network in normal circumstances, both signals are sent by a light emitting node of the corresponding processor. There is also a continuous laser wavelength 1310nm sent by each node and received by next node on both working and backup fibers to monitor their healthy states, but it does not carry any message like telemetry signals do. When fibers of two sensor units are completely damaged, the master processor will lose the communication with the node between the damaged ones.However we install RF module in each node to solve the possible problem. Finally, the whole network state is transmitted to host computer by master processor. Operator could know and control the network by human-machine interface if needed.

LENS (lithography enhancement toward nano scale): a European project to support double exposure and double patterning technology development

NASA Astrophysics Data System (ADS)

Cantu, Pietro; Baldi, Livio; Piacentini, Paolo; Sytsma, Joost; Le Gratiet, Bertrand; Gaugiran, Stéphanie; Wong, Patrick; Miyashita, Hiroyuki; Atzei, Luisa R.; Buch, Xavier; Verkleij, Dick; Toublan, Olivier; Perez-Murano, Francesco; Mecerreyes, David

2010-04-01

In 2009 a new European initiative on Double Patterning and Double Exposure lithography process development was started in the framework of the ENIAC Joint Undertaking. The project, named LENS (Lithography Enhancement Towards Nano Scale), involves twelve companies from five different European Countries (Italy, Netherlands, France, Belgium Spain; includes: IC makers (Numonyx and STMicroelectronics), a group of equipment and materials companies (ASML, Lam Research srl, JSR, FEI), a mask maker (Dai Nippon Photomask Europe), an EDA company (Mentor Graphics) and four research and development institutes (CEA-Leti, IMEC, Centro Nacional de Microelectrónica, CIDETEC). The LENS project aims to develop and integrate the overall infrastructure required to reach patterning resolutions required by 32nm and 22nm technology nodes through the double patterning and pitch doubling technologies on existing conventional immersion exposure tools, with the purpose to allow the timely development of 32nm and 22nm technology nodes for memories and logic devices, providing a safe alternative to EUV, Higher Refraction Index Fluids Immersion Lithography and maskless lithography, which appear to be still far from maturity. The project will cover the whole lithography supply chain including design, masks, materials, exposure tools, process integration, metrology and its final objective is the demonstration of 22nm node patterning on available 1.35 NA immersion tools on high complexity mask set.

Performance and stability of mask process correction for EBM-7000

NASA Astrophysics Data System (ADS)

Saito, Yasuko; Chen, George; Wang, Jen-Shiang; Bai, Shufeng; Howell, Rafael; Li, Jiangwei; Tao, Jun; VanDenBroeke, Doug; Wiley, Jim; Takigawa, Tadahiro; Ohnishi, Takayuki; Kamikubo, Takashi; Hara, Shigehiro; Anze, Hirohito; Hattori, Yoshiaki; Tamamushi, Shuichi

2010-05-01

In order to support complex optical masks today and EUV masks in the near future, it is critical to correct mask patterning errors with a magnitude of up to 20nm over a range of 2000nm at mask scale caused by short range mask process proximity effects. A new mask process correction technology, MPC+, has been developed to achieve the target requirements for the next generation node. In this paper, the accuracy and throughput performance of MPC+ technology is evaluated using the most advanced mask writing tool, the EBM-70001), and high quality mask metrology . The accuracy of MPC+ is achieved by using a new comprehensive mask model. The results of through-pitch and through-linewidth linearity curves and error statistics for multiple pattern layouts (including both 1D and 2D patterns) are demonstrated and show post-correction accuracy of 2.34nm 3σ for through-pitch/through-linewidth linearity. Implementing faster mask model simulation and more efficient correction recipes; full mask area (100cm2) processing run time is less than 7 hours for 32nm half-pitch technology node. From these results, it can be concluded that MPC+ with its higher precision and speed is a practical technology for the 32nm node and future technology generations, including EUV, when used with advance mask writing processes like the EBM-7000.

Sentinel lymph nodes detection with an imaging system using Patent Blue V dye as fluorescent tracer

NASA Astrophysics Data System (ADS)

Tellier, F.; Steibel, J.; Chabrier, R.; Rodier, J. F.; Pourroy, G.; Poulet, P.

2013-03-01

Sentinel lymph node biopsy is the gold standard to detect metastatic invasion from primary breast cancer. This method can help patients avoid full axillary chain dissection, thereby decreasing the risk of morbidity. We propose an alternative to the traditional isotopic method, to detect and map the sentinel lymph nodes. Indeed, Patent Blue V is the most widely used dye in clinical routine for the visual detection of sentinel lymph nodes. A Recent study has shown the possibility of increasing the fluorescence quantum yield of Patent Blue V, when it is bound to human serum albumin. In this study we present a preclinical fluorescence imaging system to detect sentinel lymph nodes labeled with this fluorescent tracer. The setup is composed of a black and white CCD camera and two laser sources. One excitation source with a laser emitting at 635 nm and a second laser at 785 nm to illuminate the region of interest. The prototype is operated via a laptop. Preliminary experiments permitted to determine the device sensitivity in the μmol.L-1 range as regards the detection of PBV fluorescence signals. We also present a preclinical evaluation performed on Lewis rats, during which the fluorescence imaging setup detected the accumulation and fixation of the fluorescent dye on different nodes through the skin.

DUV phase mask for 100 nm period grating printing

NASA Astrophysics Data System (ADS)

Jourlin, Y.; Bourgin, Y.; Reynaud, S.; Parriaux, O.; Talneau, A.; Karvinen, P.; Passilly, N.; Zain, A. Md.; De La Rue, R. M.

2008-04-01

Whereas microelectronic lithography is heading to the 32 nm node and discussing immersion and double-patterning strategies, there is much which can be done with the 45 nm node in microoptics for white light processing. For instance, one of the most demanding applications in terms of achievable period is the LCD lossless polarizer, which can transmit the TM polarization and reflect the TE polarization evenly all through the visible spectrum - provided that a 1D metal grid of 100 nm period can be fabricated. The manufacture of such polarizing panels cannot resort to the step & repeat cameras of microelectronics since the substrates are too large, too thin, too wavy and full of contaminants. There is therefore a need for specific fabrication techniques. It is one of these techniques that a subgroup of partners belonging to two of the Networks of Excellence of the European Community, NEMO and ePIXnet, have decided to explore together.

A random approach of test macro generation for early detection of hotspots

NASA Astrophysics Data System (ADS)

Lee, Jong-hyun; Kim, Chin; Kang, Minsoo; Hwang, Sungwook; Yang, Jae-seok; Harb, Mohammed; Al-Imam, Mohamed; Madkour, Kareem; ElManhawy, Wael; Kwan, Joe

2016-03-01

Multiple-Patterning Technology (MPT) is still the preferred choice over EUV for the advanced technology nodes, starting the 20nm node. Down the way to 7nm and 5nm nodes, Self-Aligned Multiple Patterning (SAMP) appears to be one of the effective multiple patterning techniques in terms of achieving small pitch of printed lines on wafer, yet its yield is in question. Predicting and enhancing the yield in the early stages of technology development are some of the main objectives for creating test macros on test masks. While conventional yield ramp techniques for a new technology node have relied on using designs from previous technology nodes as a starting point to identify patterns for Design of Experiment (DoE) creation, these techniques are challenging to apply in the case of introducing an MPT technique like SAMP that did not exist in previous nodes. This paper presents a new strategy for generating test structures based on random placement of unit patterns that can construct more meaningful bigger patterns. Specifications governing the relationships between those unit patterns can be adjusted to generate layout clips that look like realistic SAMP designs. A via chain can be constructed to connect the random DoE of SAMP structures through a routing layer to external pads for electrical measurement. These clips are decomposed according to the decomposition rules of the technology into the appropriate mandrel and cut masks. The decomposed clips can be tested through simulations, or electrically on silicon to discover hotspots. The hotspots can be used in optimizing the fabrication process and models to fix them. They can also be used as learning patterns for DFM deck development. By expanding the size of the randomly generated test structures, more hotspots can be detected. This should provide a faster way to enhance the yield of a new technology node.

An investigation into scalability and compliance for triple patterning with stitches for metal 1 at the 14nm node

NASA Astrophysics Data System (ADS)

Cork, Christopher; Miloslavsky, Alexander; Friedberg, Paul; Luk-Pat, Gerry

2013-04-01

Lithographers had hoped that single patterning would be enabled at the 20nm node by way of EUV lithography. However, due to delays in EUV readiness, double patterning with 193i lithography is currently relied upon for volume production for the 20nm node's metal 1 layer. At the 14nm and likely at the 10nm node, LE-LE-LE triple patterning technology (TPT) is one of the favored options [1,2] for patterning local interconnect and Metal 1 layers. While previous research has focused on TPT for contact mask, metal layers offer new challenges and opportunities, in particular the ability to decompose design polygons across more than one mask. The extra flexibility offered by the third mask and ability to leverage polygon stitching both serve to improve compliance. However, ensuring TPT compliance - the task of finding a 3-color mask decomposition for a design - is still a difficult task. Moreover, scalability concerns multiply the difficulty of triple patterning decomposition which is an NP-complete problem. Indeed previous work shows that network sizes above a few thousand nodes or polygons start to take significantly longer times to compute [3], making full chip decomposition for arbitrary layouts impractical. In practice Metal 1 layouts can be considered as two separate problem domains, namely: decomposition of standard cells and decomposition of IP blocks. Standard cells typically include only a few 10's of polygons and should be amenable to fast decomposition. Successive design iterations should resolve compliance issues and improve packing density. Density improvements are multiplied repeatedly as standard cells are placed multiple times. IP blocks, on the other hand, may involve very large networks. This paper evaluates multiple approaches to triple patterning decomposition for the Metal 1 layer. The benefits of polygon stitching, in particular, the ability to resolve commonly encountered non-compliant layout configurations and improve packing density, are weighed against the increased difficulty in finding an optimized, legal decomposition and coping with the increased scalability challenges.

Aerial image measurement technique for automated reticle defect disposition (ARDD) in wafer fabs

NASA Astrophysics Data System (ADS)

Zibold, Axel M.; Schmid, Rainer M.; Stegemann, B.; Scheruebl, Thomas; Harnisch, Wolfgang; Kobiyama, Yuji

2004-08-01

The Aerial Image Measurement System (AIMS)* for 193 nm lithography emulation has been brought into operation successfully worldwide. A second generation system comprising 193 nm AIMS capability, mini-environment and SMIF, the AIMS fab 193 plus is currently introduced into the market. By adjustment of numerical aperture (NA), illumination type and partial illumination coherence to match the conditions in 193 nm steppers or scanners, it can emulate the exposure tool for any type of reticles like binary, OPC and PSM down to the 65 nm node. The system allows a rapid prediction of wafer printability of defects or defect repairs, and critical features, like dense patterns or contacts on the masks without the need to perform expensive image qualification consisting of test wafer exposures followed by SEM measurements. Therefore, AIMS is a mask quality verification standard for high-end photo masks and established in mask shops worldwide. The progress on the AIMS technology described in this paper will highlight that besides mask shops there will be a very beneficial use of the AIMS in the wafer fab and we propose an Automated Reticle Defect Disposition (ARDD) process. With smaller nodes, where design rules are 65 nm or less, it is expected that smaller defects on reticles will occur in increasing numbers in the wafer fab. These smaller mask defects will matter more and more and become a serious yield limiting factor. With increasing mask prices and increasing number of defects and severability on reticles it will become cost beneficial to perform defect disposition on the reticles in wafer production. Currently ongoing studies demonstrate AIMS benefits for wafer fab applications. An outlook will be given for extension of 193 nm aerial imaging down to the 45 nm node based on emulation of immersion scanners.

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.

Simultaneous determination of three polyphenols in rat plasma after orally administering hawthorn leaves extract by the HPLC method.

PubMed

Ying, Xixiang; Meng, Xiansheng; Wang, Siyuan; Wang, Dong; Li, Haibo; Wang, Bing; Du, Yang; Liu, Xun; Zhang, Wenjie; Kang, Tingguo

2012-01-01

A simple and sensitive HPLC method was developed to simultaneously determine three active compounds, vitexin-4″-O-glucoside (VG), vitexin-2″-O-rhamnoside (VR) and hyperoside (HP), in rat plasma after administering the hawthorn leaves extract (HLE). An HPLC assay with baicalin as the internal standard was carried out using a Phenomsil C₁₈ analytical column with UV detection at 332 nm. The mobile phase consisted of methanol-acetonitrile-tetrahydrofuran-1% glacial acetic acid (6 : 1.5 : 18.5 : 74, v/v/v/v). The calibration curves were linear over the range of 2.5-500, 0.2-25 and 0.25-12.5 µg mL⁻¹ for VG, VR and HP, respectively. The method was reproducible and reliable, with relative standard deviations of the intra- and inter-day precision between 1.2% and 13.2% for the analysis of the three analytes. The validated HPLC method herein described was successfully applied to the pharmacokinetic study of VG, VR and HP after oral administration of HLE to rats over the dose range of 2.5-10  mL kg⁻¹.

Post place and route design-technology co-optimization for scaling at single-digit nodes with constant ground rules

NASA Astrophysics Data System (ADS)

Mattii, Luca; Milojevic, Dragomir; Debacker, Peter; Berekovic, Mladen; Sherazi, Syed Muhammad Yasser; Chava, Bharani; Bardon, Marie Garcia; Schuddinck, Pieter; Rodopoulos, Dimitrios; Baert, Rogier; Gerousis, Vassilios; Ryckaert, Julien; Raghavan, Praveen

2018-01-01

Standard-cell design, technology choices, and place and route (P&R) efficiency are deeply interrelated in CMOS technology nodes below 10 nm, where lower number of tracks cells and higher pin densities pose increasingly challenging problems to the router in terms of congestion and pin accessibility. To evaluate and downselect the best solutions, a holistic design-technology co-optimization approach leveraging state-of-the-art P&R tools is thus necessary. We adopt such an approach using the imec N7 technology platform, with contacted poly pitch of 42 nm and tightest metal pitch of 32 nm, by comparing post P&R area of an IP block for different standard cell configurations, technology options, and cell height. Keeping the technology node and the set of ground rules unchanged, we demonstrate that a careful combination of these solutions can enable area gains of up to 50%, comparable with the area benefits of migrating to another node. We further demonstrate that these area benefits can be achieved at isoperformance with >20% reduced power. As at the end of the CMOS roadmap, conventional scaling enacted through pitch reduction is made more and more challenging by constraints imposed by lithography limits, material resistivity, manufacturability, and ultimately wafer cost, the approach shown herein offers a valid, attractive, and low-cost alternative.

Fluorenone based fluorescent probe for selective "turn-on" detection of pyrophosphate and alanine

NASA Astrophysics Data System (ADS)

Daniel Thangadurai, T.; Nithya, I.; Manjubaashini, N.; Bhuvanesh, N.; Bharathi, G.; Nandhakumar, R.; Nataraj, D.

2018-06-01

To sense biologically important entities with different size and dimensions, a fluorenone based fluorescent receptor was designed and synthesized. Probe 1 displayed a distinct fluorescence enhancement emission at 565 nm for pyrophosphate and 530 nm for alanine in polar solvent. The fluorescence titration experiments confirm 1:1 stoichiometric ratio with high-binding constant and very low limit of detection (LoD) values. Receptor 1 showed a highly selective and sensitive recognition to HP2O73 - and to alanine over other competitive anions and amino acids. In addition, the fluorescence lifetime measurement and reversible binding study results support the practical importance of 1.

Identification of endogenous surrogate ligands for human P2Y receptors through an in silico search.

PubMed

Hiramoto, Takeshi; Nonaka, Yosuke; Inoue, Kazuko; Yamamoto, Takefumi; Omatsu-Kanbe, Mariko; Matsuura, Hiroshi; Gohda, Keigo; Fujita, Norihisa

2004-05-01

G protein-coupled receptors (GPCRs) are distributed widely throughout the human body, and nearly 50% of current medicines act on a GPCR. GPCRs are considered to consist of seven transmembrane alpha-helices that form an alpha-helical bundle in which agonists and antagonists bind. A 3D structure of the target GPCR is indispensable for designing novel medicines acting on a GPCR. We have previously constructed the 3D structure of human P2Y(1) (hP2Y(1)) receptor, a GPCR, by homology modeling with the 3D structure of bovine rhodopsin as a template. In the present study, we have employed an in silico screening for compounds that could bind to the hP2Y(1)-receptor model using AutoDock 3.0. We selected 21 of the 30 top-ranked compounds, and by measuring intracellular Ca(2+) concentration, we identified 12 compounds that activated or blocked the hP2Y(1) receptor stably expressed in recombinant CHO cells. 5-Phosphoribosyl-1-pyrophosphate (PRPP) was found to activate the hP2Y(1) receptor with a low ED(50) value of 15 nM. The Ca(2+) assays showed it had no significant effect on P2Y(2), P2Y(6), or P2X(2) receptors, but acted as a weak agonist on the P2Y(12) receptor. This is the first study to rationally identify surrogate ligands for the P2Y-receptor family.

Cyclodextrin-assisted synthesis of tailored mesoporous silica nanoparticles

PubMed Central

2018-01-01

Mesoporous silica nanoparticles (MSNs) have sparked considerable interest in drug/gene delivery, catalysis, adsorption, separation, sensing, antireflection coatings and bioimaging because of their tunable structural properties. The shape, size and pore structure of MSNs are greatly influenced by the type of additives used, e.g., solvent and pore-templating agent. Here, we studied the influence of cyclodextrin (CD) molecules on the formation of MSNs. The nanoparticles over 100 nm in diameter were synthesized by surfactant-templated, hydrolysis–polycondensation reactions in the presence of pristine CD (β-CD) or hydroxypropyl-functionalized CDs (HP-γ-CD and HP-β-CD). Depending on the formulation conditions, differently shaped MSNs, such as bean-like, spherical, ellipsoid, aggregate and faceted were generated. The morphology and size of MSNs varied with the CD-type used. Generally, spherical particles were obtained with β-CD, while a faceted morphology was observed for the particles synthesized using HP-CDs. The particle size could be tuned by adjusting the amount of CD used; increasing the CD concentration led to larger particles. MSNs synthesized in the presence of β-CD displayed a smaller particle size than those produced with HP-functional CDs. FTIR, TGA and solid-state 13C NMR demonstrated the adsorption of CDs on the particle surfaces. The proposed concept allows for the synthesis of silica nanoparticles with control over particle shape and size by adjusting the concentration of additives in a simple, one-pot reaction system for a wide range of applications. PMID:29527443

Molecular organization of cytokinesis nodes and contractile rings by super-resolution fluorescence microscopy of live fission yeast

PubMed Central

Laplante, Caroline; Huang, Fang; Tebbs, Irene R.; Bewersdorf, Joerg; Pollard, Thomas D.

2016-01-01

Cytokinesis in animals, fungi, and amoebas depends on the constriction of a contractile ring built from a common set of conserved proteins. Many fundamental questions remain about how these proteins organize to generate the necessary tension for cytokinesis. Using quantitative high-speed fluorescence photoactivation localization microscopy (FPALM), we probed this question in live fission yeast cells at unprecedented resolution. We show that nodes, protein assembly precursors to the contractile ring, are discrete structural units with stoichiometric ratios and distinct distributions of constituent proteins. Anillin Mid1p, Fes/CIP4 homology-Bin/amphiphysin/Rvs (F-BAR) Cdc15p, IQ motif containing GTPase-activating protein (IQGAP) Rng2p, and formin Cdc12p form the base of the node that anchors the ends of myosin II tails to the plasma membrane, with myosin II heads extending into the cytoplasm. This general node organization persists in the contractile ring where nodes move bidirectionally during constriction. We observed the dynamics of the actin network during cytokinesis, starting with the extension of short actin strands from nodes, which sometimes connected neighboring nodes. Later in cytokinesis, a broad network of thick bundles coalesced into a tight ring around the equator of the cell. The actin ring was ∼125 nm wide and ∼125 nm thick. These observations establish the organization of the proteins in the functional units of a cytokinetic contractile ring. PMID:27647921

Empirical OPC rule inference for rapid RET application

NASA Astrophysics Data System (ADS)

Kulkarni, Anand P.

2006-10-01

A given technological node (45 nm, 65 nm) can be expected to process thousands of individual designs. Iterative methods applied at the node consume valuable days in determining proper placement of OPC features, and manufacturing and testing mask correspondence to wafer patterns in a trial-and-error fashion for each design. Repeating this fabrication process for each individual design is a time-consuming and expensive process. We present a novel technique which sidesteps the requirement to iterate through the model-based OPC analysis and pattern verification cycle on subsequent designs at the same node. Our approach relies on the inference of rules from a correct pattern at the wafer surface it relates to the OPC and pre-OPC pattern layout files. We begin with an offline phase where we obtain a "gold standard" design file that has been fab-tested at the node with a prepared, post-OPC layout file that corresponds to the intended on-wafer pattern. We then run an offline analysis to infer rules to be used in this method. During the analysis, our method implicitly identifies contextual OPC strategies for optimal placement of RET features on any design at that node. Using these strategies, we can apply OPC to subsequent designs at the same node with accuracy comparable to the original design file but significantly smaller expected runtimes. The technique promises to offer a rapid and accurate complement to existing RET application strategies.

Alternating phase-shift mask and binary mask for 45-nm node and beyond: the impact on the mask error control

NASA Astrophysics Data System (ADS)

Kojima, Yosuke; Shirasaki, Masanori; Chiba, Kazuaki; Tanaka, Tsuyoshi; Inazuki, Yukio; Yoshikawa, Hiroki; Okazaki, Satoshi; Iwase, Kazuya; Ishikawa, Kiichi; Ozawa, Ken

2007-05-01

For 45 nm node and beyond, the alternating phase-shift mask (alt. PSM), one of the most expected resolution enhancement technologies (RET) because of its high image contrast and small mask error enhancement factor (MEEF), and the binary mask (BIM) attract attention. Reducing CD and registration errors and defect are their critical issues. As the solution, the new blank for alt. PSM and BIM is developed. The top film of new blank is thin Cr, and the antireflection film and shielding film composed of MoSi are deposited under the Cr film. The mask CD performance is evaluated for through pitch, CD linearity, CD uniformity, global loading, resolution and pattern fidelity, and the blank performance is evaluated for optical density, reflectivity, sheet resistance, flatness and defect level. It is found that the performance of new blank is equal to or better than that of conventional blank in all items. The mask CD performance shows significant improvement. The lithography performance of new blank is confirmed by wafer printing and AIMS measurement. The full dry type alt. PSM has been used as test plate, and the test results show that new blank can almost meet the specifications of pi-0 CD difference, CD uniformity and process margin for 45 nm node. Additionally, the new blank shows the better pattern fidelity than that of conventional blank on wafer. AIMS results are almost same as wafer results except for the narrowest pattern. Considering the result above, this new blank can reduce the mask error factors of alt. PSM and BIM for 45 nm node and beyond.

Assessment of a Low-Power 65 nm CMOS Technology for Analog Front-End Design

NASA Astrophysics Data System (ADS)

Manghisoni, Massimo; Gaioni, Luigi; Ratti, Lodovico; Re, Valerio; Traversi, Gianluca

2014-02-01

This work is concerned with the study of the analog properties of MOSFET devices belonging to a 65 nm CMOS technology with emphasis on intrinsic voltage gain and noise performance. This node appears to be a robust and promising solution to cope with the unprecedented requirements set by silicon vertex trackers in experiments upgrades and future colliders as well as by imaging detectors at light sources and free electron lasers. In this scaled-down technology, the impact of new dielectric materials and processing techniques on the analog behavior of MOSFETs has to be carefully evaluated. An inversion level design methodology has been adopted to analyze data obtained from device measurements and provide a powerful tool to establish design criteria for detector front-ends in this nanoscale CMOS process. A comparison with data coming from less scaled technologies, such as 90 nm and 130 nm nodes, is also provided and can be used to evaluate the resolution limits achievable for low-noise charge sensitive amplifiers in the 100 nm minimum feature size range.

Patterning with metal-oxide EUV photoresist: patterning capability, resist smoothing, trimming, and selective stripping

NASA Astrophysics Data System (ADS)

Mao, Ming; Lazzarino, Frederic; De Schepper, Peter; De Simone, Danilo; Piumi, Daniele; Luong, Vinh; Yamashita, Fumiko; Kocsis, Michael; Kumar, Kaushik

2017-03-01

Inpria metal-oxide photoresist (PR) serves as a thin spin-on patternable hard mask for EUV lithography. Compared to traditional organic photoresists, the ultrathin metal-oxide photoresist ( 12nm after development) effectively mitigates pattern collapse. Because of the high etch resistance of the metal-oxide resist, this may open up significant scope for more aggressive etches, new chemistries, and novel integration schemes. We have previously shown that metal-oxide PR can be successfully used to pattern the block layer for the imec 7-nm technology node[1] and advantageously replace a multiple patterning approach, which significantly reduces the process complexity and effectively decreases the cost. We also demonstrated the formation of 16nm half pitch 1:1 line/space with EUV single print[2], which corresponds to a metal 2 layer for the imec 7-nm technology node. In this paper, we investigate the feasibility of using Inpria's metal-oxide PR for 16nm line/space patterning. In meanwhile, we also explore the different etch process for LWR smoothing, resist trimming and resist stripping.

Simulation study of reticle enhancement technology applications for 157-nm lithography

NASA Astrophysics Data System (ADS)

Schurz, Dan L.; Flack, Warren W.; Karklin, Linard

2002-03-01

The acceleration of the International Technology Roadmap for Semiconductors (ITRS) is placing significant pressure on the industry's infrastructure, particularly the lithography equipment. As recently as 1997, there was no optical solution offered past the 130 nm design node. The current roadmap has the 65 nm node (reduced from 70 nm) pulled in one year to 2007. Both 248 nm and 193 nm wavelength lithography tools will be pushed to their practical resolution limits in the near term. Very high numerical aperture (NA) 193 nm exposure tools in conjunction with resolution enhancement techniques (RET) will postpone the requirement for 157 nm lithography in manufacturing. However, ICs produced at 70 nm design rules with manufacturable k 1 values will require that 157 nm wavelength lithography tools incorporate the same RETs utilized in 248nm, and 193 nm tools. These enhancements will include Alternating Phase Shifting Masks (AltPSM) and Optical Proximity Correction (OPC) on F 2 doped quartz reticle substrates. This study investigates simulation results when AltPSM is applied to sub-100 nm test patterns in 157 nm lithography in order to maintain Critical Dimension (CD) control for both nested and isolated geometries. Aerial image simulations are performed for a range of numerical apertures, chrome regulators, gate pitches and gate widths. The relative performance for phase shifted versus binary structures is also compared. Results are demonstrated in terms of aerial image contrast and process window changes. The results clearly show that a combination of high NA and RET is necessary to achieve usable process windows for 70 nm line/space structures. In addition, it is important to consider two-dimensional proximity effects for sub-100 nm gate structures.

A novel multi-scale adaptive sampling-based approach for energy saving in leak detection for WSN-based water pipelines

NASA Astrophysics Data System (ADS)

Saqib, Najam us; Faizan Mysorewala, Muhammad; Cheded, Lahouari

2017-12-01

In this paper, we propose a novel monitoring strategy for a wireless sensor networks (WSNs)-based water pipeline network. Our strategy uses a multi-pronged approach to reduce energy consumption based on the use of two types of vibration sensors and pressure sensors, all having different energy levels, and a hierarchical adaptive sampling mechanism to determine the sampling frequency. The sampling rate of the sensors is adjusted according to the bandwidth of the vibration signal being monitored by using a wavelet-based adaptive thresholding scheme that calculates the new sampling frequency for the following cycle. In this multimodal sensing scheme, the duty-cycling approach is used for all sensors to reduce the sampling instances, such that the high-energy, high-precision (HE-HP) vibration sensors have low duty cycles, and the low-energy, low-precision (LE-LP) vibration sensors have high duty cycles. The low duty-cycling (HE-HP) vibration sensor adjusts the sampling frequency of the high duty-cycling (LE-LP) vibration sensor. The simulated test bed considered here consists of a water pipeline network which uses pressure and vibration sensors, with the latter having different energy consumptions and precision levels, at various locations in the network. This is all the more useful for energy conservation for extended monitoring. It is shown that by using the novel features of our proposed scheme, a significant reduction in energy consumption is achieved and the leak is effectively detected by the sensor node that is closest to it. Finally, both the total energy consumed by monitoring as well as the time to detect the leak by a WSN node are computed, and show the superiority of our proposed hierarchical adaptive sampling algorithm over a non-adaptive sampling approach.

Structure, texture, and mechanical properties of an MA2-1hp magnesium alloy after two-stage equal-channel angular pressing and intermediate annealing

NASA Astrophysics Data System (ADS)

Serebryany, V. N.; Perezhogin, V. Yu.; Raab, G. I.; Kopylov, V. I.; Tabachkova, N. Yu.; Sirotinkin, V. P.; Dobatkin, S. V.

2015-01-01

The effect of two-stage equal-channel angular pressing (ECAP) on the microstructure, the texture, and the mechanical properties of an MA2-1hp magnesium alloy is analyzed. ECAP leads to the formation of a submicrocrystalline structure with an average grain size of 640 nm, which includes Mg17Al12 phase particles with an average grain size of 240 nm and a volume fracture of 5.5%. A scattered tilted basal texture forms after ECAP, and its experimental pole figures are used for calculating orientation distribution functions and determining the volume fractions of the main orientations and the Schmid factors for different deformation systems. An increased activation of basal slip is found after both the first and the second stages of ECAP. As a result of two-stage ECAP, the strength properties of the alloy that correspond to the minimum acceptable values achieved by direct compression are obtained. Ductility is 44 and 18% after the first stage of ECAP plus subsequent annealing and after the second stage, respectively, which is almost four and two times higher than the initial value. The resulting strength mechanical properties of the alloy after the first and the second ECAP stages are analyzed using the Hall-Petch relation.

Fluorescence-based methods for the detection of pressure-induced spore germination and inactivation

NASA Astrophysics Data System (ADS)

Baier, Daniel; Reineke, Kai; Doehner, Isabel; Mathys, Alexander; Knorr, Dietrich

2011-03-01

The application of high pressure (HP) provides an opportunity for the non-thermal preservation of high-quality foods, whereas highly resistant bacterial endospores play an important role. It is known that the germination of spores can be initiated by the application of HP. Moreover, the resistance properties of spores are highly dependent on their physiological states, which are passed through during the germination. To distinguish between different physiological states and to detect the amount of germinated spores after HP treatments, two fluorescence-based methods were applied. A flow cytometric method using a double staining with SYTO 16 as an indicator for germination and propidium iodide as an indicator for membrane damage was used to detect different physiological states of the spores. During the first step of germination, the spore-specific dipicolinic acid (DPA) is released [P. Setlow, Spore germination, Curr. Opin. Microbiol. 6 (2003), pp. 550-556]. DPA reacts with added terbium to form a distinctive fluorescent complex. After measuring the fluorescence intensity at 270 nm excitation wavelength in a fluorescence spectrophotometer, the amount of germinated spores can be determined. Spores of Bacillus subtilis were treated at pressures from 150 to 600 MPa and temperatures from 37 °C to 60 °C in 0.05 M ACES buffer solution (pH 7) for dwell times of up to 2 h. During the HP treatments, inactivation up to 2log 10 cycles and thermal sensitive populations up to 4log 10 cycles could be detected by plate counts. With an increasing number of thermal sensitive spores, an increased proportion of spores in germinated states was detected by flow cytometry. Also the released amount of DPA increased during the dwell times. Moreover, a clear pressure-temperature-time-dependency was shown by screening different conditions. The fluorescence-based measurement of the released DPA can provide the opportunity of an online monitoring of the germination of spores under HP inside the HP vessel. Implementation can be done using diamond anvil cells, units with inspection glasses or by inserting an optical fiber into the HP vessel. The analytical methods used can help to understand the complex mechanism of germination and inactivation of bacterial spores. Due to its universal, process-independent character, the application of these methods is feasible for established and emerging technologies.

Way for LEEPL technology to succeed in memory device application

NASA Astrophysics Data System (ADS)

Kim, In-Sung; Woo, Sang-Gyun; Cho, Han-Ku; Han, Woo-Sung; Moon, Joo-Tae

2004-05-01

Lithography for 65nm-node device is drawing a lot of attentions these days especially because lithography solution for this node is not clear and even tool makers tend to wait for the consensus in lithography roadmap to avoid the risk of erroneous amount of investment. Recently proposed concept of low energy electron-beam proximity-projection lithography (LEEPL)1,2 technology has already released its first production machine in 2003, which is being expected to cover the design rule down to 65nm-node and even smaller3. Although production of semiconductor device has been pursuing optical lithography, without any optical technology that is proved as a convincing solution for 65nm node and below, we need to take account of all the candidates. So we made an investigation on LEEPL technology and evaluated beta and first production tool to see the feasibility of printing sub-70nm resolution and of optic-first mix-and-match overlay from a chip maker"s point of view. Two different kinds of stencil masks were fabricated for the evaluation, which are fabricated in SiC and Si membrane. The former mask is for sparse contact holes(C/H) and the latter for dense C/Hs. Beta-tool showed a good resolving power of sub-70nm sparse C/Hs of SRAM with negligibly small proximity effect. It implies that LEEPL does not require much effort for proximity correction comparing to that required in optical lithography, which is one of the biggest issues in low-k1. LEEPL also showed a good capability of optic-first mix-and-match overlay correction and this is the most stringent and important functionality for optic-first mix-and-match application. However random intra-membrane image placement(IP) error that is a little bit larger than the requirement for sub-70nm node was observed, which is interpreted to come from the larger stress of 100MPa in 3X3mm2 dry-etched SiC unit membrane. For dense C/Hs, we failed, to the contrary, to obtain any good quality of stencil masks for DRAM cell patterns because of e-beam proximity effect which is unavoidable in the reversed order of front-side forward direct writing and back-side later membrane formation. Pros and cons of LEEPL technology are discussed based on the evaluation results and estimation from the memory device standpoint. We also propose a novel concept of stencil mask that can be helpful in memory device application.

Exploring EUV and SAQP pattering schemes at 5nm technology node

NASA Astrophysics Data System (ADS)

Hamed Fatehy, Ahmed; Kotb, Rehab; Lafferty, Neal; Jiang, Fan; Word, James

2018-03-01

For years, Moore's law keeps driving the semiconductors industry towards smaller dimensions and higher density chips with more devices. Earlier, the correlation between exposure source's wave length and the smallest resolvable dimension, mandated the usage of Deep Ultra-Violent (DUV) optical lithography system which has been used for decades to sustain Moore's law, especially when immersion lithography was introduced with 193nm ArF laser sources. As dimensions of devices get smaller beyond Deep Ultra-Violent (DUV) optical resolution limits, the need for Extremely Ultra-Violent (EUV) optical lithography systems was a must. However, EUV systems were still under development at that time for the mass-production in semiconductors industry. Theretofore, Multi-Patterning (MP) technologies was introduced to swirl about DUV optical lithography limitations in advanced nodes beyond minimum dimension (CD) of 20nm. MP can be classified into two main categories; the first one is to split the target itself across multiple masks that give the original target patterns when they are printed. This category includes Double, Triple and Quadruple patterning (DP, TP, and QP). The second category is the Self-Aligned Patterning (SAP) where the target is divided into Mandrel patterns and non-Mandrel patterns. The Mandrel patterns get printed first, then a self-aligned sidewalls are grown around these printed patterns drawing the other non-Mandrel targets, afterword, a cut mask(s) is used to define target's line-ends. This approach contains Self-Aligned-Double Pattering (SADP) and Self-Aligned- Quadruple-Pattering (SAQP). DUV and MP along together paved the way for the industry down to 7nm. However, with the start of development at the 5nm node and the readiness of EUV, the differentiation question is aroused again, which pattering approach should be selected, direct printing using EUV or DUV with MP, or a hybrid flow that contains both DUV-MP and EUV. In this work we are comparing two potential pattering techniques for Back End Of Line (BEOL) metal layers in the 5nm technology node, the first technique is Single Exposure EUV (SE-EUV) with a Direct Patterning EUV lithography process, and the second one is Self-Aligned Quadruple Patterning (SAQP) with a hybrid lithography processes, where the drawn metal target layer is decomposed into a Mandrel mask and Blocks/Cut mask, Mandrel mask is printed using DUV 193i lithography process, while Block/Cut Mask is printed using SE-EUV lithography process. The pros and cons of each technique are quantified based on Edge-Placement-Error (EPE) and Process Variation Band (PVBand) measured at 1D and 2D edges. The layout used in this comparison is a candidate layout for Foundries 5nm process node.

DUV mask writer for BEOL 90-nm technology layers

NASA Astrophysics Data System (ADS)

Hong, Dongsung; Krishnan, Prakash; Coburn, Dianna; Jeewakhan, Nazneen; Xie, Shengqi; Broussard, Joshua; Ferguson, Bradley; Green, Kent G.; Buck, Peter; Jackson, Curt A.; Martinez, Larry

2003-12-01

Mask CD resolution and uniformity requirements for back end of line (BEOL) layers for the 90nm Technology Node push the capability of I-line mask writers; yet, do not require the capability offered by more expensive 50KeV ebeam mask writers. This suite of mask layers seems to be a perfect match for the capabilities of the DUV mask writing tools, which offer a lower cost option to the 50KeV platforms. This paper will evaluate both the mask and wafer results from all three platforms of mask writers (50KeV VSB,ETEC Alta 4300TM DUV laser and ETEC Alta 3500TM I-line laser) for a Cypress 90nm node Metal 1 layer, and demonstrate the benefits of the DUV platform with no change to OPC for this layer.

Scanner focus metrology and control system for advanced 10nm logic node

NASA Astrophysics Data System (ADS)

Oh, Junghun; Maeng, Kwang-Seok; Shin, Jae-Hyung; Choi, Won-Woong; Won, Sung-Keun; Grouwstra, Cedric; El Kodadi, Mohamed; Heil, Stephan; van der Meijden, Vidar; Hong, Jong Kyun; Kim, Sang-Jin; Kwon, Oh-Sung

2018-03-01

Immersion lithography is being extended beyond the 10-nm node and the lithography performance requirement needs to be tightened further to ensure good yield. Amongst others, good on-product focus control with accurate and dense metrology measurements is essential to enable this. In this paper, we will present new solutions that enable onproduct focus monitoring and control (mean and uniformity) suitable for high volume manufacturing environment. We will introduce the concept of pure focus and its role in focus control through the imaging optimizer scanner correction interface. The results will show that the focus uniformity can be improved by up to 25%.

Comparison of the effects of weight loss from a high-protein versus standard-protein energy-restricted diet on strength and aerobic capacity in overweight and obese men.

PubMed

Wycherley, Thomas P; Buckley, Jonathan D; Noakes, Manny; Clifton, Peter M; Brinkworth, Grant D

2013-02-01

To compare the effects of two low-fat, hypoenergetic diets differing in carbohydrate-to-protein ratio, on strength and aerobic capacity measures in overweight and obese men. In a parallel design, 56 men (age, 45.5 ± 8.7 years; BMI, 33.6 ± 3.9 kg/m(2)) were randomly assigned to a low-fat, energy-restricted diet (7,000 kJ/day) with either high protein (HP: protein/carbohydrate/fat % energy, 35:40:25) or standard protein (SP, 17:58:25). Body weight, body composition, muscle strength and aerobic capacity were assessed at baseline and after 12 weeks. Forty-two participants completed the study (HP, n = 21; SP, n = 21). Both groups experienced similar reductions in body weight (HP, -10.7 ± 5.3 kg [-9.8%]; SP, -8.7 ± 3.5 kg [-8.4%]) and fat-free mass (HP, -2.8 ± 3.6 kg; SP, -3.2 ± 2.7 kg; P < 0.001 time; P > 0.14 time × group interaction). There was a trend for a greater reduction in fat mass in the HP diet group, (-7.7 ± 4.3 kg [-21.2%] vs. -5.4 ± 3.3 kg [-15.1%]; P < 0.001 time; P = 0.06 time × group interaction). Absolute peak oxygen uptake did not change in either group (P = 0.39 time; P = 0.50 time × group interaction). Overall, in both groups, relative peak oxygen uptake increased (2.9 ± 2.8 ml kg(-1) min(-1) [8.9%]), peak isometric knee extensor strength increased (14.1 ± 35.7 Nm [7.1%]) and peak handgrip strength decreased (-1.6 ± 4.1 kg [-3%]) (P ≤ 0.02 time for all), with no diet effect (P ≤ 0.23 time × group interaction). In overweight and obese men, both a HP and SP diet reduced body weight and improved body composition with similar effects on strength and aerobic capacity.

Enhanced bioavailability of orally administered flurbiprofen by combined use of hydroxypropyl-cyclodextrin and poly(alkyl-cyanoacrylate) nanoparticles.

PubMed

Zhao, Xiaoyun; Li, Wei; Luo, Qiuhua; Zhang, Xiangrong

2014-03-01

Flurbiprofen was formulated into nanoparticle suspension to improve its oral bioavailability. Hydroxypropyl-β-cyclodextrin inclusion-flurbiprofen complex (HP-β-CD-FP) was prepared, then incorporating this complex into poly(alkyl-cyanoacrylate) (PACA) nanoparticles. HP-β-CD-FP-PACA nanoparticle was prepared by the emulsion solvent polymerization method. The zeta potential was -26.8 mV, the mean volume particle diameter was 134 nm, drug encapsulation efficiency was 53.3 ± 3.6 % and concentration was 1.5 mg/mL. The bioavailability of flurbiprofen from optimized nanoparticles was assessed in male Wistar rats at a dose of 15 mg/kg. As compared to the flurbiprofen suspension, 211.6 % relative bioavailability was observed for flurbiprofen nanoparticles. The reduced particle size and increased surface area may contribute to improve oral bioavailability of flurbiprofen.

Dual Interlocked Logic for Single-Event Transient Mitigation

DTIC Science & Technology

2017-03-01

SPICE simulation and fault-injection analysis. Exemplar SPICE simulations have been performed in a 32nm partially- depleted silicon-on-insulator...in this work. The model has been validated at the 32nm SOI technology node with extensive heavy-ion data [7]. For the SPICE simulations, three

Expression and significance of CD44s, CD44v6, and nm23 mRNA in human cancer.

PubMed

Liu, Yong-Jun; Yan, Pei-Song; Li, Jun; Jia, Jing-Fen

2005-11-14

To investigate the relationship between the expression levels of nm23 mRNA, CD44s, and CD44v6, and oncogenesis, development and metastasis of human gastric adenocarcinoma, colorectal adenocarcinoma, intraductal carcinoma of breast, and lung cancer. Using tissue microarray by immuhistochemical (IHC) staining and in situ hybridization (ISH), we examined the expression levels of nm23 mRNA, CD44s, and CD44v6 in 62 specimens of human gastric adenocarcinoma and 62 specimens of colorectal adenocarcinoma; the expression of CD44s and CD44v6 in 120 specimens of intraductal carcinoma of breast and 20 specimens of normal breast tissue; the expression of nm23 mRNA in 72 specimens of human lung cancer and 23 specimens of normal tissue adjacent to cancer. The expression of nm23 mRNA in the tissues of gastric and colorectal adenocarcinoma was not significantly different from that in the normal tissues adjacent to cancer (P>0.05), and was not associated with the invasion of tumor and the pathology grade of adenocarcinoma (P>0.05). However, the expression of nm23 mRNA was correlated negatively to the lymph node metastasis of gastric and colorectal adenocarcinoma (r = -0.49, P<0.01; r = -4.93, P<0.01). The expression of CD44s in the tissues of gastric and colorectal adenocarcinoma was significantly different from that in the normal tissues adjacent to cancer (P<0.05; P<0.01). CD44v6 was expressed in the tissues of gastric and colorectal adenocarcinoma only, the expression of CD44v6 was significantly associated with the lymph node metastasis, invasion and pathological grade of the tumor (r = 0.47, P<0.01; r = 5.04, P<0.01). CD44s and CD44v6 were expressed in intraductal carcinoma of breast, the expression of CD44s and CD44v6 was significantly associated with lymph node metastases and invasion (P<0.01). However, neither of them was expressed in the normal breast tissue. In addition, the expression of CD44v6 was closely related to the degree of cell differentiation of intraductal carcinoma of breast (c2 = 5.68, P<0.05). The expressional level of nm23 mRNA was closely related to the degree of cell differentiation (P<0.05) and lymph node metastasis (P<0.01), but the expression of nm23 gene was not related to sex, age, and type of histological classification (P>0.05). Patients with overexpression of CD44s and CD44v6 and low expression of nm23 mRNA have a higher lymph node metastatic rate and invasion. In addition, overexpression of CD44v6 is closely related to the degree of cell differentiation. Detection of the three genes is able to provide a reliable index to evaluate the invasion and metastasis of tumor cells.

Toward the 5nm technology: layout optimization and performance benchmark for logic/SRAMs using lateral and vertical GAA FETs

NASA Astrophysics Data System (ADS)

Huynh-Bao, Trong; Ryckaert, Julien; Sakhare, Sushil; Mercha, Abdelkarim; Verkest, Diederik; Thean, Aaron; Wambacq, Piet

2016-03-01

In this paper, we present a layout and performance analysis of logic and SRAM circuits for vertical and lateral GAA FETs using 5nm (iN5) design rules. Extreme ultra-violet lithography (EUVL) processes are exploited to print the critical features: 32 nm gate pitch and 24 nm metal pitch. Layout architectures and patterning compromises for enabling the 5nm node will be discussed in details. A distinct standard-cell template for vertical FETs is proposed and elaborated for the first time. To assess electrical performances, a BSIM-CMG model has been developed and calibrated with TCAD simulations, which accounts for the quasi-ballistic transport in the nanowire channel. The results show that the inbound power rail layout construct for vertical devices could achieve the highest density while the interleaving diffusion template can maximize the port accessibility. By using a representative critical path circuit of a generic low power SoCs, it is shown that the VFET-based circuit is 40% more energy efficient than LFET designs at iso-performance. Regarding SRAMs, benefits given by vertical channel orientation in VFETs has reduced the SRAM area by 20%~30% compared to lateral SRAMs. A double exposures with EUV canner is needed to reach a minimum tip-to-tip (T2T) of 16 nm for middle-of-line (MOL) layers. To enable HD SRAMs with two metal layers, a fully self-aligned gate contact for LFETs and 2D routing of the top electrode for VFETs are required. The standby leakage of vertical SRAMs is 4~6X lower than LFET-based SRAMs at iso-performance and iso-area. The minimum operating voltage (Vmin) of vertical SRAMs is 170 mV lower than lateral SRAMs. A high-density SRAM bitcell of 0.014 um2 can be obtained for the iN5 technology node, which fully follows the SRAM scaling trend for the 45nm nodes and beyond.

Self-aligned blocking integration demonstration for critical sub-30nm pitch Mx level patterning with EUV self-aligned double patterning

NASA Astrophysics Data System (ADS)

Raley, Angélique; Lee, Joe; Smith, Jeffrey T.; Sun, Xinghua; Farrell, Richard A.; Shearer, Jeffrey; Xu, Yongan; Ko, Akiteru; Metz, Andrew W.; Biolsi, Peter; Devilliers, Anton; Arnold, John; Felix, Nelson

2018-04-01

We report a sub-30nm pitch self-aligned double patterning (SADP) integration scheme with EUV lithography coupled with self-aligned block technology (SAB) targeting the back end of line (BEOL) metal line patterning applications for logic nodes beyond 5nm. The integration demonstration is a validation of the scalability of a previously reported flow, which used 193nm immersion SADP targeting a 40nm pitch with the same material sets (Si3N4 mandrel, SiO2 spacer, Spin on carbon, spin on glass). The multi-color integration approach is successfully demonstrated and provides a valuable method to address overlay concerns and more generally edge placement error (EPE) as a whole for advanced process nodes. Unbiased LER/LWR analysis comparison between EUV SADP and 193nm immersion SADP shows that both integrations follow the same trend throughout the process steps. While EUV SADP shows increased LER after mandrel pull, metal hardmask open and dielectric etch compared to 193nm immersion SADP, the final process performance is matched in terms of LWR (1.08nm 3 sigma unbiased) and is only 6% higher than 193nm immersion SADP for average unbiased LER. Using EUV SADP enables almost doubling the line density while keeping most of the remaining processes and films unchanged, and provides a compelling alternative to other multipatterning integrations, which present their own sets of challenges.

Sentinel lymph node detection in gynecologic malignancies by a handheld fluorescence camera

NASA Astrophysics Data System (ADS)

Hirsch, Ole; Szyc, Lukasz; Muallem, Mustafa Zelal; Ignat, Iulia; Chekerov, Radoslav; Macdonald, Rainer; Sehouli, Jalid; Braicu, Ioana; Grosenick, Dirk

2017-02-01

Near-infrared fluorescence imaging using indocyanine green (ICG) as a tracer is a promising technique for mapping the lymphatic system and for detecting sentinel lymph nodes (SLN) during cancer surgery. In our feasibility study we have investigated the application of a custom-made handheld fluorescence camera system for the detection of lymph nodes in gynecological malignancies. It comprises a low cost CCD camera with enhanced NIR sensitivity and two groups of LEDs emitting at wavelengths of 735 nm and 830 nm for interlaced recording of fluorescence and reflectance images of the tissue, respectively. With the help of our system, surgeons can observe fluorescent tissue structures overlaid onto the anatomical image on a monitor in real-time. We applied the camera system for intraoperative lymphatic mapping in 5 patients with vulvar cancer, 5 patients with ovarian cancer, 3 patients with cervical cancer, and 3 patients with endometrial cancer. ICG was injected at four loci around the primary malignant tumor during surgery. After a residence time of typically 15 min fluorescence images were taken in order to visualize the lymph nodes closest to the carcinomas. In cases with vulvar cancer about half of the lymph nodes detected by routinely performed radioactive SLN mapping have shown fluorescence in vivo as well. In the other types of carcinomas several lymph nodes could be detected by fluorescence during laparotomy. We conclude that our low cost camera system has sufficient sensitivity for lymphatic mapping during surgery.

SL2+: H5 use case

NASA Astrophysics Data System (ADS)

Ito, Kosuke; Liu, Steven; Lee, Isaac; Dover, Russell; Yu, Paul

2008-10-01

Photomask contamination inspections, whether performed at maskshops as an outgoing inspection or at wafer fabs for incoming shipping and handling or progressive defect monitoring, have been performed by KLA-Tencor STARlight systems for a number of design nodes. STARlight has evolved since it first appeared on the 3xx generation of KLA-Tencor mask inspection tools. It was improved with the TeraStar (also known as SLF) based tools with the SL1 algorithm. SL2 first appeared on the TeraScan systems (also known as 5xx) and has been widely adopted in both mask shops and wafer fabs. Design rules continue to advance as do inspection challenges. Advances in computer processing power have enabled more complex and powerful algorithms to be developed and applied to the STARlight technology. The current generation of STARlight, which is known as SL2+, implements improved modeling fidelity as well as a completely new paradigm to the existing STARlight technology known as HiRes5, or simply "H5". H5 is integrated seamlessly within SL2+ and provides die-to-die-like performance in both transmitted and reflected light, in addition to the STARlight detection, in unit time. It achieves this by automatically identifying repeating structures in both X and Y directions and applying image alignment and difference threshold. A leading mask shop partnered with KLA-Tencor in order to evaluate SL2+ at its facility. SL2+ demonstrated a high level of sensitivity on all test reticles, with good inspectability on advanced production reticles. High sensitivity settings were used for 45 nm HP and smaller design rule masks and low false detections were achieved. H5 provided additional sensitivity on production plates, demonstrating the ability to extend the use of SL2+ to cover 32 nm DR plate inspections. This paper reports the findings and results of this evaluation.

Manufacturability of the X Architecture at the 90-nm technology node

NASA Astrophysics Data System (ADS)

Smayling, Michael C.; Sarma, Robin C.; Nagata, Toshiyuki; Arora, Narain; Duane, Michael P.; Oemardani, Shiany; Shah, Santosh

2004-05-01

In this paper, we discuss the results from a test chip that demonstrate the manufacturability and integration-worthiness of the X Architecture at the 90-nm technology node. We discuss how a collaborative effort between the design and chip making communities used the current generation of mask, lithography, wafer processing, inspection and metrology equipment to create 45 degree wires in typical metal pitches for the upper layers on a 90-nm device in a production environment. Cadence Design Systems created the test structure design and chip validation tools for the project. Canon"s KrF ES3 and ArF AS2 scanners were used for the lithography. Applied Materials used its interconnect fabrication technologies to produce the multilayer copper, low-k interconnect on 300-mm wafers. The results were confirmed for critical dimension and defect levels using Applied Materials" wafer inspection and metrology systems.

Advanced process and defect characterization methodology to support process development of advanced patterning structures

NASA Astrophysics Data System (ADS)

Ketkar, Supriya; Lee, Junhan; Asokamani, Sen; Cho, Winston; Mishra, Shailendra

2018-03-01

This paper discusses the approach and solution adopted by GLOBALFOUNDRIES, a high volume manufacturing (HVM) foundry, for dry-etch related edge-signature surface particle defects issue facing the sub-nm node in the gate-etch sector. It is one of the highest die killers for the company in the 14-nm node. We have used different approaches to attack and rectify the edge signature surface particle defect. Several process-related & hardware changes have been successively implemented to achieve defect reduction improvement by 63%. Each systematic process and/or hardware approach has its own unique downstream issues and they have been dealt in a route-cause-effect technique to address the issue.

Evaluating diffraction based overlay metrology for double patterning technologies

NASA Astrophysics Data System (ADS)

Saravanan, Chandra Saru; Liu, Yongdong; Dasari, Prasad; Kritsun, Oleg; Volkman, Catherine; Acheta, Alden; La Fontaine, Bruno

2008-03-01

Demanding sub-45 nm node lithographic methodologies such as double patterning (DPT) pose significant challenges for overlay metrology. In this paper, we investigate scatterometry methods as an alternative approach to meet these stringent new metrology requirements. We used a spectroscopic diffraction-based overlay (DBO) measurement technique in which registration errors are extracted from specially designed diffraction targets for double patterning. The results of overlay measurements are compared to traditional bar-in-bar targets. A comparison between DBO measurements and CD-SEM measurements is done to show the correlation between the two approaches. We discuss the total measurement uncertainty (TMU) requirements for sub-45 nm nodes and compare TMU from the different overlay approaches.

Nanosatellite optical downlink experiment: design, simulation, and prototyping

NASA Astrophysics Data System (ADS)

Clements, Emily; Aniceto, Raichelle; Barnes, Derek; Caplan, David; Clark, James; Portillo, Iñigo del; Haughwout, Christian; Khatsenko, Maxim; Kingsbury, Ryan; Lee, Myron; Morgan, Rachel; Twichell, Jonathan; Riesing, Kathleen; Yoon, Hyosang; Ziegler, Caleb; Cahoy, Kerri

2016-11-01

The nanosatellite optical downlink experiment (NODE) implements a free-space optical communications (lasercom) capability on a CubeSat platform that can support low earth orbit (LEO) to ground downlink rates>10 Mbps. A primary goal of NODE is to leverage commercially available technologies to provide a scalable and cost-effective alternative to radio-frequency-based communications. The NODE transmitter uses a 200-mW 1550-nm master-oscillator power-amplifier design using power-efficient M-ary pulse position modulation. To facilitate pointing the 0.12-deg downlink beam, NODE augments spacecraft body pointing with a microelectromechanical fast steering mirror (FSM) and uses an 850-nm uplink beacon to an onboard CCD camera. The 30-cm aperture ground telescope uses an infrared camera and FSM for tracking to an avalanche photodiode detector-based receiver. Here, we describe our approach to transition prototype transmitter and receiver designs to a full end-to-end CubeSat-scale system. This includes link budget refinement, drive electronics miniaturization, packaging reduction, improvements to pointing and attitude estimation, implementation of modulation, coding, and interleaving, and ground station receiver design. We capture trades and technology development needs and outline plans for integrated system ground testing.

An improved method for characterizing photoresist lithographic and defectivity performance for sub-20nm node lithography

NASA Astrophysics Data System (ADS)

Amblard, Gilles; Purdy, Sara; Cooper, Ryan; Hockaday, Marjory

2016-03-01

The overall quality and processing capability of lithographic materials are critical for ensuring high device yield and performance at sub-20nm technology nodes in a high volume manufacturing environment. Insufficient process margin and high line width roughness (LWR) cause poor manufacturing control, while high defectivity causes product failures. In this paper, we focus on the most critical layer of a sub-20nm technology node LSI device, and present an improved method for characterizing both lithographic and post-patterning defectivity performance of state-of-the-art immersion photoresists. Multiple formulations from different suppliers were used and compared. Photoresists were tested under various process conditions, and multiple lithographic metrics were investigated (depth of focus, exposure dose latitude, line width roughness, etc.). Results were analyzed and combined using an innovative approach based on advanced software, providing clearer results than previously available. This increased detail enables more accurate performance comparisons among the different photoresists. Post-patterning defectivity was also quantified, with defects reviewed and classified using state-of-the-art inspection tools. Correlations were established between the lithographic and post-patterning defectivity performances for each material, and overall ranking was established among the photoresists, enabling the selection of the best performer for implementation in a high volume manufacturing environment.

Material design of negative-tone polyphenol resist for EUV and EB lithography

NASA Astrophysics Data System (ADS)

Kojima, Kyoko; Mori, Shigeki; Shiono, Daiju; Hada, Hideo; Onodera, Junichi

2007-03-01

In order to enable design of a negative-tone polyphenol resist using polarity-change reaction, five resist compounds (3M6C-MBSA-BLs) with different number of functional group of γ-hydroxycarboxyl acid were prepared and evaluated by EB lithography. The resist using mono-protected compound (3M6C-MBSA-BL1a) showed 40-nm hp resolution at an improved dose of 52 μC/cm2 probably due to removal of a non-protected polyphenol while the sensitivity of the resist using a compound of protected ratio of 1.1 on average with distribution of different protected ratio was 72 μC/cm2. For evaluation of the di-protected compound based resist, a di-protected polyphenol was synthesized by a newly developed synthetic route of 3-steps reaction, which is well-suited for mass production. The resist using di-protected compound (3M6C-MBSA-BL2b) also showed 40-nm hp resolution at a dose of 40 μC/cm2, which was faster than that of mono-protected resist. Fundamental EUV lithographic evaluation of the resist using 3M6C-MBSA-BL2b by an EUV open frame exposure tool (EUVES-7000) gave its estimated optimum sensitivity of 7 mJ/cm2 and a proof of fine development behavior without any swelling.

Preparation and evaluation of cilnidipine microemulsion

PubMed Central

Tandel, Hemal; Raval, Krunal; Nayani, Anil; Upadhay, Manish

2012-01-01

Cilnidipine, a calcium channel blocker having neuroprotective action and BCS Class II drug, hence formulating in Microemulsion will increase solubility, absorption and bioavailability. The formulation was prepared using titration method by tocotrienol, tween 20 and transcutol HP as oil, surfactant and co-surfactant and characterized for dilutability, dye solubility, assay (98.39±0.06), pH (6.6±1.5), Viscosity (98±1.0 cps) and Conductivity (0.2±0.09 μS/cm). The formulation was optimized on basis of percentage transmittance (99.269±0.23 at 700 nm), Globule size (13.31±4.3 nm) and zeta potential (–11.4±2.3 mV). Cilnidipine microemulsion was found to be stable for 3 months. PMID:23066184

Fluorescence properties and conformational stability of the beta-hemocyanin of Helix pomatia.

PubMed

Idakieva, Krassimira; Siddiqui, Nurul I; Parvanova, Katja; Nikolov, Peter; Gielens, Constant

2006-04-01

The beta-hemocyanin (beta-HpH) is one of the three dioxygen-binding proteins found freely dissolved in the hemolymph of the gastropodan mollusc Helix pomatia. The didecameric molecule (molecular mass 9 MDa) is built up of only one type of subunits. The fluorescence properties of the oxygenated and apo-form (copper-deprived) of the didecamer and its subunits were characterized. Upon excitation of the hemocyanins at 295 or 280 nm, tryptophyl residues buried in the hydrophobic interior of the protein determine the fluorescence emission. This is confirmed by quenching experiments with acrylamide, cesium chloride and potassium iodide. The copper-dioxygen system at the binuclear active site quenches the tryptophan emission of the oxy-beta-HpH. The removal of this system increases the fluorescence quantum yield and causes structural rearrangement of the microenvironment of the emitting tryptophyl residues in the apo-form. Time-resolved fluorescence measurements show that the oxygenated and copper-deprived forms of the beta-HpH and its subunits exist in different conformations. The thermal stability of the oxy- and apo-beta-HpH is characterized by a transition temperature (Tm) of 84 degrees C and 63 degrees C, respectively, obtained by differential scanning calorimetry. Increase of the temperature influences the active site at lower temperatures than the environments of tryptophans and tyrosines causing a loss of oxygen bound to the copper atoms. This process is, at least partially, reversible as after cooling of the protein samples, around 60% reinstatement of the copper-peroxide band has been observed. The results confirm the role of the copper-dioxygen complex for the stabilization of the hemocyanin structure in solution. The other important stabilizing factor is oligomerization of the hemocyanin molecule.

RELATIONSHIP BETWEEN THE PRESENCE OF HELICOBACTER PYLORI WITH INFLAMMATORY ENDOSCOPIC CHANGES IN GASTRODUODENAL MUCOSA.

PubMed

Ribeiro, Irma Cláudia Saboya; Kubrusly, Luiz Fernandao; Nassif, Paulo Afonso Nunes; Ribeiro, Patrícia Fernanda Saboya; Veras, Rodrigo de Oliveira; Neppel, Aline

2016-01-01

The influence of Helicobacter pylori (HP) in inflammatory disorders of the digestive mucosa has been the subject of several studies since socioeconomic, personal and environmental factors were implicated in the bacteria transmission. To correlate the inflammatory endoscopic findings with HP infection and the onset of mucosal diseases mucous of the upper digestive tract. Comparative observational study, in which were collected data from 2247 patients who underwent upper endoscopy and biopsies for HP with urease test. The patients were divided into two groups: HP+ and HP- (control) in which endoscopic findings were observed for the following changes: esophagitis, esophageal ulcer, gastritis, erosive gastritis, gastric ulcer, bulboduodenitis, bulbar ulcer and without disease. As for esophagitis, there was little disparity in the distribution favorable to HP+ group (HP+ =67.11% and HP- =69.89%) and esophageal ulcer (HP+ =0% and HP- =0, 21%). Gastritis was favorable to HP- group (HP+ =78.34% and HP- =73.63%), as well as erosive gastritis (HP+ = 67,11% and HP- = 64,55%), in bulboduodenitis (HP+ =1,87% and HP- 1,23%), in gastric ulcer (HP+ =2,14% and HP- =2,03%) and in the absence of alterations in the HP+ group (4.81%) with the HP- control group (6,30%), in which there was little disproportion in favor of HP- group, but without statistical significance. As for the bulbar ulcer (HP +=10.16% and HP- =4.48%), there was statistically significant (p=0.00001). There is no difference between HP+ and HP- groups in inflammatory changes in endoscopic gastroduodenal mucosa, except for the relationship between HP and bulbar ulcer. A influência do Helicobacter pylori (HP) nas alterações inflamatórias das mucosas digestivas tem sido objeto de vários estudos uma vez que fatores socioeconômicos, pessoais e ambientais são implicados na transmissão da bactéria, facilitando-a. Relacionar os achados inflamatórios endoscópicos com a infecção pelo HP e o aparecimento de doenças mucosas do trato digestivo alto. Estudo observacional comparativo, o qual foram coletados dados de 2247 pacientes submetidos à endoscopia digestiva alta e biópsias para HP com teste de urease. Os pacientes foram divididos em dois grupos: HP+ e o controle HP-dentro dos quais foram observados os achados endoscópicos referentes às seguintes alterações: esofagite, úlcera esofágica, gastrite, gastrite erosiva, úlcera gástrica, bulboduodenite, úlcera bulbar e sem doença. Quanto à esofagite, observou-se pequena desproporção na distribuição, favorável ao grupo HP+ (HP+ =67,11% e HP- =69,89%) bem como na úlcera esofágica (HP+ =0% e HP- =0,21%). Na gastrite foi favorável ao grupo HP- (HP+ =78.34% e HP- =73.63%), assim como na gastrite erosiva (HP+ = 67,11% e HP- = 64,55%), na bulboduodenite (HP+ = 1,87% e HP- 1,23%), na úlcera gástrica (HP+ =2,14% e HP- =2,03%) e na ausência de alterações no grupo HP+ (4.81%) com o grupo controle HP- (6,30%), nos quais há pequena desproporção favorável ao grupo HP-, porém, sem significância estatística. Já quanto à úlcera bulbar (HP+ =10,16% e HP- =4,48%), houve significância estatística (p=0,00001). Não há diferenciação entre os grupos HP+ e HP- nas alterações endoscópicas inflamatórias na mucosa gastroduodenal, exceto para a relação entre HP e úlcera bulbar.

Exploration of BEOL line-space patterning options at 12 nm half-pitch and below

NASA Astrophysics Data System (ADS)

Decoster, S.; Lazzarino, F.; Petersen Barbosa Lima, L.; Li, W.; Versluijs, J.; Halder, S.; Mallik, A.; Murdoch, G.

2018-03-01

While the semiconductor industry is almost ready for high-volume manufacturing of the 7 nm technology node, research centers are defining and troubleshooting the patterning options for the 5 nm technology node (N5) and below. The target dimension for imec's N5 BEOL applications is 20-24 nm Metal Pitch (MP), which requires Self-Aligned multiple (Double/Quadruple/Octuple) Patterning approaches (SAxP) in combination with EUV or immersion lithography at 193 nm. There are numerous technical challenges to enable gratings at the hard mask level such as good uniformity across wafer, low line edge/width roughness (LER/LWR), large process window, and all of this at low cost. An even greater challenge is to transfer these gratings into the dielectric material at such critical dimensions, where increased line edge roughness, line wiggling and even pattern collapse can be expected for materials with small mechanical stability such as highly porous low-k dielectrics. In this work we first compare three different patterning options for 12 nm half-pitch gratings at the hard mask level: EUV-based SADP and 193i-based SAQP and SAOP. This comparison will be based on process window, line edge/width roughness and cost. Next, the transfer of 12 nm line/space gratings in the dielectric material is discussed and presented. The LER of the dielectric lines is investigated as a function of the dielectric material, the trench depth, and the stress in the sacrificial hard mask. Finally, we elaborate on the different options to enable scaling down from 24 nm MP to 16 nm MP, and demonstrate 8 nm line/space gratings with 193i-based SAOP.

High-speed logic integrated circuits with solution-processed self-assembled carbon nanotubes

NASA Astrophysics Data System (ADS)

Han, Shu-Jen; Tang, Jianshi; Kumar, Bharat; Falk, Abram; Farmer, Damon; Tulevski, George; Jenkins, Keith; Afzali, Ali; Oida, Satoshi; Ott, John; Hannon, James; Haensch, Wilfried

2017-09-01

As conventional monolithic silicon technology struggles to meet the requirements for the 7-nm technology node, there has been tremendous progress in demonstrating the scalability of carbon nanotube field-effect transistors down to the size that satisfies the 3-nm node and beyond. However, to date, circuits built with carbon nanotubes have overlooked key aspects of a practical logic technology and have stalled at simple functionality demonstrations. Here, we report high-performance complementary carbon nanotube ring oscillators using fully manufacturable processes, with a stage switching frequency of 2.82 GHz. The circuit was built on solution-processed, self-assembled carbon nanotube arrays with over 99.9% semiconducting purity, and the complementary feature was achieved by employing two different work function electrodes.

Application of resist-profile-aware source optimization in 28 nm full chip optical proximity correction

NASA Astrophysics Data System (ADS)

Zhu, Jun; Zhang, David Wei; Kuo, Chinte; Wang, Qing; Wei, Fang; Zhang, Chenming; Chen, Han; He, Daquan; Hsu, Stephen D.

2017-07-01

As technology node shrinks, aggressive design rules for contact and other back end of line (BEOL) layers continue to drive the need for more effective full chip patterning optimization. Resist top loss is one of the major challenges for 28 nm and below technology nodes, which can lead to post-etch hotspots that are difficult to predict and eventually degrade the process window significantly. To tackle this problem, we used an advanced programmable illuminator (FlexRay) and Tachyon SMO (Source Mask Optimization) platform to make resistaware source optimization possible, and it is proved to greatly improve the imaging contrast, enhance focus and exposure latitude, and minimize resist top loss thus improving the yield.

High-speed logic integrated circuits with solution-processed self-assembled carbon nanotubes.

PubMed

Han, Shu-Jen; Tang, Jianshi; Kumar, Bharat; Falk, Abram; Farmer, Damon; Tulevski, George; Jenkins, Keith; Afzali, Ali; Oida, Satoshi; Ott, John; Hannon, James; Haensch, Wilfried

2017-09-01

As conventional monolithic silicon technology struggles to meet the requirements for the 7-nm technology node, there has been tremendous progress in demonstrating the scalability of carbon nanotube field-effect transistors down to the size that satisfies the 3-nm node and beyond. However, to date, circuits built with carbon nanotubes have overlooked key aspects of a practical logic technology and have stalled at simple functionality demonstrations. Here, we report high-performance complementary carbon nanotube ring oscillators using fully manufacturable processes, with a stage switching frequency of 2.82 GHz. The circuit was built on solution-processed, self-assembled carbon nanotube arrays with over 99.9% semiconducting purity, and the complementary feature was achieved by employing two different work function electrodes.

Micropropagation and hairy root culture of Ophiorrhiza alata Craib for camptothecin production.

PubMed

Ya-ut, Pornwilai; Chareonsap, Piyarat; Sukrong, Suchada

2011-12-01

An efficient system was developed for the in vitro micropropagation and hairy root culture of Ophiorrhiza alata Craib for camptothecin (CPT) production. Shoot multiplication on leaf and node explants from germinated seeds of O. alata was successful on half-strength Murashige and Skoog medium supplemented with varying amounts of kinetin and α-naphthaleneacetic acid. Node explants grown in vitro were successfully infected by Agrobacterium rhizogenes TISTR 1450 for the establishment of hairy root culture. The amount of CPT in various parts of O. alata was analyzed by HPLC. The accumulation of CPT in transformed hairy roots was twice that in soil-grown plants (785 ± 52 and 388 ± 32 μg/g dry wt, respectively). In the presence of a polystyrene resin (Diaion HP-20) that absorbed CPT, the CPT content in the culture media increased sevenfold compared with controls (1,036 and 151 μg per 250 ml medium, respectively). These results enable the feasible production of CPT of O. alata by means of a cell culture strategy. These measures can help safeguard the plant from extinction. © Springer Science+Business Media B.V. 2011

A novel double patterning approach for 30nm dense holes

NASA Astrophysics Data System (ADS)

Hsu, Dennis Shu-Hao; Wang, Walter; Hsieh, Wei-Hsien; Huang, Chun-Yen; Wu, Wen-Bin; Shih, Chiang-Lin; Shih, Steven

2011-04-01

Double Patterning Technology (DPT) was commonly accepted as the major workhorse beyond water immersion lithography for sub-38nm half-pitch line patterning before the EUV production. For dense hole patterning, classical DPT employs self-aligned spacer deposition and uses the intersection of horizontal and vertical lines to define the desired hole patterns. However, the increase in manufacturing cost and process complexity is tremendous. Several innovative approaches have been proposed and experimented to address the manufacturing and technical challenges. A novel process of double patterned pillars combined image reverse will be proposed for the realization of low cost dense holes in 30nm node DRAM. The nature of pillar formation lithography provides much better optical contrast compared to the counterpart hole patterning with similar CD requirements. By the utilization of a reliable freezing process, double patterned pillars can be readily implemented. A novel image reverse process at the last stage defines the hole patterns with high fidelity. In this paper, several freezing processes for the construction of the double patterned pillars were tested and compared, and 30nm double patterning pillars were demonstrated successfully. A variety of different image reverse processes will be investigated and discussed for their pros and cons. An economic approach with the optimized lithography performance will be proposed for the application of 30nm DRAM node.

Research of ALA combined with HpD-PDT which induced s180 ascitic tumor cells, death or apoptosis on cytology

NASA Astrophysics Data System (ADS)

Zhu, Jing; Yan, Min; Zhang, Hui-Guo; Li, Enling; Luo, Hongyu

2005-07-01

To ascertain the adequate dosage of ALA combined with HpD-PDT which induced tumor cell death or apoptosis on cytology. And to study the different effect of ALA-PDT and HPD-PDT used only. Rat ascitic tumor cells(S180) were randomly divided into several groups and incubated with ALA（20μg/ml 、40μg/ml、80μg/ml 、160μg/ml）、HPD（2.5μg/ml、5μg/ml、10μg/ml）and their combination dosages. 630nm light (total output 2W) was delivered to tumor cells at a constant fluence rate: 200mw/cm2 and a constant irradiated time period: 20 minutes. We set 3 groups (no photosensitizers or no irradiation or neither) to be the control groups. We used inversion microscopy to observe the morphological change of tumor cells and flow cytometry technology to detect the death or apoptosis of tumor cells during the experiment. ..

In-die mask registration measurement on 28nm-node and beyond

NASA Astrophysics Data System (ADS)

Chen, Shen Hung; Cheng, Yung Feng; Chen, Ming Jui

2013-09-01

As semiconductor go to smaller node, the critical dimension (CD) of process become more and more small. For lithography, RET (Resolution Enhancement Technology) applications can be used for wafer printing of smaller CD/pitch on 28nm node and beyond. SMO (Source Mask Optimization), DPT (Double Patterning Technology) and SADP (Self-Align Double Patterning) can provide lower k1 value for lithography. In another way, image placement error and overlay control also become more and more important for smaller chip size (advanced node). Mask registration (image placement error) and mask overlay are important factors to affect wafer overlay control/performance especially for DPT or SADP. In traditional method, the designed registration marks (cross type, square type) with larger CD were put into scribe-line of mask frame for registration and overlay measurement. However, these patterns are far way from real patterns. It does not show the registration of real pattern directly and is not a convincing method. In this study, the in-die (in-chip) registration measurement is introduced. We extract the dummy patterns that are close to main pattern from post-OPC (Optical Proximity Correction) gds by our desired rule and choose the patterns that distribute over whole mask uniformly. The convergence test shows 100 points measurement has a reliable result.

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.

Looking into the crystal ball: future device learning using hybrid e-beam and optical lithography (Keynote Paper)

NASA Astrophysics Data System (ADS)

Steen, S. E.; McNab, S. J.; Sekaric, L.; Babich, I.; Patel, J.; Bucchignano, J.; Rooks, M.; Fried, D. M.; Topol, A. W.; Brancaccio, J. R.; Yu, R.; Hergenrother, J. M.; Doyle, J. P.; Nunes, R.; Viswanathan, R. G.; Purushothaman, S.; Rothwell, M. B.

2005-05-01

Semiconductor process development teams are faced with increasing process and integration complexity while the time between lithographic capability and volume production has remained more or less constant over the last decade. Lithography tools have often gated the volume checkpoint of a new device node on the ITRS roadmap. The processes have to be redeveloped after the tooling capability for the new groundrule is obtained since straight scaling is no longer sufficient. In certain cases the time window that the process development teams have is actually decreasing. In the extreme, some forecasts are showing that by the time the 45nm technology node is scheduled for volume production, the tooling vendors will just begin shipping the tools required for this technology node. To address this time pressure, IBM has implemented a hybrid-lithography strategy that marries the advantages of optical lithography (high throughput) with electron beam direct write lithography (high resolution and alignment capability). This hybrid-lithography scheme allows for the timely development of semiconductor processes for the 32nm node, and beyond. In this paper we will describe how hybrid lithography has enabled early process integration and device learning and how IBM applied e-beam & optical hybrid lithography to create the world's smallest working SRAM cell.

A Rigidity-Enhanced Antimicrobial Activity: A Case for Linear Cationic α-Helical Peptide HP(2–20) and Its Four Analogues

PubMed Central

Liu, Li; Fang, Ying; Huang, Qingsheng; Wu, Jianhua

2011-01-01

Linear cationic α-helical antimicrobial peptides are referred to as one of the most likely substitutes for common antibiotics, due to their relatively simple structures (≤40 residues) and various antimicrobial activities against a wide range of pathogens. Of those, HP(2–20) was isolated from Helicobacter pylori ribosomal protein. To reveal a mechanical determinant that may mediate the antimicrobial activities, we examined the mechanical properties and structural stabilities of HP(2–20) and its four analogues of same chain length by steered molecular dynamics simulation. The results indicated the following: the resistance of H-bonds to the tensile extension mediated the early extensive stage; with the loss of H-bonds, the tensile force was dispensed to prompt the conformational phase transition; and Young's moduli (N/m2) of the peptides were about 4∼8×109. These mechanical features were sensitive to the variation of the residue compositions. Furthermore, we found that the antimicrobial activity is rigidity-enhanced, that is, a harder peptide has stronger antimicrobial activity. It suggests that the molecular spring constant may be used to seek a new structure-activity relationship for different α-helical peptide groups. This exciting result was reasonably explained by a possible mechanical mechanism that regulates both the membrane pore formation and the peptide insertion. PMID:21283643

Phthalocyanines And Their Sulfonated Derivatives As Photosensitizers In Photodynamic Therapy.

NASA Astrophysics Data System (ADS)

Riesz, Peter; Krishna, C. Murali

1988-02-01

Photodynamic therapy (PDT) of human tumors with hematoporphyrin derivative (HpD) has achieved encouraging results. However, HpD is a complex mixture whose composition varies in different preparations and with time of storage. The future promise of PDT for cancer treatment depends on the development of new chemically defined sensitizers which absorb more strongly than HpD in the 600-800 nm region. A shift to higher wavelengths is desirable since it allows increased light penetration in human tissues. In vivo, these sensitizers should be non-toxic, localize selectively in tumors and generate cytotoxic species upon illumination with a high quantum yield. These damaging species may be singlet oxygen (1O2) produced by the transfer of energy from the triplet state of the sensitizer to oxygen (Type II) or superoxide anion radicals formed by electron transfer to oxygen or substrate radicals generated by electron or hydrogen transfer directly from the sensitizer (Type I). The recent work of several groups indicating that phthalocyanines and their water soluble derivatives are promising candidates for PDT is reviewed. The photophysics, photochemistry, photosensitized killing of cultured mammalian cells and the use for in vivo photodynamic therapy of phthalocyanines is outlined. Our studies of the post-illumination photohemolysis of human red blood cells as a model system for membrane photomodification sensitized by phthalocyanine sulfonates are consistent with the predominant role of 1O2 as the damaging species.

Portable widefield imaging device for ICG-detection of the sentinel lymph node

NASA Astrophysics Data System (ADS)

Govone, Angelo Biasi; Gómez-García, Pablo Aurelio; Carvalho, André Lopes; Capuzzo, Renato de Castro; Magalhães, Daniel Varela; Kurachi, Cristina

2015-06-01

Metastasis is one of the major cancer complications, since the malignant cells detach from the primary tumor and reaches other organs or tissues. The sentinel lymph node (SLN) is the first lymphatic structure to be affected by the malignant cells, but its location is still a great challenge for the medical team. This occurs due to the fact that the lymph nodes are located between the muscle fibers, making it visualization difficult. Seeking to aid the surgeon in the detection of the SLN, the present study aims to develop a widefield fluorescence imaging device using the indocyanine green as fluorescence marker. The system is basically composed of a 780nm illumination unit, optical components for 810nm fluorescence detection, two CCD cameras, a laptop, and dedicated software. The illumination unit has 16 diode lasers. A dichroic mirror and bandpass filters select and deliver the excitation light to the interrogated tissue, and select and deliver the fluorescence light to the camera. One camera is responsible for the acquisition of visible light and the other one for the acquisition of the ICG fluorescence. The software developed at the LabVIEW® platform generates a real time merged image where it is possible to observe the fluorescence spots, related to the lymph nodes, superimposed at the image under white light. The system was tested in a mice model, and a first patient with tongue cancer was imaged. Both results showed the potential use of the presented fluorescence imaging system assembled for sentinel lymph node detection.

Driving down defect density in composite EUV patterning film stacks

NASA Astrophysics Data System (ADS)

Meli, Luciana; Petrillo, Karen; De Silva, Anuja; Arnold, John; Felix, Nelson; Johnson, Richard; Murray, Cody; Hubbard, Alex; Durrant, Danielle; Hontake, Koichi; Huli, Lior; Lemley, Corey; Hetzer, Dave; Kawakami, Shinichiro; Matsunaga, Koichi

2017-03-01

Extreme ultraviolet lithography (EUVL) technology is one of the leading candidates for enabling the next generation devices, for 7nm node and beyond. As the technology matures, further improvement is required in the area of blanket film defectivity, pattern defectivity, CD uniformity, and LWR/LER. As EUV pitch scaling approaches sub 20 nm, new techniques and methods must be developed to reduce the overall defectivity, mitigate pattern collapse and eliminate film related defect. IBM Corporation and Tokyo Electron Limited (TELTM) are continuously collaborating to develop manufacturing quality processes for EUVL. In this paper, we review key defectivity learning required to enable 7nm node and beyond technology. We will describe ongoing progress in addressing these challenges through track-based processes (coating, developer, baking), highlighting the limitations of common defect detection strategies and outlining methodologies necessary for accurate characterization and mitigation of blanket defectivity in EUV patterning stacks. We will further discuss defects related to pattern collapse and thinning of underlayer films.

Layout decomposition of self-aligned double patterning for 2D random logic patterning

NASA Astrophysics Data System (ADS)

Ban, Yongchan; Miloslavsky, Alex; Lucas, Kevin; Choi, Soo-Han; Park, Chul-Hong; Pan, David Z.

2011-04-01

Self-aligned double pattering (SADP) has been adapted as a promising solution for sub-30nm technology nodes due to its lower overlay problem and better process tolerance. SADP is in production use for 1D dense patterns with good pitch control such as NAND Flash memory applications, but it is still challenging to apply SADP to 2D random logic patterns. The favored type of SADP for complex logic interconnects is a two mask approach using a core mask and a trim mask. In this paper, we first describe layout decomposition methods of spacer-type double patterning lithography, then report a type of SADP compliant layouts, and finally report SADP applications on Samsung 22nm SRAM layout. For SADP decomposition, we propose several SADP-aware layout coloring algorithms and a method of generating lithography-friendly core mask patterns. Experimental results on 22nm node designs show that our proposed layout decomposition for SADP effectively decomposes any given layouts.

Classification and printability of EUV mask defects from SEM images

NASA Astrophysics Data System (ADS)

Cho, Wonil; Price, Daniel; Morgan, Paul A.; Rost, Daniel; Satake, Masaki; Tolani, Vikram L.

2017-10-01

Classification and Printability of EUV Mask Defects from SEM images EUV lithography is starting to show more promise for patterning some critical layers at 5nm technology node and beyond. However, there still are many key technical obstacles to overcome before bringing EUV Lithography into high volume manufacturing (HVM). One of the greatest obstacles is manufacturing defect-free masks. For pattern defect inspections in the mask-shop, cutting-edge 193nm optical inspection tools have been used so far due to lacking any e-beam mask inspection (EBMI) or EUV actinic pattern inspection (API) tools. The main issue with current 193nm inspection tools is the limited resolution for mask dimensions targeted for EUV patterning. The theoretical resolution limit for 193nm mask inspection tools is about 60nm HP on masks, which means that main feature sizes on EUV masks will be well beyond the practical resolution of 193nm inspection tools. Nevertheless, 193nm inspection tools with various illumination conditions that maximize defect sensitivity and/or main-pattern modulation are being explored for initial EUV defect detection. Due to the generally low signal-to-noise in the 193nm inspection imaging at EUV patterning dimensions, these inspections often result in hundreds and thousands of defects which then need to be accurately reviewed and dispositioned. Manually reviewing each defect is difficult due to poor resolution. In addition, the lack of a reliable aerial dispositioning system makes it very challenging to disposition for printability. In this paper, we present the use of SEM images of EUV masks for higher resolution review and disposition of defects. In this approach, most of the defects detected by the 193nm inspection tools are first imaged on a mask SEM tool. These images together with the corresponding post-OPC design clips are provided to KLA-Tencor's Reticle Decision Center (RDC) platform which provides ADC (Automated Defect Classification) and S2A (SEM-to-Aerial printability) analysis of every defect. First, a defect-free or reference mask SEM is rendered from the post-OPC design, and the defective signature is detected from the defect-reference difference image. These signatures help assess the true nature of the defect as evident in e-beam imaging; for example, excess or missing absorber, line-edge roughness, contamination, etc. Next, defect and reference contours are extracted from the grayscale SEM images and fed into the simulation engine with an EUV scanner model to generate corresponding EUV defect and reference aerial images. These are then analyzed for printability and dispositioned using an Aerial Image Analyzer (AIA) application to automatically measure and determine the amount of CD errors. Thus by integrating EUV ADC and S2A applications together, every defect detection is characterized for its type and printability which is essential for not only determining which defects to repair, but also in monitoring the performance of EUV mask process tools. The accuracy of the S2A print modeling has been verified with other commercially-available simulators, and will also be verified with actual wafer print results. With EUV lithography progressing towards volume manufacturing at 5nm technology, and the likelihood of EBMI inspectors approaching the horizon, the EUV ADC-S2A system will continue serving an essential role of dispositioning defects off e-beam imaging.

Scalable Triadic Analysis of Large-Scale Graphs: Multi-Core vs. Multi-Processor vs. Multi-Threaded Shared Memory Architectures

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

Chin, George; Marquez, Andres; Choudhury, Sutanay

2012-09-01

Triadic analysis encompasses a useful set of graph mining methods that is centered on the concept of a triad, which is a subgraph of three nodes and the configuration of directed edges across the nodes. Such methods are often applied in the social sciences as well as many other diverse fields. Triadic methods commonly operate on a triad census that counts the number of triads of every possible edge configuration in a graph. Like other graph algorithms, triadic census algorithms do not scale well when graphs reach tens of millions to billions of nodes. To enable the triadic analysis ofmore » large-scale graphs, we developed and optimized a triad census algorithm to efficiently execute on shared memory architectures. We will retrace the development and evolution of a parallel triad census algorithm. Over the course of several versions, we continually adapted the code’s data structures and program logic to expose more opportunities to exploit parallelism on shared memory that would translate into improved computational performance. We will recall the critical steps and modifications that occurred during code development and optimization. Furthermore, we will compare the performances of triad census algorithm versions on three specific systems: Cray XMT, HP Superdome, and AMD multi-core NUMA machine. These three systems have shared memory architectures but with markedly different hardware capabilities to manage parallelism.« less

Cognitive Models for Learning to Control Dynamic Systems

DTIC Science & Technology

2008-05-30

2 3N NM NM NMK NK M− + + + + constraints, including KN M+ equality constraints, 7 2NM M+ inequality non- timing constraints and the rest are... inequality timing constraints. The size of the MILP model grows rapidly with the increase of problem size. So it is a big challenge to deal with more...task requirement, are studied in the section. An assumption is made in advance that the time of attack delay and flight time to the sink node are

Electron beam mask writer EBM-9500 for logic 7nm node generation

NASA Astrophysics Data System (ADS)

Matsui, Hideki; Kamikubo, Takashi; Nakahashi, Satoshi; Nomura, Haruyuki; Nakayamada, Noriaki; Suganuma, Mizuna; Kato, Yasuo; Yashima, Jun; Katsap, Victor; Saito, Kenichi; Kobayashi, Ryoei; Miyamoto, Nobuo; Ogasawara, Munehiro

2016-10-01

Semiconductor scaling is slowing down because of difficulties of device manufacturing below logic 7nm node generation. Various lithography candidates which include ArF immersion with resolution enhancement technology (like Inversed Lithography technology), Extreme Ultra Violet lithography and Nano Imprint lithography are being developed to address the situation. In such advanced lithography, shot counts of mask patterns are estimated to increase explosively in critical layers, and then it is hoped that multi beam mask writer (MBMW) is released to handle them within realistic write time. However, ArF immersion technology with multiple patterning will continue to be a mainstream lithography solution for most of the layers. Then, the shot counts in less critical layers are estimated to be stable because of the limitation of resolution in ArF immersion technology. Therefore, single beam mask writer (SBMW) can play an important role for mask production still, relative to MBMW. Also the demand of SBMW seems actually strong for the logic 7nm node. To realize this, we have developed a new SBMW, EBM-9500 for mask fabrication in this generation. A newly introduced electron beam source enables higher current density of 1200A/cm2. Heating effect correction function has also been newly introduced to satisfy the requirements for both pattern accuracy and throughput. In this paper, we will report the configuration and performance of EBM-9500.

Haptoglobin polymorphism among Saharian and West African groups. Haptoglobin phenotype determination by radioimmunoelectrophoresis on Hp O samples.

PubMed Central

Constans, J; Viau, M; Gouaillard, C; Clerc, A

1981-01-01

The haptoglobin (Hp) polymorphism is investigated in 11 African groups living in an area from the Algerian Sahara to Central Africa. More than 4,000 samples were examined. In the Saharian samples, the Hp1 gene frequency is higher than in any other African group. From north to south, a decrease in the Hp1 gene frequency is observed; in the Pygmy sample only, this frequency is lower than the frequency of the Hp2 gene. By means of a sensitive radioimmunoelectrophoresis, the presence of a residual Hp in Hp O sera in which the Hp polymorphism can also be determined can be revealed. Absence of Hp 1-1 and significant excess of Hp 2-2 individuals were observed. More Hp 2-1M phenotypes were detected in the Hp O population than in the non-Hp O population examined. In the Hp O samples, the influence of the phenotype distribution on the Hp gene frequencies is discussed. The heavy polymers of the Hp related to the presence of the alpha 2 chain (Hp2 gene product) are involved only in the biological mechanisms responsible for the presence of Hp O and Hp 2-1 M phenotypes among African groups. Images Fig. 1 PMID:7258189

Hemicellulose block copolymers made from woods for wide-range directed self-assembly lithography enabling wider range of applicable patterning size

NASA Astrophysics Data System (ADS)

Morita, Kazuyo; Yamamoto, Kimiko

2017-03-01

Xylan, one of hemicellulose family, block copolymer was newly developed for wide-range directed self-assembly lithography (DSA). Xylan is higher hydrophilic material because of having many hydroxy groups in one molecule. It means that xylan block copolymer has a possibility of high-chi block copolymer. Generally, DSA is focused on microphase separation for smaller size with high-chi block copolymer and not well known for larger size. In this study, xylan block copolymer was confirmed enabling wider range of patterning size, from smaller size to larger size. The key of xylan block copolymer is a new molecular structure of block copolymer and sugar chain control technology. Sugar content is the important parameter for not only micro-phase separation property but also line edge roughness (LER) and defects. Based on the sugar control technology, wide-range (hp 8.3nm to 26nm L/S and CD 10nm to 51nm hole) DSA patterning was demonstrated. Additionally it was confirmed that xylan block copolymer is suitable for sequential infiltration synthesis (SIS) process.

Range pattern matching with layer operations and continuous refinements

NASA Astrophysics Data System (ADS)

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

2018-03-01

At advanced and mainstream process nodes (e.g., 7nm, 14nm, 22nm, and 55nm process nodes), lithography hotspots can exist in layouts of integrated circuits even if the layouts pass design rule checking (DRC). Existence of lithography hotspots in a layout can cause manufacturability issues, which can result in yield losses of manufactured integrated circuits. In order to detect lithography hotspots existing in physical layouts, pattern matching (PM) algorithms and commercial PM tools have been developed. However, there are still needs to use DRC tools to perform PM operations. In this paper, we propose a PM synthesis methodology, which uses a continuous refinement technique, for the automatic synthesis of a given lithography hotspot pattern into a DRC deck, which consists of layer operation commands, so that an equivalent PM operation can be performed by executing the synthesized deck with the use of a DRC tool. Note that the proposed methodology can deal with not only exact patterns, but also range patterns. Also, lithography hotspot patterns containing multiple layers can be processed. Experimental results show that the proposed methodology can accurately and efficiently detect lithography hotspots in physical layouts.

[Study on genetic instability of nm23H1 gene in Chinese with original gallbladder tumor].

PubMed

Lu, Hai Ying; Zhang, Guo Qiang; Li, Ji Cheng

2006-06-01

The aim of this study was to examine the microsatellite instability (MSI) and loss of heterozygosity (LOH) of locus D17S396 on chromosome 17 and their influence on the expression of nm23H1 in gallbladder tumors, which may provide experimental basis for the tumor occurrence and metastasis. Techniques such as DNA extraction from formalin-fixed paraffin-embedded tissues, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), ordinary silver stain were used to study MSI and LOH of locus D17S396. Envision immunohistochemistry and Leica-Qwin computer imaging techniques were used to assess the expression of gene nm23H1. In our experiment, the frequency of genetic instability of malignant gallbladder tumors was 42.55%, which was higher than that of gallbladder adenomas, while there were no genetic instability occurred in chronic cholecystitis tissue. The frequency of LOH seemed higher with the deteriorism of gallbladder tumor. Among 47 gallbladder carcinomas, the frequency of LOH and MSI were different between different differentiation cases (P < 0.05), and the frequency of LOH in liver and lymph node metastasis cases was significantly higher than those without metastasis (P < 0.01). Moreover, the frequency of LOH was higher in stage Nevin IV and V when compared with stage I, II and III. However, the frequency of MSI showed contrary correlation with some clinicopathologic characteristics. The expression of nm23H1 in gallbladder carcinoma, gallbladder adenoma and chronic cholecystitis tissue were different (P < 0.05). The case with lymph node metastasis showed significantly lower nm23H1 expression than those without lymph node metastasis (P < 0.01). Nevin stage IV and V also exhibited lower nm23H1 expression levels compared with stage I, II and Ill. Furthermore, there was no difference in nm23H1 protein expression intensity analyzed by computer imaging techniques. In gallbladder carcinomas, the positive frequency of nm23H1 protein in LOH positive group was lower than that of LOH negative group (P < 0.05). The results indicated that the genetic instability of nm23H1 gene might be implicated in pathogenesis and progression of gallbladder tumor. Both MSI and LOH of nm23H1 gene controlled the development of gallbladder tumor independently in different paths. MSI may be an early stage molecule marker of gallbladder carcinoma. LOH may be molecule marker for the deteriorism of gallbladder tissue, which could inhibit the expression of nm23H1 in local tissue of gallbladder carcinoma and endow it with high aggressive and poor prognosis. Increasing the amount of nm23H1 protein expression could effectively restrain gallbladder carcinoma metastasis and improve prognosis of patients.

Adenine Nucleotide Analogues Locked in a Northern Methanocarba Conformation: Enhanced Stability and Potency as P2Y1 Receptor Agonists

PubMed Central

Ravi, R. Gnana; Kim, Hak Sung; Servos, Jörg; Zimmermann, Herbert; Lee, Kyeong; Maddileti, Savitri; Boyer, José L.; Harden, T. Kendall; Jacobson, Kenneth A.

2016-01-01

Preference for the Northern (N) ring conformation of the ribose moiety of nucleotide 5′-triphosphate agonists at P2Y1, P2Y2, P2Y4, and P2Y11 receptors, but not P2Y6 receptors, was established using a ring-constrained methanocarba (a 3.1.0-bicyclohexane) ring as a ribose substitute (Kim et al. J. Med. Chem. 2002, 45, 208–218.). We have now combined the ring-constrained (N)-methanocarba modification of adenine nucleotides with other functionalities known to enhance potency at P2 receptors. The potency of the newly synthesized analogues was determined in the stimulation of phospholipase C through activation of turkey erythrocyte P2Y1 or human P2Y1 and P2Y2 receptors stably expressed in astrocytoma cells. An (N)-methanocarba-2-methylthio-ADP analogue displayed an EC50 at the hP2Y1 receptor of 0.40 nM and was 55-fold more potent than the corresponding triphosphate and 16-fold more potent than the riboside 5′-diphosphate. 2-Cl–(N)-methanocarba-ATP and its N6-Me analogue were also highly selective, full agonists at P2Y1 receptors. The (N)-methanocarba-2-methylthio and 2-chloromonophosphate analogues were full agonists exhibiting micromolar potency at P2Y1 receptors, while the corresponding ribosides were inactive. Although β,γ-methylene-ATP was inactive at P2Y receptors, β,γ-methylene-(N)-methanocarba-ATP was a potent hP2Y1 receptor agonist with an EC50 of 160 nM and was selective versus hP2Y2 and hP2Y4 receptors. The rates of hydrolysis of Northern (N) and Southern (S) methanocarba analogues of AMP by rat 5′-ectonucleotidase were negligible. The rates of hydrolysis of the corresponding triphosphates by recombinant rat NTPDase1 and 2 were studied. Both isomers were hydrolyzed by NTPDase 1 at about half the rate of ATP hydrolysis. The (N) isomer was hardly hydrolyzed by NTPDase 2, while the (S) isomer was hydrolyzed at one-third of the rate of ATP hydrolysis. This suggests that new, more stable and selective nucleotide agonists may be designed on the basis of the (N)-conformation, which greatly enhanced potency at P2Y1 receptors. PMID:11985476

25 Gbps 850 nm photodiode for emerging 100 Gb ethernet applications

NASA Astrophysics Data System (ADS)

Joshi, Abhay; Rue, Jim; Becker, Don; Datta, Shubhashish; McFaul, Will

2011-06-01

The IEEE Std 802.3ba-2010 for 40 Gb and 100 Gb Ethernet was released in July, 2010. This standard will continue to evolve over the next several years. Two of the challenging transmit/receive architectures contained in this standard are the 100GBASE-LR4 (<10 km range) and 100GBASE-ER4 (<40 km range). Although presently envisioned for 1310 nm optical wavelengths, both of these 4 lane, 25.78 GBaud formats may be adopted for the impending 850 nm short reach optical backplane market, whose range is below 150 m. Driven by major computer server companies, such as IBM, HP and Oracle, the 850 nm Active Optical Cable (AOC) market is presently undergoing an increase of serial rates up to 25 Gbaud to enhance backplane interconnectivity. With AOCs up to 16 channels, the potential for up to 400 Gbps backhaul composite data rates will soon be possible. We report a 25 Gbps photodiode with quantum efficiency ~ 0.6 at 850 nm. This InGaAs/InP device was optimized for high quantum efficiency at 850 nm. When pigtailed with multimode fiber and integrated with an application-specific RF amplifier, the resultant photoreceiver will provide multiple functionalities for these 100 Gb Ethernet markets.

Low molecular weight polyethylenimine cross-linked by 2-hydroxypropyl-gamma-cyclodextrin coupled to peptide targeting HER2 as a gene delivery vector.

PubMed

Huang, Hongliang; Yu, Hai; Tang, Guping; Wang, Qingqing; Li, Jun

2010-03-01

Gene delivery is one of the critical steps for gene therapy. Non-viral vectors have many advantages but suffered from low gene transfection efficiency. Here, in order to develop new polymeric gene vectors with low cytotoxicity and high gene transfection efficiency, we synthesized a cationic polymer composed of low molecular weight polyethylenimine (PEI) of molecular weight of 600 Da cross-linked by 2-hydroxypropyl-gamma-cyclodextrin (HP gamma-CD) and then coupled to MC-10 oligopeptide containing a sequence of Met-Ala-Arg-Ala-Lys-Glu. The oligopeptide can target to HER2, the human epidermal growth factor receptor 2, which is often over expressed in many breast and ovary cancers. The new gene vector was expected to be able to target delivery of genes to HER2 positive cancer cells for gene therapy. The new gene vector was composed of chemically bonded HP gamma-CD, PEI (600 Da), and MC-10 peptide at a molar ratio of 1:3.3:1.2. The gene vector could condense plasmid DNA at an N/P ratio of 6 or above. The particle size of HP gamma-CD-PEI-P/DNA complexes at N/P ratios 40 was around 170-200 nm, with zeta potential of about 20 mV. The gene vector showed very low cytotoxicity, strong targeting specificity to HER2 receptor, and high efficiency of delivering DNA to target cells in vitro and in vivo with the reporter genes. The delivery of therapeutic IFN-alpha gene mediated by the new gene vector and the therapeutic efficiency were also studied in mice animal model. The animal study results showed that the new gene vector HP gamma-CD-PEI-P significantly enhanced the anti-tumor effect on tumor-bearing nude mice as compared to PEI (25 kDa), HP gamma-CD-PEI, and other controls, indicating that this new polymeric gene vector is a potential candidate for cancer gene therapy. (c) 2009 Elsevier Ltd. All rights reserved.

Exact sampling of graphs with prescribed degree correlations

NASA Astrophysics Data System (ADS)

Bassler, Kevin E.; Del Genio, Charo I.; Erdős, Péter L.; Miklós, István; Toroczkai, Zoltán

2015-08-01

Many real-world networks exhibit correlations between the node degrees. For instance, in social networks nodes tend to connect to nodes of similar degree and conversely, in biological and technological networks, high-degree nodes tend to be linked with low-degree nodes. Degree correlations also affect the dynamics of processes supported by a network structure, such as the spread of opinions or epidemics. The proper modelling of these systems, i.e., without uncontrolled biases, requires the sampling of networks with a specified set of constraints. We present a solution to the sampling problem when the constraints imposed are the degree correlations. In particular, we develop an exact method to construct and sample graphs with a specified joint-degree matrix, which is a matrix providing the number of edges between all the sets of nodes of a given degree, for all degrees, thus completely specifying all pairwise degree correlations, and additionally, the degree sequence itself. Our algorithm always produces independent samples without backtracking. The complexity of the graph construction algorithm is {O}({NM}) where N is the number of nodes and M is the number of edges.

Acute glandular fever-like illness in a patient with HTLV-III antibody.

PubMed

McCaul, T F; Tovey, G; Farthing, C F; Gazzard, B; Zuckerman, A J

1985-10-01

A lymph node biopsy obtained from a patient with human T-cell lymphocytotropic virus III/lymphadenopathy-associated virus (HTLV-III/LAV) antibody, presenting with an acute glandular fever-like illness, was examined by electron microscopy. Numerous pathological changes were present in the biopsy, including hypertrophy of smooth endoplasmic reticulum, intracytoplasmic rod-like inclusions within the cisternae of endoplasmic reticulum, multivesicular bodies, test-tube and ring-shaped forms, and tubulo-reticular structures. Intranuclear and intracytoplasmic viral-like particles measuring 105-120 nm in diameter and small cytoplasmic particles measuring 50-70 nm in diameter were found in some degenerating lymph node cells. These pathological findings may reflect a host cell response to various pathological and viral stimuli resulting from immune deficiency owing to infection with HTLV-III/LAV.

Materials and fabrication sequences for water soluble silicon integrated circuits at the 90 nm node

NASA Astrophysics Data System (ADS)

Yin, Lan; Bozler, Carl; Harburg, Daniel V.; Omenetto, Fiorenzo; Rogers, John A.

2015-01-01

Tungsten interconnects in silicon integrated circuits built at the 90 nm node with releasable configurations on silicon on insulator wafers serve as the basis for advanced forms of water-soluble electronics. These physically transient systems have potential uses in applications that range from temporary biomedical implants to zero-waste environmental sensors. Systematic experimental studies and modeling efforts reveal essential aspects of electrical performance in field effect transistors and complementary ring oscillators with as many as 499 stages. Accelerated tests reveal timescales for dissolution of the various constituent materials, including tungsten, silicon, and silicon dioxide. The results demonstrate that silicon complementary metal-oxide-semiconductor circuits formed with tungsten interconnects in foundry-compatible fabrication processes can serve as a path to high performance, mass-produced transient electronic systems.

Simultaneous frequency stabilization and high-power dense wavelength division multiplexing (HP-DWDM) using an external cavity based on volume Bragg gratings (VBGs)

NASA Astrophysics Data System (ADS)

Hengesbach, Stefan; Klein, Sarah; Holly, Carlo; Witte, Ulrich; Traub, Martin; Hoffmann, Dieter

2016-03-01

Multiplexing technologies enable the development of high-brightness diode lasers for direct industrial applications. We present a High-Power Dense Wavelength Division Multiplexer (HP-DWDM) with an average channel spacing of 1.7 (1.5) nm and a subsequent external cavity mirror to provide feedback for frequency stabilization and multiplexing in one step. The "self-optimizing" multiplexing unit consists of four reflective Volume Bragg Gratings (VBGs) with 99% diffraction efficiency and seven dielectric mirrors to overlay the radiation of five input channels with an adjustable channel spacing of 1-2 nm. In detail, we focus on the analysis of the overall optical efficiency, the change of the beam parameter product and the spectral width. The performance is demonstrated using five 90 μm multimode 9xx single emitters with M2<=17. Because of the feedback the lateral (multimodal) spatial and angular intensity distribution changes strongly and the beam parameter product decreases by a factor of 1.2 to 1.9. Thereby the angular intensity distribution is more affected than the width of the beam waist. The spectral width per emitter decreases to 3-200 pm (FWHM) depending on the injection current and the reflectance of the feedback mirror (0.75%, 1.5%, 4%, 6% or 8%). The overall optical multiplexing efficiency ranges between 77% and 86%. With some modifications (e.g. enhanced AR-coatings) we expect 90-95%.

Process variation challenges and resolution in the negative-tone develop double patterning for 20nm and below technology node

NASA Astrophysics Data System (ADS)

Mehta, Sohan S.; Ganta, Lakshmi K.; Chauhan, Vikrant; Wu, Yixu; Singh, Sunil; Ann, Chia; Subramany, Lokesh; Higgins, Craig; Erenturk, Burcin; Srivastava, Ravi; Singh, Paramjit; Koh, Hui Peng; Cho, David

2015-03-01

Immersion based 20nm technology node and below becoming very challenging to chip designers, process and integration due to multiple patterning to integrate one design layer . Negative tone development (NTD) processes have been well accepted by industry experts for enabling technologies 20 nm and below. 193i double patterning is the technology solution for pitch down to 80 nm. This imposes tight control in critical dimension(CD) variation in double patterning where design patterns are decomposed in two different masks such as in litho-etch-litho etch (LELE). CD bimodality has been widely studied in LELE double patterning. A portion of CD tolerance budget is significantly consumed by variations in CD in double patterning. The objective of this work is to study the process variation challenges and resolution in the Negative Tone Develop Process for 20 nm and Below Technology Node. This paper describes the effect of dose slope on CD variation in negative tone develop LELE process. This effect becomes even more challenging with standalone NTD developer process due to q-time driven CD variation. We studied impact of different stacks with combination of binary and attenuated phase shift mask and estimated dose slope contribution individually from stack and mask type. Mask 3D simulation was carried out to understand theoretical aspect. In order to meet the minimum insulator requirement for the worst case on wafer the overlay and critical dimension uniformity (CDU) budget margins have slimmed. Besides the litho process and tool control using enhanced metrology feedback, the variation control has other dependencies too. Color balancing between the two masks in LELE is helpful in countering effects such as iso-dense bias, and pattern shifting. Dummy insertion and the improved decomposition techniques [2] using multiple lower priority constraints can help to a great extent. Innovative color aware routing techniques [3] can also help with achieving more uniform density and color balanced layouts.

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.

Dry etch challenges for CD shrinkage in memory process

NASA Astrophysics Data System (ADS)

Matsushita, Takaya; Matsumoto, Takanori; Mukai, Hidefumi; Kyoh, Suigen; Hashimoto, Kohji

2015-03-01

Line pattern collapse attracts attention as a new problem of the L&S formation in sub-20nm H.P feature. Line pattern collapse that occurs in a slight non-uniformity of adjacent CD (Critical dimension) space using double patterning process has been studied with focus on micro-loading effect in Si etching. Bias RF pulsing plasma etching process using low duty cycle helped increase of selectivity Si to SiO2. In addition to the effect of Bias RF pulsing process, the thin mask obtained from improvement of selectivity has greatly suppressed micro-loading in Si etching. However it was found that micro-loading effect worsen again in sub-20nm space width. It has been confirmed that by using cycle etch process to remove deposition with CFx based etching micro-loading effect could be suppressed. Finally, Si etching process condition using combination of results above could provide finer line and space without "line pattern collapse" in sub-20nm.

Transcriptional Profiling of Type II Toxin-Antitoxin Genes of Helicobacter pylori under Different Environmental Conditions: Identification of HP0967-HP0968 System.

PubMed

Cárdenas-Mondragón, María G; Ares, Miguel A; Panunzi, Leonardo G; Pacheco, Sabino; Camorlinga-Ponce, Margarita; Girón, Jorge A; Torres, Javier; De la Cruz, Miguel A

2016-01-01

Helicobacter pylori is a Gram-negative bacterium that colonizes the human gastric mucosa and is responsible for causing peptic ulcers and gastric carcinoma. The expression of virulence factors allows the persistence of H. pylori in the stomach, which results in a chronic, sometimes uncontrolled inflammatory response. Type II toxin-antitoxin (TA) systems have emerged as important virulence factors in many pathogenic bacteria. Three type II TA systems have previously been identified in the genome of H. pylori 26695: HP0315-HP0316, HP0892-HP0893, and HP0894-HP0895. Here we characterized a heretofore undescribed type II TA system in H. pylori , HP0967-HP0968, which is encoded by the bicistronic operon hp0968-hp0967 and belongs to the Vap family. The predicted HP0967 protein is a toxin with ribonuclease activity whereas HP0968 is an antitoxin that binds to its own regulatory region. We found that all type II TA systems were expressed in H. pylori during early stationary growth phase, and differentially expressed in the presence of urea, nickel, and iron, although, the hp0968-hp0967 pair was the most affected under these environmental conditions. Transcription of hp0968-hp0967 was strongly induced in a mature H. pylori biofilm and when the bacteria interacted with AGS epithelial cells. Kanamycin and chloramphenicol considerably boosted transcription levels of all the four type II TA systems. The hp0968-hp0967 TA system was the most frequent among 317 H. pylori strains isolated from all over the world. This study is the first report on the transcription of type II TA genes in H. pylori under different environmental conditions. Our data show that the HP0967 and HP0968 proteins constitute a bona fide type II TA system in H. pylori , whose expression is regulated by environmental cues, which are relevant in the context of infection of the human gastric mucosa.

Anticipating and controlling mask costs within EDA physical design

NASA Astrophysics Data System (ADS)

Rieger, Michael L.; Mayhew, Jeffrey P.; Melvin, Lawrence S.; Lugg, Robert M.; Beale, Daniel F.

2003-08-01

For low k1 lithography, more aggressive OPC is being applied to critical layers, and the number of mask layers with OPC treatments is growing rapidly. The 130 nm, process node required, on average, 8 layers containing rules- or model-based OPC. The 90 nm node will have 16 OPC layers, of which 14 layers contain aggressive model-based OPC. This escalation of mask pattern complexity, coupled with the predominant use of vector-scan e-beam (VSB) mask writers contributes to the rising costs of advanced mask sets. Writing times for OPC layouts are several times longer than for traditional layouts, making mask exposure the single largest cost component for OPC masks. Lower mask yields, another key factor in higher mask costs, is also aggravated by OPC. Historical mask set costs are plotted below. The initial cost of a 90 nm-node mask set will exceed one million dollars. The relative impact of mask cost on chip depends on how many total wafers are printed with each mask set. For many foundry chips, where unit production is often well below 1000 wafers, mask costs are larger than wafer processing costs. Further increases in NRE may begin to discourage these suppliers' adoption to 90 nm and smaller nodes. In this paper we will outline several alternatives for reducing mask costs by strategically leveraging dimensional margins. Dimensional specifications for a particular masking layer usually are applied uniformly to all features on that layer. As a practical matter, accuracy requirements on different features in the design may vary widely. Take a polysilicon layer, for example: global tolerance specifications for that layer are driven by the transistor-gate requirements; but these parameters over-specify interconnect feature requirements. By identifying features where dimensional accuracy requirements can be reduced, additional margin can be leveraged to reduce OPC complexity. Mask writing time on VSB tools will drop in nearly direct proportion to reduce shot count. By inspecting masks with reference to feature-dependent margins, instead of uniform specifications, mask yield can be effectively increased further reducing delivered mask expense.

Verification of E-Beam direct write integration into 28nm BEOL SRAM technology

NASA Astrophysics Data System (ADS)

Hohle, Christoph; Choi, Kang-Hoon; Gutsch, Manuela; Hanisch, Norbert; Seidel, Robert; Steidel, Katja; Thrun, Xaver; Werner, Thomas

2015-03-01

Electron beam direct write lithography (EBDW) potentially offers advantages for low-volume semiconductor manufacturing, rapid prototyping or design verification due to its high flexibility without the need of costly masks. However, the integration of this advanced patterning technology into complex CMOS manufacturing processes remains challenging. The low throughput of today's single e-Beam tools limits high volume manufacturing applications and maturity of parallel (multi) beam systems is still insufficient [1,2]. Additional concerns like transistor or material damage of underlying layers during exposure at high electron density or acceleration voltage have to be addressed for advanced technology nodes. In the past we successfully proved that potential degradation effects of high-k materials or ULK shrink can be neglected and were excluded by demonstrating integrated electrical results of 28nm node transistor and BEOL performance following 50kV electron beam dry exposure [3]. Here we will give an update on the integration of EBDW in the 300mm CMOS manufacturing processes of advanced integrated circuits at the 28nm SRAM node of GLOBALFOUNDRIES Dresden. The work is an update to what has been previously published [4]. E-beam patterning results of BEOL full chip metal and via layers with a dual damascene integration scheme using a 50kV VISTEC SB3050DW variable shaped electron beam direct writer at Fraunhofer IPMSCNT are demonstrated. For the patterning of the Metal layer a Mix & Match concept based on the sequence litho - etch -litho -etch (LELE) was developed and evaluated wherein several exposure fields were blanked out during the optical exposure. Etch results are shown and compared to the POR. Results are also shown on overlay performance and optimized e-Beam exposure time using most advanced data prep solutions and resist processes. The patterning results have been verified using fully integrated electrical measurement of metal lines and vias on wafer level. In summary we demonstrate the integration capability of EBDW into a productive CMOS process flow at the example of the 28nm SRAM technology node.

Advanced optical imaging platform for CD metrology and defect review on 130-nm to 100-nm node reticles: an overview of preliminary results

NASA Astrophysics Data System (ADS)

Hourd, Andrew C.; Grimshaw, Anthony; Scheuring, Gerd; Gittinger, Christian; Brueck, Hans-Juergen; Chen, Shiuh-Bin; Chen, Parkson W.; Hartmann, Hans; Ordynskyy, Volodymyr; Jonckheere, Rik M.; Philipsen, Vicky; Schaetz, Thomas; Sommer, Karl

2002-08-01

Critical Dimension fidelity continues to be one of the key driving parameters defining photomask quality and printing performance. The present advanced optical CD metrology systems, operating at i-line, will very soon be challenged as viable tools owing to their restricted resolution and measurement linearity impact on the ability to produce repeatable measurements. Alternative measurement technologies such as CD-SEM and -AFM have started to appear, but are also not without tier concerns in the field of reticle CD metrology. This paper introduces a new optical metrology system (MueTec /) operating at DUV wavelength (248nm), which has been specifically designed to meet the resolution and measurement repeatability requirements of reticle manufacture at the 130nm and 100nm nodes. The system is based upon a specially designed mechanical-optical platform for maximum stability and very advanced optical, illumination, alignment and software systems. The at wavelength operation of this system also makes it an ideal platform for defect printability analysis and review. The system is currently part of a European Commission funded assessment project (IST-2000-28086: McD'OR) to develop a testing strategy to verify the system performance, agree on equipment specifications and demonstrate its capability on advanced production reticles - including long-term reliability. It is the preliminary results from this evaluation that are presented here.

REAP (raster e-beam advanced process) using 50-kV raster e-beam system for sub-100-nm node mask technology

NASA Astrophysics Data System (ADS)

Baik, Ki-Ho; Dean, Robert L.; Mueller, Mark; Lu, Maiying; Lem, Homer Y.; Osborne, Stephen; Abboud, Frank E.

2002-07-01

A chemically amplified resist (CAR) process has been recognized as an approach to meet the demanding critical dimension (CD) specifications of 100nm node technology and beyond. Recently, significant effort has been devoted to optimizing CAR materials, which offer the characteristics required for next generation photomask fabrication. In this paper, a process established with a positive-tone CAR from TOK and 50kV MEBES eXara system is discussed. This resist is developed for raster scan 50 kV e-beam systems. It has high contrast, good coating characteristics, good dry etch selectivity, and high environmental stability. The coating process is conducted in an environment with amine concentration less than 2 ppb. A nitrogen environment is provided during plate transfer steps. Resolution using a 60nm writing grid is 90nm line and space patterns. CD linearity is maintained down to 240nm for isolated lines or spaces by applying embedded proximity effect correction (emPEC). Optimizations of post-apply bake (PAB) and post-expose bake (PEB) time, temperature, and uniformity are completed to improve adhesion, coating uniformity, and resolution. A puddle develop process is optimized to improve line edge roughness, edge slope, and resolution. Dry etch process is optimized on a TetraT system to transfer the resist image into the chrome layer with minimum etch bias.

Studies on low-loss coupling of non-node anti-resonant hollow-core fiber and tapered fiber

NASA Astrophysics Data System (ADS)

Zhang, Naiqian; Wang, Zefeng; Liu, Wenbo; Xi, Xiaoming

2017-10-01

Up to now, near almost optical fiber gas lasers employ/adopt the scheme of free-space coupling, which increases the difficulty to adjust the optical path, and has poor stability. All-fiber structure fiber-gas lasers are important development directions in the future. We established the numerical model of SMF-28 type tapered single-mode fiber and non-node hollow-core fiber. When the SMF-28 type single-mode fiber has a waist diameter of 40μm when the light source is LP01 fundamental mode with 1550nm wavelength, the mode field diameter is the largest. Meanwhile, we simulated that the equivalent mode field diameter of non-node anti-resonant hollow-core fiber is about 75μm at the same 1550nm wavelength light source. Then, we use different waist diameters of SMF-28 type tapered fibers injected to the non-node anti-resonant hollow-core fiber in simulation and experiments. In the scheme of the single-ended low-loss coupling, the simulation results indicate that the best waist diameter of tapered fiber is 40μm, and the calculated maximum coupling efficiency is 83.55%. Meanwhile, the experimental result of maximum coupling efficiency is 80.74% when the best waist diameter of tapered fiber is also 40μm. As for the double-ended low-loss coupling, the calculated maximum coupling efficiency is near 83.38%.

The functional dissection of the plasma corona of SiO₂-NPs spots histidine rich glycoprotein as a major player able to hamper nanoparticle capture by macrophages.

PubMed

Fedeli, Chiara; Segat, Daniela; Tavano, Regina; Bubacco, Luigi; De Franceschi, Giorgia; de Laureto, Patrizia Polverino; Lubian, Elisa; Selvestrel, Francesco; Mancin, Fabrizio; Papini, Emanuele

2015-11-14

A coat of strongly-bound host proteins, or hard corona, may influence the biological and pharmacological features of nanotheranostics by altering their cell-interaction selectivity and macrophage clearance. With the goal of identifying specific corona-effectors, we investigated how the capture of amorphous silica nanoparticles (SiO2-NPs; Ø = 26 nm; zeta potential = -18.3 mV) by human lymphocytes, monocytes and macrophages is modulated by the prominent proteins of their plasma corona. LC MS/MS analysis, western blotting and quantitative SDS-PAGE densitometry show that Histidine Rich Glycoprotein (HRG) is the most abundant component of the SiO2-NP hard corona in excess plasma from humans (HP) and mice (MP), together with minor amounts of the homologous Kininogen-1 (Kin-1), while it is remarkably absent in their Foetal Calf Serum (FCS)-derived corona. HRG binds with high affinity to SiO2-NPs (HRG Kd ∼2 nM) and competes with other plasma proteins for the NP surface, so forming a stable and quite homogeneous corona inhibiting nanoparticles binding to the macrophage membrane and their subsequent uptake. Conversely, in the case of lymphocytes and monocytes not only HRG but also several common plasma proteins can interchange in this inhibitory activity. The depletion of HRG and Kin-1 from HP or their plasma exhaustion by increasing NP concentration (>40 μg ml(-1) in 10% HP) lead to a heterogeneous hard corona, mostly formed by fibrinogen (Fibr), HDLs, LDLs, IgGs, Kallikrein and several minor components, allowing nanoparticle binding to macrophages. Consistently, the FCS-derived SiO2-NP hard corona, mainly formed by hemoglobin, α2 macroglobulin and HDLs but lacking HRG, permits nanoparticle uptake by macrophages. Moreover, purified HRG competes with FCS proteins for the NP surface, inhibiting their recruitment in the corona and blocking NP macrophage capture. HRG, the main component of the plasma-derived SiO2-NPs' hard corona, has antiopsonin characteristics and uniquely confers to these particles the ability to evade macrophage capture.

Effects of 45S5 bioglass on surface properties of dental enamel subjected to 35% hydrogen peroxide

PubMed Central

Deng, Meng; Wen, Hai-Lin; Dong, Xiao-Li; Li, Feng; Xu, Xin; Li, Hong; Li, Ji-Yao; Zhou, Xue-Dong

2013-01-01

Tooth bleaching agents may weaken the tooth structure. Therefore, it is important to minimize any risks of tooth hard tissue damage caused by bleaching agents. The aim of this study was to evaluate the effects of applying 45S5 bioglass (BG) before, after, and during 35% hydrogen peroxide (HP) bleaching on whitening efficacy, physicochemical properties and microstructures of bovine enamel. Seventy-two bovine enamel blocks were prepared and randomly divided into six groups: distilled deionized water (DDW), BG, HP, BG before HP, BG after HP and BG during HP. Colorimetric and microhardness tests were performed before and after the treatment procedure. Representative specimens from each group were selected for morphology investigation after the final tests. A significant color change was observed in group HP, BG before HP, BG after HP and BG during HP. The microhardness loss was in the following order: group HP>BG before HP, BG after HP>BG during HP>DDW, BG. The most obvious morphological alteration of was observed on enamel surfaces in group HP, and a slight morphological alteration was also detected in group BG before HP and BG after HP. Our findings suggest that the combination use of BG and HP could not impede the tooth whitening efficacy. Using BG during HP brought better protective effect than pre/post-bleaching use of BG, as it could more effectively reduce the mineral loss as well as retain the surface integrity of enamel. BG may serve as a promising biomimetic adjunct for bleaching therapy to prevent/restore the enamel damage induced by bleaching agents. PMID:23743618

Effects of 45S5 bioglass on surface properties of dental enamel subjected to 35% hydrogen peroxide.

PubMed

Deng, Meng; Wen, Hai-Lin; Dong, Xiao-Li; Li, Feng; Xu, Xin; Li, Hong; Li, Ji-Yao; Zhou, Xue-Dong

2013-06-01

Tooth bleaching agents may weaken the tooth structure. Therefore, it is important to minimize any risks of tooth hard tissue damage caused by bleaching agents. The aim of this study was to evaluate the effects of applying 45S5 bioglass (BG) before, after, and during 35% hydrogen peroxide (HP) bleaching on whitening efficacy, physicochemical properties and microstructures of bovine enamel. Seventy-two bovine enamel blocks were prepared and randomly divided into six groups: distilled deionized water (DDW), BG, HP, BG before HP, BG after HP and BG during HP. Colorimetric and microhardness tests were performed before and after the treatment procedure. Representative specimens from each group were selected for morphology investigation after the final tests. A significant color change was observed in group HP, BG before HP, BG after HP and BG during HP. The microhardness loss was in the following order: group HP>BG before HP, BG after HP>BG during HP>DDW, BG. The most obvious morphological alteration of was observed on enamel surfaces in group HP, and a slight morphological alteration was also detected in group BG before HP and BG after HP. Our findings suggest that the combination use of BG and HP could not impede the tooth whitening efficacy. Using BG during HP brought better protective effect than pre/post-bleaching use of BG, as it could more effectively reduce the mineral loss as well as retain the surface integrity of enamel. BG may serve as a promising biomimetic adjunct for bleaching therapy to prevent/restore the enamel damage induced by bleaching agents.

Sentinel node detection in pre-operative axillary staging.

PubMed

Trifirò, Giuseppe; Viale, Giuseppe; Gentilini, Oreste; Travaini, Laura Lavinia; Paganelli, Giovanni

2004-06-01

The concept of sentinel lymph node biopsy in breast cancer surgery is based on the fact that the tumour drains in a logical way via the lymphatic system, from the first to upper levels. Since axillary node dissection does not improve the prognosis of patients with breast cancer, sentinel lymph node biopsy might replace complete axillary dissection for staging of the axilla in clinically N0 patients. Sentinel lymph node biopsy would represent a significant advantage as a minimally invasive procedure, considering that about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Subdermal or peritumoural injection of small aliquots (and very low activity) of radiotracer is preferred to intratumoural administration, and (99m)Tc-labelled colloids with most of the particles in the 100-200 nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. The success rate of radioguidance in localising the sentinel lymph node in breast cancer surgery is about 97% in institutions where a high number of procedures are performed, and the success rate of lymphoscintigraphy in sentinel node detection is about 100%. The sentinel lymph node should be processed for intraoperative frozen section examination in its entirety, based on conventional histopathology and, when necessary, immune staining with anti-cytokeratin antibody. Nowadays, lymphoscintigraphy is a useful procedure in patients with different clinical evidence of breast cancer.

Early Stage Blood Purification for Paraquat Poisoning: A Multicenter Retrospective Study.

PubMed

Li, An; Li, Wenxiong; Hao, Fengtong; Wang, Haishi

2016-01-01

To evaluate the efficacy of conservative treatment vs. hemoperfusion (HP) vs. HP + continuous veno-venous hemofiltration (CVVH) for acute Paraquat (PQ) poisoning. This was a multicenter retrospective study of patients with PQ poisoning between January 2013 and June 2014. Clinical data and PQ serum levels were collected at baseline and after 24, 48, and 72 h of treatment. Seventy-five, 65, and 43 underwent conservative treatment only (conservative treatment group), conservative treatment + HP (HP group), and conservative treatment + HP + CVVH (HP + CVVH group), respectively. PQ serum levels decreased in all groups after 72 h of treatment (p < 0.001); meanwhile, these values decreased faster in the HP and HP + CVVH groups compared with the conservative treatment group. More importantly, PQ blood levels were significantly lower in the HP + CVVH group compared with the HP group at 24 h (p < 0.05). Sequential organ failure assessment (ΔSOFA) values in the HP and HP + CVVH groups were significantly lower compared with that obtained for the conservative treatment group (p < 0.05). The 60-day survival rates were 21.3, 43.1 and 46.5%, respectively. Multivariate analysis indicated that age, PQ dose, admission PQ levels, and admission SOFA score were independently associated with mortality. HP and HP + CVVH were protective factors. Early HP or HP + CVVH after PQ poisoning could decrease PQ blood levels, alleviate organ damage, and increase survival. © 2016 S. Karger AG, Basel.

Transcriptional Profiling of Type II Toxin–Antitoxin Genes of Helicobacter pylori under Different Environmental Conditions: Identification of HP0967–HP0968 System

PubMed Central

Cárdenas-Mondragón, María G.; Ares, Miguel A.; Panunzi, Leonardo G.; Pacheco, Sabino; Camorlinga-Ponce, Margarita; Girón, Jorge A.; Torres, Javier; De la Cruz, Miguel A.

2016-01-01

Helicobacter pylori is a Gram-negative bacterium that colonizes the human gastric mucosa and is responsible for causing peptic ulcers and gastric carcinoma. The expression of virulence factors allows the persistence of H. pylori in the stomach, which results in a chronic, sometimes uncontrolled inflammatory response. Type II toxin–antitoxin (TA) systems have emerged as important virulence factors in many pathogenic bacteria. Three type II TA systems have previously been identified in the genome of H. pylori 26695: HP0315–HP0316, HP0892–HP0893, and HP0894–HP0895. Here we characterized a heretofore undescribed type II TA system in H. pylori, HP0967–HP0968, which is encoded by the bicistronic operon hp0968–hp0967 and belongs to the Vap family. The predicted HP0967 protein is a toxin with ribonuclease activity whereas HP0968 is an antitoxin that binds to its own regulatory region. We found that all type II TA systems were expressed in H. pylori during early stationary growth phase, and differentially expressed in the presence of urea, nickel, and iron, although, the hp0968–hp0967 pair was the most affected under these environmental conditions. Transcription of hp0968–hp0967 was strongly induced in a mature H. pylori biofilm and when the bacteria interacted with AGS epithelial cells. Kanamycin and chloramphenicol considerably boosted transcription levels of all the four type II TA systems. The hp0968–hp0967 TA system was the most frequent among 317 H. pylori strains isolated from all over the world. This study is the first report on the transcription of type II TA genes in H. pylori under different environmental conditions. Our data show that the HP0967 and HP0968 proteins constitute a bona fide type II TA system in H. pylori, whose expression is regulated by environmental cues, which are relevant in the context of infection of the human gastric mucosa. PMID:27920769

Ventilation Host and Risk Area Techniques

DTIC Science & Technology

1982-04-01

A-5 SAE *6 floi TOTAL GMAL i0OM kp FW 08I UPACES i.oRT SP*ISiPwK SP4Cflnl SMC)oE .P Ns STORIES STORES STORIES STCAIES .35? Ali&MOST AI~k POT AIM AR...h31V KV PWv PAlpM WO.W A"! 09hpII’ wvtai NM"mCOOS K? PW STORME STC’ITE STORIES STORIE W9T RI13 NOT PINK MMS Wk 00 1U9ONO 3 A606007 26 12 a6 1 970 299

A Preliminary In Vitro Study on the Efficacy of High-Power Photodynamic Therapy (HLLT): Comparison between Pulsed Diode Lasers and Superpulsed Diode Lasers and Impact of Hydrogen Peroxide with Controlled Stabilization

PubMed Central

Baldoni, Marco; Ghisalberti, Carlo Angelo; Paiusco, Alessio

2016-01-01

Aim. In periodontology lasers have been suggested for the photodynamic therapy (PDT): such therapy can be defined as the inactivation of cells, microorganisms, or molecules induced by light and not by heat. The aim of this study was to evaluate results of PDT using a 980 nm diode laser (Wiser Doctor Smile, Lambda SPA, Italy) combined with hydrogen peroxide, comparing a pulsed diode laser (LI) activity to a high-frequency superpulsed diode laser (LII). Materials and Methods. Primary fibroblasts and keratinocytes cell lines, isolated from human dermis, were irradiated every 48 h for 10 days using LI and LII combined with SiOxyL+ ™ Solution (hydrogen peroxide (HP) stabilized with a glycerol phosphate complex). Two days after the last irradiation, the treated cultures were analyzed by flow cytofluorometry (FACS) and western blotting to quantify keratin 5 and keratin 8 with monoclonal antibodies reactive to cytokeratin 5 and cytokeratin 8. Antimicrobial activity was also evaluated. Results. Both experimental models show the superiority of LII against LI. In parallel, stabilized HP provided better results in the regeneration test in respect to common HP, while the biocidal activity remains comparable. Conclusion. The use of high-frequency lasers combined with stabilized hydrogen peroxide can provide optimal results for a substantial decrease of bacterial count combined with a maximal biostimulation induction of soft tissues and osteogenesis. PMID:27631000

A Preliminary In Vitro Study on the Efficacy of High-Power Photodynamic Therapy (HLLT): Comparison between Pulsed Diode Lasers and Superpulsed Diode Lasers and Impact of Hydrogen Peroxide with Controlled Stabilization.

PubMed

Caccianiga, Gianluigi; Baldoni, Marco; Ghisalberti, Carlo Angelo; Paiusco, Alessio

2016-01-01

Aim. In periodontology lasers have been suggested for the photodynamic therapy (PDT): such therapy can be defined as the inactivation of cells, microorganisms, or molecules induced by light and not by heat. The aim of this study was to evaluate results of PDT using a 980 nm diode laser (Wiser Doctor Smile, Lambda SPA, Italy) combined with hydrogen peroxide, comparing a pulsed diode laser (LI) activity to a high-frequency superpulsed diode laser (LII). Materials and Methods. Primary fibroblasts and keratinocytes cell lines, isolated from human dermis, were irradiated every 48 h for 10 days using LI and LII combined with SiOxyL(+) ™ Solution (hydrogen peroxide (HP) stabilized with a glycerol phosphate complex). Two days after the last irradiation, the treated cultures were analyzed by flow cytofluorometry (FACS) and western blotting to quantify keratin 5 and keratin 8 with monoclonal antibodies reactive to cytokeratin 5 and cytokeratin 8. Antimicrobial activity was also evaluated. Results. Both experimental models show the superiority of LII against LI. In parallel, stabilized HP provided better results in the regeneration test in respect to common HP, while the biocidal activity remains comparable. Conclusion. The use of high-frequency lasers combined with stabilized hydrogen peroxide can provide optimal results for a substantial decrease of bacterial count combined with a maximal biostimulation induction of soft tissues and osteogenesis.

Optimization of aeromedical base locations in New Mexico using a model that considers crash nodes and paths.

PubMed

Erdemir, Elif Tokar; Batta, Rajan; Spielman, Seth; Rogerson, Peter A; Blatt, Alan; Flanigan, Marie

2008-05-01

In a recent paper, Tokar Erdemir et al. (2008) introduce models for service systems with service requests originating from both nodes and paths. We demonstrate how to apply and extend their approach to an aeromedical base location application, with specific focus on the state of New Mexico (NM). The current aeromedical base locations of NM are selected without considering motor vehicle crash paths. Crash paths are the roads on which crashes occur, where each road segment has a weight signifying relative crash occurrence. We analyze the loss in accident coverage and location error for current aeromedical base locations. We also provide insights on the relevance of considering crash paths when selecting aeromedical base locations. Additionally, we look briefly at some of the tradeoff issues in locating additional trauma centers vs. additional aeromedical bases in the current aeromedical system of NM. Not surprisingly, tradeoff analysis shows that by locating additional aeromedical bases, we always attain the required coverage level with a lower cost than with locating additional trauma centers.

A high performance pMOSFET with two-step recessed SiGe-S/D structure for 32 nm node and beyond

NASA Astrophysics Data System (ADS)

Yasutake, Nobuaki; Azuma, Atsushi; Ishida, Tatsuya; Ohuchi, Kazuya; Aoki, Nobutoshi; Kusunoki, Naoki; Mori, Shinji; Mizushima, Ichiro; Morooka, Tetsu; Kawanaka, Shigeru; Toyoshima, Yoshiaki

2007-11-01

A novel SiGe-S/D structure for high performance pMOSFET called two-step recessed SiGe-source/drain (S/D) is developed with careful optimization of recessed SiGe-S/D structure. With this method, hole mobility, short channel effect and S/D resistance in pMOSFET are improved compared with conventional recessed SiGe-S/D structure. To enhance device performance such as drain current drivability, SiGe region has to be closer to channel region. Then, conventional deep SiGe-S/D region with carefully optimized shallow SiGe SDE region showed additional device performance improvement without SCE degradation. As a result, high performance 24 nm gate length pMOSFET was demonstrated with drive current of 451 μA/μm at ∣ Vdd∣ of 0.9 V and Ioff of 100 nA/μm (552 μA/μm at ∣ Vdd∣ of 1.0 V). Furthermore, by combining with Vdd scaling, we indicate the extendability of two-step recessed SiGe-S/D structure down to 15 nm node generation.

A novel approach of ensuring layout regularity correct by construction in advanced technologies

NASA Astrophysics Data System (ADS)

Ahmed, Shafquat Jahan; Vaderiya, Yagnesh; Gupta, Radhika; Parthasarathy, Chittoor; Marin, Jean-Claude; Robert, Frederic

2017-03-01

In advanced technology nodes, layout regularity has become a mandatory prerequisite to create robust designs less sensitive to variations in manufacturing process in order to improve yield and minimizing electrical variability. In this paper we describe a method for designing regular full custom layouts based on design and process co-optimization. The method includes various design rule checks that can be used on-the-fly during leaf-cell layout development. We extract a Layout Regularity Index (LRI) from the layouts based on the jogs, alignments and pitches used in the design for any given metal layer. Regularity Index of a layout is the direct indicator of manufacturing yield and is used to compare the relative health of different layout blocks in terms of process friendliness. The method has been deployed for 28nm and 40nm technology nodes for Memory IP and is being extended to other IPs (IO, standard-cell). We have quantified the gain of layout regularity with the deployed method on printability and electrical characteristics by process-variation (PV) band simulation analysis and have achieved up-to 5nm reduction in PV band.

Data Transfers Among the HP-75, HP-86, and HP-9845 Microcomputers.

DTIC Science & Technology

1983-01-01

AD-A139 438 DAT TRANSFERS AMONG THE HP-75 HP-86 AND HP-9845 / MICROCOMPUTENS(U) AIR FORCE INST OF TECH WNIOHT-PATTERSON AFN OH D P CONNOR 1983...hereafter called the ඓ") and the HP-86 (hereafter called the ඞ"). The computers are to be used for classroom instruction and research at SOC. On...the main campus another Hewlett-Packard desktop computer, the HP-9845 (hereafter called the 񕚕"), is already in use; it controls and processes data

Radiation Status of Sub-65 nm Electronics

NASA Technical Reports Server (NTRS)

Pellish, Jonathan A.

2011-01-01

Ultra-scaled complementary metal oxide semiconductor (CMOS) includes commercial foundry capabilities at and below the 65 nm technology node Radiation evaluations take place using standard products and test characterization vehicles (memories, logic/latch chains, etc.) NEPP focus is two-fold: (1) Conduct early radiation evaluations to ascertain viability for future NASA missions (i.e. leverage commercial technology development). (2) Uncover gaps in current testing methodologies and mechanism comprehension -- early risk mitigation.

Integrated approach to improving local CD uniformity in EUV patterning

NASA Astrophysics Data System (ADS)

Liang, Andrew; Hermans, Jan; Tran, Timothy; Viatkina, Katja; Liang, Chen-Wei; Ward, Brandon; Chuang, Steven; Yu, Jengyi; Harm, Greg; Vandereyken, Jelle; Rio, David; Kubis, Michael; Tan, Samantha; Dusa, Mircea; Singhal, Akhil; van Schravendijk, Bart; Dixit, Girish; Shamma, Nader

2017-03-01

Extreme ultraviolet (EUV) lithography is crucial to enabling technology scaling in pitch and critical dimension (CD). Currently, one of the key challenges of introducing EUV lithography to high volume manufacturing (HVM) is throughput, which requires high source power and high sensitivity chemically amplified photoresists. Important limiters of high sensitivity chemically amplified resists (CAR) are the effects of photon shot noise and resist blur on the number of photons received and of photoacids generated per feature, especially at the pitches required for 7 nm and 5 nm advanced technology nodes. These stochastic effects are reflected in via structures as hole-to-hole CD variation or local CD uniformity (LCDU). Here, we demonstrate a synergy of film stack deposition, EUV lithography, and plasma etch techniques to improve LCDU, which allows the use of high sensitivity resists required for the introduction of EUV HVM. Thus, to improve LCDU to a level required by 5 nm node and beyond, film stack deposition, EUV lithography, and plasma etch processes were combined and co-optimized to enhance LCDU reduction from synergies. Test wafers were created by depositing a pattern transfer stack on a substrate representative of a 5 nm node target layer. The pattern transfer stack consisted of an atomically smooth adhesion layer and two hardmasks and was deposited using the Lam VECTOR PECVD product family. These layers were designed to mitigate hole roughness, absorb out-of-band radiation, and provide additional outlets for etch to improve LCDU and control hole CD. These wafers were then exposed through an ASML NXE3350B EUV scanner using a variety of advanced positive tone EUV CAR. They were finally etched to the target substrate using Lam Flex dielectric etch and Kiyo conductor etch systems. Metrology methodologies to assess dimensional metrics as well as chip performance and defectivity were investigated to enable repeatable patterning process development. Illumination conditions in EUV lithography were optimized to improve normalized image log slope (NILS), which is expected to reduce shot noise related effects. It can be seen that the EUV imaging contrast improvement can further reduce post-develop LCDU from 4.1 nm to 3.9 nm and from 2.8 nm to 2.6 nm. In parallel, etch processes were developed to further reduce LCDU, to control CD, and to transfer these improvements into the final target substrate. We also demonstrate that increasing post-develop CD through dose adjustment can enhance the LCDU reduction from etch. Similar trends were also observed in different pitches down to 40 nm. The solutions demonstrated here are critical to the introduction of EUV lithography in high volume manufacturing. It can be seen that through a synergistic deposition, lithography, and etch optimization, LCDU at a 40 nm pitch can be improved to 1.6 nm (3-sigma) in a target oxide layer and to 1.4 nm (3-sigma) at the photoresist layer.

Sentinel Node Mapping Using a Fluorescent Dye and Visible Light During Laparoscopic Gastrectomy for Early Gastric Cancer: Result of a Prospective Study From a Single Institute.

PubMed

Lee, Chang Min; Park, Sungsoo; Park, Seong-Heum; Jung, Sung Woo; Choe, Jung Wan; Sul, Ji-Young; Jang, You Jin; Mok, Young-Jae; Kim, Jong-Han

2017-04-01

The aim of this study was to investigate the feasibility of sentinel node mapping using a fluorescent dye and visible light in patients with gastric cancer. Recently, fluorescent imaging technology offers improved visibility with the possibility of better sensitivity or accuracy in sentinel node mapping. Twenty patients with early gastric cancer, for whom laparoscopic distal gastrectomy with standard lymphadenectomy had been planned, were enrolled in this study. Before lymphadenectomy, the patients received a gastrofiberoscopic peritumoral injection of fluorescein solution. The sentinel basin was investigated via laparoscopic fluorescent imaging under blue light (wavelength of 440-490 nm) emitted from an LED curing light. The detection rate and lymph node status were analyzed in the enrolled patients. In addition, short-term clinical outcomes were also investigated. No hypersensitivity to the dye was identified in any enrolled patients. Sentinel nodes were detected in 19 of 20 enrolled patients (95.0%), and metastatic lymph nodes were found in 2 patients. The latter lymph nodes belonged to the sentinel basin of each patient. Meanwhile, 1 patient (5.0%) experienced a postoperative complication that was unrelated to sentinel node mapping. No mortality was recorded among enrolled cases. Sentinel node mapping with visible light fluorescence was a feasible method for visualizing sentinel nodes in patients with early gastric cancer. In addition, this method is advantageous in terms of visualizing the concrete relationship between the sentinel nodes and surrounding structures.

Performance evaluation of modulation and multiple access schemes in ultraviolet optical wireless connections for two atmosphere thickness cases.

PubMed

Raptis, Nikos; Pikasis, Evangelos; Syvridis, Dimitris

2016-08-01

The exploitation of optical wireless communication channels in a non-line-of-sight regime is studied for point-to-point and networking configurations considering the use of light-emitting diodes. Two environments with different scattering center densities are considered, assuming operation at 265 nm. The bit error rate performance of both pulsed and multicarrier modulation schemes is examined, using numerical approaches. In the networking scenario, a central node only receives data, one node transmits useful data, and the rest of them act as interferers. The performance of the desirable node's transmissions is evaluated. The access to the medium is controlled by a code division multiple access scheme.

Development of Low Parasitic Light Sensitivity and Low Dark Current 2.8 μm Global Shutter Pixel †

PubMed Central

Yokoyama, Toshifumi; Tsutsui, Masafumi; Suzuki, Masakatsu; Nishi, Yoshiaki; Mizuno, Ikuo; Lahav, Assaf

2018-01-01

We developed a low parasitic light sensitivity (PLS) and low dark current 2.8 μm global shutter pixel. We propose a new inner lens design concept to realize both low PLS and high quantum efficiency (QE). 1/PLS is 7700 and QE is 62% at a wavelength of 530 nm. We also propose a new storage-gate based memory node for low dark current. P-type implants and negative gate biasing are introduced to suppress dark current at the surface of the memory node. This memory node structure shows the world smallest dark current of 9.5 e−/s at 60 °C. PMID:29370146

Development of Low Parasitic Light Sensitivity and Low Dark Current 2.8 μm Global Shutter Pixel.

PubMed

Yokoyama, Toshifumi; Tsutsui, Masafumi; Suzuki, Masakatsu; Nishi, Yoshiaki; Mizuno, Ikuo; Lahav, Assaf

2018-01-25

Abstract : We developed a low parasitic light sensitivity (PLS) and low dark current 2.8 μm global shutter pixel. We propose a new inner lens design concept to realize both low PLS and high quantum efficiency (QE). 1/PLS is 7700 and QE is 62% at a wavelength of 530 nm. We also propose a new storage-gate based memory node for low dark current. P-type implants and negative gate biasing are introduced to suppress dark current at the surface of the memory node. This memory node structure shows the world smallest dark current of 9.5 e - /s at 60 °C.

Cubature versus Fekete-Gauss nodes for spectral element methods on simplicial meshes

NASA Astrophysics Data System (ADS)

Pasquetti, Richard; Rapetti, Francesca

2017-10-01

In a recent JCP paper [9], a higher order triangular spectral element method (TSEM) is proposed to address seismic wave field modeling. The main interest of this TSEM is that the mass matrix is diagonal, so that an explicit time marching becomes very cheap. This property results from the fact that, similarly to the usual SEM (say QSEM), the basis functions are Lagrange polynomials based on a set of points that shows both nice interpolation and quadrature properties. In the quadrangle, i.e. for the QSEM, the set of points is simply obtained by tensorial product of Gauss-Lobatto-Legendre (GLL) points. In the triangle, finding such an appropriate set of points is however not trivial. Thus, the work of [9] follows anterior works that started in 2000's [2,6,11] and now provides cubature nodes and weights up to N = 9, where N is the total degree of the polynomial approximation. Here we wish to evaluate the accuracy of this cubature nodes TSEM with respect to the Fekete-Gauss one, see e.g.[12], that makes use of two sets of points, namely the Fekete points and the Gauss points of the triangle for interpolation and quadrature, respectively. Because the Fekete-Gauss TSEM is in the spirit of any nodal hp-finite element methods, one may expect that the conclusions of this Note will remain relevant if using other sets of carefully defined interpolation points.

22 years of photodynamic therapy in China

NASA Astrophysics Data System (ADS)

Li, Jun-Heng

2005-07-01

The development of laser medicine in China is correlated with the development of laser science in China. The first Chinese ruby laser was created in 1961. Chinese pharmacists produced the Chinese HpD in 1981 and the first case of PDT was treated using Chinese HpD and Chinese laser equipment in the same year in Beijing. Its success brought attention establishing a research group supported by the government in 1982. A systemic research on PDT was then carried out and obvious results were achieved. The step taken for PDT also accelerated the researches on other kinds of laser medicine and surgery. Since 1982, thousands of patients of malignant tumors including tumors of the lung, esophagus, cardia, stomach, rectum, bladder, other urinary genital organs, face and mouth, eyes, ENT, head and neck, breast, and skin were treated using PDT in China. HpD fluorescence was examined in some centers. Except the superficial tumor cases, PDT procedures were done through the endoscopes. Since 1990"s, imaging guided percutaneous PDT was adopted in the organs cannot be reached by the endoscopes, such as liver cancer, peripheral lung cancer and others. PDT can be used for non-malignant cases such as occlusion of blood vessels, for example, we invented the treatment of port wine stains by PDT. Regular surgical operation combined with PDT for cerebral glioma showed to be a very good combination. HpD has been approved by the Chinese Government as a photosensitizer, so it is legal to be used in PDT. There are some second generation photosensitizers under studying in China, such as Hematoporphyrin monomethyl ether (HMME) etc. Lasers used for PDT now are mostly the diode laser of 630nm for the cancers. Research studies for PDT in China may be focalized on the aspects as new photosensitizers; the dosimetry in laser irradiation; atoptosis induced by PDT; preclinical and clinical studies for PDT new indications and new technologies.

Formulation of avanafil in a solid self-nanoemulsifying drug delivery system for enhanced oral delivery.

PubMed

Soliman, Kareem AbuBakr; Ibrahim, Howida Kamal; Ghorab, Mahmoud Mohammed

2016-10-10

Avanafil was incorporated into solid self-nanoemulsifying systems with the aim of improving its oral bioavailability. Labrafil, Labrafac, and Miglyol 812 N were investigated as oils, Tween 80 and Cremophor EL as surfactants, and Transcutol HP as a co-surfactant. Nine formulations produced clear solutions of 13.89-38.09nm globules after aqueous dilution. Adsorption of preconcentrate onto Aeroperl 300 Pharma at a 2:1 ratio had no effect on nanoemulsion particle size. Differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy indicated that avanafil was molecularly dispersed within the solid nanosystems. A formulation containing 10% Labrafil, 60% Tween 80, and 30% Transcutol HP had the highest drug loading (44.48mg/g) and an acceptable in vitro dissolution profile (96.42% within 30min). This formulation was chemically and physically stable for 6months under accelerated storage conditions and it produced a 3.2-fold increase in bioavailability in rabbits, as compared to conventional commercially available avanafil tablets (Spedra(®)). Copyright © 2016 Elsevier B.V. All rights reserved.

Prognostic value of Helicobacter pylori sinonasal colonization for efficacy of endoscopic sinus surgery.

PubMed

Jelavic, Boris; Grgić, Marko; Cupić, Hrvoje; Kordić, Mirko; Vasilj, Mirjana; Baudoin, Tomislav

2012-10-01

Compared with rhinologic patients without chronic rhinosinusitis (CRS), a higher prevalence of sinonasal Helicobacter pylori (HP) in patients with CRS was found. This study investigated if HP sinonasal colonization has a prognostic value for efficacy of functional endoscopic sinus surgery (FESS). Nasal polyps of 40 patients with CRS, undergoing FESS, were analyzed for presence of HP using immunohistochemistry (IHC). Patients were categorized as to whether the IHC was positive (HP+ group) or negative (HP- group). HP+ group and HP- group were compared according to the nasal polyp eosinophil density, and to the improvement (difference between pre- and post-operative scores) of the subjective symptom scores, and the nasal endoscopic scores. Nasal polyps in 28 (70%) patients were positive for HP. There were no significant differences between HP+ group and HP- group comparing the eosinophils, and the improvement of the single symptom and the total symptom scores. HP+ group had significantly greater improvement of the nasal endoscopic scores (F[1.38] = 6.212; P = 0.017). There is no influence of sinonasal HP on tissue eosinophilia and on CRS symptoms. There is a prognostic value for endonasal findings: CRS patients with HP have statistically significant greater improvement of the postoperative endoscopic scores.

Haptoglobin gene subtypes in three Brazilian population groups of different ethnicities

PubMed Central

2009-01-01

Haptoglobin is a plasma hemoglobin-binding protein that limits iron loss during normal erythrocyte turnover and hemolysis, thereby preventing oxidative damage mediated by iron excess in the circulation. Haptoglobin polymorphism in humans, characterized by the Hp*1 and Hp *2 alleles, results in distinct phenotypes known as Hp1-1, Hp2-1 and Hp2-2, whose frequencies vary according to the ethnic origin of the population. The Hp*1 allele has two subtypes, Hp *1F and Hp *1S , that also vary in their frequencies among populations worldwide. In this work, we examined the distribution frequencies of haptoglobin subtypes in three Brazilian population groups of different ethnicities. The haptoglobin genotypes of Kayabi Amerindians (n = 56), Kalunga Afro-descendants (n = 70) and an urban population (n = 132) were determined by allele-specific PCR. The Hp*1F allele frequency was highest in Kalunga (29.3%) and lowest in Kayabi (2.6%). The Hp*1F/Hp*1S allele frequency ratios were 0.6, 1.0 and 0.26 for the Kayabi, Kalunga and urban populations, respectively. This variation was attributable largely to the Hp*1F allele. However, despite the large variation in Hp*1F frequencies, results of F ST (0.0291) indicated slight genetic differentiation among subpopulations of the general Brazilian population studied here. This is the first Brazilian report of variations in the Hp*1F and Hp*1S frequencies among non-Amerindian Brazilians. PMID:21637505

Haptoglobin gene subtypes in three Brazilian population groups of different ethnicities.

PubMed

Miranda-Vilela, Ana L; Akimoto, Arthur K; Alves, Penha C Z; Hiragi, Cássia O; Penalva, Guilherme C; Oliveira, Silviene F; Grisolia, Cesar K; Klautau-Guimarães, Maria N

2009-07-01

Haptoglobin is a plasma hemoglobin-binding protein that limits iron loss during normal erythrocyte turnover and hemolysis, thereby preventing oxidative damage mediated by iron excess in the circulation. Haptoglobin polymorphism in humans, characterized by the Hp(*1) and Hp (*2) alleles, results in distinct phenotypes known as Hp1-1, Hp2-1 and Hp2-2, whose frequencies vary according to the ethnic origin of the population. The Hp(*1) allele has two subtypes, Hp (*1F) and Hp (*1S) , that also vary in their frequencies among populations worldwide. In this work, we examined the distribution frequencies of haptoglobin subtypes in three Brazilian population groups of different ethnicities. The haptoglobin genotypes of Kayabi Amerindians (n = 56), Kalunga Afro-descendants (n = 70) and an urban population (n = 132) were determined by allele-specific PCR. The Hp(*1F) allele frequency was highest in Kalunga (29.3%) and lowest in Kayabi (2.6%). The Hp(*1F)/Hp(*1S) allele frequency ratios were 0.6, 1.0 and 0.26 for the Kayabi, Kalunga and urban populations, respectively. This variation was attributable largely to the Hp(*1F) allele. However, despite the large variation in Hp(*1F) frequencies, results of F (ST) (0.0291) indicated slight genetic differentiation among subpopulations of the general Brazilian population studied here. This is the first Brazilian report of variations in the Hp(*1F) and Hp(*1S) frequencies among non-Amerindian Brazilians.

Haptoglobin Phenotype Among Arab Patients With Mental Disorders.

PubMed

Armaly, Zaher; Farhat, Kamal; Kinaneh, Safa; Farah, Joseph

2018-03-01

Depression, schizophrenia and panic disorder are common mental disorders in the community and hospitalized patients. These mental disorders negatively affect life quality and even expectancy of life. Haptoglobin (Hp) phenotype (Hp 1-1, 1-2, or 2-2) is associated with risk for cardiovascular diseases, but its association with psychiatric disorders, a growing concern in the modern society, has not been studied thoroughly. The aim of the study was to examine whether Hp phenotype is associated with common mental disorders such as depression, schizophrenia, and panic disorder. The study included 92 Arab patients with mental disorders, and among them 44 suffered from schizophrenia (mean age 39 ± 1.5 years), 17 from depression (mean age 44.5 ± 3.1 years), 31 from panic disorder (mean age of 44.9 ± 2.7 years), and 206 healthy Arab control subjects with a mean age of 42.6 ± 0.9 years. Beck's depression inventory assessment and Hamilton depression scale were administered for depression and panic disorder diagnosis. Schizophrenia was evaluated with positive and negative affect schedule (Panas) test. All mental disorders were evaluated by clinical review. Blood analysis for Hp phenotype was performed. Diagnosis was made using the Diagnostic and Statistical Manual of Mental Disorders axis to correlate depression with Hp phenotype. In mentally healthy controls, 10.7% were Hp 1-1, 38.8% Hp 2-1, and 50.5% Hp 2-2. In patients with the studied psychiatric disorders, Hp phenotype was comparable to healthy subjects; 8.7% were Hp 1-1, 50% Hp 2-1, and 41.3% Hp 2-2. When Hp phenotyping was analyzed in the psychiatric subgroups, Hp 2-1 was more common among depressed and schizophrenic patients, as compared with healthy subjects (58.8% and 52.3% vs. 38.8%). In patients who suffer from panic disorder, Hp phenotype distribution was 6.5% Hp 1-1, 41.9% Hp 2-1, and 51.6% Hp 2-2, suggesting a lower prevalence among Hp 1-1 phenotype. Arab patients who carry Hp 2-1 phenotype may be at risk to develop depression or schizophrenia more than the general healthy population. In contrast, Hp 1-1 subjects have a lower prevalence of panic disorder.

Pharmacogenomic interaction between the Haptoglobin genotype and vitamin E on atherosclerotic plaque progression and stability.

PubMed

Veiner, Hilla-Lee; Gorbatov, Rostic; Vardi, Moshe; Doros, Gheorghe; Miller-Lotan, Rachel; Zohar, Yaniv; Sabo, Edmond; Asleh, Rabea; Levy, Nina S; Goldfarb, Levi J; Berk, Thomas A; Haas, Tali; Shalom, Hadar; Suss-Toby, Edith; Kam, Adi; Kaplan, Marielle; Tamir, Ronit; Ziskind, Anna; Levy, Andrew P

2015-03-01

Homozygosity for a 1.7 kb intragenic duplication of the Haptoglobin (Hp) gene (Hp 2-2 genotype), present in 36% of the population, has been associated with a 2-3 fold increased incidence of atherothrombosis in individuals with Diabetes (DM) in 10 longitudinal studies compared to DM individuals not homozygous for this duplication (Hp 1-1/2-1). The increased CVD risk associated with the Hp 2-2 genotype has been shown to be prevented with vitamin E supplementation in man. We sought to determine if there was an interaction between the Hp genotype and vitamin E on atherosclerotic plaque growth and stability in a transgenic model of the Hp polymorphism. Brachiocephalic artery atherosclerotic plaque volume was serially assessed by high resolution ultrasound in 28 Hp 1-1 and 26 Hp 2-2 mice in a C57Bl/6 ApoE(-/-) background. Hp 2-2 mice had more rapid plaque growth and an increased incidence of plaque hemorrhage and rupture. Vitamin E significantly reduced plaque growth in Hp 2-2 but not in Hp 1-1 mice with a significant pharmacogenomic interaction between the Hp genotype and vitamin E on plaque growth. These results may help explain why vitamin E supplementation in man can prevent CVD in Hp 2-2 DM but not in non Hp 2-2 DM individuals. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A comparison of advanced overlay technologies

NASA Astrophysics Data System (ADS)

Dasari, Prasad; Smith, Nigel; Goelzer, Gary; Liu, Zhuan; Li, Jie; Tan, Asher; Koh, Chin Hwee

2010-03-01

The extension of optical lithography to 22nm and beyond by Double Patterning Technology is often challenged by CDU and overlay control. With reduced overlay measurement error budgets in the sub-nm range, relying on traditional Total Measurement Uncertainty (TMU) estimates alone is no longer sufficient. In this paper we will report scatterometry overlay measurements data from a set of twelve test wafers, using four different target designs. The TMU of these measurements is under 0.4nm, within the process control requirements for the 22nm node. Comparing the measurement differences between DBO targets (using empirical and model based analysis) and with image-based overlay data indicates the presence of systematic and random measurement errors that exceeds the TMU estimate.

Epidemiology and Health-Related Quality of Life in Hypoparathyroidism in Norway

PubMed Central

Løvås, Kristian; Debowska, Aleksandra; Eriksen, Erik F.; Evang, Johan A.; Fossum, Christian; Fougner, Kristian J.; Holte, Synnøve E.; Lima, Kari; Moe, Ragnar B.; Myhre, Anne Grethe; Kemp, E. Helen; Nedrebø, Bjørn G.; Svartberg, Johan; Husebye, Eystein S.

2016-01-01

Objective: The epidemiology of hypoparathyroidism (HP) is largely unknown. We aimed to determine prevalence, etiologies, health related quality of life (HRQOL) and treatment pattern of HP. Methods: Patients with HP and 22q11 deletion syndrome (DiGeorge syndrome) were identified in electronic hospital registries. All identified patients were invited to participate in a survey. Among patients who responded, HRQOL was determined by Short Form 36 and Hospital Anxiety and Depression scale. Autoantibodies were measured and candidate genes (CaSR, AIRE, GATA3, and 22q11-deletion) were sequenced for classification of etiology. Results: We identified 522 patients (511 alive) and estimated overall prevalence at 102 per million divided among postsurgical HP (64 per million), nonsurgical HP (30 per million), and pseudo-HP (8 per million). Nonsurgical HP comprised autosomal dominant hypocalcemia (21%), autoimmune polyendocrine syndrome type 1 (17%), DiGeorge/22q11 deletion syndrome (15%), idiopathic HP (44%), and others (4%). Among the 283 respondents (median age, 53 years [range, 9–89], 75% females), seven formerly classified as idiopathic were reclassified after genetic and immunological analyses, whereas 26 (37% of nonsurgical HP) remained idiopathic. Most were treated with vitamin D (94%) and calcium (70%), and 10 received PTH. HP patients scored significantly worse than the normative population on Short Form 36 and Hospital Anxiety and Depression scale; patients with postsurgical scored worse than those with nonsurgical HP and pseudo-HP, especially on physical health. Conclusions: We found higher prevalence of nonsurgical HP in Norway than reported elsewhere. Genetic testing and autoimmunity screening of idiopathic HP identified a specific cause in 21%. Further research is necessary to unravel the causes of idiopathic HP and to improve the reduced HRQOL reported by HP patients. PMID:27186861

Epidemiology and Health-Related Quality of Life in Hypoparathyroidism in Norway.

PubMed

Astor, Marianne C; Løvås, Kristian; Debowska, Aleksandra; Eriksen, Erik F; Evang, Johan A; Fossum, Christian; Fougner, Kristian J; Holte, Synnøve E; Lima, Kari; Moe, Ragnar B; Myhre, Anne Grethe; Kemp, E Helen; Nedrebø, Bjørn G; Svartberg, Johan; Husebye, Eystein S

2016-08-01

The epidemiology of hypoparathyroidism (HP) is largely unknown. We aimed to determine prevalence, etiologies, health related quality of life (HRQOL) and treatment pattern of HP. Patients with HP and 22q11 deletion syndrome (DiGeorge syndrome) were identified in electronic hospital registries. All identified patients were invited to participate in a survey. Among patients who responded, HRQOL was determined by Short Form 36 and Hospital Anxiety and Depression scale. Autoantibodies were measured and candidate genes (CaSR, AIRE, GATA3, and 22q11-deletion) were sequenced for classification of etiology. We identified 522 patients (511 alive) and estimated overall prevalence at 102 per million divided among postsurgical HP (64 per million), nonsurgical HP (30 per million), and pseudo-HP (8 per million). Nonsurgical HP comprised autosomal dominant hypocalcemia (21%), autoimmune polyendocrine syndrome type 1 (17%), DiGeorge/22q11 deletion syndrome (15%), idiopathic HP (44%), and others (4%). Among the 283 respondents (median age, 53 years [range, 9-89], 75% females), seven formerly classified as idiopathic were reclassified after genetic and immunological analyses, whereas 26 (37% of nonsurgical HP) remained idiopathic. Most were treated with vitamin D (94%) and calcium (70%), and 10 received PTH. HP patients scored significantly worse than the normative population on Short Form 36 and Hospital Anxiety and Depression scale; patients with postsurgical scored worse than those with nonsurgical HP and pseudo-HP, especially on physical health. We found higher prevalence of nonsurgical HP in Norway than reported elsewhere. Genetic testing and autoimmunity screening of idiopathic HP identified a specific cause in 21%. Further research is necessary to unravel the causes of idiopathic HP and to improve the reduced HRQOL reported by HP patients.

Mask manufacturing of advanced technology designs using multi-beam lithography (part 2)

NASA Astrophysics Data System (ADS)

Green, Michael; Ham, Young; Dillon, Brian; Kasprowicz, Bryan; Hur, Ik Boum; Park, Joong Hee; Choi, Yohan; McMurran, Jeff; Kamberian, Henry; Chalom, Daniel; Klikovits, Jan; Jurkovic, Michal; Hudek, Peter

2016-09-01

As optical lithography is extended into 10nm and below nodes, advanced designs are becoming a key challenge for mask manufacturers. Techniques including advanced optical proximity correction (OPC) and Inverse Lithography Technology (ILT) result in structures that pose a range of issues across the mask manufacturing process. Among the new challenges are continued shrinking sub-resolution assist features (SRAFs), curvilinear SRAFs, and other complex mask geometries that are counter-intuitive relative to the desired wafer pattern. Considerable capability improvements over current mask making methods are necessary to meet the new requirements particularly regarding minimum feature resolution and pattern fidelity. Advanced processes using the IMS Multi-beam Mask Writer (MBMW) are feasible solutions to these coming challenges. In this paper, Part 2 of our study, we further characterize an MBMW process for 10nm and below logic node mask manufacturing including advanced pattern analysis and write time demonstration.

Quantum storage of entangled telecom-wavelength photons in an erbium-doped optical fibre

NASA Astrophysics Data System (ADS)

Saglamyurek, Erhan; Jin, Jeongwan; Verma, Varun B.; Shaw, Matthew D.; Marsili, Francesco; Nam, Sae Woo; Oblak, Daniel; Tittel, Wolfgang

2015-02-01

The realization of a future quantum Internet requires the processing and storage of quantum information at local nodes and interconnecting distant nodes using free-space and fibre-optic links. Quantum memories for light are key elements of such quantum networks. However, to date, neither an atomic quantum memory for non-classical states of light operating at a wavelength compatible with standard telecom fibre infrastructure, nor a fibre-based implementation of a quantum memory, has been reported. Here, we demonstrate the storage and faithful recall of the state of a 1,532 nm wavelength photon entangled with a 795 nm photon, in an ensemble of cryogenically cooled erbium ions doped into a 20-m-long silica fibre, using a photon-echo quantum memory protocol. Despite its currently limited efficiency and storage time, our broadband light-matter interface brings fibre-based quantum networks one step closer to reality.

Near-infrared autofluorescence imaging to detect parathyroid glands in thyroid surgery.

PubMed

Ladurner, R; Al Arabi, N; Guendogar, U; Hallfeldt, Kkj; Stepp, H; Gallwas, Jks

2018-01-01

Objective To identify and save parathyroid glands during thyroidectomy by displaying their autofluorescence. Methods Autofluorescence imaging was carried out during thyroidectomy with and without central lymph node dissection. After visual recognition by the surgeon, the parathyroid glands and the surrounding tissue were exposed to near-infrared light with a wavelength of 690-770 nm using a modified Karl Storz near infrared/indocyanine green endoscopic system. Parathyroid tissue was expected to show near infrared autofluorescence at 820 nm, captured in the blue channel of the camera. Results We investigated 41 parathyroid glands from 20 patients; 37 glands were identified correctly based on near-infrared autofluorescence. Neither lymph nodes nor thyroid revealed substantial autofluorescence and nor did adipose tissue. Conclusions Parathyroid tissue is characterised by showing autofluorescence in the near-infrared spectrum. This effect can be used to identify and preserve parathyroid glands during thyroidectomy.

EUV local CDU healing performance and modeling capability towards 5nm node

NASA Astrophysics Data System (ADS)

Jee, Tae Kwon; Timoshkov, Vadim; Choi, Peter; Rio, David; Tsai, Yu-Cheng; Yaegashi, Hidetami; Koike, Kyohei; Fonseca, Carlos; Schoofs, Stijn

2017-10-01

Both local variability and optical proximity correction (OPC) errors are big contributors to the edge placement error (EPE) budget which is closely related to the device yield. The post-litho contact hole healing will be demonstrated to meet after-etch local variability specifications using a low dose, 30mJ/cm2 dose-to-size, positive tone developed (PTD) resist with relevant throughput in high volume manufacturing (HVM). The total local variability of the node 5nm (N5) contact holes will be characterized in terms of local CD uniformity (LCDU), local placement error (LPE), and contact edge roughness (CER) using a statistical methodology. The CD healing process has complex etch proximity effects, so the OPC prediction accuracy is challenging to meet EPE requirements for the N5. Thus, the prediction accuracy of an after-etch model will be investigated and discussed using ASML Tachyon OPC model.

Low leakage Ru-strontium titanate-Ru metal-insulator-metal capacitors for sub-20 nm technology node in dynamic random access memory

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

Popovici, M., E-mail: Mihaela.Ioana.Popovici@imec.be; Swerts, J.; Redolfi, A.

2014-02-24

Improved metal-insulator-metal capacitor (MIMCAP) stacks with strontium titanate (STO) as dielectric sandwiched between Ru as top and bottom electrode are shown. The Ru/STO/Ru stack demonstrates clearly its potential to reach sub-20 nm technology nodes for dynamic random access memory. Downscaling of the equivalent oxide thickness, leakage current density (J{sub g}) of the MIMCAPs, and physical thickness of the STO have been realized by control of the Sr/Ti ratio and grain size using a heterogeneous TiO{sub 2}/STO based nanolaminate stack deposition and a two-step crystallization anneal. Replacement of TiN with Ru as both top and bottom electrodes reduces the amount of electricallymore » active defects and is essential to achieve a low leakage current in the MIM capacitor.« less

Optical characterization of ex-vivo axillary lymph nodes of breast-cancer patients using a custom-built spectrophotometer

NASA Astrophysics Data System (ADS)

Sampathkumar, Ashwin; Saegusa-Beecroft, Emi; Mamou, Jonathan; Chitnis, Parag V.; Machi, Junji; Feleppa, Ernest J.

2014-03-01

Quantitative photoacoustics is emerging as a new hybrid modality to investigate diseases and cells in human pathology and cytology studies. Optical absorption of light is the predominant mechanism behind the photoacoustic effect. Therefore, a need exits to characterize the optical properties of specimens and to identify the relevant operating wavelengths for photoacoustic imaging. We have developed a custom low-cost spectrophotometer to measure the optical properties of human axillary lymph nodes dissected for breast-cancer staging. Optical extinction curves of positive and negative nodes were determined in the spectral range of 400 to 1000 nm. We have developed a model to estimate tissue optical properties, taking into account the role of fat and saline. Our results enabled us to select the optimal optical wavelengths for maximizing the imaging contrast between metastatic and noncancerous tissue in axillary lymph nodes.

Influence of twin boundaries on superconducting gap nodes in FeSe single crystal studied by STM/STS

NASA Astrophysics Data System (ADS)

Watashige, T.; Hanaguri, T.; Kohsaka, Y.; Iwaya, K.; Fu, Y.; Kasahara, S.; Watanabe, D.; Mizukami, Y.; Mikami, T.; Kawamoto, Y.; Kurata, S.; Shibauchi, T.; Matsuda, Y.; Böhmer, A. E.; Wolf, T.; Meingast, C.; Löhneysen, H. V.

2014-03-01

We performed scanning tunneling microscopy (STM) and spectroscopy (STS) measurements on high-quality FeSe single crystals grown by vapor transport technique to examine the superconducting-gap structure. In MBE-grown FeSe thin films, based on the V-shaped tunneling spectra, nodal superconductivity is suggested. It is interesting to investigate how the nodes are affected by various kinds of defects. We found that twin boundaries bring about drastic effects on the gap nodes. With approaching to the twin boundary, V-shaped spectra gradually change to U-shaped ones. Interestingly, in the area between the twin boundaries separated by about 30 nm, the gap node is completely lifted and there appears a finite gap over +/-0.4 meV. This unusual twin-boundary effect will give us a hint to elucidate the superconducting-gap structure.

MIGRATION OF INTRADERMALLY INJECTED QUANTUM DOTS TO SENTINEL ORGANS IN MICE

PubMed Central

Gopee, Neera V.; Roberts, Dean W.; Webb, Peggy; Cozart, Christy R.; Siitonen, Paul H.; Warbritton, Alan R.; Yu, William W.; Colvin, Vicki L.; Walker, Nigel J.; Howard, Paul C.

2012-01-01

Topical exposure to nanoscale materials is likely from a variety of sources including sunscreens and cosmetics. Because the in vivo disposition of nanoscale materials is not well understood, we have evaluated the distribution of quantum dots (QD) following intradermal injection into female SKH-1 hairless mice as a model system for determining tissue localization following intradermal infiltration. The QD [CdSe core, CdS capped, poly(ethylene glycol) (PEG) coated, 37 nm diameter, 621 nm fluorescence emission] were injected intradermally on the right dorsal flank. Within minutes following intradermal injection, the highly UV fluorescent QD could be observed moving from the injection sites apparently through the lymphatic duct system to regional lymph nodes. Residual fluorescent QD remained at the site of injection until necropsy at 24 hours. Quantification of cadmium and selenium levels after 0, 4, 8, 12 or 24 hours in multiple tissues, using inductively coupled plasma mass spectrometry (ICP-MS) showed a time-dependent loss of cadmium from the injection site, and accumulation in the liver, regional draining lymph nodes, kidney, spleen, and hepatic lymph node. Fluorescence microscopy corroborated the ICP-MS results regarding the tissue distribution of QD. The results indicated that (a) intradermally injected nanoscale QD remained as a deposit in skin and penetrated the surrounding viable subcutis, (b) QD were distributed to draining lymph nodes through the subcutaneous lymphatics and to the liver and other organs, and (c) sentinel organs are effective locations for monitoring transdermal penetration of nanoscale materials into animals. PMID:17404394

Lung Transplantation for Hypersensitivity Pneumonitis

PubMed Central

Singer, Jonathan P.; Koth, Laura; Mooney, Joshua; Golden, Jeff; Hays, Steven; Greenland, John; Wolters, Paul; Ghio, Emily; Jones, Kirk D.; Leard, Lorriana; Kukreja, Jasleen; Blanc, Paul D.

2015-01-01

BACKGROUND: Hypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may necessitate the need for lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared with referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF). METHODS: To identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000 to 2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to referents with IPF. We also reviewed diagnoses of HP discovered only by explant pathology and looked for evidence of recurrent HP after transplant. Survival was compared using Kaplan-Meier methods and Cox proportional hazard modeling. RESULTS: We analyzed 31 subjects with HP and 91 with IPF among 183 cases undergoing lung transplantation for ILD. Survival at 1, 3, and 5 years after lung transplant in HP compared with IPF was 96%, 89%, and 89% vs 86%, 67%, and 49%, respectively. Subjects with HP manifested a reduced adjusted risk for death compared with subjects with IPF (hazard ratio, 0.25; 95% CI, 0.08-0.74; P = .013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in five (16%). Two subjects developed recurrent HP in their allografts. CONCLUSIONS: Overall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk for death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft. PMID:25412059

The haptoglobin promoter polymorphism rs5471 is the most definitive genetic determinant of serum haptoglobin level in a Ghanaian population.

PubMed

Soejima, Mikiko; Teye, Kwesi; Koda, Yoshiro

2018-08-01

The serum haptoglobin (HP) level varies in various clinical conditions and among individuals. Recently, the common HP alleles, rs5472, and rs2000999 have been reported to associate with serum HP level, but no studies have been done on Africans. Here, we explored the relationship of not only these polymorphisms but also rs5470 and rs5471 to the serum HP level in 121 Ghanaians. Genotyping of rs2000999 was performed by PCR using hydrolysis probes, while the other polymorphisms have been already genotyped. Serum HP level was measured by a sandwich ELISA. We observed a significant association between rs5471 and the serum HP level (p = 0.026). It was also observed within the subgroups of HP 2 /HP 2 and HP 2 /HP 1 . In addition, we detected a trend toward lower HP levels for individuals with the A allele of rs2000999 than those without A, but it was not statistically significant (p = 0.156). However, we did not observe the clear associations between other polymorphisms and serum HP level that were observed for Europeans and Asians because of the small sample size and the complexity of SNPs affecting the HP level. We suggest that rs5471 is a strong genetic determinant of HP levels in Ghanaians, and this seems to be characteristic of Africans. Further investigation using large scale samples will help in understanding the genetic background of individual variability of the serum HP level. Copyright © 2018 Elsevier B.V. All rights reserved.

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Science.gov Websites

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Effective EUVL mask cleaning technology solutions for mask manufacturing and in-fab mask maintenance

NASA Astrophysics Data System (ADS)

Dietze, Uwe; Dress, Peter; Waehler, Tobias; Singh, Sherjang; Jonckheere, Rik; Baudemprez, Bart

2011-03-01

Extreme Ultraviolet Lithography (EUVL) is considered the leading lithography technology choice for semiconductor devices at 16nm HP node and beyond. However, before EUV Lithography can enter into High Volume Manufacturing (HVM) of advanced semiconductor devices, the ability to guarantee mask integrity at point-of-exposure must be established. Highly efficient, damage free mask cleaning plays a critical role during the mask manufacturing cycle and throughout the life of the mask, where the absence of a pellicle to protect the EUV mask increases the risk of contamination during storage, handling and use. In this paper, we will present effective EUVL mask cleaning technology solutions for mask manufacturing and in-fab mask maintenance, which employs an intelligent, holistic approach to maximize Mean Time Between Cleans (MBTC) and extend the useful life span of the reticle. The data presented will demonstrate the protection of the capping and absorber layers, preservation of pattern integrity as well as optical and mechanical properties to avoid unpredictable CD-linewidth and overlay shifts. Experiments were performed on EUV blanks and pattern masks using various process conditions. Conditions showing high particle removal efficiency (PRE) and minimum surface layer impact were then selected for durability studies. Surface layer impact was evaluated over multiple cleaning cycles by means of UV reflectivity metrology XPS analysis and wafer prints. Experimental results were compared to computational models. Mask life time predictions where made using the same computational models. The paper will provide a generic overview of the cleaning sequence which yielded best results, but will also provide recommendations for an efficient in-fab mask maintenance scheme, addressing handling, storage, cleaning and inspection.

PEGylated polylysine dendrimers increase lymphatic exposure to doxorubicin when compared to PEGylated liposomal and solution formulations of doxorubicin.

PubMed

Ryan, Gemma M; Kaminskas, Lisa M; Bulitta, Jürgen B; McIntosh, Michelle P; Owen, David J; Porter, Christopher J H

2013-11-28

Improved delivery of chemotherapeutic drugs to the lymphatic system has the potential to augment outcomes for cancer therapy by enhancing activity against lymph node metastases. Uptake of small molecule chemotherapeutics into the lymphatic system, however, is limited. Nano-sized drug carriers have the potential to promote access to the lymphatics, but to this point, this has not been examined in detail. The current study therefore evaluated the lymphatic exposure of doxorubicin after subcutaneous and intravenous administration as a simple solution formulation or when formulated as a doxorubicin loaded PEGylated poly-lysine dendrimer (hydrodynamic diameter 12 nm), a PEGylated liposome (100 nm) and various pluronic micellar formulations (~5 nm) to thoracic lymph duct cannulated rats. Plasma and lymph pharmacokinetics were analysed by compartmental pharmacokinetic modelling in S-ADAPT, and Berkeley Madonna software was used to predict the lymphatic exposure of doxorubicin over an extended period of time. The micelle formulations displayed poor in vivo stability, resulting in doxorubicin profiles that were similar to that observed after administration of the doxorubicin solution formulation. In contrast, the dendrimer formulation significantly increased the recovery of doxorubicin in the thoracic lymph after both intravenous and subcutaneous dosing when compared to the solution or micellar formulation. Dendrimer-doxorubicin also resulted in increases in lymphatic doxorubicin concentrations when compared to the liposome formulation, although liposomal doxorubicin did increase lymphatic transport when compared to the solution formulation. Specifically, the dendrimer formulation increased the recovery of doxorubicin in the lymph up to 30 h post dose by up to 685 fold and 3.7 fold when compared to the solution and liposomal formulations respectively. Using the compartmental model to predict lymphatic exposure to longer time periods suggested that doxorubicin exposure to the lymphatic system would ultimately be 9796 times and 6.1 times greater after administration of dendrimer doxorubicin when compared to the solution and liposome formulations respectively. The recovery of doxorubicin in the sentinel lymph nodes draining the subcutaneous injection site was also quantified directly, and consistent with the lymph pharmacokinetic data, lymph node recovery was greatest for the dendrimer formulation (12% of dosed doxorubicin/g node) when compared to the liposome (1.4%/g node) and solution (<1%/g node) formulations. The data suggest that dendrimer-based drug delivery systems have the potential to enhance drug exposure to lymph-based drug targets such as lymphatic metastases. © 2013.

Panel discussion summary: do we need a revolution in design and process integration to enable sub-100-nm technology nodes?

NASA Astrophysics Data System (ADS)

Grobman, Warren D.

2002-07-01

Dramatically increasing mask set costs, long-loop design-fabrication iterations, and lithography of unprecedented complexity and cost threaten to disrupt time-accepted IC industry progression as described by Moore"s Law. Practical and cost-effective IC manufacturing below the 100nm technology node presents significant and unique new challenges spanning multiple disciplines and overlapping traditionally separable components of the design-through-chip manufacturing flow. Lithographic and other process complexity is compounded by design, mask, and infrastructure technologies, which do not sufficiently account for increasingly stringent and complex manufacturing issues. Deep subwavelength and atomic-scale process and device physics effects increasingly invade and impact the design flow strongly at a time when the pressures for increased design productivity are escalating at a superlinear rate. Productivity gaps, both upstream in design and downstream in fabrication, are anticipated by many to increase due to dramatic increases in inherent complexity of the design-to-chip equation. Furthermore, the cost of lithographic equipment is increasing at an aggressive compound growth rate so large that we can no longer economically derive the benefit of the increased number of circuits per unit area unless we extend the life of lithographic equipment for more generations, and deeper into the subwavelength regime. Do these trends unambiguously lead to the conclusion that we need a revolution in design and design-process integration to enable the sub-100nm nodes? Or is such a premise similar to other well-known predictions of technology brick walls that never came true?

Comparative ileal amino acid digestibility of distillers' grains for growing pigs.

PubMed

Adeola, Olayiwola; Ragland, Darryl

2016-12-01

The objective of the experiment reported here was to investigate and compare the amino acid (AA) digestibility of distillers' dried grains (DDG), distillers' dried grains with solubles (DDGS), high protein distillers' dried grains (HP-DDG), and high protein distillers' dried grains with solubles (HP-DDGS) in growing pigs. Five semi-purified diets consisting of DDG, DDGS, HP-DDG, HP-DDGS, and nitrogen-free diet (NFD) were fed to pigs fitted with simple T-cannula for 5 observations per diet. Endogenous losses of AA at the terminal ileum of pigs that received the NFD were used to calculate standardized ileal digestibility (SID) of AA from apparent ileal digestibility (AID) of AA. The AID of Lys in DDGS was lower ( P  < 0.05) than that in DDG, which was also lower ( P  < 0.05) than that in HP-DDG. There were no differences in AID of Met among DDG, DDGS and HP-DDGS, but was greater ( P  < 0.05) in HP-DDG than in DDG or DDGS. The AID of Thr in HP-DDG was greater ( P  < 0.05) than that in DDGS but not different from that in DDG or HP-DDGS. The branched-chain AA Ile and Leu had greater ( P  < 0.05) AID in HP-DDG than in DDG, DDGS or HP-DDGS, and there was no difference among DDG, DDGS, and HP-DDGS. The AID of Trp in DDG and DDGS or HP-DDG and HP-DDGS were not different, but the AID of Trp in HP-DDGS was greater ( P  < 0.05) than that of DDGS. The greatest SID of the indispensable AA was in HP-DDG. Except for Arg and Lys in which DDG had greater ( P  < 0.05) digestibility, there was no difference between DDG and DDGS in the SID of the indispensable AA. The SID of Lys in DDG was greater ( P  < 0.05) than that of DDGS but there was no difference between that of DDG and HP-DDGS. Only His, Ile, and Met had lower ( P  < 0.05) SID in HP-DDGS than HP-DDG within the indispensable AA. The SID of Ala, Asp, Cys, Glu, Gly, Ser and Tyr were lower ( P  < 0.05) in DDGS than in HP-DDG. There SID of dispensable AA in DDG was not different from that of HP-DDGS. The current study provided apparent and standardized ileal amino acids digestibility values for traditional and high-protein corn distillers' dried grains coproducts for use in formulating swine diets. Amino acid digestibility was generally higher in HP-DDG than in other tested co-products of the dry grind processing of corn for ethanol.

Relationship between shoulder roll and hand propulsion in the front crawl stroke.

PubMed

Kudo, Shigetada; Sakurai, Yoshihisa; Miwa, Takahiro; Matsuda, Yuji

2017-05-01

This study re-evaluated the magnitude of hand propulsion (HP) in the pull and push phases of the front crawl stroke and investigated the association between the angular velocity of shoulder roll (ω SR ) and hand propulsive lift (HP L ). ω SR was computed in the plane normal to a forward direction for 16 skilled swimmers performing the front crawl stroke at a maximal sprinting pace. HP, hand propulsive drag (HP D ) and HP L were determined by a dynamic pressure approach. HP and HP D in the pull phase were greater than in the push phase (P < 0.05) while HP L in the pull phase was similar to that in the push phase. Eleven swimmers out of the 16 swimmers had a significant within-swimmers correlation between ω SR and HP L in the push phase (P < 0.05). That is, HP L increased in the push phase as the ω SR of rolling back to the neutral position became faster. A swimmer should use more drag for hand propulsion in the pull phase and propulsion from drag and lift equally in the push phase. Based on the relationship between ω SR and HP L in the push phase, a possible stroke technique to enhance HP L using ω SR is discussed.

Effect of carboxyl-reduced heparin on the growth inhibition of bovine pulmonary artery smooth muscle cells

PubMed Central

G.Garg, Hari; Mrabat, Hicham; Yu, Lunyin; Freeman, Craig; Li, Boyangzi; Zhang, Fuming; Linhardt, Robert J.; Hales, Charles A.

2010-01-01

Heparin (HP) inhibits the proliferation of bovine pulmonary artery smooth muscle cells (BPASMC's), among other cell types in vitro. In order to develop a potential therapeutic agent to reverse vascular remodeling, we are involved in deciphering the relationship between the native HP structure and its antiproliferative potency. We have previously reported the influence of the molecular size and the effects of various O-sulfo and N-acetyl groups of HP on growth-inhibitory activity. In this study, to understand the influence of carboxyl groups in the HP structure required for endogenous activity, a chemically modified derivative of native HP was prepared by converting the carboxyl groups of hexuronic acid residues in HP to primary hydroxyl groups. This modification procedure involves the treatment of HP with N-(3-dimethylaminopropyl)-N-ethylcarbodiimide followed by reduction with NaBH4 to yield carboxyl-reduced heparin (CR-HP). When compared to the antiproliferative potency of native HP on cultured BPASMC's at three dose levels (1, 10, and 100 μg/mL), the CR-HP showed significantly less potency at all the doses. These results suggest that hexuronic acid residues in both major and variable sequences in HP are essential for the antiproliferative properties of native HP. PMID:20399420

Analysis of Gastric Microbiota by Pyrosequencing: Minor Role of Bacteria Other Than Helicobacter pylori in the Gastric Carcinogenesis.

PubMed

Jo, Hyun Jin; Kim, Jaeyeon; Kim, Nayoung; Park, Ji Hyun; Nam, Ryoung Hee; Seok, Yeong-Jae; Kim, Yeon-Ran; Kim, Joo Sung; Kim, Jung Mogg; Kim, Jung Min; Lee, Dong Ho; Jung, Hyun Chae

2016-10-01

Little is known about the role of gastric microbiota except for Helicobacter pylori (HP) in human health and disease. We compared the differences of human gastric microbiota according to gastric cancer or control and HP infection status and assessed the role of bacteria other than HP. Gastric microbiota of 63 antral mucosal and 18 corpus mucosal samples were analyzed by bar-coded 454 pyrosequencing of the 16S rRNA gene. Antral samples were divided into four subgroups based on HP positivity in pyrosequencing and the presence of cancer. The analysis was focused on bacteria other than HP, especially nitrosating or nitrate-reducing bacteria (NB). The changes of NB in antral mucosa of 16 subjects were followed up. The number of NB other than HP (non-HP-NB) was two times higher in the cancer groups than in the control groups, but it did not reach statistical significance. The number of non-HP-NB tends to increase over time, but this phenomenon was prevented by HP eradication in the HP-positive control group, but not in the HP-positive cancer group. We could not find the significant role of bacteria other than HP in the gastric carcinogenesis. © 2016 John Wiley & Sons Ltd.

Evaluation of Eye Protection Filters Used with Broad-Spectrum and Conventional LED Curing Lights.

PubMed

Soares, Carlos José; Rodrigues, Monise de Paula; Vilela, Andomar Bruno Fernandes; Rizo, Erick René Cerda; Ferreira, Lorraine Braga; Giannini, Marcelo; Price, Richard Bengt

2017-01-01

The high irradiance and the different emission spectra from contemporary light curing units (LCU) may cause ocular damage. This study evaluated the ability of 15 eye protection filters: 2 glasses, 1 paddle design, and 12 dedicated filters to block out harmful light from a monowave (HP-3M ESPE) and a broad-spectrum (Valo, Ultradent) LED LCU. Using the anterior sensor in the MARC-Patient Simulator (BlueLight Analytics) the irradiance that was delivered through different eye protection filters was measured three times. The LCUs delivered a similar irradiance to the top of the filter. The mean values of the light that passed through the filters as percent of the original irradiance were analyzed using two-way ANOVA followed by Tukey test (a= 0.05). The emission spectra from the LCUs and through the filters were also obtained. Two-way ANOVA showed that the interaction between protective filters and LCUs significantly influenced the amount of light transmitted (p< 0.001). Tukey test showed that the amount of light transmitted through the protective filters when using the HP-3M-ESPE was significantly greater compared to when using the Valo, irrespective of the protective filter tested. When using the HP-3M-ESPE, the Glasses filter allowed significantly more light through, followed by XL 3000, ORTUS, Google Professional, Gnatus filters. The Valo filter was the most effective at blocking out the harmful light. Some protective filters were less effective at blocking the lower wavelengths of light (<420 nm). However, even in the worst scenario, the filters were able to block at least 97% of the irradiance.

Free radical reactions of isoxazole and pyrazole derivatives of hispolon: kinetics correlated with molecular descriptors.

PubMed

Shaikh, Shaukat Ali M; Barik, Atanu; Singh, Beena G; Modukuri, Ramani V; Balaji, Neduri V; Subbaraju, Gottumukkala V; Naik, Devidas B; Priyadarsini, K Indira

2016-12-01

Hispolon (HS), a natural polyphenol found in medicinal mushrooms, and its isoxazole (HI) and pyrazole (HP) derivatives have been examined for free radical reactions and in vitro antioxidant activity. Reaction of these compounds with one-electron oxidant, azide radicals ([Formula: see text]) and trichloromethyl peroxyl radicals ([Formula: see text]), model peroxyl radicals, studied by nanosecond pulse radiolysis technique, indicated formation of phenoxyl radicals absorbing at 420 nm with half life of few hundred microseconds (μs). The formation of phenoxyl radicals confirmed that the phenolic OH is the active centre for free radical reactions. Rate constant for the reaction of these radicals with these compounds were in the order k HI ≅ k HP  >   k HS . Further the compounds were examined for their ability to inhibit lipid peroxidation in model membranes and also for the scavenging of 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical and superoxide ([Formula: see text]) radicals. The results suggested that HP and HI are less efficient than HS towards these radical reactions. Quantum chemical calculations were performed on these compounds to understand the mechanism of reaction with different radicals. Lower values of adiabatic ionization potential (AIP) and elevated highest occupied molecular orbital (HOMO) for HI and HP compared with HS controlled their activity towards [Formula: see text] and [Formula: see text] radicals, whereas the contribution of overall anion concentration was responsible for higher activity of HS for DPPH, [Formula: see text], and lipid peroxyl radical. The results confirm the role of different structural moieties on the antioxidant activity of hispolon derivatives.

Design considerations and emerging challenges for nanotube-, nanowire-, and negative capacitor-field effect transistors

NASA Astrophysics Data System (ADS)

Wahab, Md. Abdul

As the era of classical planar metal-oxide-semiconductor field-effect transistors (MOSFETs) comes to an end, the semiconductor industry is beginning to adopt 3D device architectures, such as FinFETs, starting at the 22 nm technology node. Since physical limits such as short channel effect (SCE) and self-heating may dominate, it may be difficult to scale Si FinFET below 10 nm. In this regard, transistors with different materials, geometries, or operating principles may help. For example, gate has excellent electrostatic control over 2D thin film channel with planar geometry, and 1D nanowire (NW) channel with gate-all-around (GAA) geometry to reduce SCE. High carrier mobility of single wall carbon nanotube (SWNT) or III-V channels may reduce VDD to reduce power consumption. Therefore, as channel of transistor, 2D thin film of array SWNTs and 1D III-V multi NWs are promising for sub 10 nm technology nodes. In this thesis, we analyze the potential of these transistors from process, performance, and reliability perspectives. For SWNT FETs, we discuss a set of challenges (such as how to (i) characterize diameter distribution, (ii) remove metallic (m)-SWNTs, and (iii) avoid electrostatic cross-talk among the neighboring SWNTs), and demonstrate solution strategies both theoretically and experimentally. Regarding self-heating in these new class of devices (SWNT FET and GAA NW FET including state-of-the-art FinFET), higher thermal resistance from poor thermal conducting oxides results significant temperature rise, and reduces the IC life-time. For GAA NW FETs, we discuss accurate self-heating evaluation with good spatial, temporal, and thermal resolutions. The introduction of negative capacitor (NC), as gate dielectric stack of transistor, allows sub 60 mV/dec operation to reduce power consumption significantly. Taken together, our work provides a comprehensive perspective regarding the challenges and opportunities of sub 10 nm technology nodes.

ILT optimization of EUV masks for sub-7nm lithography

NASA Astrophysics Data System (ADS)

Hooker, Kevin; Kuechler, Bernd; Kazarian, Aram; Xiao, Guangming; Lucas, Kevin

2017-06-01

The 5nm and 7nm technology nodes will continue recent scaling trends and will deliver significantly smaller minimum features, standard cell areas and SRAM cell areas vs. the 10nm node. There are tremendous economic pressures to shrink each subsequent technology, though in a cost-effective and performance enhancing manner. IC manufacturers are eagerly awaiting EUV so that they can more aggressively shrink their technology than they could by using complicated MPT. The current 0.33NA EUV tools and processes also have their patterning limitations. EUV scanner lenses, scanner sources, masks and resists are all relatively immature compared to the current lithography manufacturing baseline of 193i. For example, lens aberrations are currently several times larger (as a function of wavelength) in EUV scanners than for 193i scanners. Robustly patterning 16nm L/S fully random logic metal patterns and 40nm pitch random logic rectangular contacts with 0.33NA EUV are tough challenges that will benefit from advanced OPC/RET. For example, if an IC manufacturer can push single exposure device layer resolution 10% tighter using improved ILT to avoid using DPT, there will be a significant cost and process complexity benefit to doing so. ILT is well known to have considerable benefits in finding flexible 193i mask pattern solutions to improve process window, improve 2D CD control, improve resolution in low K1 lithography regime and help to delay the introduction of DPT. However, ILT has not previously been applied to EUV lithography. In this paper, we report on new developments which extend ILT method to EUV lithography and we characterize the benefits seen vs. traditional EUV OPC/RET methods.

Sensitivity study and parameter optimization of OCD tool for 14nm finFET process

NASA Astrophysics Data System (ADS)

Zhang, Zhensheng; Chen, Huiping; Cheng, Shiqiu; Zhan, Yunkun; Huang, Kun; Shi, Yaoming; Xu, Yiping

2016-03-01

Optical critical dimension (OCD) measurement has been widely demonstrated as an essential metrology method for monitoring advanced IC process in the technology node of 90 nm and beyond. However, the rapidly shrunk critical dimensions of the semiconductor devices and the increasing complexity of the manufacturing process bring more challenges to OCD. The measurement precision of OCD technology highly relies on the optical hardware configuration, spectral types, and inherently interactions between the incidence of light and various materials with various topological structures, therefore sensitivity analysis and parameter optimization are very critical in the OCD applications. This paper presents a method for seeking the optimum sensitive measurement configuration to enhance the metrology precision and reduce the noise impact to the greatest extent. In this work, the sensitivity of different types of spectra with a series of hardware configurations of incidence angles and azimuth angles were investigated. The optimum hardware measurement configuration and spectrum parameter can be identified. The FinFET structures in the technology node of 14 nm were constructed to validate the algorithm. This method provides guidance to estimate the measurement precision before measuring actual device features and will be beneficial for OCD hardware configuration.

Precuring implant photoresists for shrink and patterning control

NASA Astrophysics Data System (ADS)

Winroth, Gustaf; Rosseel, Erik; Delvaux, Christie; Sanchez, Efrain Altamirano; Ercken, Monique

2013-10-01

193-nm compatible photoresists are turning out to be the new platform for implant lithography, due to the increasing requirements in both resolution and overlay. Shrinkage of such resists is becoming progressively the most topical issue for aggressive nodes, where conventional pretreatments from older resist platforms, such as ultraviolet flood exposures, are not directly transferable to (meth-)acrylate-type resists. The precuring options available for state-of-the-art implant photoresists for 193-nm lithography is explored, in which we target to reduce the shrinkage during implantation for trenching critical dimensions (CDs) that are relevant for nodes <20 nm. An extensive study comprising different approaches, including laser-, ion-, and electron-based treatments, is presented. Each treatment is individually investigated with the aim to find not only a valid pretreatment for shrinkage control during implantation, but also to understand what effect alternative pretreatments have on the morphology and the CDs of thick photoresists used as implant stopping layers. Viable options for further process optimization in order to integrate them into device process flows are found. To this extent, the shrink behavior after pretreatment is shown, and the additional shrink dynamics after implantation are compared.

A general design strategy for block copolymer directed self-assembly patterning of integrated circuits contact holes using an alphabet approach.

PubMed

Yi, He; Bao, Xin-Yu; Tiberio, Richard; Wong, H-S Philip

2015-02-11

Directed self-assembly (DSA) is a promising lithography candidate for technology nodes beyond 14 nm. Researchers have shown contact hole patterning for random logic circuits using DSA with small physical templates. This paper introduces an alphabet approach that uses a minimal set of small physical templates to pattern all contacts configurations on integrated circuits. We illustrate, through experiments, a general and scalable template design strategy that links the DSA material properties to the technology node requirements.

Haptoglobin genotyping of Vietnamese: global distribution of HP del, complete deletion allele of the HP gene.

PubMed

Soejima, Mikiko; Agusa, Tetsuro; Iwata, Hisato; Fujihara, Junko; Kunito, Takashi; Takeshita, Haruo; Lan, Vi Thi Mai; Minh, Tu Binh; Takahashi, Shin; Trang, Pham Thi Kim; Viet, Pham Hung; Tanabe, Shinsuke; Koda, Yoshiro

2015-01-01

The haptoglobin (HP) gene deletion allele (HP(del)) is responsible for anhaptoglobinemia and a genetic risk factor for anaphylaxis reaction after transfusion due to production of the anti-HP antibody. The distribution of this allele has been explored by several groups including ours. Here, we studied the frequency of HP(del) in addition to the distribution of common HP genotypes in 293 Vietnamese. The HP(del) was encountered with the frequency of 0.020. The present result suggested that this deletion allele is restricted to East and Southeast Asians. Thus, this allele seems to be a potential ancestry informative marker for these populations. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Possible biomarkers modulating haloperidol efficacy and/or tolerability.

PubMed

Porcelli, Stefano; Crisafulli, Concetta; Calabrò, Marco; Serretti, Alessandro; Rujescu, Dan

2016-04-01

Haloperidol (HP) is widely used in the treatment of several forms of psychosis. Despite of its efficacy, HP use is a cause of concern for the elevated risk of adverse drug reactions. adverse drug reactions risk and HP efficacy greatly vary across subjects, indicating the involvement of several factors in HP mechanism of action. The use of biomarkers that could monitor or even predict HP treatment impact would be of extreme importance. We reviewed the elements that could potentially be used as peripheral biomarkers of HP effectiveness. Although a validated biomarker still does not exist, we underlined the several potential findings (e.g., about cytokines, HP metabolites and genotypic biomarkers) which could pave the way for future research on HP biomarkers.

HP-1γ Controls High-Affinity Antibody Response to T-Dependent Antigens

PubMed Central

Ha, Ngoc; Pham, Duc-Hung; Shahsafaei, Aliakbar; Naruse, Chie; Asano, Masahide; Thai, To-Ha

2014-01-01

In vitro observations suggest a role for the mouse heterochromatin protein 1γ (HP-1γ) in the immune system. However, it has not been shown if and how HP-1γ contributes to immunity in vivo. Here we show that in mice, HP-1γ positively regulates the germinal center reaction and high-affinity antibody response to thymus (T)-dependent antigens by limiting the size of CD8+ regulatory T-cell (Treg) compartment without affecting progenitor B- or T-cell-development. Moreover, HP-1γ does not control cell proliferation or class switch recombination. Haploinsufficiency of cbx-3 (gene encoding HP-1γ) is sufficient to expand the CD8+ Treg population and impair the immune response in mice despite the presence of wild-type HP-1α and HP-1β. This is the first in vivo evidence demonstrating the non-redundant role of HP-1γ in immunity. PMID:24971082

Evaluation of the tracing effect of carbon nanoparticle and carbon nanoparticle-epirubicin suspension in axillary lymph node dissection for breast cancer treatment.

PubMed

Du, Junze; Zhang, Yongsong; Ming, Jia; Liu, Jing; Zhong, Ling; Liang, Quankun; Fan, Linjun; Jiang, Jun

2016-06-22

Carbon nanoparticle suspension, using smooth carbon particles at a diameter of 21 nm added with suspending agents, is a stable suspension of carbon pellets of 150 nm in diameter. It is obviously inclined to the lymphatic system. There were some studies reporting that carbon nanoparticles are considered as superior tracers for sentinel lymph nodes because of their stability and operational feasibility. However, there were few study concerns about the potential treatment effect including tracing and local chemotherapeutic effect of carbon nanoparticle-epirubicin suspension on breast cancer with axillary metastasis. In the current study, a randomized controlled analysis was performed to investigate the potential treatment effect of carbon nanoparticle-epirubicin suspension on breast cancer with axillary metastasis. A total of 90 breast cancer patients were randomly divided into three equal groups: control, tracer, and drug-load groups. The control group patients did not receive any lymphatic tracers, the tracer group patients were subcutaneously injected with 1 ml carbon nanoparticle suspension, and the drug-load group patients were injected with 3 ml carbon nanoparticle-epirubicin suspension at four separate sites around the areola 24 h before surgery. Modified radical mastectomy, endoscopic subcutaneous mammary resection plus axillary lymph node dissection, and immediate reconstruction with implants or breast-conserving surgery were performed. The mean number of the dissected lymph nodes per patient was significantly higher in the tracer (21.3 ± 6.1) and drug-load (19.5 ± 3.7) groups than in the control group (16.7 ± 3.4) (P < 0.05). Most lymph nodes in the former two groups were stained black (75.7 and 73.3 %, respectively), but with no significant difference between the groups. Most metastatic lymph nodes were also stained black in the tracer group (68.6 %) and drug-load group (78.1 %) and with no significant difference between the groups (P = 0.198). Microscopic examination revealed that the carbon nanoparticles were localized around or among the cancer cell masses and residues of necrotized cancer cells surrounded by fibroblastic proliferation could be found within the stained lymph nodes in the drug-load group. The majority of axillary lymph nodes were stained black by the suspension of carbon nanoparticles, which helped identify the lymph nodes from the surrounding tissues and avoided aggressive axillary treatment. Thus, a combination therapy of carbon nanoparticles with epirubicin could play an important role in lymphatic chemotherapy without affecting tracing. ChiCTRTRC13003419.

Azithromycin and risk of COPD exacerbations in patients with and without Helicobacter pylori.

PubMed

Ra, Seung Won; Sze, Marc A; Lee, Eun Chong; Tam, Sheena; Oh, Yeni; Fishbane, Nick; Criner, Gerard J; Woodruff, Prescott G; Lazarus, Stephen C; Albert, Richard; Connett, John E; Han, Meilan K; Martinez, Fernando J; Aaron, Shawn D; Reed, Robert M; Man, S F Paul; Sin, Don D

2017-05-30

Helicobacter pylori (HP) infection is associated with reduced lung function and systemic inflammation in chronic obstructive pulmonary disease (COPD) patients. Azithromycin (AZ) is active against HP and reduces the risk of COPD exacerbation. We determined whether HP infection status modifies the effects of AZ in COPD patients. Plasma samples from 1018 subjects with COPD who participated in the Macrolide Azithromycin (MACRO) in COPD Study were used to determine the HP infection status at baseline and 12 months of follow-up using a serologic assay. Based on HP infection status and randomization to either AZ or placebo (PL), the subjects were divided into 4 groups: HP+/AZ, HP-/AZ, HP+/PL, and HP-/PL. Time to first exacerbation was compared across the 4 groups using Kaplan-Meier survival analysis and a Cox proportional hazards model. The rates of exacerbation were compared using both the Kruskal-Wallis test and negative binomial analysis. Blood biomarkers at enrolment and at follow-up visits 3, 12, and 13 (1 month after treatment was stopped) months were measured. One hundred eighty one (17.8%) patients were seropositive to HP. Non-Caucasian participants were nearly three times more likely to be HP seropositive than Caucasian participants (37.4% vs 13.6%; p < 0.001). The median time to first exacerbation was significantly different across the four groups (p = 0.001) with the longest time in the HP+/AZ group (11.2 months, 95% CI; 8.4-12.5+) followed by the HP-/AZ group (8.0 months, 95% CI; 6.7-9.7). Hazard ratio (HR) for exacerbations was lowest in the HP+/AZ group after adjustment for age, sex, smoking status, ethnicity, history of peptic ulcer, dyspnea, previous hospital admission, GOLD grade of severity, and forced vital capacity (HR, 0.612; 95% CI, 0.442-0.846 vs HR, 0.789; 95% CI, 0.663-0.938 in the HP-/AZ group). Circulating levels of soluble tumor necrosis factor receptor-75 were reduced only in the HP+/AZ group after 3 months of AZ treatment (-0.87 ± 0.31 μg/L; p = 0.002); levels returned to baseline after discontinuing AZ. AZ is effective in preventing COPD exacerbations in patients with HP seropositivity, possibly by modulating TNF pathways related to HP infection.

Contact patterning strategies for 32nm and 28nm technology

NASA Astrophysics Data System (ADS)

Morgenfeld, Bradley; Stobert, Ian; An, Ju j.; Kanai, Hideki; Chen, Norman; Aminpur, Massud; Brodsky, Colin; Thomas, Alan

2011-04-01

As 193 nm immersion lithography is extended indefinitely to sustain technology roadmaps, there is increasing pressure to contain escalating lithography costs by identifying patterning solutions that can minimize the use of multiple-pass processes. Contact patterning for the 32/28 nm technology nodes has been greatly facilitated by just-in-time introduction of new process enablers that allow the simultaneous support of flexible foundry-oriented ground rules alongside highperformance technology, while also migrating to a single-pass patterning process. The incorporation of device based performance metrics along with rigorous patterning and structural variability studies were critical in the evaluation of material innovation for improved resolution and CD shrink along with novel data preparation flows utilizing aggressive strategies for SRAF insertion and retargeting.

FDSOI 28nm performances study for RF energy scavenging

NASA Astrophysics Data System (ADS)

Rochefeuille, E.; Alicalapa, F.; Douyère, A.; Vuong, T. P.

2018-03-01

This paper presents a study on an integrated technology: Fully-Depleted-Silicon-On-Insulator (FDSOI) at a 28nm node. FDSOI results are compared to another technology: Complementary-Metal-Oxide-Semiconductor (CMOS) 350nm. The aim of this work was to demonstrate the advantages of using FDSOI technology in RF energy scavenging applications. Characteristics of transistors are pointed out and results showed an improved 22%-output voltage gain for a series rectifier and a 13%-output voltage gain for a Dickson charge pump in FDSOI technology compared to CMOS, for an input voltage and power of 0.5 V and 0 dBm respectively. Those results allowed to prove that FDSOI 28nm is a better technology choice for energy scavenging and low-power applications.

High-pressure studies with x-rays using diamond anvil cells

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

Shen, Guoyin; Mao, Ho Kwang

2016-11-22

Pressure profoundly alters all states of matter. The symbiotic development of ultrahigh-pressure diamond anvil cells, to compress samples to sustainable multi-megabar pressures; and synchrotron x-ray techniques, to probe materials' properties in situ, has enabled the exploration of rich high-pressure (HP) science. In this article, we first introduce the essential concept of diamond anvil cell technology, together with recent developments and its integration with other extreme environments. We then provide an overview of the latest developments in HP synchrotron techniques, their applications, and current problems, followed by a discussion of HP scientific studies using x-rays in the key multidisciplinary fields. Thesemore » HP studies include: HP x-ray emission spectroscopy, which provides information on the filled electronic states of HP samples; HP x-ray Raman spectroscopy, which probes the HP chemical bonding changes of light elements; HP electronic inelastic x-ray scattering spectroscopy, which accesses high energy electronic phenomena, including electronic band structure, Fermi surface, excitons, plasmons, and their dispersions; HP resonant inelastic x-ray scattering spectroscopy, which probes shallow core excitations, multiplet structures, and spin-resolved electronic structure; HP nuclear resonant x-ray spectroscopy, which provides phonon densities of state and time-resolved Mössbauer information; HP x-ray imaging, which provides information on hierarchical structures, dynamic processes, and internal strains; HP x-ray diffraction, which determines the fundamental structures and densities of single-crystal, polycrystalline, nanocrystalline, and non-crystalline materials; and HP radial x-ray diffraction, which yields deviatoric, elastic and rheological information. Integrating these tools with hydrostatic or uniaxial pressure media, laser and resistive heating, and cryogenic cooling, has enabled investigations of the structural, vibrational, electronic, and magnetic properties of materials over a wide range of pressure-temperature conditions.« less

Diabetic patients infected with helicobacter pylori have a higher Insulin Resistance Degree

PubMed Central

Vafaeimanesh, Jamshid; Bagherzadeh, Mohammad; Heidari, Akram; Motii, Fatemeh; Parham, Mahmoud

2014-01-01

Background: The association of H.pylori (HP) and insulin resistance degree (IR) has not been evaluated in the diabetic patients so far. In this study, we evaluated the association between HP seropositivity and the homeostatic model assessment for insulin resistance (HOMA-IR) in diabetic patients. Methods: In this study, 211 diabetic patients admitted to the endocrinology clinic of Shahid Beheshti Hospital of Qom for routine diabetic check-ups were evaluated. The patients were divided into HP+ and HP- groups based on the seropositivity of helicobacter pylori IgG antibody. The serum H. pylori IgG antibody, blood sugar, serum insulin, HbA1c, LDL, HDL, cholesterol, triglyceride, HOMA-IR and BMI were measured. Results: The mean age of 72 HP- patient was 51.5±8.3 and 139 HP+ subjects was 53.5±9 years (P=0.128). The mean HDL in HP- cases was 69.2±29.2 mg/dl and for HP+ cases was 60.7±26.7 mg/dl (P=0.037). The mean serum insulin in HP- was 60.97±5.64 and HP+ subjects was 10.12±7.72IU/ml (P=0.002). The Homa-IR degree for HP- cases was 3.2±3.3 and for HP+ cases was 4.5±3.8 (P=0.013). There were no significant differences between these groups according to the short-term or the long-term indices of glycemic control as well as most of the diabetic risk factors or complications. The treatment type was also not significantly different between these groups. Conclusion: It seems that the HP+ diabetic patients require higher levels of serum insulin to reach the same degree of glycemic control compared to the HP- ones. PMID:25202440

High-pressure studies with x-rays using diamond anvil cells

NASA Astrophysics Data System (ADS)

Shen, Guoyin; Mao, Ho Kwang

2017-01-01

Pressure profoundly alters all states of matter. The symbiotic development of ultrahigh-pressure diamond anvil cells, to compress samples to sustainable multi-megabar pressures; and synchrotron x-ray techniques, to probe materials’ properties in situ, has enabled the exploration of rich high-pressure (HP) science. In this article, we first introduce the essential concept of diamond anvil cell technology, together with recent developments and its integration with other extreme environments. We then provide an overview of the latest developments in HP synchrotron techniques, their applications, and current problems, followed by a discussion of HP scientific studies using x-rays in the key multidisciplinary fields. These HP studies include: HP x-ray emission spectroscopy, which provides information on the filled electronic states of HP samples; HP x-ray Raman spectroscopy, which probes the HP chemical bonding changes of light elements; HP electronic inelastic x-ray scattering spectroscopy, which accesses high energy electronic phenomena, including electronic band structure, Fermi surface, excitons, plasmons, and their dispersions; HP resonant inelastic x-ray scattering spectroscopy, which probes shallow core excitations, multiplet structures, and spin-resolved electronic structure; HP nuclear resonant x-ray spectroscopy, which provides phonon densities of state and time-resolved Mössbauer information; HP x-ray imaging, which provides information on hierarchical structures, dynamic processes, and internal strains; HP x-ray diffraction, which determines the fundamental structures and densities of single-crystal, polycrystalline, nanocrystalline, and non-crystalline materials; and HP radial x-ray diffraction, which yields deviatoric, elastic and rheological information. Integrating these tools with hydrostatic or uniaxial pressure media, laser and resistive heating, and cryogenic cooling, has enabled investigations of the structural, vibrational, electronic, and magnetic properties of materials over a wide range of pressure-temperature conditions.

40 CFR Table 1 to Subpart Jjjj of... - NOX, CO, and VOC Emission Standards for Stationary Non-Emergency SI Engines ≥100 HP (Except...

Code of Federal Regulations, 2011 CFR

2011-07-01

... Stationary Non-Emergency SI Engines â¥100 HP (Except Gasoline and Rich Burn LPG), Stationary SI Landfill... Standards for Stationary Non-Emergency SI Engines ≥100 HP (Except Gasoline and Rich Burn LPG), Stationary SI...-Emergency SI Natural Gas b and Non-Emergency SI Lean Burn LPG b 100≤HP HP 25 HP Table 1 to Subpart JJJJ of...

Beneficial effects of hydroxyapatite on enamel subjected to 30% hydrogen peroxide.

PubMed

Jiang, Tao; Ma, Xiao; Wang, Zhejun; Tong, Hua; Hu, Jiming; Wang, Yining

2008-11-01

To evaluate the effect of combination of hydroxyapatite (HA) and hydrogen peroxide (HP) on color, microhardness and morphology of human tooth enamel. Forty-eight human dental blocks were obtained from 12 pairs of premolars and were randomly divided into four groups. Group DW was treated with distilled water, group HP with 30% HP, group HA+DW with HA mixed with distilled water and group HA+HP with HA mixed with 30% HP. Baseline and final color measurements and microhardness test were carried out before and after bleaching experiments. Two specimens from each group were selected for morphological investigation after final tests. The DeltaE of group HP and HA+HP were significantly higher than those of group DW (p=0.000 and p=0.000) and group HA+DW (p=0.000 and p=0.000). The percentage microhardness loss of group HA+HP was significantly lower than that of group HP (p=0.047), but significantly higher than those of group DW (p=0.000) and group HA+DW (p=0.000). The obvious variation of morphology was only observed on enamel surfaces in group HP. This study suggested that combination of HA and HP was effective in tooth whitening. HA could significantly reduce the microhardness loss of enamel caused by 30% HP and keep enamel surface morphology almost unchanged.

Hypothermic in situ perfusion of the porcine liver using Celsior or Ringer-lactate solution.

PubMed

Dinant, S; Roseboom, H J; Levi, M; van Vliet, A K; van Gulik, T M

2009-01-01

Hypothermic perfusion (HP) of the liver is applied during total vascular exclusion (TVE) to reduce ischemic injury during liver resection. No studies have been performed comparing different perfusion solutions for HP. The aim of this experimental study was to compare Ringer-lactate solution (RL) with Celsior solution (Cs) for HP in a pig model of 60-min TVE. Twenty pigs underwent 60-min TVE of the liver. Groups were TVE without HP (no-HP, n = 9), TVE with HP using RL (n = 6), and TVE with HP using Cs (n = 5). Blood and liver tissue samples were taken before TVE and during 24-h reperfusion. In the no-HP group, plasma aspartate aminotransferase values were significantly increased during reperfusion (p < 0.05), while liver tissue pO(2) levels (p < 0.01) were decreased when compared to the HP groups. After 24-h reperfusion, bile production and liver tissue glutathione content were significantly higher (p < 0.05) in the Cs group (42.0 +/- 1.7 mL/h and 44.9 +/- 2.2 nmol/mg, respectively) as compared to the RL group (31.5 +/- 3.5 mL/h and 19.6 +/- 1.8 nmol/mg, respectively). The protective effect of HP during TVE was confirmed in this study. HP with Cs was more effective in reducing ischemic injury as compared to HP with RL.

Reducing peanut allergens by high pressure combined with polyphenol oxidase

NASA Astrophysics Data System (ADS)

Chung, Si-Yin; Houska, Milan; Reed, Shawndrika

2013-12-01

Polyphenol oxidase (PPO) has been shown to reduce major peanut allergens. Since high pressure (HP) can increase enzyme activity, we postulated that further reduction of peanut allergens can be achieved through HP combined with PPO. Peanut extracts containing caffeic acid were treated with each of the following: (1) HP; (2) HP+PPO; (3) PPO; and (4) none. HP was conducted at 300 and 500 MPa, each for 3 and 10 min, 37 °C. After treatment, SDS-PAGE was performed and allergenic capacity (IgE binding) was determined colorimetrically in inhibition enzyme-linked immunosorbent assay and Western blots, using a pooled plasma from peanut-allergic patients. Data showed that HP alone had no effect on major peanut allergens. However, HP at 500 MPa combined with PPO (HP500/PPO) induced a higher (approximately twofold) reduction of major peanut allergens and IgE binding than PPO alone or HP300/PPO. There was no difference between treatment times. We concluded that HP500/PPO at 3-min enhanced a twofold reduction of the allergenic capacity of peanut extracts, as compared to PPO itself.

Novel contact hole reticle design for enhanced lithography process window in IC manufacturing

NASA Astrophysics Data System (ADS)

Chang, Chung-Hsing

2005-01-01

For 90nm node generation, 65nm, and beyond, dark field mask types such as contact-hole, via, and trench patterns that all are very challenging to print with satisfactory process windows for day-to-day lithography manufacturing. Resolution enhancement technology (RET) masks together with ArF high numerical aperture (NA) scanners have been recognized as the inevitable choice of method for 65nm node manufacturing. Among RET mask types, the alternating phase shifting mask (AltPSM) is one of the well-known strong enhancement techniques. However AltPSM can have a very strong optical proximity effect that comes with the use of small on-axis illumination sigma setting. For very dense contact features, it may be possible for AltPSM to overcome the phase conflict by limiting the mask design rules. But it is not feasible to resolve the inherent phase conflict for the semi-dense, semi-isolated and isolated contact areas. Hence the adoption of this strong enhancement technique for dark filed mask types in today"s IC manufacturing has been very limited. In this paper, we present a novel yet a very powerful design method to achieve contact and via masks printing for 90nm, 65nm, and beyond. We name our new mask design as: Novel Improved Contact-hole pattern Exposure PSM (NICE PSM) with off-axis illumination, such as QUASAR. This RET masks design can enhance the process window of isolated, semi-isolated contact hole and via hole patterns. The main concepts of NICE PSM with QUASAR off-axis illumination are analogous to the Super-FLEX pupil filter technology.

Novel contact hole reticle design for enhanced lithography process window in IC manufacturing

NASA Astrophysics Data System (ADS)

Chang, Chung-Hsing

2004-10-01

For 90nm node generation, 65nm, and beyond, dark field mask types such as contact-hole, via, and trench patterns that all are very challenging to print with satisfactory process windows for day-to-day lithography manufacturing. Resolution enhancement technology (RET) masks together with ArF high numerical aperture (NA) scanners have been recognized as the inevitable choice of method for 65nm node manufacturing. Among RET mask types, the alternating phase shifting mask (AltPSM) is one of the well-known strong enhancement techniques. However, AltPSM can have a very strong optical proximity effect that comes with the use of small on-axis illumination sigma setting. For very dense contact features, it may be possible for AltPSM to overcome the phase conflict by limiting the mask design rules. But it is not feasible to resolve the inherent phase conflict for the semi-dense, semi-isolated and isolated contact areas. Hence the adoption of this strong enhancement technique for dark filed mask types in today"s IC manufacturing has been very limited. In this paper, we report a novel yet a very powerful design method to achieve contact and via masks printing for 90nm, 65nm, and beyond. We name our new mask design as: Novel Improved Contact-hole pattern Exposure PSM (NICE PSM) with off-axis illumination, such as QUASAR. This RET masks design can enhance the process window of isolated, semi-isolated contact hole and via hole patterns. The main concepts of NICE PSM with QUASAR off-axis illumination are analogous to the Super-FLEX pupil filter technology.

Line roughness improvements on self-aligned quadruple patterning by wafer stress engineering

NASA Astrophysics Data System (ADS)

Liu, Eric; Ko, Akiteru; Biolsi, Peter; Chae, Soo Doo; Hsieh, Chia-Yun; Kagaya, Munehito; Lee, Choongman; Moriya, Tsuyoshi; Tsujikawa, Shimpei; Suzuki, Yusuke; Okubo, Kazuya; Imai, Kiyotaka

2018-04-01

In integrated circuit and memory devices, size shrinkage has been the most effective method to reduce production cost and enable the steady increment of the number of transistors per unit area over the past few decades. In order to reduce the die size and feature size, it is necessary to minimize pattern formation in the advance node development. In the node of sub-10nm, extreme ultra violet lithography (EUV) and multi-patterning solutions based on 193nm immersionlithography are the two most common options to achieve the size requirement. In such small features of line and space pattern, line width roughness (LWR) and line edge roughness (LER) contribute significant amount of process variation that impacts both physical and electrical performances. In this paper, we focus on optimizing the line roughness performance by using wafer stress engineering on 30nm pitch line and space pattern. This pattern is generated by a self-aligned quadruple patterning (SAQP) technique for the potential application of fin formation. Our investigation starts by comparing film materials and stress levels in various processing steps and material selection on SAQP integration scheme. From the cross-matrix comparison, we are able to determine the best stack of film selection and stress combination in order to achieve the lowest line roughness performance while obtaining pattern validity after fin etch. This stack is also used to study the step-by-step line roughness performance from SAQP to fin etch. Finally, we will show a successful patterning of 30nm pitch line and space pattern SAQP scheme with 1nm line roughness performance.

Molecular modeling and cytotoxicity of diffractaic acid: HP-β-CD inclusion complex encapsulated in microspheres.

PubMed

Silva, Camilla V N S; Barbosa, Jéssica A P; Ferraz, Milena S; Silva, Nicácio H; Honda, Neli K; Rabello, Marcelo M; Hernandes, Marcelo Z; Bezerra, Beatriz P; Cavalcanti, Isabella M F; Ayala, Alejandro P; Santos, Noemia P S; Santos-Magalhães, Nereide S

2016-11-01

In this pioneer study, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) was used to improve the solubility of the diffractaic acid (DA) via inclusion complex (DA:HP-β-CD). Subsequently, DA:HP-β-CD was incorporated into poly-ε-caprolactone (PCL) microspheres (DA:HP-β-CD-MS). Microspheres containing DA (DA-MS) or DA:HP-β-CD (DA:HP-β-CD-MS) were prepared using the multiple W/O/W emulsion-solvent evaporation technique. The phase-solubility diagram of DA in HP-β-CD (10-50mM) showed an A L type curve with a stability constant K 1:1 =821M -1 . 1 H NMR, FTIR, X-ray diffraction and thermal analysis showed changes in the molecular environment of DA in DA:HP-β-CD. The molecular modeling approach suggests a guest-host complex formation between the carboxylic moiety of both DA and the host (HP-β-CD). The mean particle size of the microspheres were ∅ DA-MS =5.23±1.65μm and ∅ DA:HP-β-CD-MS =4.11±1.39μm, respectively. The zeta potential values of the microspheres were ζ DA-MS =-7.85±0.32mV and ζ DA:HP-β-CD-MS =-6.93±0.46mV. Moreover, the encapsulation of DA:HP-β-CD into microspheres resulted in a more slower release (k 2 =0.042±0.001; r 2 =0.996) when compared with DA-MS (k 2 =0.183±0.005; r 2 =0.996). The encapsulation of DA or DA:HP-β-CD into microspheres reduced the cytotoxicity of DA (IC 50 =43.29μM) against Vero cells (IC 50 of DA-MS=108.48μM and IC 50 of DA:HP-β-CD-MS=142.63μM). Copyright © 2016 Elsevier B.V. All rights reserved.

Latest evolution in a 300mm graphoepitaxy pilot line flow for L/S applications

NASA Astrophysics Data System (ADS)

Claveau, G.; Argoud, M.; Pimenta-Barros, P.; Chamiot-Maitral, G.; Tiron, R.; Chevalier, X.; Navarro, C.

2017-03-01

Directed Self Assembly (DSA) of block-copolymers (BCPs) used as a complementary technique to the 193nm immersion lithography has demonstrated sub-10nm node applications in both via and line/space patterning. We propose however to study the performance of graphoepitaxy which allows DSA with thicker initial BCP layer, higher multiplication factors and stronger orientation control of lamellae. The aim of this work is to use the 300mm pilot line available at LETI and Arkema's advanced materials to evaluate the performances of a novel graphoepitaxy process based on the work on a 38nm period lamellar PS-b-PMMA (L38) reported before.

Operation of the HP2250 with the HP9000 series 200 using PASCAL 3.0

NASA Technical Reports Server (NTRS)

Perry, John; Stroud, C. W.

1986-01-01

A computer program has been written to provide an interface between the HP Series 200 desktop computers, operating under HP Standard Pascal 3.0, and the HP2250 Data Acquisition and Control System. Pascal 3.0 for the HP9000 desktop computer gives a number of procedures for handling bus communication at various levels. It is necessary, however, to reach the lowest possible level in Pascal to handle the bus protocols required by the HP2250. This makes programming extremely complex since these protocols are not documented. The program described solves those problems and allows the user to immediately program, simply and efficiently, any measurement and control language (MCL/50) application with a few procedure calls. The complete set of procedures is available on a 5 1/4 inch diskette from Cosmic. Included in this group of procedures is an Exerciser which allows the user to exercise his HP2250 interactively. The exerciser operates in a fashion similar to the Series 200 operating system programs, but is adapted to the requirements of the HP2250. The programs on the diskette and the user's manual assume the user is acquainted with both the MCL/50 programming language and HP Standard Pascal 3.0 for the HP series 200 desktop computers.

Salt and stress synergize H. pylori-induced gastric lesions, cell proliferation, and p21 expression in Mongolian gerbils.

PubMed

Gamboa-Dominguez, Armando; Ubbelohde, Tom; Saqui-Salces, Milena; Romano-Mazzoti, Luis; Cervantes, Minerva; Domínguez-Fonseca, Claudia; de la Luz Estreber, Maria; Ruíz-Palacios, Guillermo M

2007-06-01

Our aim was to determine if salt and stress enhance Helicobacter pylori (Hp) lesions in Meriones unguiculatus. Two hundred seventy-eight pathogen-free gerbils were allocated to seven groups: Hp-Sydney strain (45), 8% higher-salt diet (38), stress (60% space reduction/water immersion; 36), Hp + salt (33), Hp + stress (34), N-methyl-N-nitro-N-nitrosoguanidine (34), and sham (58). Gerbils were sacrificed at 1 week (67), 12 weeks (73), 52 weeks (65), and 68 weeks (73). Sydney, Padova, and Lauren classifications were blindly used. Proliferation, p53, p21, and apoptosis were assessed. Follicular active gastritis (grade 2/3) was observed in 10% of Hp gerbils, 38% of Hp + salt gerbils, and 29% of Hp + stress gerbils at 52 weeks and 67%, 83%, and 43% at 68 weeks (P < 0.05). Heterotopic proliferative glands were identified in synergy groups from 52 weeks, with increases in their number and size by 68 weeks. Higher proliferative rates were observed in Hp+salt gerbils (P < 0.0001), and p21 overexpression in Hp+salt and Hp+stress gerbils (both P's < 0.0001), by 68 weeks, without p53 increases. We conclude that salt and stress synergize Hp damage and increase pseudo-invasive gland foci.

Space shuttle heat pipe thermal control systems

NASA Technical Reports Server (NTRS)

Alario, J.

1973-01-01

Heat pipe (HP) thermal control systems designed for possible space shuttle applications were built and tested under this program. They are: (1) a HP augmented cold rail, (2) a HP/phase change material (PCM) modular heat sink and (3) a HP radiating panel for compartment temperature control. The HP augmented cold rail is similar to a standard two-passage fluid cold rail except that it contains an integral, centrally located HP throughout its length. The central HP core helps to increase the local power density capability by spreading concentrated heat inputs over the entire rail. The HP/PCM modular heat sink system consists of a diode HP connected in series to a standard HP that has a PCM canister attached to its mid-section. It is designed to connect a heat source to a structural heat sink during normal operation, and to automatically decouple from it and sink to the PCM whenever structural temperatures are too high. The HP radiating panel is designed to conductively couple the panel feeder HPs directly to a fluid line that serves as a source of waste heat. It is a simple strap-on type of system that requires no internal or external line modifications to distribute the heat to a large radiating area.

Inhibition of Prostaglandin E2 Production by Anti-inflammatory Hypericum perforatum Extracts and Constituents in RAW264.7 Mouse Macrophage Cells

PubMed Central

Hammer, Kimberly D. P.; Hillwig, Matthew L.; Solco, Avery K. S.; Dixon, Philip M.; Delate, Kathleen; Murphy, Patricia A.; Wurtele, Eve S.; Birt, Diane F.

2008-01-01

Hypericum perforatum (Hp) is commonly known for its antiviral, antidepressant, and cytotoxic properties, but traditionally Hp was also used to treat inflammation. In this study, the anti-inflammatory activity and cytotoxicity of different Hp extractions and accessions and constituents present within Hp extracts were characterized. In contrast to the antiviral activity of Hp, the anti-inflammatory activity observed with all Hp extracts was light-independent. When pure constituents were tested, the flavonoids, amentoflavone, hyperforin, and light-activated pseudohypericin, displayed anti-inflammatory activity, albeit at concentrations generally higher than the amount present in the Hp extracts. Constituents that were present in the Hp extracts at concentrations that inhibited the production of prostaglandin E2 (PGE2) were pseudohypericin and hyperforin, suggesting that they are the primary anti-inflammatory constituents along with the flavonoids, and perhaps the interactions of these constituents and other unidentified compounds are important for the anti-inflammatory activity of the Hp extracts. PMID:17696442

Helicobacter pylori antigen HP0986 (TieA) interacts with cultured gastric epithelial cells and induces IL8 secretion via NF-κB mediated pathway.

PubMed

Devi, Savita; Ansari, Suhail A; Vadivelu, Jamuna; Mégraud, Francis; Tenguria, Shivendra; Ahmed, Niyaz

2014-02-01

The envisaged roles and partly understood functional properties of Helicobacter pylori protein HP0986 are significant in the context of proinflammatory and or proapoptotic activities, the two important facilitators of pathogen survival and persistence. In addition, sequence analysis of this gene predicts a restriction endonuclease function which remained unknown thus far. To evaluate the role of HP0986 in gastric inflammation, we studied its expression profile using a large number of clinical isolates but a limited number of biopsies and patient sera. Also, we studied antigenic role of HP0986 in altering cytokine responses of human gastric epithelial (AGS) cells including its interaction with and localization within the AGS cells. For in vitro expression study of HP0986, 110 H. pylori clinical isolates were cultured from patients with functional dyspepsia. For expression analysis by qRT PCR of HP0986, 10 gastric biopsy specimens were studied. HP0986 was also used to detect antibodies in patient sera. AGS cells were incubated with recombinant HP0986 to determine cytokine response and NF-κB activation. Transient transfection with HP0986 cloned in pEGFPN1 was used to study its subcellular localization or homing in AGS cells. Out of 110 cultured H. pylori strains, 34 (31%) were positive for HP0986 and this observation was correlated with in vitro expression profiles. HP0986 mRNA was detected in 7 of the 10 biopsy specimens. Further, HP0986 induced IL-8 secretion in gastric epithelial cells in a dose and time-dependent manner via NF-κB pathway. Serum antibodies against HP0986 were positively associated with H. pylori positive patients. Transient transfection of AGS cells revealed both cytoplasmic and nuclear localization of HP0986. HP0986 was moderately prevalent in clinical isolates and its expression profile in cultures and gastric biopsies points to its being naturally expressed. Collective observations including the induction of IL-8 via TNFR1 and NF-κB, subcellular localization, and seropositivity data point to a significant role of HP0986 in gastroduodenal inflammation. We propose to name the HP0986 gene/protein as 'TNFR1 interacting endonuclease A (TieA or tieA)'. © 2013 John Wiley & Sons Ltd.

Effects of the concentration and composition of in-office bleaching gels on hydrogen peroxide penetration into the pulp chamber.

PubMed

Mena-Serrano, A P; Parreiras, S O; do Nascimento, E M S; Borges, C P F; Berger, S B; Loguercio, A D; Reis, A

2015-01-01

In tooth whitening, the hydrogen peroxide (HP) diffuses in the enamel and dentin, reaching the pulp. This in vitro study aimed to quantify the penetration of HP in the pulp chamber in teeth submitted to bleaching agents of different concentrations of HP without calcium (HP 20% [20CF], HP 35% [35CF]) and with calcium (HP 20% [20CC], HP 35% [35CC]). Fifty human premolars were sectioned 3 mm from the cemento-enamel junction and the pulp tissue was removed. The teeth were divided into five groups according to treatment and with a control group (n=10). An acetate buffer solution was placed in the pulp chamber of all teeth. The control group was exposed only to distilled water, while the other groups were treated with a bleaching procedure, according to the manufacturer's recommendations. After treatment, the acetate buffer solution was transferred to a glass tube in which leuco-crystal violet and peroxidase solutions were added, resulting in a blue solution. The optical density of this blue solution was determined spectrophotometrically and converted into micrograms equivalent to the HP. Data were analyzed using analysis of variance and Tukey tests (α=0.05). The HP concentration did not affect the HP inside the pulp chamber, but the presence of calcium significantly reduced it (p<0.0001). The amount of HP that reaches the pulp chamber depends on the bleaching protocol and the product employed, and it seems to be less affected by HP concentration.

Glycogen Synthase Kinase 3β Promotes the Endocytosis of Transferrin in the African Trypanosome.

PubMed

Guyett, Paul J; Xia, Shuangluo; Swinney, David C; Pollastri, Michael P; Mensa-Wilmot, Kojo

2016-07-08

Human parasite Trypanosoma brucei proliferates in the blood of its host, where it takes up iron via receptor-mediated endocytosis of transferrin (Tf). Mechanisms of Tf endocytosis in the trypanosome are not fully understood. Small molecule lapatinib inhibits Tf endocytosis in T. brucei and associates with protein kinase GSK3β (TbGSK3β). Therefore, we hypothesized that Tf endocytosis may be regulated by TbGSK3β, and we used three approaches (both genetic and small molecule) to test this possibility. First, the RNAi knock-down of TbGSK3β reduced Tf endocytosis selectively, without affecting the uptake of haptaglobin-hemoglobin (Hp-Hb) or bovine serum albumin (BSA). Second, the overexpression of TbGSK3β increased the Tf uptake. Third, small-molecule inhibitors of TbGSK3β, TWS119 (IC50 = 600 nM), and GW8510 (IC50 = 8 nM) reduced Tf endocytosis. Furthermore, TWS119, but not GW8510, selectively blocked Tf uptake. Thus, TWS119 phenocopies the selective endocytosis effects of a TbGSK3β knockdown. Two new inhibitors of TbGSK3β, LY2784544 (IC50 = 0.6 μM) and sorafenib (IC50 = 1.7 μM), were discovered in a focused screen: at low micromolar concentrations, they prevented Tf endocytosis as well as trypanosome proliferation (GI50's were 1.0 and 3.1 μM, respectively). These studies show that (a) TbGSK3β regulates Tf endocytosis, (b) TWS119 is a small-molecule tool for investigating the endocytosis of Tf, (c) endocytosis of GPI-anchored TfR and HpHbR are differentially regulated, and (d) the imidazopyridazine aminopyrazole scaffold of LY2784544 is attractive for a hit-to-lead optimization program in antitrypanosome drug discovery.

Roughness and uniformity improvements on self-aligned quadruple patterning technique for 10nm node and beyond by wafer stress engineering

NASA Astrophysics Data System (ADS)

Liu, Eric; Ko, Akiteru; O'Meara, David; Mohanty, Nihar; Franke, Elliott; Pillai, Karthik; Biolsi, Peter

2017-05-01

Dimension shrinkage has been a major driving force in the development of integrated circuit processing over a number of decades. The Self-Aligned Quadruple Patterning (SAQP) technique is widely adapted for sub-10nm node in order to achieve the desired feature dimensions. This technique provides theoretical feasibility of multiple pitch-halving from 193nm immersion lithography by using various pattern transferring steps. The major concept of this approach is to a create spacer defined self-aligned pattern by using single lithography print. By repeating the process steps, double, quadruple, or octuple are possible to be achieved theoretically. In these small architectures, line roughness control becomes extremely important since it may contribute to a significant portion of process and device performance variations. In addition, the complexity of SAQP in terms of processing flow makes the roughness improvement indirective and ineffective. It is necessary to discover a new approach in order to improve the roughness in the current SAQP technique. In this presentation, we demonstrate a novel method to improve line roughness performances on 30nm pitch SAQP flow. We discover that the line roughness performance is strongly related to stress management. By selecting different stress level of film to be deposited onto the substrate, we can manipulate the roughness performance in line and space patterns. In addition, the impact of curvature change by applied film stress to SAQP line roughness performance is also studied. No significant correlation is found between wafer curvature and line roughness performance. We will discuss in details the step-by-step physical performances for each processing step in terms of critical dimension (CD)/ critical dimension uniformity (CDU)/line width roughness (LWR)/line edge roughness (LER). Finally, we summarize the process needed to reach the full wafer performance targets of LWR/LER in 1.07nm/1.13nm on 30nm pitch line and space pattern.

An In situ Analysis of the Dissolution Characteristics of Half Pitch Line and Space Extreme Ultraviolet Lithography Resist Patterns

NASA Astrophysics Data System (ADS)

Santillan, Julius Joseph; Itani, Toshiro

2013-06-01

The characterization of the resist dissolution is one fundamental area of research that has been continuously investigated. This paper focuses on the preliminary work on the application the high speed atomic force microscope (HS-AFM) for the in situ dissolution analysis half-pitch (hp) lines and spaces (L/S) at standard developer concentration. In earlier works, this has been difficult but through extensive optimization and the use of carbon nano fiber-tipped cantilevers, the dissolution characterization of a 32 nm hp L/S pattern at 0.26 N aqueous tetramethylammonium hydroxide developer (standard developer concentration) was successfully achieved. Based on the results obtained using the EIDEC standard resist (ESR1) it was found that regardless of analysis condition such as resist pattern configuration (isolated or L/S pattern) and developer concentration (diluted or standard), similar dissolution characteristics in the form of resist swelling of exposed areas was observed. Moreover, further investigations using other types of model resist polymer platforms such as poly(hydroxystyrene) (PHS)-based and hybrid (PHS-methacryl)-based model resists have confirmed that dissolution behavior is not affected by the analysis conditions applied.

The Strength-Grain Size Relationship in Ultrafine-Grained Metals

NASA Astrophysics Data System (ADS)

Balasubramanian, N.; Langdon, Terence G.

2016-12-01

Metals processed by severe plastic deformation (SPD) techniques, such as equal-channel angular pressing (ECAP) and high-pressure torsion (HPT), generally have submicrometer grain sizes. Consequently, they exhibit high strength as expected on the basis of the Hall-Petch (H-P) relationship. Examples of this behavior are discussed using experimental data for Ti, Al, and Ni. These materials typically have grain sizes greater than 50 nm where softening is not expected. An increase in strength is usually accompanied by a decrease in ductility. However, both high strength and high ductility may be achieved simultaneously by imposing high strain to obtain ultrafine-grain sizes and high fractions of high-angle grain boundaries. This facilitates grain boundary sliding, and an example is presented for a cast Al-7 pct Si alloy processed by HPT. In some materials, SPD may result in a weakening even with a very fine grain size, and this is due to microstructural changes during processing. Examples are presented for an Al-7034 alloy processed by ECAP and a Zn-22 pct Al alloy processed by HPT. In some SPD-processed materials, it is possible that grain boundary segregation and other features are present leading to higher strengths than predicted by the H-P relationship.

Association Between Helicobacter Pylori Infection and Long-term Outcome in Patients with Drug-eluting Stent Implantation

NASA Astrophysics Data System (ADS)

Wang, Rui; Chen, Lei-Lei; Wang, De-Zhao; Chen, Bu-Xing

2017-07-01

To investigate the relationship between Helicobacter pylori (Hp) infection and the long-term outcome in acute coronary syndrome (ACS) patients with drug-eluting stent (DES) implantation and so as to explore the significance of Hp eradication therapy in preventing major adverse cardiac events (MACE) and upper gastrointestinal bleeding (UGIB). 539 ACS patients with DES implantation from January 1, 2010 to December 31, 2012 were analyzed. All the patients were divided into two groups according to the result of 13C urea breath test. 253 patients with Hp infection were put into group A (Hp+), and 286 cases without Hp infection were put into group B (Hp-). Demographic data was collected and all patients went through biochemical indicators and other routine blood examinations. We explored the correlations of Hp infection with MACE and UGIB after 3 to 5 years of follow-up using survival analysis. Survival analysis showed that Hp infection was a predictor of MACE and UGI. Sub-group analysis showed that patients with Hp eradication therapy had no relationship with MACE but had a lower rate of UGIB than those without Hp eradication therapy.

Acute phase protein haptoglobin as inflammatory marker in serum and synovial fluid in an equine model of arthritis.

PubMed

Barrachina, Laura; Remacha, Ana Rosa; Soler, Lourdes; García, Natalia; Romero, Antonio; Vázquez, Francisco José; Vitoria, Arantza; Álava, María Ángeles; Lamprave, Fermín; Rodellar, Clementina

2016-12-01

Acute phase proteins are useful inflammatory markers in horses. Haptoglobin (Hp) serum level is increased in horses undergoing different inflammatory processes, including arthritis. However, Hp concentration has not been assessed in inflammatory synovial fluid (SF). The aim of the present study was to investigate the Hp response in serum and SF in horses undergoing experimentally induced arthritis. For this purpose, serum and SF samples were collected from 12 animals before amphotericin B-induced arthritis was created (T0, healthy) and 15days after the lesion induction (T1, joint inflammation) and Hp was determined by single radial immunodiffusion. The Hp increase between T0 and T1 was significant in both serum and SF, and serum Hp concentration at T0 was significantly higher than in SF, but significant differences were not found at T1, indicating a higher Hp increase in SF. A significant positive correlation for Hp concentration between serum and SF samples was found. These results highlight the potential usefulness of Hp as inflammatory marker in horses, showing for the first time the increase of Hp in SF from joint inflammation in the horse. Copyright © 2016 Elsevier B.V. All rights reserved.

The role of calcium signalling in the chondrogenic response of mesenchymal stem cells to hydrostatic pressure.

PubMed

Steward, A J; Kelly, D J; Wagner, D R

2014-10-28

The object of this study was to elucidate the role of Ca++ signalling in the chondrogenic response of mesenchymal stem cells (MSCs) to hydrostatic pressure (HP). MSCs were seeded into agarose hydrogels, subjected to HP or kept in free swelling conditions, and were cultured either with or without pharmacological inhibitors of Ca++ mobility and downstream targets. Chelating free Ca++, inhibiting voltage-gated calcium channels, and depleting intracellular calcium storessuppressed the beneficial effect of HP on chondrogenesis, indicating that Ca++ mobility may play an important role in the mechanotransduction of HP. However, inhibition of stretch-activated calcium channels in the current experiment yielded similar results to the control group, suggesting that mechanotransduction of HP is distinct from loads that generate cell deformations. Inhibition of the downstream targets calmodulin, calmodulin kinase II, and calcineurin all knocked down the effect of HP on chondrogenesis, implicating these targets in MSCs response to HP. All of the pharmacological inhibitors that abolished the chondrogenic response to HP also maintained a punctate vimentin organisation in the presence of HP, as opposed to the mechanoresponsive groups where the vimentin structure became more diffuse. These results suggest that Ca++ signalling may transduce HP via vimentin adaptation to loading.

A non-canonical DNA structure enables homologous recombination in various genetic systems.

PubMed

Masuda, Tokiha; Ito, Yutaka; Terada, Tohru; Shibata, Takehiko; Mikawa, Tsutomu

2009-10-30

Homologous recombination, which is critical to genetic diversity, depends on homologous pairing (HP). HP is the switch from parental to recombinant base pairs, which requires expansion of inter-base pair spaces. This expansion unavoidably causes untwisting of the parental double-stranded DNA. RecA/Rad51-catalyzed ATP-dependent HP is extensively stimulated in vitro by negative supercoils, which compensates for untwisting. However, in vivo, double-stranded DNA is relaxed by bound proteins and thus is an unfavorable substrate for RecA/Rad51. In contrast, Mhr1, an ATP-independent HP protein required for yeast mitochondrial homologous recombination, catalyzes HP without the net untwisting of double-stranded DNA. Therefore, we questioned whether Mhr1 uses a novel strategy to promote HP. Here, we found that, like RecA, Mhr1 induced the extension of bound single-stranded DNA. In addition, this structure was induced by all evolutionarily and structurally distinct HP proteins so far tested, including bacterial RecO, viral RecT, and human Rad51. Thus, HP includes the common non-canonical DNA structure and uses a common core mechanism, independent of the species of HP proteins. We discuss the significance of multiple types of HP proteins.

64nm pitch metal1 double patterning metrology: CD and OVL control by SEMCD, image based overlay and diffraction based overlay

NASA Astrophysics Data System (ADS)

Ducoté, Julien; Dettoni, Florent; Bouyssou, Régis; Le-Gratiet, Bertrand; Carau, Damien; Dezauzier, Christophe

2015-03-01

Patterning process control of advanced nodes has required major changes over the last few years. Process control needs of critical patterning levels since 28nm technology node is extremely aggressive showing that metrology accuracy/sensitivity must be finely tuned. The introduction of pitch splitting (Litho-Etch-Litho-Etch) at 14FDSOInm node requires the development of specific metrologies to adopt advanced process control (for CD, overlay and focus corrections). The pitch splitting process leads to final line CD uniformities that are a combination of the CD uniformities of the two exposures, while the space CD uniformities are depending on both CD and OVL variability. In this paper, investigations of CD and OVL process control of 64nm minimum pitch at Metal1 level of 14FDSOI technology, within the double patterning process flow (Litho, hard mask etch, line etch) are presented. Various measurements with SEMCD tools (Hitachi), and overlay tools (KT for Image Based Overlay - IBO, and ASML for Diffraction Based Overlay - DBO) are compared. Metrology targets are embedded within a block instanced several times within the field to perform intra-field process variations characterizations. Specific SEMCD targets were designed for independent measurement of both line CD (A and B) and space CD (A to B and B to A) for each exposure within a single measurement during the DP flow. Based on those measurements correlation between overlay determined with SEMCD and with standard overlay tools can be evaluated. Such correlation at different steps through the DP flow is investigated regarding the metrology type. Process correction models are evaluated with respect to the measurement type and the intra-field sampling.

The hypersensitivity pneumonitis diagnostic index: use of non-invasive testing to diagnose hypersensitivity pneumonitis in metalworkers.

PubMed

Dangman, Kenneth H; Cole, Solon R; Hodgson, Michael J; Kuhn, Charles; Metersky, Mark L; Schenck, Paula; Storey, Eileen

2002-08-01

Since 1993, several outbreaks of hypersensitivity pneumonitis (HP) have been reported in metalworkers. We report the largest outbreak of HP in metalworkers yet known. It occurred in a Connecticut factory that produces precision parts for the aerospace industry. The workers typically presented with systemic and respiratory problems ("sick fatigue," myalgias, cough, dyspnea, wheezing, and chest tightness). They had variable findings on clinical tests, which complicated diagnosis. An HP diagnostic index was developed to help reduce the uncertainties in case identification. Data from 16 biopsy-confirmed cases and 14 non-HP patients were compared, and the HP diagnostic index was derived using variables that best discriminated between the two groups. The index is based on (a) work-related symptoms, (b) dry crackles on auscultation, (c) restrictive spirometry, (d) decreased diffusion capacity and/or increased A-a oxygen gradient, (e) elevated erythrocyte sedimentation rate, (f) abnormal radiographic images, and (g) abnormal gallium scans. We then applied the HP diagnostic index and, for comparison, the "Kenosha epidemiological case criteria" (developed during a recent HP outbreak in an automobile factory) to our data set. The HP diagnostic index and the Kenosha criteria confirmed HP in overlapping sets of 36 and 34 patients, respectively, that were both in good agreement with the clinical diagnoses. The HP diagnostic index relies less heavily on symptoms, subjective evaluations, and invasive tests than the Kenosha criteria, but both identified similar subsets of the 61 patients as having HP. The HP diagnostic index could provide a useful tool in future HP outbreaks, which are increasingly being recognized in metalworking facilities. Copyright 2002 Wiley-Liss, Inc.

Calciuric effects of protein and potassium bicarbonate but not of sodium chloride or phosphate can be detected acutely in adult women and men.

PubMed

Whiting, S J; Anderson, D J; Weeks, S J

1997-05-01

An acute load test was used to test the influence of dietary factors on urinary calcium excretion. In study 1, 10 fasting premenopausal women consumed test meals providing a moderate amount of protein (MP; 23 g), MP plus 23 mmol KHCO3 (MP+K), MP plus 23 mmol NaCl (MP+Na), and a high amount of protein (HP; 53 g), HP plus 70 mmol KHCO3 (HP+K), and HP plus 70 mmol NaCl (HP+Na). Protein was casein:lactalbumin (80:20), except for the treatments with added sodium chloride, to which only casein was added. In study 2, the effects of HP and HP plus 50 mmol KHCO3 (HP+K) were compared with those of MP or MP plus 7.5 mmol phosphate (MP+Pi), equaling the additional phosphate of HP, in 10 adult men. Subjects completed all treatments in random order. In study 1, the peak of calcium excretion was at 3 h for all treatments, except for HP+K, which indicated an acute hypocalciuric effect of potassium. Unexpectedly, there was no hypercalciuric effect of adding sodium chloride, nor was urine sodium increased. In study 2, calcium excretion was significantly higher with HP than with MP+Pi but not with MP at 3 h, indicating an acute hypercalciuric effect of protein alone. A hypocalciuric effect of potassium (HP+K compared with HP) but not of phosphate (MP compared with MP+Pi) was seen. An acute load test measuring changes 3 h postload was appropriate for examining the calciuric effects of protein and potassium bicarbonate, but not those of sodium chloride or phosphate in adults.

Performance of ASML YieldStar μDBO overlay targets for advanced lithography nodes C028 and C014 overlay process control

NASA Astrophysics Data System (ADS)

Blancquaert, Yoann; Dezauzier, Christophe; Depre, Jerome; Miqyass, Mohamed; Beltman, Jan

2013-04-01

Continued tightening of overlay control budget in semiconductor lithography drives the need for improved metrology capabilities. Aggressive improvements are needed for overlay metrology speed, accuracy and precision. This paper is dealing with the on product metrology results of a scatterometry based platform showing excellent production results on resolution, precision, and tool matching for overlay. We will demonstrate point to point matching between tool generations as well as between target sizes and types. Nowadays, for the advanced process nodes a lot of information is needed (Higher order process correction, Reticle fingerprint, wafer edge effects) to quantify process overlay. For that purpose various overlay sampling schemes are evaluated: ultra- dense, dense and production type. We will show DBO results from multiple target type and shape for on product overlay control for current and future node down to at least 14 nm node. As overlay requirements drive metrology needs, we will evaluate if the new metrology platform meets the overlay requirements.

Purinergic Signaling Regulates the Transforming Growth Factor-β3-Induced Chondrogenic Response of Mesenchymal Stem Cells to Hydrostatic Pressure.

PubMed

Steward, Andrew J; Kelly, Daniel J; Wagner, Diane R

2016-06-01

Although hydrostatic pressure (HP) is known to regulate chondrogenic differentiation of mesenchymal stromal/stem cells (MSCs), improved insight into the mechanotransduction of HP may form the basis for novel tissue engineering strategies. Previously, we demonstrated that matrix stiffness and calcium ion (Ca(++)) mobility regulate the mechanotransduction of HP; however, the mechanisms, by which these Ca(++) signaling pathways are initiated, are currently unknown. The purinergic pathway, in which adenosine triphosphate (ATP) is released and activates P-receptors to initiate Ca(++) signaling, plays a key role in the mechanotransduction of compression, but has yet to be investigated with regard to HP. Therefore, the objective of this study was to investigate the interplay between purinergic signaling, matrix stiffness, and the chondrogenic response of MSCs to HP. Porcine bone marrow-derived MSCs were seeded into soft or stiff agarose hydrogels and subjected to HP (10 MPa at 1 Hz for 4 h/d for 21 days) or kept in free swelling conditions. Stiff constructs were incubated with pharmacological inhibitors of extracellular ATP, P2 receptors, or hemichannels, or without any inhibitors as a control. As with other loading modalities, HP significantly increased ATP release in the control group; however, inhibition of hemichannels completely abrogated this response. The increase in sulfated glycosaminoglycan (sGAG) synthesis and vimentin reorganization observed in the control group in response to HP was suppressed in the presence of all three inhibitors, suggesting that purinergic signaling is involved in the mechanoresponse of MSCs to HP. Interestingly, ATP was released from both soft and stiff hydrogels in response to HP, but HP only enhanced chondrogenesis in the stiff hydrogels, indicating that matrix stiffness may act downstream of purinergic signaling to regulate the mechanoresponse of MSCs to HP. Addition of exogenous ATP did not replicate the effects of HP on chondrogenesis, suggesting that mechanisms other than purinergic signaling also regulate the response of MSCs to HP.

Role of porcine serum haptoglobin in the host-parasite relationship of Taenia solium cysticercosis.

PubMed

Navarrete-Perea, José; Toledano-Magaña, Yanis; De la Torre, Patricia; Sciutto, Edda; Bobes, Raúl José; Soberón, Xavier; Laclette, Juan Pedro

2016-06-01

Human and porcine cysticercosis is a parasitic disease caused by the larval stage (cysts) of the tapeworm Taenia solium. Cysts may live in several host tissues such as skeletal muscle or brain. We have previously described the presence of host haptoglobin (Hp) and hemoglobin (Hb) in different protein extracts of the T. solium cysts. Here, we report the binding of host Hp and Hb to a number of cyst proteins, evaluated through measuring electrophoretic and light absorbance changes. In the sera obtained from 18 cysticercotic pigs, Hp-Hb complexes were abundant, whereas free Hp was undetectable. In contrast, in the sera from non 18 cysticercotic pigs, Hp-Hb and free Hp were found. In the soluble protein fraction of cysts tissue, free Hp was detected showing a considerable Hb-binding ability, whereas in the vesicular fluid, Hp is mainly bound to Hb. Interestingly, assays carried out with the insoluble fraction of T. solium cysts tissue, showed binding of Hp and Hp-Hb in a saturable way, suggesting the existence of specific interactions. Our results suggested that the parasite can take advantage of the uptaken host Hp and Hb, either free or in complexes, as a source of iron or as a way to modulate the inflammatory response surrounding the T. solium cysts. Copyright © 2016 Elsevier B.V. All rights reserved.

The transport kinetics and selectivity of HpUreI, the urea channel from Helicobacter pylori†

PubMed Central

Gray, Lawrence R; Gu, Sean X; Quick, Matthias; Khademi, Shahram

2017-01-01

Helicobacter pylori’s unique ability to colonize and survive in the acidic environment of the stomach is critically dependent on uptake of urea through the urea channel, HpUreI. Hence, HpUreI may represent a promising target for the development of specific drugs against this human pathogen. To obtain insight into the structure/function relationship of this channel, we have developed conditions for the high-yield expression and purification of stable recombinant HpUreI that allowed its detailed kinetic characterization in solubilized form and reconstituted into liposomes. Detergent-solubilized HpUreI forms homo-trimer, as determined by chemical cross-linking. Urea dissociation kinetics of purified HpUreI were determined by means of the scintillation proximity assay (SPA), whereas urea efflux was measured in HpUreI-containing proteoliposomes using stopped-flow spectrometry to determine the kinetics and selectivity of the urea channel. The kinetic analyses revealed that urea conduction in HpUreI is pH sensitive and saturable with a half-saturation concentration (or K0.5) of ~163 mM. Binding of urea by HpUreI was increased at lower pH; however, the apparent affinity of urea binding (~150 mM) was not significantly pH dependent. The solute selectivity analysis indicated that HpUreI is highly selective for urea and hydroxyurea. Removing either amino group of urea molecules diminishes their permeability through HpUreI. Similar to urea conduction, water diffusion through HpUreI is pH-dependent with low water permeability at neutral pH. PMID:21877689

Effect of high- or low-concentration bleaching agents containing calcium and/or fluoride on enamel microhardness.

PubMed

Furlan, Isabella Spinardi; Bridi, Enrico Coser; Amaral, Flávia Lucisano Botelho do; França, Fabiana Mantovani Gomes; Turssi, Cecilia Pedroso; Basting, Roberta Tarkany

2017-01-01

The aim of this in vitro study was to evaluate enamel microhardness following bleaching treatments using either high- or low-concentration hydrogen peroxide (HP) agents containing calcium and/or fluoride. Sixty enamel blocks were bleached with 1 of 6 different bleaching agents (n = 10). The high-concentration HP agents were Whiteness HP Maxx (35% HP), Whiteness HP Blue (35% HP, 2% calcium gluconate), Pola Office+ (37.5% HP, 5% potassium nitrate), and Opalescence Boost (38% HP, 1.1% fluoride ion, 3% potassium nitrate). The low-concentration HP agents evaluated were Pola Day (9.5% HP) and White Class (10% HP, potassium nitrate, calcium, fluoride). High-concentration agents were applied in 3 sessions, whereas low-concentration agents were applied for 14 days. Knoop microhardness measurements were taken on the surface of the enamel before bleaching, at various timepoints during bleaching, and 14 days after the final bleaching treatment. The 2-way analysis of variance test showed that microhardness values were significantly influenced by the bleaching agent (P < 0.001) and application time (P < 0.001). The Tukey test showed that enamel bleached with Whiteness HP Maxx or White Class presented lower microhardness values than did the enamel treated with the remaining products. There was a reduction in micro-hardness values up to the end of the treatment. The results showed that the composition, concentration, and application protocol for each bleaching agent influenced the enamel microhardness values in that the microhardness decreased over time, regardless of the agent used or the addition of calcium and/or fluoride.

Optimization of Extracellular Matrix Synthesis and Accumulation by Human Articular Chondrocytes in 3-Dimensional Construct with Repetitive Hydrostatic Pressure.

PubMed

Ogura, Takahiro; Tsuchiya, Akihiro; Minas, Tom; Mizuno, Shuichi

2018-04-01

Objective The effects of hydrostatic pressure (HP) on the matrix synthesis by human articular chondrocytes have been reported elsewhere. In order to optimize the production of extracellular matrix, we aimed to clarify the effects of repetitive HP on metabolic function by human articular chondrocytes. Design The human articular chondrocytes were expanded and embedded within a collagen gel/sponge scaffold. We incubated these constructs with and without HP followed by atmospheric pressure (AP) and repeated the second HP followed by AP over 14 days. Genomic, biochemical, and histological evaluation were performed to compare the effects of each regimen on the constructs. Results The gene expressions of collagen type II and aggrecan core protein were significantly upregulated with repetitive HP regimens compared with a single HP or AP by 14 days ( P < 0.01 or 0.05). Matrix metalloptoteinase-13 (MMP-13) in AP was upregulated significantly compared to other HP regimens at day 14 ( P < 0.01). No significant difference was observed in tissue inhibitor of metalloproteinases-II. Immunohistology demonstrated that application of HP (both repetitive and single) promoted the accumulation of specific extracellular matrix and reduced a MMP-13. A single regimen of HP followed by AP significantly increased the amount of sulfated glycosaminoglycan than that of the AP, whereas repetitive HP remained similar level of that of the AP. Conclusions Repetitive HP had a greater effect on anabolic activity by chondrocytes than a single HP regimen, which will be advantageous for producing a matrix-rich cell construct.

Irreversible blockade of sigma-1 receptors by haloperidol and its metabolites in guinea pig brain and SH-SY5Y human neuroblastoma cells.

PubMed

Cobos, Enrique J; del Pozo, Esperanza; Baeyens, José M

2007-08-01

We evaluated the effect of haloperidol (HP) and its metabolites on [(3)H](+)-pentazocine binding to sigma(1) receptors in SH-SY5Y human neuroblastoma cells and guinea pig brain P(1), P(2) and P(3) subcellular fractions. Three days after a single i.p. injection in guinea pigs of HP (but not of other sigma(1) antagonists or (-)-sulpiride), [(3)H](+)-pentazocine binding to brain membranes was markedly decreased. Recovery of sigma(1) receptor density to steady state after HP-induced inactivation required more than 30 days. HP-metabolite II (reduced HP, 4-(4-chlorophenyl)-alpha-(4-fluorophenyl)-4-hydroxy-1-piperidinebutanol), but not HP-metabolite I (4-(4-chlorophenyl)-4-hydroxypiperidine), irreversibly blocked sigma(1) receptors in guinea pig brain homogenate and P(2) fraction in vitro. We found similar results in SH-SY5Y cells, which suggests that this process may also take place in humans. HP irreversibly inactivated sigma(1) receptors when it was incubated with brain homogenate and SH-SY5Y cells, but not when incubated with P(2) fraction membranes, which suggests that HP is metabolized to inactivate sigma(1) receptors. Menadione, an inhibitor of the ketone reductase activity that leads to the production of HP-metabolite II, completely prevented HP-induced inactivation of sigma(1) receptors in brain homogenates. These results suggest that HP may irreversibly inactivate sigma(1) receptors in guinea pig and human cells, probably after metabolism to reduced HP.

Localized hippocampus measures are associated with Alzheimer pathology and cognition independent of total hippocampal volume.

PubMed

Carmichael, Owen; Xie, Jing; Fletcher, Evan; Singh, Baljeet; DeCarli, Charles

2012-06-01

Hippocampal injury in the Alzheimer's disease (AD) pathological process is region-specific and magnetic resonance imaging (MRI)-based measures of localized hippocampus (HP) atrophy are known to detect region-specific changes associated with clinical AD, but it is unclear whether these measures provide information that is independent of that already provided by measures of total HP volume. Therefore, this study assessed the strength of association between localized HP atrophy measures and AD-related measures including cerebrospinal fluid (CSF) amyloid beta and tau concentrations, and cognitive performance, in statistical models that also included total HP volume as a covariate. A computational technique termed localized components analysis (LoCA) was used to identify 7 independent patterns of HP atrophy among 390 semiautomatically delineated HP from baseline magnetic resonance imaging of participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Among cognitively normal participants, multiple measures of localized HP atrophy were significantly associated with CSF amyloid concentration, while total HP volume was not. In addition, among all participants, localized HP atrophy measures and total HP volume were both independently and additively associated with CSF tau concentration, performance on numerous neuropsychological tests, and discrimination between normal, mild cognitive impairment (MCI), and AD clinical diagnostic groups. Together, these results suggest that regional measures of hippocampal atrophy provided by localized components analysis may be more sensitive than total HP volume to the effects of AD pathology burden among cognitively normal individuals and may provide information about HP regions whose deficits may have especially profound cognitive consequences throughout the AD clinical course. Copyright © 2012 Elsevier Inc. All rights reserved.

Microeconomics of process control in semiconductor manufacturing

NASA Astrophysics Data System (ADS)

Monahan, Kevin M.

2003-06-01

Process window control enables accelerated design-rule shrinks for both logic and memory manufacturers, but simple microeconomic models that directly link the effects of process window control to maximum profitability are rare. In this work, we derive these links using a simplified model for the maximum rate of profit generated by the semiconductor manufacturing process. We show that the ability of process window control to achieve these economic objectives may be limited by variability in the larger manufacturing context, including measurement delays and process variation at the lot, wafer, x-wafer, x-field, and x-chip levels. We conclude that x-wafer and x-field CD control strategies will be critical enablers of density, performance and optimum profitability at the 90 and 65nm technology nodes. These analyses correlate well with actual factory data and often identify millions of dollars in potential incremental revenue and cost savings. As an example, we show that a scatterometry-based CD Process Window Monitor is an economically justified, enabling technology for the 65nm node.

Differential effects of DEAE negative mode chromatography and gel-filtration chromatography on the charge status of Helicobacter pylori neutrophil-activating protein

PubMed Central

Pan, Timothy; Tzeng, Huey-Fen

2017-01-01

Helicobacter pylori neutrophil-activating protein (HP-NAP) is involved in H. pylori-associated gastric inflammation. HP-NAP is also a vaccine candidate, a possible drug target, and a potential diagnostic marker for H. pylori-associated diseases. Previously, we purified recombinant HP-NAP by one-step diethylaminoethyl (DEAE) negative mode chromatography by collecting the unbound fraction at pH 8.0 at 4°C. It remains unclear why HP-NAP does not bind to DEAE resins at the pH above its isoelectric point during the purification. To investigate how pH affects the surface net charge of HP-NAP and its binding to DEAE resins during the purification, recombinant HP-NAP expressed in Escherichia coli was subjected to DEAE negative mode chromatography at pH ranging from 7.0 to 9.0 at 25°C and the surface charge of purified HP-NAP was determined by capillary electrophoresis. A minimal amount of HP-NAP was detected in the elution fraction of DEAE Sepharose resin at pH 8.5, whereas recombinant HP-NAP was detected in the elution fraction of DEAE Sephadex resin only at pH 7.0 and 8.0. The purified recombinant HP-NAP obtained from the unbound fractions was not able to bind to DEAE resins at pH 7.0 to 9.0. In addition, the surface charge of the purified HP-NAP was neutral at pH 7.0 to 8.0 and was either neutral or slightly negative at pH 8.5 and 9.0. However, recombinant HP-NAP purified from gel-filtration chromatography was able to bind to DEAE Sepharose resin at pH 7.0 to 9.0 and DEAE Sephadex resin at pH 7.0. At pH 8.5 and 9.0, only the negatively charged species of HP-NAP were found. Thus, recombinant HP-NAP with different charge status can be differentially purified by DEAE negative mode chromatography and gel-filtration chromatography. Furthermore, the charge distribution on the surface of HP-NAP, the presence of impure proteins, and the overall net charge of the resins all affect the binding of HP-NAP to DEAE resins during the negative purification. PMID:28328957

Hydrostatic pressure-driven three-dimensional cartilage induction using human adipose-derived stem cells and collagen gels.

PubMed

Ogawa, Rei; Orgill, Dennis P; Murphy, George F; Mizuno, Shuichi

2015-01-01

The chondrogenic potential of adipose-derived stem cells (ASCs) has been previously demonstrated, although several reports have indicated that ASCs produce less cartilage-specific matrix than bone marrow-derived mesenchymal stem cells. In this study, we intended to improve chondrogenic phenotypes of ASCs using hydrostatic pressure (HP), without utilizing any growth factors other than the transforming growth factor-β1. Human ASCs (CD13(+), 44(+), 90(+), 14(-), 31(-), 34(-)) were harvested and cultured. After three passages, the cells were suspended in 0.3% neutralized collagen type I solution and injected into semipermeable membrane tubes, from which 66 pouches were constructed. After a day of incubation, the 66 pouches were divided into three groups. Group HP1: Pouches were incubated for 1 week with treatment of cyclic HP at 0-0.5 MPa (4.93 atm), 0.5 Hz, with a medium replenishment rate of 0.1 mL/min at 37°C, 3% O2, and 5% CO2 in air using a bioprocessor. This was followed by 3 weeks with no HP and without pouches. Group HP2: Pouches were incubated for the first and third week (2 total weeks) with the same condition of Group HP1. No HP was applied in the second and fourth week. Group AP: Pouches with one end opened were incubated without HP. We evaluated the cell constructs histologically and immunohistochemically, as well as for specific gene expression. Accumulation of the matrix in the HP1 and HP2 groups was much denser than AP groups, particularly after 2 weeks. Cell numbers in the HP groups increased gradually in the middle zone and peaked at 1 week after incubation, maintaining their numbers for the entire course on the surface layer of the construct. In the genomic study results, COL 2A1, COL 10A1, ACAN, SOX9, MMP3, and MMP13 were upregulated and COL 1A1, ITGB1, and PCNA were downregulated by HP. There were no significant differences between HP1 and HP2 gene expression. It was suggested that HP is especially beneficial in the early stage of chondrogenesis of ASCs. Moreover, the expression profile of genes related to chondrocyte differentiation/proliferation was significantly enhanced by HP loading compared with the AP control.

Differential effects of DEAE negative mode chromatography and gel-filtration chromatography on the charge status of Helicobacter pylori neutrophil-activating protein.

PubMed

Hong, Zhi-Wei; Yang, Yu-Chi; Pan, Timothy; Tzeng, Huey-Fen; Fu, Hua-Wen

2017-01-01

Helicobacter pylori neutrophil-activating protein (HP-NAP) is involved in H. pylori-associated gastric inflammation. HP-NAP is also a vaccine candidate, a possible drug target, and a potential diagnostic marker for H. pylori-associated diseases. Previously, we purified recombinant HP-NAP by one-step diethylaminoethyl (DEAE) negative mode chromatography by collecting the unbound fraction at pH 8.0 at 4°C. It remains unclear why HP-NAP does not bind to DEAE resins at the pH above its isoelectric point during the purification. To investigate how pH affects the surface net charge of HP-NAP and its binding to DEAE resins during the purification, recombinant HP-NAP expressed in Escherichia coli was subjected to DEAE negative mode chromatography at pH ranging from 7.0 to 9.0 at 25°C and the surface charge of purified HP-NAP was determined by capillary electrophoresis. A minimal amount of HP-NAP was detected in the elution fraction of DEAE Sepharose resin at pH 8.5, whereas recombinant HP-NAP was detected in the elution fraction of DEAE Sephadex resin only at pH 7.0 and 8.0. The purified recombinant HP-NAP obtained from the unbound fractions was not able to bind to DEAE resins at pH 7.0 to 9.0. In addition, the surface charge of the purified HP-NAP was neutral at pH 7.0 to 8.0 and was either neutral or slightly negative at pH 8.5 and 9.0. However, recombinant HP-NAP purified from gel-filtration chromatography was able to bind to DEAE Sepharose resin at pH 7.0 to 9.0 and DEAE Sephadex resin at pH 7.0. At pH 8.5 and 9.0, only the negatively charged species of HP-NAP were found. Thus, recombinant HP-NAP with different charge status can be differentially purified by DEAE negative mode chromatography and gel-filtration chromatography. Furthermore, the charge distribution on the surface of HP-NAP, the presence of impure proteins, and the overall net charge of the resins all affect the binding of HP-NAP to DEAE resins during the negative purification.

Dielectrophoresis enhances the whitening effect of carbamide peroxide on enamel.

PubMed

Ivanoff, Chris S; Hottel, Timothy L; Garcia-Godoy, Franklin; Riga, Alan T

2011-10-01

To compare the enamel whitening effect of a 20-minute dielectrophoresis enhanced electrochemical delivery to a 20-minute diffusion treatment. Forty freshly extracted human teeth without detectable caries or restoration were stored in distilled water at 4 degrees C and used within 1 month of extraction. Two different bleaching gels (Plus White 5 Minute Speed Whitening Gel and 35% Opalescence PF gel) were tested. The study had two parts: Part 1--Quantitative comparison of hydrogen peroxide (H2O2, HP) absorption--following application of an over-the-counter 35% HP whitening gel (Plus White 5 Minute Speed Whitening Gel) to 30 (n = 30) extracted human teeth by conventional diffusion or dielectrophoresis. The amount of H2O2 that diffused from the dentin was measured by a colorimetric oxidation-reduction reaction kit. HP concentration was measured by UV-Vis spectroscopy at 550 nm. Part 2--HP diffusion in stained teeth--35% carbamide peroxide whitening gel (35% Opalescence PF gel) was applied to 10 extracted human teeth (n = 10) stained by immersion in a black tea solution for 48 hours. The teeth were randomly assigned to the 20-minute dielectrophoresis or diffusion treatment group; whitening was evaluated by a dental spectrophotometer and macro-photography. Part 1: The analysis found significant differences between both groups with relative percent errors of 3% or less (a single outlier had an RPE of 12%). The average absorbance for the dielectrophoresis group in round 1 was 79% greater than the diffusion group. The average absorbance for the dielectrophoresis group in round 2 was 130% greater than the diffusion group. A single-factor ANOVA found a statistically significant difference between the diffusion and dielectrophoresis groups (P = 0.01). Part 2--The average change in Shade Guide Units (SGU) was 0.6 for the diffusion group, well under the error of measurement of 0.82 SGU. The average change in SGU for the dielectrophoresis group was 9, significantly above the error of measurement and 14 times or 1,400% greater than the diffusion group average. A single-factor ANOVA found a statistically significant difference between the diffusion and dielectrophoresis treatment groups (P < 0.001).

Sex Differences in the Effects of Captivity on Hippocampus Size in Brown-Headed Cowbirds (Molothrus ater obscurus)

PubMed Central

Day, Lainy B.; Guerra, Marjorie; Schlinger, Barney A.; Rothstein, Stephen I.

2010-01-01

In brood parasitic cowbirds, hippocampus (Hp) size is correlated with environmental spatial memory demands. Searching for host nests is the presumed causal factor influencing cowbird Hp size, because Hp volumes vary across species, sexes, and seasons according to nest-searching participation. Brown-headed cowbirds have female-only nest searching and, at least in the eastern subspecies, a larger Hp in females than in males, suggesting that nest searching influences cowbird Hp size. We predicted that female brown-headed cowbirds housed in aviaries lacking host nests would have a smaller Hp than wild-caught females whereas males would be unaffected. We found that the Hp was smaller in captive females, but not males, compared to their wild-caught counterparts. This did not appear to be due to general effects of an impoverished environment on all brain regions. Our results imply that interruption of nest searching in cowbirds prevents seasonal increase in Hp size in females. Future studies should isolate which behavioral differences between wild and captive birds contributed to captivity-induced changes in Hp volume in females while not affecting males. PMID:18513123

Hybrid propulsion technology program: Phase 1, volume 2

NASA Technical Reports Server (NTRS)

Schuler, A. L.; Wiley, D. R.

1989-01-01

The program objectives of developing hybrid propulsion technology (HPT) to enable its application for manned and unmanned high thrust, high performance space launch vehicles are examined. The studies indicate that the hybrid propulsion (HP) is very attractive, especially when applied to large boosters for programs such as the Advanced Launch System (ALS) and the second generation Space Shuttle. Some of the advantages of HP are identified. Space launch vehicles using HP are less costly than those flying today because their propellant and insulation costs are much less and there are fewer operational restraints due to reduced safety requirements. Boosters using HP have safety features that are highly desirable, particularly for manned flights. HP systems will have a clean exhaust and high performance. Boosters using HP readily integrate with launch vehicles and their launch operations, because they are very compact for the amount of energy contained. Hybrid propulsion will increase the probability of mission success. In order to properly develop the technologies of HP, preliminary HP concepts are evaluated. System analyses and trade studies were performed to identify technologies applicable to HP.

The effect of pH and triethanolamine on sulfisoxazole complexation with hydroxypropyl-beta-cyclodextrin.

PubMed

Gladys, Granero; Claudia, Garnero; Marcela, Longhi

2003-11-01

A novel complexation of sulfisoxazole with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) was studied. Two systems were used: binary complexes prepared with HP-beta-CD and multicomponent system (HP-beta-CD and the basic compound triethanolamine (TEA)). Inclusion complex formation in aqueous solutions and in solid state were investigated by the solubility method, thermal analysis (differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA)), Fourier-transform infrared spectroscopy (FT-IR) and dissolution studies. The solid complexes of sulfisoxazole were prepared by freeze-drying the homogeneous concentrated aqueous solutions in molar ratios of sulfisoxazole:HP-beta-CD 1:1 and 1:2, and sulfisoxazole:TEA:HP-beta-CD 1:1:2. FT-IR and thermal analysis showed differences among sulfisoxazole:HP-beta-CD and sulfisoxazole:TEA:HP-beta-CD and their corresponding physical mixtures and individual components. The HP-beta-CD solubilization of sulfisoxazole could be improved by ionization of the drug molecule through pH adjustments. However, larger improvements of the HP-beta-CD solubilization are obtained when multicomponent systems are used, allowing to reduce the amount of CD necessary to prepare the target formulation.

Pulmonary haptoglobin (pHp) is part of the surfactant system in the human lung.

PubMed

Abdullah, Mahdi; Goldmann, Torsten

2012-11-20

Since the existence of pHp was demonstrated, it has been shown that this molecule and its receptor CD163 are regulated by different stimuli. Furthermore, a comparably fast secretion of pHp was described as well as the immuno-stimulatory effects. The intention of this study was to elucidate the role of pHp in the human lungs further. Here we show, by means of confocal microscopy and immune-electron-microscopy, a clear co-localization of pHp with surfactant protein-B in lamellar bodies of alveolar epithelial cells type II. These results are underlined by immunohistochemical stainings in differently fixed human lung tissues, which show pHp in vesicular and released form. The images of the released form resemble the intended position of surfactant in the human alveolus. pHp is secreted by Alveolar epithelial cells type II as previously shown. Moreover, pHp is co-localized with Surfactant protein-B. We conclude that the presented data shows that pHp is a native part of the surfactant system in the human lung. http://www.diagnosticpathology.diagnomx.eu/vs/2563584738239912.

Multipotent Adult Progenitor Cells Suppress T Cell Activation in In Vivo Models of Homeostatic Proliferation in a Prostaglandin E2-Dependent Manner

PubMed Central

Carty, Fiona; Corbett, Jennifer M.; Cunha, João Paulo M. C. M.; Reading, James L.; Tree, Timothy I. M.; Ting, Anthony E.; Stubblefield, Samantha R.; English, Karen

2018-01-01

Lymphodepletion strategies are used in the setting of transplantation (including bone marrow, hematopoietic cell, and solid organ) to create space or to prevent allograft rejection and graft versus host disease. Following lymphodepletion, there is an excess of IL-7 available, and T cells that escape depletion respond to this cytokine undergoing accelerated proliferation. Moreover, this environment promotes the skew of T cells to a Th1 pro-inflammatory phenotype. Existing immunosuppressive regimens fail to control this homeostatic proliferative (HP) response, and thus the development of strategies to successfully control HP while sparing T cell reconstitution (providing a functioning immune system) represents a significant unmet need in patients requiring lymphodepletion. Multipotent adult progenitor cells (MAPC®) have the capacity to control T cell proliferation and Th1 cytokine production. Herein, this study shows that MAPC cells suppressed anti-thymocyte globulin-induced cytokine production but spared T cell reconstitution in a pre-clinical model of lymphodepletion. Importantly, MAPC cells administered intraperitoneally were efficacious in suppressing interferon-γ production and in promoting the expansion of regulatory T cells in the lymph nodes. MAPC cells administered intraperitoneally accumulated in the omentum but were not present in the spleen suggesting a role for soluble factors. MAPC cells suppressed lymphopenia-induced cytokine production in a prostaglandin E2-dependent manner. This study suggests that MAPC cell therapy may be useful as a novel strategy to target lymphopenia-induced pathogenic T cell responses in lymphodepleted patients. PMID:29740426

Meeting critical gate linewidth control needs at the 65 nm node

NASA Astrophysics Data System (ADS)

Mahorowala, Arpan; Halle, Scott; Gabor, Allen; Chu, William; Barberet, Alexandra; Samuels, Donald; Abdo, Amr; Tsou, Len; Yan, Wendy; Iseda, Seiji; Patel, Kaushal; Dirahoui, Bachir; Nomura, Asuka; Ahsan, Ishtiaq; Azam, Faisal; Berg, Gary; Brendler, Andrew; Zimmerman, Jeffrey; Faure, Tom

2006-03-01

With the nominal gate length at the 65 nm node being only 35 nm, controlling the critical dimension (CD) in polysilicon to within a few nanometers is essential to achieve a competitive power-to-performance ratio. Gate linewidths must be controlled, not only at the chip level so that the chip performs as the circuit designers and device engineers had intended, but also at the wafer level so that more chips with the optimum power-to-performance ratio are manufactured. Achieving tight across-chip linewidth variation (ACLV) and chip mean variation (CMV) is possible only if the mask-making, lithography, and etching processes are all controlled to very tight specifications. This paper identifies the various ACLV and CMV components, describes their root causes, and discusses a methodology to quantify them. For example, the site-to-site ACLV component is divided into systematic and random sub-components. The systematic component of the variation is attributed in part to pattern density variation across the field, and variation in exposure dose across the slit. The paper demonstrates our team's success in achieving the tight gate CD tolerances required for 65 nm technology. Certain key challenges faced, and methods employed to overcome them are described. For instance, the use of dose-compensation strategies to correct the small but systematic CD variations measured across the wafer, is described. Finally, the impact of immersion lithography on both ACLV and CMV is briefly discussed.

Tannic acid-modified silver nanoparticles for wound healing: the importance of size

PubMed Central

Orlowski, Piotr; Zmigrodzka, Magdalena; Tomaszewska, Emilia; Ranoszek-Soliwoda, Katarzyna; Czupryn, Monika; Antos-Bielska, Malgorzata; Szemraj, Janusz; Celichowski, Grzegorz; Grobelny, Jaroslaw

2018-01-01

Introduction Silver nanoparticles (AgNPs) have been shown to promote wound healing and to exhibit antimicrobial properties against a broad range of bacteria. In our previous study, we prepared tannic acid (TA)-modified AgNPs showing a good toxicological profile and immunomodulatory properties useful for potential dermal applications. Methods In this study, in vitro scratch assay, antimicrobial tests, modified lymph node assay as well as a mouse splint wound model were used to access the wound healing potential of TA-modified and unmodified AgNPs. Results TA-modified but not unmodified AgNPs exhibited effective antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli and stimulated migration of keratinocytes in vitro. The tests using the mouse splint wound model showed that TA-modified 33 and 46 nm AgNPs promoted better wound closure, epithelialization, angiogenesis and formation of the granulation tissue. Additionally, AgNPs elicited expression of VEGF-α, PDGF-β and TGF-β1 cytokines involved in wound healing more efficiently in comparison to control and TA-treated wounds. However, both the lymph node assay and the wound model showed that TA-modified AgNPs sized 13 nm can elicit strong inflammatory response not only during wound healing but also when applied to the damaged skin. Conclusion TA-modified AgNPs sized >26 nm promote wound healing better than TA-modified or unmodified AgNPs. These findings suggest that TA-modified AgNPs sized >26 nm may have a promising application in wound management. PMID:29497293

Mitotic centromeric targeting of HP1 and its binding to Sgo1 are dispensable for sister-chromatid cohesion in human cells

PubMed Central

Kang, Jungseog; Chaudhary, Jaideep; Dong, Hui; Kim, Soonjoung; Brautigam, Chad A.; Yu, Hongtao

2011-01-01

Human Shugoshin 1 (Sgo1) protects centromeric sister-chromatid cohesion during prophase and prevents premature sister-chromatid separation. Heterochromatin protein 1 (HP1) has been proposed to protect centromeric sister-chromatid cohesion by directly targeting Sgo1 to centromeres in mitosis. Here we show that HP1α is targeted to mitotic centromeres by INCENP, a subunit of the chromosome passenger complex (CPC). Biochemical and structural studies show that both HP1–INCENP and HP1–Sgo1 interactions require the binding of the HP1 chromo shadow domain to PXVXL/I motifs in INCENP or Sgo1, suggesting that the INCENP-bound, centromeric HP1α is incapable of recruiting Sgo1. Consistently, a Sgo1 mutant deficient in HP1 binding is functional in centromeric cohesion protection and localizes normally to centromeres in mitosis. By contrast, INCENP or Sgo1 mutants deficient in HP1 binding fail to localize to centromeres in interphase. Therefore, our results suggest that HP1 binding by INCENP or Sgo1 is dispensable for centromeric cohesion protection during mitosis of human cells, but might regulate yet uncharacterized interphase functions of CPC or Sgo1 at the centromeres. PMID:21346195

High- and Low-mobility Populations of HP1 in Heterochromatin of Mammalian CellsD⃞

PubMed Central

Schmiedeberg, Lars; Weisshart, Klaus; Diekmann, Stephan; Meyer zu Hoerste, Gabriele; Hemmerich, Peter

2004-01-01

Heterochromatin protein 1 (HP1) is a conserved nonhistone chromosomal protein with functions in euchromatin and heterochromatin. Here we investigated the diffusional behaviors of HP1 isoforms in mammalian cells. Using fluorescence correlation spectroscopy (FCS) and fluorescence recovery after photobleaching (FRAP) we found that in interphase cells most HP1 molecules (50–80%) are highly mobile (recovery halftime: t1/2 ≈ 0.9 s; diffusion coefficient: D ≈ 0.6–0.7 μm2 s-1). Twenty to 40% of HP1 molecules appear to be incorporated into stable, slow-moving oligomeric complexes (t1/2 ≈ 10 s), and constitutive heterochromatin of all mammalian cell types analyzed contain 5–7% of very slow HP1 molecules. The amount of very slow HP1 molecules correlated with the chromatin condensation state, mounting to more than 44% in condensed chromatin of transcriptionally silent cells. During mitosis 8–14% of GFP-HP1α, but not the other isoforms, are very slow within pericentromeric heterochromatin, indicating an isoform-specific function of HP1α in heterochromatin of mitotic chromosomes. These data suggest that mobile as well as very slow populations of HP1 may function in concert to maintain a stable conformation of constitutive heterochromatin throughout the cell cycle. PMID:15064352

Increase in telencephalic dopamine and cerebellar norepinephrine contents by hydrostatic pressure in goldfish: the possible involvement in hydrostatic pressure-related locomotion.

PubMed

Ikegami, Taro; Takemura, Akihiro; Choi, Eunjung; Suda, Atsushi; Tomonaga, Shozo; Badruzzaman, Muhammad; Furuse, Mitsuhiro

2015-10-01

Fish are faced with a wide range of hydrostatic pressure (HP) in their natural habitats. Additionally, freshwater fish are occasionally exposed to rapid changes in HP due to heavy rainfall, flood and/or dam release. Accordingly, variations in HP are one of the most important environmental cues for fish. However, little information is available on how HP information is perceived and transmitted in the central nervous system of fish. The present study examined the effect of HP (water depth of 1.3 m) on the quantities of monoamines and their metabolites in the telencephalon, optic tectum, diencephalon, cerebellum (including partial mesencephalon) and vagal lobe (including medulla oblongata) of the goldfish, Carassius auratus, using high-performance liquid chromatography. HP affected monoamine and metabolite contents in restricted brain regions, including the telencephalon, cerebellum and vagal lobe. In particular, HP significantly increased the levels of dopamine (DA) in the telencephalon at 15 min and that of norepinephrine (NE) in the cerebellum at 30 min. In addition, HP also significantly increased locomotor activity at 15 and 30 min after HP treatment. It is possible that HP indirectly induces locomotion in goldfish via telencephalic DA and cerebellar NE neuronal activity.

Effects of high-pressure argon and nitrogen treatments on respiration, browning and antioxidant potential of minimally processed pineapples during shelf life.

PubMed

Wu, Zhi-shuang; Zhang, Min; Wang, Shao-jin

2012-08-30

High-pressure (HP) inert gas processing causes inert gas and water molecules to form clathrate hydrates that restrict intracellular water activity and enzymatic reactions. This technique can be used to preserve fruits and vegetables. In this study, minimally processed (MP) pineapples were treated with HP (∼10 MPa) argon (Ar) and nitrogen (N) for 20 min. The effects of these treatments on respiration, browning and antioxidant potential of MP pineapples were investigated after cutting and during 20 days of storage at 4 °C. Lower respiration rate and ethylene production were found in HP Ar- and HP N-treated samples compared with control samples. HP Ar and HP N treatments effectively reduced browning and loss of total phenols and ascorbic acid and maintained antioxidant capacity of MP pineapples. They did not cause a significant decline in tissue firmness or increase in juice leakage. HP Ar treatments had greater effects than HP N treatments on reduction of respiration rate and ethylene production and maintenance of phenolic compounds and DPPH(•) and ABTS(•+) radical-scavenging activities. Both HP Ar and HP N processing had beneficial effects on MP pineapples throughout 20 days of storage at 4 °C. Copyright © 2012 Society of Chemical Industry.

Haloperidol-loaded lipid-core polymeric nanocapsules reduce DNA damage in blood and oxidative stress in liver and kidneys of rats

NASA Astrophysics Data System (ADS)

Roversi, Katiane; Benvegnú, Dalila M.; Roversi, Karine; Trevizol, Fabíola; Vey, Luciana T.; Elias, Fabiana; Fracasso, Rafael; Motta, Mariana H.; Ribeiro, Roseane F.; dos S. Hausen, Bruna; Moresco, Rafael N.; Garcia, Solange C.; da Silva, Cristiane B.; Burger, Marilise E.

2015-04-01

Haloperidol (HP) nanoencapsulation improves therapeutic efficacy, prolongs the drug action time, and reduces its motor side effects. However, in a view of HP toxicity in organs like liver and kidneys in addition to the lack of knowledge regarding the toxicity of polymeric nanocapsules, our aim was to verify the influence of HP-nanoformulation on toxicity and oxidative stress markers in the liver and kidneys of rats, also observing the damage caused in the blood. For such, 28 adult male Wistar rats were designated in four experimental groups ( n = 7) and treated with vehicle (C group), free haloperidol suspension (FH group), blank nanocapsules suspension (B-Nc group), and haloperidol-loaded lipid-core nanocapsules suspension (H-Nc group). The nanocapsules formulation presented the size of approximately 250 nm. All suspensions were administered to the animals (0.5 mg/kg/day-i.p.) for a period of 28 days. Our results showed that FH caused damage in the liver, evidenced by increased lipid peroxidation, plasma levels of aspartate aminotransferase, and alanine aminotransferase, as well as decreased cellular integrity and vitamin C levels. In kidneys, FH treatment caused damage to a lesser extent, observed by decreased activity of δ-aminolevulinate dehydratase (ALA-D) and levels of VIT C. In addition, FH treatment was also related to a higher DNA damage index in blood. On the other hand, animals treated with H-Nc and B-Nc did not show damage in liver, kidneys, and DNA. Our study indicates that the nanoencapsulation of haloperidol was able to prevent the sub-chronic toxicity commonly observed in liver, kidneys, and DNA, thus reflecting a pharmacological superiority in relation to free drug.

Evaluation of porphyrin C analogues for photodynamic therapy of cerebral glioma.

PubMed

Karagianis, G; Hill, J S; Stylli, S S; Kaye, A H; Varadaxis, N J; Reiss, J A; Phillips, D R

1996-02-01

A series of monomeric porphyrins (2-8) based on porphyrin C (1) have been tested as sensitisers for photodynamic therapy (PDT) of cerebral glioma using the in vitro/in vivo C6 intracerebral animal tumour model. The in vivo screening, consisting of cytotoxicity, phototoxicity (red light) and subcellular localisation studies, revealed two sensitisers (porphyrin 7, molecular weight 863 Da and porphyrin 8, molecular weight 889 Da), which had greater photoactivity than porphyrin C and similar photoactivity to haematoporphyrin derivative (HpD) although at a 5-fold higher dose than HpD. Both sensitisers showed intracellular localisation to discrete organelle sites and exhibited considerably less 'dark' cytotoxicity than HpD. The kinetics of uptake of porphyrins 7 and 8 was studied in the mouse C6 glioma model as well as in biopsy samples from normal brain, liver, spleen and blood. Maximal drug uptake levels in tumour occurred 9 and 6 h after intraperitoneal injection for 7 and 8 respectively, at which time the tumour to normal brain ratios were 15:1 and 13:1 respectively. The effect of PDT using porphyrin 7 activated by the gold metal vapour laser tuned to 627.8 nm was studied in Wistar rats bearing intracerebral C6 glioma. At a drug dose of 10 mg porphyrin 7 kg-1 body weight and laser doses of up to 400 J cm-2 light, selective tumour kill with sparing of normal brain was achieved, with a maximal depth of tumour kill of 1.77+/-0.40. mm. Irradiation following a higher drug dose of 75 mg porphyrin 7 kg-1 body weight resulted in a greater depth of tumour kill, but also significantly increased the likelihood and extent of necrosis in normal brain.

Heat transfer capacity of heat pipes: An application in coalfield wildfire in China

NASA Astrophysics Data System (ADS)

Li, Bei; Deng, Jun; Xiao, Yang; Zhai, Xiaowei; Shu, Chi-Min; Gao, Wei

2018-01-01

Coalfield wildfires are serious catastrophes associated with mining activities. Generally, the coal wildfire areas have tremendous heat accumulation regions. Eliminating the internal heat is an effective method for coal wildfire control. In this study, high thermal conductivity component of a heat pipe (HP) was used for enhancing the heat dissipation efficiency and impeding heat accumulation. An experimental system was set up to analyze the thermal resistance network of the coal-HP system. A coal-HP heat removal model was also established for studying the heat transfer performance of HP on the coal pile. The HP exhibited outstanding cooling performance in the initial period, resulting in the highest temperature difference between the coal pile and ambient temperature. However, the effect of the HP on the distribution temperature of coal piles decreased with increasing distance. The largest decline in the coal temperature occurred in a 20-mm radius of the HP; the temperature decreased from 84.3 to 50.9 °C, a decline of 39.6%. The amount of energy transfer by the HP after 80 h was 1.0865, 2.1680, and 3.3649 MJ under the initial heat source temperatures of 100, 150, and 200 °C, respectively. The coal was governed below 80 °C with the HP under the experimental conditions. It revealed that the HP had a substantial effect on thermal removal and inhibited spontaneous coal combustion. In addition, this paper puts forward the technological path of HP to control typical coalfield wildfire.

Celiac disease and Helicobacter pylori infection in children: Is there any Association?

PubMed

Narang, Manish; Puri, Amarender Singh; Sachdeva, Sanjeev; Singh, Jatinderpal; Kumar, Ajay; Saran, Ravindra K

2017-06-01

Helicobacter pylori (HP) infection can influence the inflammatory and immune responses in the gut and may therefore play a role in the development of gluten-related enteropathy in genetically susceptible individuals. Our objective was to assess the relationship between celiac disease and HP infection in children. Children (1-18 years) diagnosed as celiac disease (CD) (n = 324) with submission of gastric and duodenal biopsies and duodenal histology having Marsh grade III features were eligible for the study. Non-celiac patients referred for endoscopy were selected as controls. We studied proportion of HP prevalence in children with confirmed CD as compared with HP prevalence in reference group comprising non-celiac children referred for endoscopy. We also evaluated predictors of HP infection in children with celiac disease. Of the 324 participants with CD, gastric HP was seen in 37 (11.4%) patients. The prevalence of HP in patients without CD (50%, P < 0.001) was significantly higher. Among patients with CD, HP infection was most frequent in patients with Marsh IIIa. In the stepwise regression analysis for risk factors of HP infection in CD patients: presence of gastritis, hemoglobin, and absence of scalloping were found to be independent predictors in a multivariate setup. Celiac disease and gastric HP infection have inverse relationship that raises the question whether development of HP infection confers protection against CD. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Health promotion interventions in social economy companies in Flanders (Belgium).

PubMed

Hublet, Anne; Maes, Lea; Mommen, Jasmine; Deforche, Benedicte; De Bourdeaudhuij, Ilse

2016-01-05

Disadvantaged groups are often not reached by mainstream health promotion interventions. Implementing health promotion (HP) interventions in social economy companies, can be an opportunity to reach those people. The implementation of these interventions in social economy companies was studied. Factors that could be related to the implementation of HP and being supportive towards implementation in the future, were investigated. An online, quantitative survey was sent to all 148 sheltered and social workshops in Flanders. In the questionnaire, the status of HP interventions and characteristics of the workshop were explored. Personal factors (such as attitudes towards HP, behavioural control, social norms and moral responsibility) were asked to the person responsible for implementation of HP interventions. Univariate and multivariate logistic regressions were performed. Respondents of 88 workshops completed the questionnaire. Almost 60% of the workshops implemented environmental or policy interventions. Having a positive attitude towards HP, being more morally responsible, and having the subjective norm that employees are positive towards health promotion at work, were related to being more supportive towards the implementation of HP in the univariate analyses. Only attitude stayed significantly related to being more supportive towards the implementation of HP in the multivariate analyses. Sheltered and social workshops are open to HP interventions, but more can be done to optimize the implementation. To persuade persons responsible for the implementation of HP to invest more in HP, changing attitudes concerning the benefits of health promotion for the employee and the company, is an important strategy.

ONR Far East Scientific Bulletin. Volume 12, Number 3, July-September 1987,

DTIC Science & Technology

1987-09-01

populated, some- sediment transport. times right down to the beaches. Sea Wave data for a 5-year period walls have been built for the last 30 or have...The average wave power varies season that the sea walls just do not from 15.5 kW/m (i.e., 1.34 hp/m work. In order to combat the problems, parallel to...to 1980. Dr. Burt’s current interest is in air- sea interaction. P . N P nSN nM’lVa ME nMln n °. .’V 4,i 4 .4 ’% %’ " , * .., , STATUS OF FRACTURE

Ultimate intra-wafer critical dimension uniformity control by using lithography and etch tool corrections

NASA Astrophysics Data System (ADS)

Kubis, Michael; Wise, Rich; Reijnen, Liesbeth; Viatkina, Katja; Jaenen, Patrick; Luca, Melisa; Mernier, Guillaume; Chahine, Charlotte; Hellin, David; Kam, Benjamin; Sobieski, Daniel; Vertommen, Johan; Mulkens, Jan; Dusa, Mircea; Dixit, Girish; Shamma, Nader; Leray, Philippe

2016-03-01

With shrinking design rules, the overall patterning requirements are getting aggressively tighter. For the 7-nm node and below, allowable CD uniformity variations are entering the Angstrom region (ref [1]). Optimizing inter- and intra-field CD uniformity of the final pattern requires a holistic tuning of all process steps. In previous work, CD control with either litho cluster or etch tool corrections has been discussed. Today, we present a holistic CD control approach, combining the correction capability of the etch tool with the correction capability of the exposure tool. The study is done on 10-nm logic node wafers, processed with a test vehicle stack patterning sequence. We include wafer-to-wafer and lot-to-lot variation and apply optical scatterometry to characterize the fingerprints. Making use of all available correction capabilities (lithography and etch), we investigated single application of exposure tool corrections and of etch tool corrections as well as combinations of both to reach the lowest CD uniformity. Results of the final pattern uniformity based on single and combined corrections are shown. We conclude on the application of this holistic lithography and etch optimization to 7nm High-Volume manufacturing, paving the way to ultimate within-wafer CD uniformity control.

IR-drop analysis for validating power grids and standard cell architectures in sub-10nm node designs

NASA Astrophysics Data System (ADS)

Ban, Yongchan; Wang, Chenchen; Zeng, Jia; Kye, Jongwook

2017-03-01

Since chip performance and power are highly dependent on the operating voltage, the robust power distribution network (PDN) is of utmost importance in designs to provide with the reliable voltage without voltage (IR)-drop. However, rapid increase of parasitic resistance and capacitance (RC) in interconnects makes IR-drop much worse with technology scaling. This paper shows various IR-drop analyses in sub 10nm designs. The major objectives are to validate standard cell architectures, where different sizes of power/ground and metal tracks are validated, and to validate PDN architecture, where types of power hook-up approaches are evaluated with IR-drop calculation. To estimate IR-drops in 10nm and below technologies, we first prepare physically routed designs given standard cell libraries, where we use open RISC RTL, synthesize the CPU, and apply placement & routing with process-design kits (PDK). Then, static and dynamic IR-drop flows are set up with commercial tools. Using the IR-drop flow, we compare standard cell architectures, and analysis impacts on performance, power, and area (PPA) with the previous technology-node designs. With this IR-drop flow, we can optimize the best PDN structure against IR-drops as well as types of standard cell library.

Boundary-based cellwise OPC for standard-cell layouts

NASA Astrophysics Data System (ADS)

Pawlowski, David M.; Deng, Liang; Wong, Martin D. F.

2007-03-01

Model based optical proximity correction (OPC) has become necessary at 90nm technology node. Cellwise OPC is an attractive technique to reduce the mask data size as well as the prohibitive runtime of full-chip OPC. As feature dimensions have gotten smaller, the radius of influence for edge features has extended further into neighboring cells such that it is no longer sufficient to perform cellwise OPC independent of neighboring cells, especially for the critical layers. The methodology described in this work accounts for features in neighboring cells and allows a cellwise approach to be applied to cells with a printed gate length of 45nm with the projection that it can also be applied to future technology nodes. OPC-ready cells are generated at library creation (independent of placement) using a boundary-based technique. Each cell has a tractable number of OPC-ready versions due to an intelligent characterization of standard cell layout features. Results are very promising: the average edge placement error (EPE) for all metal1 features in 100 layouts is 0.731nm which is less than 1% of metal1 width; the maximum EPE for poly features reduced to 1/3, compared to cellwise OPC without considering boundaries, creating similar levels of lithographic accuracy while obviating any of the drawbacks inherent in layout specific full-chip model-based OPC.

Heterotropic Effect of β-lactam Antibiotics on Antioxidant Property of Haptoglobin (2-2)-Hemoglobin Complex.

PubMed

Tayari, Masoumeh; Moosavi-Nejad, Zahra; Moosavi Nejad, Fatemeh; Rezaei-Tavirani, Mostafa; Dehghan Shasaltaneh, Marzieh

2011-01-01

Haptoglobin (Hp) is a mammalian serum glycoprotein showing a genetic polymorphism with three types, 1-1, 2-2 and 1-2. Hp appears to conserve the recycling of heme-iron by forming an essentially irreversible but non-covalent complex with hemoglobin which is released into the plasma by erythrocyte lysis. As an important consequence, Haptoglobin-Hemoglobin complex (Hp-Hb) shows considerable antioxidant property. In this study, antioxidant activity of Hp (2-2)-Hb complex on hydrogen peroxide has been studied and analyzed in the absence and presence of two beta-lactam antibiotics in-vitro. For this purpose, non-Michaelis behavior of peroxidase activity of Hp (2-2)-Hb complex was analyzed using Eadie-Hofstee, Clearance and Hill plots, in the absence and presence of pharmaceutical dose of ampicillin and coamoxiclav. The results have shown that peroxidase activity of Hp (2-2)-Hb complex is modulated via homotropic effect of hydrogen peroxide as an allostric substrate. On the other hand antioxidant property of Hp (2-2)-Hb complex increased via heterotropic effect of both antibiotics on the peroxidase activity of the complex. Both drugs also have mild effect on quality of homotropic property of the peroxidase activity of Hp (2-2)-Hb complex. Therefore, it can be concluded from our study that both beta-lactam antibiotics can increase peroxidase activity of Hp (2-2)-Hb complex via heterotropic effect. Thus, the two antibiotics (especially ampicillin) may help those individuals with Hp (2-2) phenotype to improve the Hp-Hb complex efficiency of removing hydrogen peroxide from serum under oxidative stress. This can be important in the individuals with phenotype Hp 2-2 who have less antioxidant activity relative to other phenotypes and are susceptible to cardiovascular disorders, as has been reported by other researchers.

Chromoplast-specific carotenoid-associated protein appears to be important for enhanced accumulation of carotenoids in hp1 tomato fruits.

PubMed

Kilambi, Himabindu Vasuki; Kumar, Rakesh; Sharma, Rameshwar; Sreelakshmi, Yellamaraju

2013-04-01

Tomato (Solanum lycopersicum) high-pigment mutants with lesions in diverse loci such as DNA Damage-Binding Protein1 (high pigment1 [hp1]), Deetiolated1 (hp2), Zeaxanthin Epoxidase (hp3), and Intense pigment (Ip; gene product unknown) exhibit increased accumulation of fruit carotenoids coupled with an increase in chloroplast number and size. However, little is known about the underlying mechanisms exaggerating the carotenoid accumulation and the chloroplast number in these mutants. A comparison of proteome profiles from the outer pericarp of hp1 mutant and wild-type (cv Ailsa Craig) fruits at different developmental stages revealed at least 72 differentially expressed proteins during ripening. Hierarchical clustering grouped these proteins into three clusters. We found an increased abundance of chromoplast-specific carotenoid-associated protein (CHRC) in hp1 fruits at red-ripe stage that is also reflected in its transcript level. Western blotting using CHRC polyclonal antibody from bell pepper (Capsicum annuum) revealed a 2-fold increase in the abundance of CHRC protein in the red-ripe stage of hp1 fruits compared with the wild type. CHRC levels in hp2 were found to be similar to that of hp1, whereas hp3 and Ip showed intermediate levels to those in hp1, hp2, and wild-type fruits. Both CHRC and carotenoids were present in the isolated plastoglobules. Overall, our results suggest that loss of function of DDB1, DET1, Zeaxanthin Epoxidase, and Ip up-regulates CHRC levels. Increase in CHRC levels may contribute to the enhanced carotenoid content in these high-pigment fruits by assisting in the sequestration and stabilization of carotenoids.

Chromoplast-Specific Carotenoid-Associated Protein Appears to Be Important for Enhanced Accumulation of Carotenoids in hp1 Tomato Fruits1[C][W][OA

PubMed Central

Kilambi, Himabindu Vasuki; Kumar, Rakesh; Sharma, Rameshwar; Sreelakshmi, Yellamaraju

2013-01-01

Tomato (Solanum lycopersicum) high-pigment mutants with lesions in diverse loci such as DNA Damage-Binding Protein1 (high pigment1 [hp1]), Deetiolated1 (hp2), Zeaxanthin Epoxidase (hp3), and Intense pigment (Ip; gene product unknown) exhibit increased accumulation of fruit carotenoids coupled with an increase in chloroplast number and size. However, little is known about the underlying mechanisms exaggerating the carotenoid accumulation and the chloroplast number in these mutants. A comparison of proteome profiles from the outer pericarp of hp1 mutant and wild-type (cv Ailsa Craig) fruits at different developmental stages revealed at least 72 differentially expressed proteins during ripening. Hierarchical clustering grouped these proteins into three clusters. We found an increased abundance of chromoplast-specific carotenoid-associated protein (CHRC) in hp1 fruits at red-ripe stage that is also reflected in its transcript level. Western blotting using CHRC polyclonal antibody from bell pepper (Capsicum annuum) revealed a 2-fold increase in the abundance of CHRC protein in the red-ripe stage of hp1 fruits compared with the wild type. CHRC levels in hp2 were found to be similar to that of hp1, whereas hp3 and Ip showed intermediate levels to those in hp1, hp2, and wild-type fruits. Both CHRC and carotenoids were present in the isolated plastoglobules. Overall, our results suggest that loss of function of DDB1, DET1, Zeaxanthin Epoxidase, and Ip up-regulates CHRC levels. Increase in CHRC levels may contribute to the enhanced carotenoid content in these high-pigment fruits by assisting in the sequestration and stabilization of carotenoids. PMID:23400702

Aurora-B/AIM-1 Regulates the Dynamic Behavior of HP1α at the G2–M Transition

PubMed Central

2006-01-01

Heterochromatin protein 1 (HP1) plays an important role in heterochromatin formation and undergoes large-scale, progressive dissociation from heterochromatin in prophase cells. However, the mechanisms regulating the dynamic behavior of HP1 are poorly understood. In this study, the role of Aurora-B was investigated with respect to the dynamic behavior of HP1α. Mammalian Aurora-B, AIM-1, colocalizes with HP1α to the heterochromatin in G2. Depletion of Aurora-B/AIM-1 inhibited dissociation of HP1α from the chromosome arms at the G2–M transition. In addition, depletion of INCENP led to aberrant cellular localization of Aurora-B/AIM-1, but it did not affect heterochromatin targeting of HP1α. It was proposed in the binary switch hypothesis that phosphorylation of histone H3 at Ser-10 negatively regulates the binding of HP1α to the adjacent methylated Lys-9. However, Aurora-B/AIM-1-mediated phosphorylation of H3 induced dissociation of the HP1α chromodomain but not of the intact protein in vitro, indicating that the center and/or C-terminal domain of HP1α interferes with the effect of H3 phosphorylation on HP1α dissociation. Interestingly, Lys-9 methyltransferase SUV39H1 is abnormally localized together along the metaphase chromosome arms in Aurora-B/AIM-1–depleted cells. In conclusion, these results showed that Aurora-B/AIM-1 is necessary for regulated histone modifications involved in binding of HP1α by the N terminus of histone H3 during mitosis. PMID:16687578

Ethnicity/culture modulates the relationships of the haptoglobin (Hp) 1-1 phenotype with cognitive function in older individuals with type 2 diabetes.

PubMed

Guerrero-Berroa, Elizabeth; Ravona-Springer, Ramit; Heymann, Anthony; Schmeidler, James; Hoffman, Hadas; Preiss, Rachel; Koifmann, Keren; Greenbaum, Lior; Levy, Andrew; Silverman, Jeremy M; Leroith, Derek; Sano, Mary; Schnaider-Beeri, Michal

2016-05-01

The haptoglobin (Hp) genotype has been associated with cognitive function in type 2 diabetes. Because ethnicity/culture has been associated with both cognitive function and Hp genotype frequencies, we examined whether it modulates the association of Hp with cognitive function. This cross-sectional study evaluated 787 cognitively normal older individuals (>65 years of age) with type 2 diabetes participating in the Israel Diabetes and Cognitive Decline study. Interactions in two-way analyses of covariance compared Group (Non-Ashkenazi versus Ashkenazi Jews) on the associations of Hp phenotype (Hp 1-1 versus non- Hp 1-1) with five cognitive outcome measures. The primary control variables were age, gender, and education. Compared with Ashkenazi Jews, non-Ashkenazi Jews with the Hp 1-1 phenotype had significantly poorer cognitive function than non-Hp 1-1 in the domains of Attention/Working Memory (p = 0.035) and Executive Function (p = 0.023), but not in Language/Semantic Categorization (p = 0.432), Episodic Memory (p = 0.268), or Overall Cognition (p = 0.082). After controlling for additional covariates (type 2 diabetes-related characteristics, cardiovascular risk factors, Mini-mental State Examination, and extent of depressive symptoms), Attention/Working Memory (p = 0.038) and Executive Function (p = 0.013) remained significant. Older individuals from specific ethnic/cultural backgrounds with the Hp 1-1 phenotype may benefit more from treatment targeted at decreasing or halting the detrimental effects of Hp 1-1 on the brain. Future studies should examine differential associations of Hp 1-1 and cognitive impairment, especially for groups with high prevalence of both, such as African-Americans and Hispanics. Copyright © 2015 John Wiley & Sons, Ltd.

G-quadruplex based Exo III-assisted signal amplification aptasensor for the colorimetric detection of adenosine.

PubMed

Xu, Lei; Shen, Xin; Li, Bingzhi; Zhu, Chunhong; Zhou, Xuemin

2017-08-08

Adenosine is an endogenous nucleotide pivotally involved in nucleic acid and energy metabolism. Its excessive existence may indicate tumorigenesis, typically lung cancer. Encouraged by its significance as the clinical biomarker, sensitive assay methods towards adenosine have been popularized, with high cost and tedious procedures as the inevitable defects. Herein, we report a label-free aptamer-based exonuclease III (Exo III) amplification colorimetric aptasensor for the highly sensitive and cost-effective detection of adenosine. The strategy employed two unlabeled hairpin DNA oligonucleotides (HP1 and HP2), where HP1 contained the aptamer towards adenosine and HP2 embedded the guanine-rich sequence (GRS). In the presence of adenosine, hairpin HP1 could form specific binding with adenosine and trigger the unfolding of HP1's hairpin structure. The resulting adenosine-HP1 complex could hybridize with HP2, generating the Exo III recognition site. After Exo III-assisted degradation, the GRS was released from HP2, and the adenosine-HP1 was released back to the solution to combine another HP2, inducing the cycling amplification. After multiple circulations, the released ample GRSs were induced to form G-quadruplex, further catalyzing the oxidation of TMB, yielding a color change which was finally mirrored in the absorbance change. On the contrary, the absence of adenosine failed to unfold HP1, remaining color unchanged eventually. Thanks to the amplification strategy, the limit of detection was lowered to 17 nM with a broad linear range from 50 nM to 6 μM. The proposed method was successfully applied to the detection of adenosine in biological samples and satisfying recoveries were acquired. Copyright © 2017 Elsevier B.V. All rights reserved.

A Low-Complexity Euclidean Orthogonal LDPC Architecture for Low Power Applications.

PubMed

Revathy, M; Saravanan, R

2015-01-01

Low-density parity-check (LDPC) codes have been implemented in latest digital video broadcasting, broadband wireless access (WiMax), and fourth generation of wireless standards. In this paper, we have proposed a high efficient low-density parity-check code (LDPC) decoder architecture for low power applications. This study also considers the design and analysis of check node and variable node units and Euclidean orthogonal generator in LDPC decoder architecture. The Euclidean orthogonal generator is used to reduce the error rate of the proposed LDPC architecture, which can be incorporated between check and variable node architecture. This proposed decoder design is synthesized on Xilinx 9.2i platform and simulated using Modelsim, which is targeted to 45 nm devices. Synthesis report proves that the proposed architecture greatly reduces the power consumption and hardware utilizations on comparing with different conventional architectures.

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.

FPGA chip performance improvement with gate shrink through alternating PSM 90nm process

NASA Astrophysics Data System (ADS)

Yu, Chun-Chi; Shieh, Ming-Feng; Liu, Erick; Lin, Benjamin; Ho, Jonathan; Wu, Xin; Panaite, Petrisor; Chacko, Manoj; Zhang, Yunqiang; Lei, Wen-Kang

2005-11-01

In the post-physical verification space called 'Mask Synthesis' a key component of design-for-manufacturing (DFM), double-exposure based, dark-field, alternating PSM (Alt-PSM) is being increasingly applied at the 90nm node in addition with other mature resolution enhancement techniques (RETs) such as optical proximity correction (OPC) and sub-resolution assist features (SRAF). Several high-performance IC manufacturers already use alt-PSM technology in 65nm production. At 90nm having strong control over the lithography process is a critical component in meeting targeted yield goals. However, implementing alt-PSM in production has been challenging due to several factors such as phase conflict errors, mask manufacturing, and the increased production cost due to the need for two masks in the process. Implementation of Alt-PSM generally requires phase compliance rules and proper phase topology in the layout and this has been successful for the technology node with these rules implemented. However, this may not be true for a mature, production process technology, in this case 90 nm. Especially, in the foundry-fabless business model where the foundry provides a standard set of design rules to its customers for a given process technology, and where not all the foundry customers require Alt-PSM in their tapeout flow. With minimum design changes, design houses usually are motivated by higher product performance for the existing designs. What follows is an in-depth review of the motivation to apply alt-PSM on a production FPGA, the DFM challenges to each partner faced, its effect on the tapeout flow, and how design, manufacturing, and EDA teams worked together to resolve phase conflicts, tapeout the chip, and finally verify the silicon results in production.

Self-aligned blocking integration demonstration for critical sub-40nm pitch Mx level patterning

NASA Astrophysics Data System (ADS)

Raley, Angélique; Mohanty, Nihar; Sun, Xinghua; Farrell, Richard A.; Smith, Jeffrey T.; Ko, Akiteru; Metz, Andrew W.; Biolsi, Peter; Devilliers, Anton

2017-04-01

Multipatterning has enabled continued scaling of chip technology at the 28nm node and beyond. Selfaligned double patterning (SADP) and self-aligned quadruple patterning (SAQP) as well as Litho- Etch/Litho-Etch (LELE) iterations are widely used in the semiconductor industry to enable patterning at sub 193 immersion lithography resolutions for layers such as FIN, Gate and critical Metal lines. Multipatterning requires the use of multiple masks which is costly and increases process complexity as well as edge placement error variation driven mostly by overlay. To mitigate the strict overlay requirements for advanced technology nodes (7nm and below), a self-aligned blocking integration is desirable. This integration trades off the overlay requirement for an etch selectivity requirement and enables the cut mask overlay tolerance to be relaxed from half pitch to three times half pitch. Selfalignement has become the latest trend to enable scaling and self-aligned integrations are being pursued and investigated for various critical layers such as contact, via, metal patterning. In this paper we propose and demonstrate a low cost flexible self-aligned blocking strategy for critical metal layer patterning for 7nm and beyond from mask assembly to low -K dielectric etch. The integration is based on a 40nm pitch SADP flow with 2 cut masks compatible with either cut or block integration and employs dielectric films widely used in the back end of the line. As a consequence this approach is compatible with traditional etch, deposition and cleans tools that are optimized for dielectric etches. We will review the critical steps and selectivities required to enable this integration along with bench-marking of each integration option (cut vs. block).

OPC model data collection for 45-nm technology node using automatic CD-SEM offline recipe creation

NASA Astrophysics Data System (ADS)

Fischer, Daniel; Talbi, Mohamed; Wei, Alex; Menadeva, Ovadya; Cornell, Roger

2007-03-01

Optical and Process Correction in the 45nm node is requiring an ever higher level of characterization. The greater complexity drives a need for automation of the metrology process allowing more efficient, accurate and effective use of the engineering resources and metrology tool time in the fab, helping to satisfy what seems an insatiable appetite for data by lithographers and modelers charged with development of 45nm and 32nm processes. The scope of the work referenced here is a 45nm design cycle "full-loop automation", starting with gds formatted target design layout and ending with the necessary feedback of one and two dimensional printed wafer metrology. In this paper the authors consider the key elements of software, algorithmic framework and Critical Dimension Scanning Electron Microscope (CDSEM) functionality necessary to automate its recipe creation. We evaluate specific problems with the methodology of the former art, "on-tool on-wafer" recipe construction, and discuss how the implementation of the design based recipe generation improves upon the overall metrology process. Individual target-by-target construction, use of a one pattern recognition template fits all approach, a blind navigation to the desired measurement feature, lengthy sessions on tool to construct recipes and limited ability to determine measurement quality in the resultant data set are each discussed as to how the state of the art Design Based Metrology (DBM) approach is implemented. The offline created recipes have shown pattern recognition success rates of up to 100% and measurement success rates of up to 93% for line/space as well as for 2D Minimum/Maximum measurements without manual assists during measurement.

Using temperature to reduce noise in quantum frequency conversion.

PubMed

Kuo, Paulina S; Pelc, Jason S; Langrock, Carsten; Fejer, M M

2018-05-01

Quantum frequency conversion is important in quantum networks to interface nodes operating at different wavelengths and to enable long-distance quantum communication using telecommunications wavelengths. Unfortunately, frequency conversion in actual devices is not a noise-free process. One main source of noise is spontaneous Raman scattering, which can be reduced by lowering the device operating temperature. We explore frequency conversion of 1554 nm photons to 837 nm using a 1813 nm pump in a periodically poled lithium niobate waveguide device. By reducing the temperature from 85°C to 40°C, we show a three-fold reduction in dark count rates, which is in good agreement with theory.

Development of monoclonal antibodies to pre-haptoglobin 2 and their use in an enzyme-linked immunosorbent assay (ELISA).

PubMed

Flanagan, J J; Arjomandi, A; Delanoy, M L; Du Paty, E; Galea, P; Laune, D; Rieunier, F; Walker, R P; Binder, S R

2014-04-01

Haptoglobins (HPs) are alpha 2-globulin proteins that bind free hemoglobin in plasma to prevent oxidative damage. HPs are produced as preproteins that are proteolytically cleaved in the ER into alpha and beta chains prior to forming mature, functional tetramers. Two alleles exist in humans (HP1 and HP2), therefore three genotypes are present in the population, i.e., HP1-1, HP2-1, and HP2-2. A biochemical role for nascent haptoglobin 2 (pre-haptoglobin 2 or pre-HP2) as the only known modulator of intestinal permeability has been established. In addition, elevated levels of serum pre-HP2 have been detected in multiple conditions including celiac disease and type I diabetes, which are believed to result in part through dysregulation of the intestinal barrier. In this study, we report the development of a monoclonal antibody that is specific for pre-HP2 with a binding affinity in the nanomolar range. Additional antibodies with specificities for preHP but not mature haptoglobin were also characterized. A sandwich enzyme-linked immunosorbent assay (ELISA) was established and validated. The ELISA showed high specificity for pre-HP2 even in the presence of excess pre-HP1 or mature haptoglobins, and has excellent linearity and inter- and intra-assay reproducibility with a working range from 3.1ng/mL to 200ng/mL. Testing of sera from 76 healthy patients revealed a non-Gaussian distribution of pre-HP2 levels with a mean concentration of 221.2ng/mL (95% CI: 106.5-335.9ng/mL) and a median value of 23.9ng/mL. Compared to current approaches, this ELISA offers a validated, monoclonal-based method with high sensitivity and specificity for measuring pre-HP2 in human serum. Copyright © 2014 Elsevier B.V. All rights reserved.

Functional and evolutionary analyses of Helicobacter pylori HP0231 (DsbK) protein with strong oxidative and chaperone activity characterized by a highly diverged dimerization domain

PubMed Central

Bocian-Ostrzycka, Katarzyna M.; Łasica, Anna M.; Dunin-Horkawicz, Stanisław; Grzeszczuk, Magdalena J.; Drabik, Karolina; Dobosz, Aneta M.; Godlewska, Renata; Nowak, Elżbieta; Collet, Jean-Francois; Jagusztyn-Krynicka, Elżbieta K.

2015-01-01

Helicobacter pylori does not encode the classical DsbA/DsbB oxidoreductases that are crucial for oxidative folding of extracytoplasmic proteins. Instead, this microorganism encodes an untypical two proteins playing a role in disulfide bond formation – periplasmic HP0231, which structure resembles that of EcDsbC/DsbG, and its redox partner, a membrane protein HpDsbI (HP0595) with a β-propeller structure. The aim of presented work was to assess relations between HP0231 structure and function. We showed that HP0231 is most closely related evolutionarily to the catalytic domain of DsbG, even though it possesses a catalytic motif typical for canonical DsbA proteins. Similarly, the highly diverged N-terminal dimerization domain is homologous to the dimerization domain of DsbG. To better understand the functioning of this atypical oxidoreductase, we examined its activity using in vivo and in vitro experiments. We found that HP0231 exhibits oxidizing and chaperone activities but no isomerizing activity, even though H. pylori does not contain a classical DsbC. We also show that HP0231 is not involved in the introduction of disulfide bonds into HcpC (Helicobacter cysteine-rich protein C), a protein involved in the modulation of the H. pylori interaction with its host. Additionally, we also constructed a truncated version of HP0231 lacking the dimerization domain, denoted HP0231m, and showed that it acts in Escherichia coli cells in a DsbB-dependent manner. In contrast, HP0231m and classical monomeric EcDsbA (E. coli DsbA protein) were both unable to complement the lack of HP0231 in H. pylori cells, though they exist in oxidized forms. HP0231m is inactive in the insulin reduction assay and possesses high chaperone activity, in contrast to EcDsbA. In conclusion, HP0231 combines oxidative functions characteristic of DsbA proteins and chaperone activity characteristic of DsbC/DsbG, and it lacks isomerization activity. PMID:26500620

Functional and evolutionary analyses of Helicobacter pylori HP0231 (DsbK) protein with strong oxidative and chaperone activity characterized by a highly diverged dimerization domain.

PubMed

Bocian-Ostrzycka, Katarzyna M; Łasica, Anna M; Dunin-Horkawicz, Stanisław; Grzeszczuk, Magdalena J; Drabik, Karolina; Dobosz, Aneta M; Godlewska, Renata; Nowak, Elżbieta; Collet, Jean-Francois; Jagusztyn-Krynicka, Elżbieta K

2015-01-01

Helicobacter pylori does not encode the classical DsbA/DsbB oxidoreductases that are crucial for oxidative folding of extracytoplasmic proteins. Instead, this microorganism encodes an untypical two proteins playing a role in disulfide bond formation - periplasmic HP0231, which structure resembles that of EcDsbC/DsbG, and its redox partner, a membrane protein HpDsbI (HP0595) with a β-propeller structure. The aim of presented work was to assess relations between HP0231 structure and function. We showed that HP0231 is most closely related evolutionarily to the catalytic domain of DsbG, even though it possesses a catalytic motif typical for canonical DsbA proteins. Similarly, the highly diverged N-terminal dimerization domain is homologous to the dimerization domain of DsbG. To better understand the functioning of this atypical oxidoreductase, we examined its activity using in vivo and in vitro experiments. We found that HP0231 exhibits oxidizing and chaperone activities but no isomerizing activity, even though H. pylori does not contain a classical DsbC. We also show that HP0231 is not involved in the introduction of disulfide bonds into HcpC (Helicobacter cysteine-rich protein C), a protein involved in the modulation of the H. pylori interaction with its host. Additionally, we also constructed a truncated version of HP0231 lacking the dimerization domain, denoted HP0231m, and showed that it acts in Escherichia coli cells in a DsbB-dependent manner. In contrast, HP0231m and classical monomeric EcDsbA (E. coli DsbA protein) were both unable to complement the lack of HP0231 in H. pylori cells, though they exist in oxidized forms. HP0231m is inactive in the insulin reduction assay and possesses high chaperone activity, in contrast to EcDsbA. In conclusion, HP0231 combines oxidative functions characteristic of DsbA proteins and chaperone activity characteristic of DsbC/DsbG, and it lacks isomerization activity.

Off-loading of cyclic hydrostatic pressure promotes production of extracellular matrix by chondrocytes.

PubMed

Tatsumura, Masaki; Sakane, Masataka; Ochiai, Naoyuki; Mizuno, Shuichi

2013-01-01

The addition of cyclic hydrostatic pressure (cHP) to cell culture medium has been used to promote extracellular matrix (ECM) production by articular chondrocytes. Though a combination of cHP followed by atmospheric pressure (AP) has been examined previously, the rationale of such a combination was unclear. We compared the effects of loading once versus twice (combinations of cHP followed by AP) regarding both gene expression and biochemical and histological phenotypes of chondrocytes. Isolated bovine articular chondrocytes were embedded in a collagen gel and incubated for 14 days under conditions combining cHP and AP. The gene expression of aggrecan core protein and collagen type II were upregulated in response to cHP, and those levels were maintained for at least 4 days after cHP treatment. Accumulation of cartilage-specific sulfated glycosaminoglycans following cHP for 7 days and subsequent AP for 7 days was significantly greater than that of the AP control (p < 0.05). Therefore, incubation at AP after loading with cHP was found to beneficially affect ECM accumulation. Manipulating algorithms of cHP combined with AP will be useful in producing autologous chondrocyte-based cell constructs for implantation. © 2014 S. Karger AG, Basel.

Pulmonary haptoglobin (pHp) is part of the surfactant system in the human lung

PubMed Central

2012-01-01

Abstract Since the existence of pHp was demonstrated, it has been shown that this molecule and its receptor CD163 are regulated by different stimuli. Furthermore, a comparably fast secretion of pHp was described as well as the immuno-stimulatory effects. The intention of this study was to elucidate the role of pHp in the human lungs further. Here we show, by means of confocal microscopy and immune-electron-microscopy, a clear co-localization of pHp with Surfactant protein-B in lamellar bodies of Alveolar Epithelial Cells Type II. These results are underlined by immunohistochemical stainings in differently fixed human lung tissues, which show pHp in vesicular and released form. The images of the released form resemble the intended position of surfactant in the human alveolus. pHp is secreted by Alveolar epithelial cells type II as previously shown. Moreover, pHp is co-localized with Surfactant protein-B. We conclude that the presented data shows that pHp is a native part of the surfactant system in the human lung. Virtual slides http://www.diagnosticpathology.diagnomx.eu/vs/2563584738239912. PMID:23164167

Determination of thiopental in urine sample with high-performance liquid chromatography using iodine-azide reaction as a postcolumn detection system.

PubMed

Zakrzewski, Robert; Ciesielski, Witold

2005-09-25

The reaction between iodine and azide ions induced by thiopental was utilized as a postcolumn reaction for chromatographic determination of thiopental. The method is based on the separation of thiopental on an Nova-Pak CN HP column with an acetonitrile-aqueous solution of sodium azide as a mobile phase, followed by spectrophotometric measurement of the residual iodine (lambda=350 nm) from the postcolumn iodine-azide reaction induced by thiopental after mixing an iodine solution containing iodide ions with the column effluent containing azide ions and thiopental. Chromatograms obtained for thiopental showed negative peaks as a result of the decrease in background absorbance. The detection limit (defined as S/N=3) was 20 nM (0.4 pmol injected amount) for thiopental. Calibration graphs, plotted as peak area versus concentrations, were linear from 40 nM. The elaborated method was applied to determine thiopental in urine samples. The detection limit (defined as S/N=3) was 0.025 nmol/ml urine. Calibration graphs, plotted as peak area versus concentrations, were linear from 0.05 nmol/ml urine. Authentic urine samples were analyzed, thiopental was determined at nmol/ml urine level.

New cancer-treatment model of photodynamic therapy combined with a type I topoisomerase inhibitor, CPT-11, against HeLa cell tumors in nude mice used by OPO parametric tunable laser

NASA Astrophysics Data System (ADS)

Yoshida, Takato O.; Matsuzawa, Eiji; Matsuo, Tetsumichi; Koide, Yukio; Terakawa, Susumu; Yokokura, Teruo; Hirano, Toru

1995-03-01

A new cancer-treatment model, photodynamic therapy (PDT) combined with a type I topoisomerase inhibitor, camptothecin derivative (CPT-11), against HeLa cell tumors in BALB/c nude mice has been developed using a wide-band tunable coherent light source operated on optical parametric oscillation (OPO parametric tunable laser). The Photosan-3 PDT and CPT-11 combined therapy was remarkably effective, that is the inhibition rate (I.R.) 40 - 80%, as compared to PDT only in vivo. The analysis of HpD (Photosan-3) and CPT-11 effects on cultured HeLa cells in vitro has been studied by a video-enhanced contrast differential interference contrast microscope (VEC-DIC). Photosan-3 with 600 nm light killed cells by mitochondrial damage within 50 min, but not with 700 nm light. CPT-11 with 700 - 400 nm light killed cells within 50 min after nucleolus damage appeared after around 30 min. The localization of CPT-11 in cells was observed as fluorescence images in the nucleus, particularly the nucleoral area produced clear images using an Argus 100.

The Reduction of TED in Ion Implanted Silicon

NASA Astrophysics Data System (ADS)

Jain, Amitabh

2008-11-01

The leading challenge in the continued scaling of junctions made by ion implantation and annealing is the control of the undesired transient enhanced diffusion (TED) effect. Spike annealing has been used as a means to reduce this effect and has proven successful in previous nodes. The peak temperature in this process is typically 1050 °C and the time spent within 50 °C of the peak is of the order of 1.5 seconds. As technology advances along the future scaling roadmap, further reduction or elimination of the enhanced diffusion effect is necessary. We have shown that raising the peak temperature to 1175 °C or more and reduction of the anneal time at peak temperature to less than a millisecond is effective in eliminating enhanced diffusion. We show that it is possible to employ a sequence of millisecond anneal followed by spike anneal to obtain profiles that do not exhibit gradient degradation at the junction and have junction depth and sheet resistance appropriate to the needs of future technology nodes. We have implemented millisecond annealing using a carbon dioxide laser to support high-volume manufacturing of 65 nm microprocessors and system-on-chip products. We further show how the use of molecular ion implantation to produce amorphousness followed by laser annealing to produce solid phase epitaxial regrowth results in junctions that meet the shallow depth and abruptness requirements of the 32 nm node.

The WRKY transcription factor HpWRKY44 regulates CytP450-like1 expression in red pitaya fruit (Hylocereus polyrhizus).

PubMed

Cheng, Mei-Nv; Huang, Zi-Juan; Hua, Qing-Zhu; Shan, Wei; Kuang, Jian-Fei; Lu, Wang-Jin; Qin, Yong-Hua; Chen, Jian-Ye

2017-01-01

Red pitaya ( Hylocereus polyrhizus ) fruit is a high-value, functional food, containing a high level of betalains. Several genes potentially related to betalain biosynthesis, such as cytochrome P450-like ( CytP450-like ), have been identified in pitaya fruit, while their transcriptional regulation remains unclear. In this work, the potential involvement of a WRKY transcription factor, HpWRKY44, in regulating CytP450-like1 expression in pitaya fruit was examined. HpWRKY44, a member of the Group 1 WRKY family, contains two conserved WRKY motifs and is localized in the nucleus. HpWRKY44 also exhibits trans-activation ability. Gene expression analysis showed that the expression of HpCytP450-like1 and HpWRKY44 increased steadily during pitaya fruit coloration, which corresponded with the production of elevated betalain levels in the fruit. HpWRKY44 was also demonstrated to directly bind to and activate the HpCytP450-like1 promoter via the recognition of the W-box element present in the promoter. Collectively, our findings indicate that HpWRKY44 transcriptionally activates HpCytP450-like1 , which perhaps, at least in part, contributes to betalain biosynthesis in pitaya fruit. The information provided in the current study provides novel insights into the regulatory network associated with betalain biosynthesis during pitaya fruit coloration.

Clearance Rate and BP-ANN Model in Paraquat Poisoned Patients Treated with Hemoperfusion

PubMed Central

Hu, Lufeng; Hong, Guangliang; Ma, Jianshe; Wang, Xianqin; Lin, Guanyang; Zhang, Xiuhua; Lu, Zhongqiu

2015-01-01

In order to investigate the effect of hemoperfusion (HP) on the clearance rate of paraquat (PQ) and develop a clearance model, 41 PQ-poisoned patients who acquired acute PQ intoxication received HP treatment. PQ concentrations were determined by high performance liquid chromatography (HPLC). According to initial PQ concentration, study subjects were divided into two groups: Low-PQ group (0.05–1.0 μg/mL) and High-PQ group (1.0–10 μg/mL). After initial HP treatment, PQ concentrations decreased in both groups. However, in the High-PQ group, PQ levels remained in excess of 0.05 μg/mL and increased when the second HP treatment was initiated. Based on the PQ concentrations before and after HP treatment, the mean clearance rate of PQ calculated was 73 ± 15%. We also established a backpropagation artificial neural network (BP-ANN) model, which set PQ concentrations before HP treatment as input data and after HP treatment as output data. When it is used to predict PQ concentration after HP treatment, high prediction accuracy (R = 0.9977) can be obtained in this model. In conclusion, HP is an effective way to clear PQ from the blood, and the PQ concentration after HP treatment can be predicted by BP-ANN model. PMID:25695058

Integrating health promotion with quality improvement in a Swedish hospital.

PubMed

Astnell, Sandra; von Thiele Schwarz, Ulrica; Hasson, Henna; Augustsson, Hanna; Stenfors-Hayes, Terese

2016-09-01

Integration of workplace employee health promotion (HP) and occupational health and safety (OHS) work into organizational quality improvement systems is suggested as a way to strengthen HP and OHS activities in an organization. The aim of this article was to study what consequences integration of HP, OHS and a quality improvement system called kaizen has on the frequency and type of HP and OHS activities. A quasi-experimental study design was used where an integration of the three systems for HP, OHS respectively kaizen, was performed at six intervention units at a Swedish hospital. The remaining six units served as controls. Document analysis of all employees' written improvement suggestions (kaizen notes) during 2013 was conducted. The findings show that the intervention group had more suggestions concerning HP and OHS (n = 114) when compared with the control group (n = 78) and a greater variety of HP and OHS suggestions. In addition, only the intervention group had included HP aspects. In both groups, most kaizen notes with health consideration had a preventive focus rather than rehabilitative. The intervention, i.e. the integration of HP, OHS and kaizen work, had a favourable effect on HP and OHS work when compared with the controls. The results of the study support that this system can work in practice at hospitals. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Synthesis and characterization of Poloxamer 188-grafted heparin copolymer.

PubMed

Tian, Ji-Lai; Zhao, Ying-Zheng; Jin, Zhuo; Lu, Cui-Tao; Tang, Qin-Qin; Xiang, Qi; Sun, Chang-Zheng; Zhang, Lu; Xu, Yan-Yan; Gao, Hui-Sheng; Zhou, Zhi-Cai; Li, Xiao-Kun; Zhang, Ying

2010-07-01

Poloxamer 188 is a safe biocompatible polymer that can be used in protein drug delivery system. In this study, a new heparin-poloxamer 188 conjugate (HP) was synthesized and its physicochemical properties were investigated. HP structure was confirmed by Fourier transform infrared spectroscopy (FTIR) and Hydrogen-1 nuclear magnetic resonance spectroscopy ((1)H-NMR). Content of the conjugated heparin was analyzed using Toluidine Blue. The critical micelle concentration (CMC) of the copolymer was determined by a fluorescence probe technique. The effect of HP on the gelation of poloxamer 188 was characterized by the rheological properties of the HP-poloxamer hydrogels. Solubility and viscosity of HP were also evaluated compared with poloxamer 188. From the results, the solubility of the conjugated heparin was increased compared with free heparin. The content of heparin in HP copolymer was 62.9%. The CMC of HP and poloxamer 188 were 0.483 and 0.743 mg/mL, respectively. The gelation temperature of 0.4 g/mL HP was 43.5 degrees C, whereas that of the same concentration of poloxamer 188 was 37.3 degrees C. With HP content in poloxamer 188 solution increasing, a V-shape change of gelation temperature was observed. Considering the importance of poloxamer 188 in functional material, HP may prove to be a facile temperature-sensitive material for protein drug-targeted therapy.

Tonsillar colonization is unlikely to play important role in Helicobacter pylori infection in children.

PubMed

Jelavic, Boris; Bevanda, Miljenko; Ostojic, Maja; Leventic, Miro; Vasilj, Mirjana; Knezevic, Ervin

2007-04-01

To determine (i) seroprevalence of Helicobacter pylori (HP) infection in children undergoing tonsillectomy, (ii) possible HP colonization on tonsils of children and its importance in HP transmission, and (iii) if four examined socio-economic factors are the risk factors for HP transmission and HP colonization on tonsils in children. Rapid urease test (RUT) of tonsils, and serologic blood tests for HP were performed in 77 children (aged 4-14 years) in Bosnia and Herzegovina (B-H), undergoing tonsillectomy. RUT positive tonsils were cultured for HP. RUT positive children were tested using (13)Carbon-urea breath test ((13)C-UBT). Information about socio-economic potential risk factors was obtained from the parents. Out of 139 pharyngeal and palatine tonsils, 17 palatine tonsils in 14 children were RUT positive and had negative HP culture. Eight children had positive both RUT and (13)C-UBT. There was no significant difference between children with hypertrophy and those with recurrent tonsillitis comparing their serologic tests results. There was no significant difference between seronegative (n=61) and seropositive (n=16) children comparing their age, sex, parental education level, owning a family courtyard, attending a children's collective, and owning a pet cat. The results in this prospective study do not support the notion that tonsils are an important reservoir for HP transmission in children in B-H. The examined socio-economic factors did not enhance HP seropositivity rate in children.

A statistical data analysis and plotting program for cloud microphysics experiments

NASA Technical Reports Server (NTRS)

Jordan, A. J.

1981-01-01

The analysis software developed for atmospheric cloud microphysics experiments conducted in the laboratory as well as aboard a KC-135 aircraft is described. A group of four programs was developed and implemented on a Hewlett Packard 1000 series F minicomputer running under HP's RTE-IVB operating system. The programs control and read data from a MEMODYNE Model 3765-8BV cassette recorder, format the data on the Hewlett Packard disk subsystem, and generate statistical data (mean, variance, standard deviation) and voltage and engineering unit plots on a user selected plotting device. The programs are written in HP FORTRAN IV and HP ASSEMBLY Language with the graphics software using the HP 1000 Graphics. The supported plotting devices are the HP 2647A graphics terminal, the HP 9872B four color pen plotter, and the HP 2608A matrix line printer.

Hazard property classification of waste according to the recent propositions of the EC using different methods.

PubMed

Hennebert, Pierre; van der Sloot, Hans A; Rebischung, Flore; Weltens, Reinhilde; Geerts, Lieve; Hjelmar, Ole

2014-10-01

Hazard classification of waste is a necessity, but the hazard properties (named "H" and soon "HP") are still not all defined in a practical and operational manner at EU level. Following discussion of subsequent draft proposals from the Commission there is still no final decision. Methods to implement the proposals have recently been proposed: tests methods for physical risks, test batteries for aquatic and terrestrial ecotoxicity, an analytical package for exhaustive determination of organic substances and mineral elements, surrogate methods for the speciation of mineral elements in mineral substances in waste, and calculation methods for human toxicity and ecotoxicity with M factors. In this paper the different proposed methods have been applied to a large assortment of solid and liquid wastes (>100). Data for 45 wastes - documented with extensive chemical analysis and flammability test - were assessed in terms of the different HP criteria and results were compared to LoW for lack of an independent classification. For most waste streams the classification matches with the designation provided in the LoW. This indicates that the criteria used by LoW are similar to the HP limit values. This data set showed HP 14 'Ecotoxic chronic' is the most discriminating HP. All wastes classified as acute ecotoxic are also chronic ecotoxic and the assessment of acute ecotoxicity separately is therefore not needed. The high number of HP 14 classified wastes is due to the very low limit values when stringent M factors are applied to total concentrations (worst case method). With M factor set to 1 the classification method is not sufficiently discriminating between hazardous and non-hazardous materials. The second most frequent hazard is HP 7 'Carcinogenic'. The third most frequent hazard is HP 10 'Toxic for reproduction' and the fourth most frequent hazard is HP 4 "Irritant - skin irritation and eye damage". In a stepwise approach, it seems relevant to assess HP 14 first, then, if the waste is not classified as hazardous, to assess subsequently HP 7, HP 10 and HP 4, and then if still not classified as hazardous, to assess the remaining properties. The elements triggering the HP 14 classification in order of importance are Zn, Cu, Pb, Cr, Cd and Hg. Progress in the speciation of Zn and Cu is essential for HP 14. Organics were quantified by the proposed method (AFNOR XP X30-489) and need no speciation. Organics can contribute significantly to intrinsic toxicity in many waste materials, but they are only of minor importance for the assessment of HP 14 as the metal concentrations are the main HP 14 classifiers. Organic compounds are however responsible for other toxicological characteristics (hormone disturbance, genotoxicity, reprotoxicity…) and shall be taken into account when the waste is not HP 14 classified. Copyright © 2014 Elsevier Ltd. All rights reserved.

Heat transfer capacity of heat pipes: An application in coalfield wildfire in China

NASA Astrophysics Data System (ADS)

Li, Bei; Deng, Jun; Xiao, Yang; Zhai, Xiaowei; Shu, Chi-Min; Gao, Wei

2018-06-01

Coalfield wildfires are serious catastrophes associated with mining activities. Generally, the coal wildfire areas have tremendous heat accumulation regions. Eliminating the internal heat is an effective method for coal wildfire control. In this study, high thermal conductivity component of a heat pipe (HP) was used for enhancing the heat dissipation efficiency and impeding heat accumulation. An experimental system was set up to analyze the thermal resistance network of the coal-HP system. A coal-HP heat removal model was also established for studying the heat transfer performance of HP on the coal pile. The HP exhibited outstanding cooling performance in the initial period, resulting in the highest temperature difference between the coal pile and ambient temperature. However, the effect of the HP on the distribution temperature of coal piles decreased with increasing distance. The largest decline in the coal temperature occurred in a 20-mm radius of the HP; the temperature decreased from 84.3 to 50.9 °C, a decline of 39.6%. The amount of energy transfer by the HP after 80 h was 1.0865, 2.1680, and 3.3649 MJ under the initial heat source temperatures of 100, 150, and 200 °C, respectively. The coal was governed below 80 °C with the HP under the experimental conditions. It revealed that the HP had a substantial effect on thermal removal and inhibited spontaneous coal combustion. In addition, this paper puts forward the technological path of HP to control typical coalfield wildfire. [Figure not available: see fulltext.

Expression of macrophage migration-inhibitory factor in duodenal ulcer and its relation to Helicobacter pylori infection.

PubMed

Yu, X H; Zhang, Q; Yang, X P; Yang, W; Dai, F; Qian, Z; Wang, Z L; Wu, C F; Zhao, H Z; Wang, G H

2015-10-30

The aim of this study was to examine the expression of macrophage migration-inhibitory factor (MIF) in duodenal ulcer epithelial cells and its relation to Helicobacter pylori (Hp) infection, and to discuss the pathogenic roles of MIF expression and Hp infection in duodenal ulcer. MIF protein and mRNA expression was examined in samples from patients with duodenal ulcer with and without Hp infection (N = 40 each, experimental group), and in normal duodenal bulb mucosal tissue (N = 40, control group) using immunohistochemistry and in situ hybridization. Patients without Hp infection received routine treatment, and treatment was provided to the patients positive for Hp to eradicate Hp infection. Hp and MIF expression levels before treatment and after the ulcer had been cured were compared. The positive rates of MIF protein and mRNA in patients with Hp infection before treatment were 67.5 and 65%, respectively, and were 18.9 and 21.6% in the 37 patients from whom Hp was eliminated. These were statistically different both before and after treatment compared with controls (P < 0.05). In the patients without Hp infection, the positive rates of MIF protein and mRNA expression before (45 and 47.5%, respectively) and after (32.5 and 30%) treatment were not significantly different (P > 0.05). The results of this study suggested that MIF is related to the development of duodenal ulcer, and that the presence of Hp is closely related with the expression of MIF in the duodenal mucosa and the development of duodenal ulcer.

Effect of Hydrogen and Carbamide Peroxide in Bleaching, Enamel Morphology, and Mineral Composition: In vitro Study.

PubMed

Llena, Carmen; Esteve, Irene; Forner, Leopoldo

2017-07-01

The aim of the study was to evaluate the bleaching effect, morphological changes, and variations in calcium (Ca) and phosphate (P) in the enamel with hydrogen peroxide (HP) and carbamide peroxide (CP) after the use of different application regimens. Four groups of five teeth were randomly assigned, according to the treatment protocol: HP 37.5% applied for 30 or 60 minutes (HP30, HP60), CP 16% applied for 14 or 28 hours (CP14, CP28). Changes in dental color were evaluated, according to the following formula: ΔE = [(L a -L b ) 2 +(a a -a b ) 2 + (b a -b b ) 2 ] 1/2 . Enamel morphology and Ca and P compositions were evaluated by confocal laser scanning microscope and environmental scanning electron microscopy. ΔE HP30 was significantly greater than CP14 (10.37 ± 2.65/8.56 ± 1.40), but not between HP60 and CP28. HP60 shows greater morphological changes than HP30. No morphological changes were observed in the groups treated with CP. The reduction in Ca and P was significantly greater in HP60 than in CP28 (p < 0.05). Both formulations improved tooth color; HP produced morphological changes and Ca and P a gradual decrease, while CP produced no morphological changes, and the decrease in mineral component was smaller. CP 16% applied during 2 weeks could be equally effective and safer for tooth whitening than to administer two treatment sessions with HP 37.5%.

Global investigations of the satellite-based Fugro OmniSTAR HP service

NASA Astrophysics Data System (ADS)

Pflugmacher, Andreas; Heister, Hansbert; Heunecke, Otto

2009-12-01

OmniSTAR is one of the world's leading suppliers of satellite-based augmentation services for onshore and offshore GNSS applications. OmniSTAR currently offers three services: VBS, HP and XP. OmniSTAR VBS is the code-based service, suitable for sub-metre positioning accuracy. The HP and XP services provide sub-decimetre accuracy, with the HP service based on a precise differential methodology and the XP service uses precise absolute positioning. The sub-decimetre HP and XP services both have distinctive convergence behaviour, and the positioning task is essentially a time-dependent process during which the accuracy of the estimated coordinates continuously improves over time. To validate the capabilities of the OmniSTAR services, and in particular the HP (High Performance) service, globally distributed measurement campaigns were performed. The results of these investigations confirm that the HP service satisfies its high accuracy specification, but only after a sufficient initialisation phase. Two kinds of disturbances can handicap HP operation: lack of GNSS observations and outages of the augmentation signal. The most serious kind of disturbance is the former. Within a few seconds the achieved convergence level is completely lost. Outages in the reception of augmentation data merely affect the relevant period of the outage - the accuracy during the outage is degraded. Only longer interruptions lead to a loss of the HP solution. When HP convergence is lost, the HP process has to be re-initialized. If there are known points (so-called “seed points”) available, a shortened “kick-start”-initialization is possible. With the aid of seed points it only takes a few minutes to restore convergence.

One-Step Chromatographic Purification of Helicobacter pylori Neutrophil-Activating Protein Expressed in Bacillus subtilis

PubMed Central

Shih, Kuo-Shun; Lin, Chih-Chang; Hung, Hsiao-Fang; Yang, Yu-Chi; Wang, Chung-An; Jeng, Kee-Ching; Fu, Hua-Wen

2013-01-01

Helicobacter pylori neutrophil-activating protein (HP-NAP), a major virulence factor of Helicobacter pylori (H. pylori), is capable of activating human neutrophils to produce reactive oxygen species (ROS) and secrete inammatory mediators. HP-NAP is a vaccine candidate, a possible drug target, and a potential in vitro diagnostic marker for H. pylori infection. HP-NAP has also been shown to be a novel therapeutic agent for the treatment of allergic asthma and bladder cancer. Hence, an efficient way to obtain pure HP-NAP needs to be developed. In this study, one-step anion-exchange chromatography in negative mode was applied to purify the recombinant HP-NAP expressed in Bacillus subtilis (B. subtilis). This purification technique was based on the binding of host cell proteins and/or impurities other than HP-NAP to DEAE Sephadex resins. At pH 8.0, almost no other proteins except HP-NAP passed through the DEAE Sephadex column. More than 60% of the total HP-NAP with purity higher than 91% was recovered in the flow-through fraction from this single-step DEAE Sephadex chromatography. The purified recombinant HP-NAP was further demonstrated to be a multimeric protein with a secondary structure of α-helix and capable of activating human neutrophils to stimulate ROS production. Thus, this one-step negative chromatography using DEAE Sephadex resin can efficiently yield functional HP-NAP from B. subtilis in its native form with high purity. HP-NAP purified by this method could be further utilized for the development of new drugs, vaccines, and diagnostics for H. pylori infection. PMID:23577158

Deep learning analyzes Helicobacter pylori infection by upper gastrointestinal endoscopy images.

PubMed

Itoh, Takumi; Kawahira, Hiroshi; Nakashima, Hirotaka; Yata, Noriko

2018-02-01

Helicobacter pylori (HP)-associated chronic gastritis can cause mucosal atrophy and intestinal metaplasia, both of which increase the risk of gastric cancer. The accurate diagnosis of HP infection during routine medical checks is important. We aimed to develop a convolutional neural network (CNN), which is a machine-learning algorithm similar to deep learning, capable of recognizing specific features of gastric endoscopy images. The goal behind developing such a system was to detect HP infection early, thus preventing gastric cancer.  For the development of the CNN, we used 179 upper gastrointestinal endoscopy images obtained from 139 patients (65 were HP-positive: ≥ 10 U/mL and 74 were HP-negative: < 3 U/mL on HP IgG antibody assessment). Of the 179 images, 149 were used as training images, and the remaining 30 (15 from HP-negative patients and 15 from HP-positive patients) were set aside to be used as test images. The 149 training images were subjected to data augmentation, which yielded 596 images. We used the CNN to create a learning tool that would recognize HP infection and assessed the decision accuracy of the CNN with the 30 test images by calculating the sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve (AUC).  The sensitivity and specificity of the CNN for the detection of HP infection were 86.7 % and 86.7 %, respectively, and the AUC was 0.956.  CNN-aided diagnosis of HP infection seems feasible and is expected to facilitate and improve diagnosis during health check-ups.

Reliable high-power injection locked 6kHz 60W laser for ArF immersion lithography

NASA Astrophysics Data System (ADS)

Watanabe, Hidenori; Komae, Shigeo; Tanaka, Satoshi; Nohdomi, Ryoichi; Yamazaki, Taku; Nakarai, Hiroaki; Fujimoto, Junichi; Matsunaga, Takashi; Saito, Takashi; Kakizaki, Kouji; Mizoguchi, Hakaru

2007-03-01

Reliable high power 193nm ArF light source is desired for the successive growth of ArF-immersion technology for 45nm node generation. In 2006, Gigaphoton released GT60A, high power injection locked 6kHz/60W/0.5pm (E95) laser system, to meet the demands of semiconductor markets. In this paper, we report key technologies for reliable mass production GT laser systems and GT60A high durability performance test results up to 20 billion pulses.

Modeling and characterization of shielded low loss CPWs on 65 nm node silicon

NASA Astrophysics Data System (ADS)

Hongrui, Wang; Dongxu, Yang; Li, Zhang; Lei, Zhang; Zhiping, Yu

2011-06-01

Coplanar waveguides (CPWs) are promising candidates for high quality passive devices in millimeter-wave frequency bands. In this paper, CPW transmission lines with and without ground shields have been designed and fabricated on 65 nm CMOS technology. A physical-based model is proposed to describe the frequency-dependent per-unit-length L, C, R and G parameters. Starting with a basic CPW structure, the slow-wave effect and ground-shield influence have been analyzed and incorporated into the general model. The accuracy of the model is confirmed by experimental results.

Three-dimensional Optical Coherence Tomography for Optical Biopsy of Lymph Nodes and Assessment of Metastatic Disease

PubMed Central

John, Renu; Adie, Steven G.; Chaney, Eric J.; Marjanovic, Marina; Tangella, Krishnarao V.; Boppart, Stephen A.

2013-01-01

Background Numerous techniques have been developed for localizing lymph nodes before surgical resection and for their histological assessment. Nondestructive high-resolution transcapsule optical imaging of lymph nodes offers the potential for in situ assessment of metastatic involvement, potentially during surgical procedures. Methods Three-dimensional optical coherence tomography (3-D OCT) was used for imaging and assessing resected popliteal lymph nodes from a preclinical rat metastatic tumor model over a 9-day time-course study after tumor induction. The spectral-domain OCT system utilized a center wavelength of 800 nm, provided axial and transverse resolutions of 3 and 12 µm, respectively, and performed imaging at 10,000 axial scans per second. Results OCT is capable of providing high-resolution labelfree images of intact lymph node microstructure based on intrinsic optical scattering properties with penetration depths of ~1–2 mm. The results demonstrate that OCT is capable of differentiating normal, reactive, and metastatic lymph nodes based on microstructural changes. The optical scattering and structural changes revealed by OCT from day 3 to day 9 after the injection of tumor cells into the lymphatic system correlate with inflammatory and immunological changes observed in the capsule, precortical regions, follicles, and germination centers found during histopathology. Conclusions We report for the first time a longitudinal study of 3-D transcapsule OCT imaging of intact lymph nodes demonstrating microstructural changes during metastatic infiltration. These results demonstrate the potential of OCT as a technique for intraoperative, real-time in situ 3-D optical biopsy of lymph nodes for the intraoperative staging of cancer. PMID:22688663

Complete data preparation flow for Massively Parallel E-Beam lithography on 28nm node full-field design

NASA Astrophysics Data System (ADS)

Fay, Aurélien; Browning, Clyde; Brandt, Pieter; Chartoire, Jacky; Bérard-Bergery, Sébastien; Hazart, Jérôme; Chagoya, Alexandre; Postnikov, Sergei; Saib, Mohamed; Lattard, Ludovic; Schavione, Patrick

2016-03-01

Massively parallel mask-less electron beam lithography (MP-EBL) offers a large intrinsic flexibility at a low cost of ownership in comparison to conventional optical lithography tools. This attractive direct-write technique needs a dedicated data preparation flow to correct both electronic and resist processes. Moreover, Data Prep has to be completed in a short enough time to preserve the flexibility advantage of MP-EBL. While the MP-EBL tools have currently entered an advanced stage of development, this paper will focus on the data preparation side of the work for specifically the MAPPER Lithography FLX-1200 tool [1]-[4], using the ASELTA Nanographics Inscale software. The complete flow as well as the methodology used to achieve a full-field layout data preparation, within an acceptable cycle time, will be presented. Layout used for Data Prep evaluation was one of a 28 nm technology node Metal1 chip with a field size of 26x33mm2, compatible with typical stepper/scanner field sizes and wafer stepping plans. Proximity Effect Correction (PEC) was applied to the entire field, which was then exported as a single file to MAPPER Lithography's machine format, containing fractured shapes and dose assignments. The Soft Edge beam to beam stitching method was employed in the specific overlap regions defined by the machine format as well. In addition to PEC, verification of the correction was included as part of the overall data preparation cycle time. This verification step was executed on the machine file format to ensure pattern fidelity and accuracy as late in the flow as possible. Verification over the full chip, involving billions of evaluation points, is performed both at nominal conditions and at Process Window corners in order to ensure proper exposure and process latitude. The complete MP-EBL data preparation flow was demonstrated for a 28 nm node Metal1 layout in 37 hours. The final verification step shows that the Edge Placement Error (EPE) is kept below 2.25 nm over an exposure dose variation of 8%.

Cost-effectiveness of a potential future Helicobacter pylori vaccine in the Netherlands: the impact of varying the discount rate for health.

PubMed

de Vries, Robin; Klok, Rogier M; Brouwers, Jacobus R B J; Postma, Maarten J

2009-02-05

To estimate the cost-effectiveness of a potential Helicobacter pylori (HP) vaccine for the Dutch situation, we developed a Markov model. Several HP prevalence scenarios were assessed. Additionally, we assessed the impact of the discount rate for health on the outcomes, as this influence can be profound for vaccines. When applying the current discount rate of 1.5% for health, the expected cost-effectiveness of HP vaccination is estimated below the informal Dutch threshold of euro 20,000/LYG when the HP prevalence is assumed > or =20% in the Dutch population. In conclusion, we showed that HP vaccination could possibly be a cost-effective intervention. However, this depends to a large extend on the prevalence of HP in the population. Furthermore, we showed the large impact of the discount rate for health on the cost-effectiveness of a HP vaccination program, illustrative for other vaccination programs.

Entrepreneurship in health education and health promotion: five cardinal rules.

PubMed

Eddy, James M; Stellefson, Michael L

2009-07-01

The nature of health education and health promotion (HE/HP) offers a fertile ground for entrepreneurial activity. As primary prevention of chronic diseases becomes a more central component of the health and/ or medical care continuum, entrepreneurial opportunities for health educators will continue to expand. The process used to design, implement, and evaluate health promotion and disease prevention has clear articulation with entrepreneurial, marketing management, and other business processes. Thus, entrepreneurs in HE/HP must be able to utilize business process to facilitate creative, new HE/HP business ideas. The purpose of this article is to weave theory and practical application into a primer on entrepreneurial applications in HE/HP. More specifically, the authors meld their prospective experiences and expertise to provide background thoughts on entrepreneurship in HE/HP and develop a framework for establishing an entrepreneurial venture in HE/HP. Five Cardinal Rules for Entrepreneurs in HE/HP are proposed.

Comparison of pathogenicity of highly pathogenic porcine reproductive and respiratory syndrome virus between wild and domestic pigs.

PubMed

Do, T D; Park, C; Choi, K; Jeong, J; Vo, M K; Nguyen, T T; Chae, C

2015-03-01

The objective of this study was to compare the pathogenicity of highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) infection between wild and domestic pigs based on clinical, immunological, and pathological evaluation. Upon challenge with HP-PRRSV, five wild pigs died compared to none of the domestic. Anti-PRRSV antibody titers were significantly (P < 0.05) higher in wild HP-PRRSV-infected pigs versus the domestic HP-PRRSV-infected pigs at 21 days post inoculation (dpi). Lung lesion scores at 7 dpi were also significantly (P < 0.01) higher in domestic infected pigs than wild infected pigs. The most striking difference was the viral tissue distribution between the wild and domestic HP-PRRSV-infected pigs. HP-PRRSV-positive cells were observed in bronchiolar, gastric, and renal tubular epithelial cells from wild HP-PRRSV-infected pigs only. The results in this study demonstrated a genetic difference exists between wild and domestic pigs, which could results in different clinical signs, immunological responses, and pathological outcomes to HP-PRRSV infection.

Structural basis for ligand and innate immunity factor uptake by the trypanosome haptoglobin-haemoglobin receptor.

PubMed

Lane-Serff, Harriet; MacGregor, Paula; Lowe, Edward D; Carrington, Mark; Higgins, Matthew K

2014-12-12

The haptoglobin-haemoglobin receptor (HpHbR) of African trypanosomes allows acquisition of haem and provides an uptake route for trypanolytic factor-1, a mediator of innate immunity against trypanosome infection. In this study, we report the structure of Trypanosoma brucei HpHbR in complex with human haptoglobin-haemoglobin (HpHb), revealing an elongated ligand-binding site that extends along its membrane distal half. This contacts haptoglobin and the β-subunit of haemoglobin, showing how the receptor selectively binds HpHb over individual components. Lateral mobility of the glycosylphosphatidylinositol-anchored HpHbR, and a ∼50° kink in the receptor, allows two receptors to simultaneously bind one HpHb dimer. Indeed, trypanosomes take up dimeric HpHb at significantly lower concentrations than monomeric HpHb, due to increased ligand avidity that comes from bivalent binding. The structure therefore reveals the molecular basis for ligand and innate immunity factor uptake by trypanosomes and identifies adaptations that allow efficient ligand uptake in the context of the complex trypanosome cell surface.

Helicobacter pylori-derived Heat shock protein 60 enhances angiogenesis via a CXCR2-mediated signaling pathway

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

Lin, Chen-Si; School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan; He, Pei-Juin

2010-06-25

Helicobacter pylori is a potent carcinogen associated with gastric cancer malignancy. Recently, H. pylori Heat shock protein 60 (HpHSP60) has been reported to promote cancer development by inducing chronic inflammation and promoting tumor cell migration. This study demonstrates a role for HpHSP60 in angiogenesis, a necessary precursor to tumor growth. We showed that HpHSP60 enhanced cell migration and tube formation, but not cell proliferation, in human umbilical vein endothelial cells (HUVECs). HpHSP60 also indirectly promoted HUVEC proliferation when HUVECs were co-cultured with supernatants collected from HpHSP60-treated AGS or THP-1 cells. The angiogenic array showed that HpHSP60 dramatically induced THP-1 cellsmore » and HUVECs to produce the chemotactic factors IL-8 and GRO. Inhibition of CXCR2, the receptor for IL-8 and GRO, or downstream PLC{beta}2/Ca2+-mediated signaling, significantly abolished HpHSP60-induced tube formation. In contrast, suppression of MAP K or PI3 K signaling did not affect HpHSP60-mediated tubulogenesis. These data suggest that HpHSP60 enhances angiogenesis via CXCR2/PLC{beta}2/Ca2+ signal transduction in endothelial cells.« less

Seasonal oscillation of liver-derived hibernation protein complex in the central nervous system of non-hibernating mammals

PubMed Central

Seldin, Marcus M.; Byerly, Mardi S.; Petersen, Pia S.; Swanson, Roy; Balkema-Buschmann, Anne; Groschup, Martin H.; Wong, G. William

2014-01-01

Mammalian hibernation elicits profound changes in whole-body physiology. The liver-derived hibernation protein (HP) complex, consisting of HP-20, HP-25 and HP-27, was shown to oscillate circannually, and this oscillation in the central nervous system (CNS) was suggested to play a role in hibernation. The HP complex has been found in hibernating chipmunks but not in related non-hibernating tree squirrels, leading to the suggestion that hibernation-specific genes may underlie the origin of hibernation. Here, we show that non-hibernating mammals express and regulate the conserved homologous HP complex in a seasonal manner, independent of hibernation. Comparative analyses of cow and chipmunk HPs revealed extensive biochemical and structural conservations. These include liver-specific expression, assembly of distinct heteromeric complexes that circulate in the blood and cerebrospinal fluid, and the striking seasonal oscillation of the HP levels in the blood and CNS. Central administration of recombinant HPs affected food intake in mice, without altering body temperature, physical activity levels or energy expenditure. Our results demonstrate that HP complex is not unique to the hibernators and suggest that the HP-regulated liver–brain circuit may couple seasonal changes in the environment to alterations in physiology. PMID:25079892

Dimensionality of Helicopter Parenting and Relations to Emotional, Decision-Making, and Academic Functioning in Emerging Adults.

PubMed

Luebbe, Aaron M; Mancini, Kathryn J; Kiel, Elizabeth J; Spangler, Brooke R; Semlak, Julie L; Fussner, Lauren M

2016-08-24

The current study tests the underlying structure of a multidimensional construct of helicopter parenting (HP), assesses reliability of the construct, replicates past relations of HP to poor emotional functioning, and expands the literature to investigate links of HP to emerging adults' decision-making and academic functioning. A sample of 377 emerging adults (66% female; ages 17-30; 88% European American) were administered several items assessing HP as well as measures of other parenting behaviors, depression, anxiety, decision-making style, grade point average, and academic functioning. Exploratory factor analysis results suggested a four-factor, 23-item measure that encompassed varying levels of parental involvement in the personal and professional lives of their children. A bifactor model was also fit to the data and suggested the presence of a reliable overarching HP factor in addition to three reliable subfactors. The fourth subfactor was not reliable and item variances were subsumed by the general HP factor. HP was found to be distinct from, but correlated in expected ways with, other reports of parenting behavior. HP was also associated with poorer functioning in emotional functioning, decision making, and academic functioning. Parents' information-seeking behaviors, when done in absences of other HP behaviors, were associated with better decision making and academic functioning. © The Author(s) 2016.

Piezo type mechanosensitive ion channel component 1 functions as a regulator of the cell fate determination of mesenchymal stem cells.

PubMed

Sugimoto, Asuna; Miyazaki, Aya; Kawarabayashi, Keita; Shono, Masayuki; Akazawa, Yuki; Hasegawa, Tomokazu; Ueda-Yamaguchi, Kimiko; Kitamura, Takamasa; Yoshizaki, Keigo; Fukumoto, Satoshi; Iwamoto, Tsutomu

2017-12-18

The extracellular environment regulates the dynamic behaviors of cells. However, the effects of hydrostatic pressure (HP) on cell fate determination of mesenchymal stem cells (MSCs) are not clearly understood. Here, we established a cell culture chamber to control HP. Using this system, we found that the promotion of osteogenic differentiation by HP is depend on bone morphogenetic protein 2 (BMP2) expression regulated by Piezo type mechanosensitive ion channel component 1 (PIEZO1) in MSCs. The PIEZO1 was expressed and induced after HP loading in primary MSCs and MSC lines, UE7T-13 and SDP11. HP and Yoda1, an activator of PIEZO1, promoted BMP2 expression and osteoblast differentiation, whereas inhibits adipocyte differentiation. Conversely, PIEZO1 inhibition reduced osteoblast differentiation and BMP2 expression. Furthermore, Blocking of BMP2 function by noggin inhibits HP induced osteogenic maker genes expression. In addition, in an in vivo model of medaka with HP loading, HP promoted caudal fin ray development whereas inhibition of piezo1 using GsMTx4 suppressed its development. Thus, our results suggested that PIEZO1 is responsible for HP and could functions as a factor for cell fate determination of MSCs by regulating BMP2 expression.

Enhanced transpiration rate in the high pigment 1 tomato mutant and its physiological significance.

PubMed

Carvalho, R F; Aidar, S T; Azevedo, R A; Dodd, I C; Peres, L E P

2011-05-01

Tomato high pigment (hp) mutants represent an interesting horticultural resource due to their enhanced accumulation of carotenoids, flavonoids and vitamin C. Since hp mutants are known for their exaggerated light responses, the molecules accumulated are likely to be antioxidants, recruited to deal with light and others stresses. Further phenotypes displayed by hp mutations are reduced growth and an apparent disturbance in water loss. Here, we examined the impact of the hp1 mutation and its near isogenic line cv Micro-Tom (MT) on stomatal conductance (gs), transpiration (E), CO(2) assimilation (A) and water use efficiency (WUE). Detached hp1 leaves lost water more rapidly than control leaves, but this behaviour was reversed by exogenous abscisic acid (ABA), indicating the ability of hp1 to respond to this hormone. Although attached hp1 leaves had enhanced gs, E and A compared to control leaves, genotypic differences were lost when water was withheld. Both instantaneous leaf-level WUE and long-term whole plant WUE did not differ between hp1 and MT. Our results indicate a link between exaggerated light response and water loss in hp1, which has important implications for the use of this mutant in both basic and horticultural research. © 2011 German Botanical Society and The Royal Botanical Society of the Netherlands.

Body indices and basic vital signs in Helicobacter pylori positive and negative persons.

PubMed

Kopácová, Marcela; Bures, Jan; Koupil, Ilona; Rejchrt, Stanislav; Vorísek, Viktor; Seifert, Bohumil; Pozler, Oldrich; Zivný, Pavel; Douda, Tomás; Palicka, Vladimír; Holcík, Jan

2007-01-01

It has been hypothesized that Helicobacter pylori (Hp) infection may contribute to reduced stature, risk of hypertension or obesity. The aim was to evaluate body indices in Hp positive and negative persons. A total of 2436 subjects (4-100 years old) were tested for Hp status by (13)C-urea breath test. Data on height and weight were collected for 84%, and blood pressure for 80% of the study subjects. The prevalence of Hp infection was 41.6%. The odds ratio for a 10-year increase in age was 1.21 (95% CI 1.17-1.25, p-value <0.001). Statistically significant negative association of Hp positivity with body height was most pronounced in the younger age groups, while a positive association of Hp positivity with body mass index was only seen in those aged 15+ years. There was a negative effect of Hp positivity on systolic and diastolic blood pressure in subjects below 25 and a relatively strong positive effect on blood pressure in subjects over 65 years. Residual confounding by social characteristics as a possible explanation for the associations of Hp positivity with height and blood pressure cannot be excluded. Unmeasured factors related to social and family environment may cause the apparent association between Hp positivity and children's growth and blood pressure.

Hydroxypropyl-sulfobutyl-β-cyclodextrin improves the oral bioavailability of edaravone by modulating drug efflux pump of enterocytes.

PubMed

Rong, Wen-Ting; Lu, Ya-Peng; Tao, Qing; Guo, Miao; Lu, Yu; Ren, Yong; Yu, Shu-Qin

2014-02-01

The objective of the study was to evaluate the effect of hydroxypropyl-sulfobutyl-β-cyclodextrin (HP-SBE-βCD) on the bioavailability and intestinal absorption of edaravone, and identify its mechanism of action. We devised HP-SBE-βCD as a carrier and modulator of P-glycoprotein (Pgp) efflux pump, and edaravone as a model drug, and prepared edaravone/HP-SBE-βCD inclusion complex. HP-SBE-βCD improved the water solubility and enhanced the bioavailability of edaravone by 10.3-fold in rats. Then, in situ single-pass intestinal perfusion showed that HP-SBE-βCD had an effect of improving the permeability and inhibiting the efflux of edaravone. Furthermore, the effects of HP-SBE-βCD on Pgp were achieved through interfering with the lipid raft and depleting the cholesterol of enterocytes membrane. From the results, we presented the novel mechanisms. First, edaravone/HP-SBE-βCD had a lower release from the inclusion compound to protect edaravone from the low pH of the stomach. Then, HP-SBE-βCD modulated the membrane microenvironment of intestinal absorption epithelial cells. At last, the result was that HP-SBE-βCD enhanced the absorption of edaravone by interfering with Pgp. In conclusion, HP-SBE-βCD improves the bioavailability of drug not only because of its enhancing water solubility of the drug, but also because it modulates the Pgp-mediated efflux from enterocytes. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Haptoglobin concentrations in free-range and temporarily captive juvenile steller sea lions.

PubMed

Thomton, Jamie D; Mellish, Jo-Ann E

2007-04-01

Haptoglobin (Hp) is an acute-phase protein synthesized in the liver that circulates at elevated concentrations in response to tissue damage caused by inflammation, infection, and trauma. As part of a larger study, sera Hp concentrations were measured in temporarily captive (n = 21) and free-range (n = 38) western stock juvenile Steller sea lions (Eumetopias jubatus) sampled from 2003 to 2006. Baseline Hp concentration at time of capture was 133.3 +/- 17.4 mg/dl. Temporarily captive animals exhibited a 3.2-fold increase in Hp concentrations during the first 4 wk of captivity, followed by a return to entry levels by week 5. Haptoglobin levels were not influenced by age, season, or parasite load. There was a significant positive correlation between Hp concentrations and white blood cell count (P < 0.001) and globulin levels (P < 0.001) and a negative correlation to red blood cell count and hematocrit (P < 0.001 for both). There was no correlation between Hp levels and platelet count (P = 0.095) or hemoglobin (P = 0.457). Routine blubber biopsies collected under gas anesthesia did not produce a measurable Hp response. One animal with a large abscess had an Hp spike of 1,006.0 mg/dl that returned to entry levels after treatment. In conclusion, serum Hp levels correlate to the stable clinical health status observed during captivity, with moderate Hp response during capture and initial acclimation to captivity and acute response to inflammation and infection.

Kinetic release of hydrogen peroxide from different whitening products.

PubMed

da Silva Marques, Duarte Nuno; Silveira, Joao Miguel; Marques, Joana Rita; Amaral, Joao Almeida; Guilherme, Nuno Marques; da Mata, António Duarte

2012-01-01

The objective of this in vitro study was to evaluate the kinetics of hydrogen peroxide (HP) release from five different bleaching products: VivaStyle® 10% fitted tray gel, VivaStyle® 30% in-office bleaching gel, VivaStyle® Paint-On Plus paint-on bleaching varnish, Opalescence PF® 10% carbamide peroxide gel and Trèswhite Supreme™ 10% HP gel. Each product was firstly titrated for its HP content by a described method. HP release kinetics was assessed by a modified spectrophotometric technique. One sample t test was performed to test for differences between the manufacturers' claimed HP concentrations and the titrated HP content in the whitening products. Analysis of variance plus Tamhane's post hoc tests and Pearson correlation analysis were used as appropriate. Values of P < 0.05 were taken as significant. Titrated HP revealed an increased content when compared to the manufacturer's specifications for all the products tested (P < 0.05), although only products from one manufacturer produced significantly higher results. All products presented a significant (P < 0.05) and sustained release of HP. However, the product with paint-on cellulose-based matrix resulted in significantly (P < 0.05) faster kinetics when compared to other products tested. These results are consistent with manufacturers' reduced recommended application times. The results of this study suggest that modifying the matrix composition may be a viable alternative to HP concentration increase, since this may result in faster release kinetics without exposure to high HP concentrations.

Coherence of neuronal firing of the entopeduncular nucleus with motor cortex oscillatory activity in the 6-OHDA rat model of Parkinson's disease with levodopa-induced dyskinesias.

PubMed

Jin, Xingxing; Schwabe, Kerstin; Krauss, Joachim K; Alam, Mesbah

2016-04-01

The pathophysiological mechanisms leading to dyskinesias in Parkinson's disease (PD) after long-term treatment with levodopa remain unclear. This study investigates the neuronal firing characteristics of the entopeduncular nucleus (EPN), the rat equivalent of the human globus pallidus internus and output nucleus of the basal ganglia, and its coherence with the motor cortex (MCx) field potentials in the unilateral 6-OHDA rat model of PD with and without levodopa-induced dyskinesias (LID). 6-hydroxydopamine-lesioned hemiparkinsonian (HP) rats, 6-OHDA-lesioned HP rats with LID (HP-LID) rats, and naïve controls were used for recording of single-unit activity under urethane (1.4 g/kg, i.p) anesthesia in the EPN "on" and "off" levodopa. Over the MCx, the electrocorticogram output was recorded. Analysis of single-unit activity in the EPN showed enhanced firing rates, burst activity, and irregularity compared to naïve controls, which did not differ between drug-naïve HP and HP-LID rats. Analysis of EPN spike coherence and phase-locked ratio with MCx field potentials showed a shift of low (12-19 Hz) and high (19-30 Hz) beta oscillatory activity between HP and HP-LID groups. EPN theta phase-locked ratio was only enhanced in HP-LID compared to HP rats. Overall, levodopa injection had no stronger effect in HP-LID rats than in HP rats. Altered coherence and changes in the phase lock ratio of spike and local field potentials in the beta range may play a role for the development of LID.

Enhancement of curcumin wound healing ability by complexation with 2-hydroxypropyl-γ-cyclodextrin in sacran hydrogel film.

PubMed

Wathoni, Nasrul; Motoyama, Keiichi; Higashi, Taishi; Okajima, Maiko; Kaneko, Tatsuo; Arima, Hidetoshi

2017-05-01

Curcumin is one of promising agents to accelerate the wound-healing process. However, the efficacy of curcumin is limited due to its poor water solubility and stability. To enhance the properties of curcumin, 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CyD) can be used through complexation. Recently, we revealed that sacran has the potential to form a hydrogel film (HGF) as a wound dressing material. Therefore, in the present study, we investigated the wound healing ability of curcumin/HP-γ-CyD (Cur/HP-γ-CyD) complex in sacran-based HGF (Sac-HGF). We prepared the Cur/HP-γ-CyD complex in Sac-HGF without surface roughness. Additionally, the amorphous form in the Cur/HP-γ-CyD complex in Sac-HGF were observed. In contrast, the curcumin in Sac-HGF and curcumin/HP-γ-CyD physical mixture in Sac-HGF formed inhomogeneous films due to crystallization of curcumin. Furthermore, HP-γ-CyD played an important role to increase the elastic modulus of the Sac-HGF with high re-swelling ability. The Cur/HP-γ-CyD complex in Sac-HGF maintained antioxidant properties of curcumin. Curcumin was gradually released from the HP-γ-CyD complex in Sac-HGF. Notably, the Cur/HP-γ-CyD complex in Sac-HGF provided the highest wound healing ability in hairless mice. These results suggest that the Cur/HP-γ-CyD complex in Sac-HGF has the potential for use as a new transdermal therapeutic system to promote the wound-healing process. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of various chemical compounds on spontaneous and hydrogen peroxide-induced reversion in strain TA104 of Salmonella typhimurium.

PubMed

Han, J S

1992-04-01

In experiments designed to determine which active oxygen species contribute to hydrogen peroxide (HP)-induced reversion in strain TA104 of Salmonella typhimurium, 1,10-phenanthroline (an iron chelator, which prevents the formation of hydroxyl radicals from HP and DNA-bound iron by the Fenton reaction), sodium azide (a singlet oxygen scavenger), and potassium iodide (an hydroxyl radical scavenger) inhibited HP-induced reversion. These results indicate that hydroxyl radicals generated from HP by the Fenton reaction, and perhaps singlet oxygen, contribute to HP-induced reversion in TA104. However, reduced glutathione (reduces Fe3+ to Fe2+ and/or HP to water), diethyldithiocarbamic acid (an inhibitor of superoxide dismutase), diethyl maleate (a glutathione scavenger), and 3-amino-1,2,4-triazole (an inhibitor of catalase) did not inhibit HP-induced reversion in TA104. Thus, superoxide radical anions and HP itself do not appear to be the cause of HP-induced reversion in this strain. In experiments on the effect of 5 common dietary compounds (beta-carotene, retinoic acid, and vitamins A, C and E), chlorophyllin (CHL), and ergothioneine, the frequency of revertants in TA104 increased above the spontaneous frequency in the presence of beta-carotene or vitamin C (about 2-fold) or vitamin A (about 3-fold). The 5 dietary antimutagens and CHL did not inhibit HP-induced reversion in TA104. However, L-ergothioneine inhibited HP-induced reversion in this strain. Therefore, it is likely that L-ergothioneine is a scavenger of hydroxyl radicals or an inhibitor of their formation, and perhaps of singlet oxygen, at the concentrations tested in TA104.

Effects of pH values of hydrogen peroxide bleaching agents on enamel surface properties.

PubMed

Xu, B; Li, Q; Wang, Y

2011-01-01

This study investigated the influence of pH values of bleaching agents on the properties of the enamel surface. Sixty freshly extracted premolars were embedded in epoxy resin and mesiodistally sectioned through the buccal aspect into two parts. The sectioned slabs were distributed among six groups (n=10) and treated using different solutions. Group HCl was treated with HCl solution (pH=3.0) and served as a positive control. Group DW, stored in distilled water (pH=7.0), served as a negative control. Four treatment groups were treated using 30% hydrogen peroxide solutions with different pH values: group HP3 (pH=3.0), group HP5 (pH=5.0), group HP7 (pH=7.0), and group HP8 (pH=8.0). The buccal slabs were subjected to spectrophotometric evaluations. Scanning electron microscopy investigation and Micro-Raman spectroscopy were used to evaluate enamel surface morphological and chemical composition alterations. pH value has a significant influence on the color changes after bleaching (p<0.001). Tukey's multiple comparisons revealed that the order of color changes was HP8, HP7>HP5, HP3>HCl>DW. No obvious morphological alterations were detected on the enamel surface in groups DW, HP7, and HP8. The enamel surface of groups HCl and HP3 showed significant alterations with an erosion appearance. No obvious chemical composition changes were detected with respect to Micro-Raman analysis. Within the limitations of this study, it was concluded that no obvious morphological or chemical composition alterations of enamel surface were detected in the neutral or alkaline bleaching solutions. Bleaching solutions with lower pH values could result in more significant erosion of enamel, which represented a slight whitening effect.

A novel approach for in-office tooth bleaching with 6% H2O2/TiO_N and LED/laser system-a controlled, triple-blinded, randomized clinical trial.

PubMed

Bortolatto, Janaina Freitas; Trevisan, Tamara Carolina; Bernardi, Priscila Sadalla Ismael; Fernandez, Eduardo; Dovigo, Livia Nordi; Loguercio, Alessandro Dourado; Batista de Oliveira Junior, Osmir; Pretel, Hermes

2016-04-01

The purpose of this randomized, parallel, triple-blinded clinical trial was to compare efficacy and tooth sensitivity (TS) after use of an in-office bleaching agent of 6% hydrogen peroxide containing nanoparticles of nitrogen-doped titanium oxide (HP6) vs. 35% hydrogen peroxide (HP35). Forty-eight volunteers were randomly divided either a HP6 or HP35. Two clinical sessions were performed with an interval of 7 days between them for each group. In each session, two consecutive applications of each bleaching agent were performed and activated by a hybrid LED/laser light. Efficacy was determined by color alteration (ΔE), recorded with reflectance spectroscopy. It was assessed at baseline and after the first and second bleaching session. TS was characterized according to occurrence, intensity, duration, and type. Efficacy was analyzed by repeated measures analysis of variance (ANOVA) and post hoc Bonferroni test, and TS was analyzed by means of chi(2) test (α = 0.05). For HP35, highest and significant values of ΔE were found after bleaching when compared to HP6 (p = 0.002). However, HP35 showed a significantly higher occurrence of TS than HP6 (p = 0.008). Also, intensity and duration were higher in HP35. The majority of volunteers classified the type experienced in their sensitivity in the form of a "shock." The use of HP6 despite reducing efficacy when compared to an in-office bleaching in higher concentration (35%) produced less tooth sensitivity. In terms of tooth sensitivity, the use of lower concentrations of in-office bleaching should be the first choice, suggesting greater biocompatibility and safety compared to a conventional HP35.

Effect of the “protein diet” and bone tissue.

PubMed

Nascimento da Silva, Zoraide; Azevedo de Jesuz, Vanessa; De Salvo Castro, Eduardo; Soares da Costa, Carlos Alberto; Teles Boaventura, Gilson; Blondet de Azeredo, Vilma

2014-01-01

The aim of this study is to evaluate the effect of the hyperproteic diet consumption on bone tissue. The study was conducted during sixty days. Twenty eight Wistar albinus rats, adults, originated from Laboratory of Experimental Nutrition were divided in four groups: (n = 7); Control 1 (C1), Control 2 (C2), Hyperproteic 1 (HP1) e Hyperproteic 2 (HP2). The C2 and HP2 groups were submitted to 30% of food restriction. The hyperproteic diet was based on the Atkins diet and prepared to simulate the protein diet. At the end of the study the animals were anesthetized to performer bone densitometry analyses by DEXA and blood and tissue collection. Serum and bone minerals analyses were conducted by colorimetric methods in automated equipment. The total bone mineral density (BMD) of the pelvis and the spine of the food restriction groups (HP2 e C2) were lower (p < 0.05) than C1 e HP1 groups. While the femur BMD of the HP2 was lower (p < 0.05) related to others groups. It had been observed reduction (p < 0.05) in the medium point of the width of femur diaphysis and in bone calcium level in the hyperproteic groups (HP1 e HP2). It was observed similar effect on the osteocalcin level, that presented lower (p < 0.05) in the hyperproteic groups. The insulin level was lower only in HP2 and serum calcium of the HP1 and HP2 groups was lower than C1. The protein diet promotes significant bone change on femur and in the hormones levels related to bone synthesis and maintenance of this tissue.

An audiovisual information resource to assist in the transition from completion of potentially curative treatment for cancer through to survivorship: a systematic development process.

PubMed

Karahalios, A; Baravelli, C; Carey, M; Schofield, P; Pollard, A; Aranda, S; Franklin, J; Jefford, M

2007-09-01

Improvements in cancer screening and treatment are resulting in an increase in the number of cancer patients completing treatment who are apparently cured of their disease. There are few information resources for people at this juncture. An evidence-based DVD was developed for individuals at this stage with information about experiences encountered as a cancer survivor (CS). Focus groups and a literature review were conducted to establish the DVD content. The DVD was developed in conjunction with a multidisciplinary committee and according to a recommended best-practice framework. Interviews with CS and evidence-based commentary by health professionals (HP) made up the DVD. The final phase of development was to evaluate the usefulness and acceptability of the DVD with CS and HP. A 52-min DVD with nine chapters was developed featuring 13 CS, a medical oncologist and a clinical psychologist. Thirty-two CS and 116 HP evaluated the DVD. Both groups considered the DVD was informative (CS 97%; HP 98%), easy to understand (CS and HP 100%), reassuring (CS 91%; HP 92%), relevant to their circumstances (CS 68%; HP 97%), did not contain too much information (CS 75%; HP 71%) and was not distressing to watch (CS 84%; HP 80%). The DVD was well accepted by both CS and HP. Modifications were made as a result of the evaluations, the most significant of which was re-filming of commentary by the two HP. Future research should evaluate the effectiveness of the DVD in controlled trials with outcomes such as quality of long term health, symptom burden and cancer specific distress. The DVD is expected to be a useful resource for CS living beyond effective treatment for cancer.

Hydrostatic Pressure–Induced Release of Stored Calcium in Cultured Rat Optic Nerve Head Astrocytes

PubMed Central

Mandal, Amritlal; Delamere, Nicholas A.

2010-01-01

Purpose. Elevated intraocular pressure is associated with glaucomatous optic nerve damage. Other investigators have shown functional changes in optic nerve head astrocytes subjected to elevated hydrostatic pressure (HP) for 1 to 5 days. Recently, the authors reported ERK1/2, p90RSK and NHE1 phosphorylation after 2 hours. Here they examine calcium responses at the onset of HP to determine what precedes ERK1/2 phosphorylation. Methods. Cytoplasmic calcium concentration ([Ca2+]i) was measured in cultured rat optic nerve astrocytes loaded with fura-2. The cells were placed in a closed imaging chamber and subjected to an HP increase of 15 mm Hg. Protein phosphorylation was detected by Western blot analysis. Results. The increase of HP caused an immediate slow increase in [Ca2+]i. The response persisted in calcium-free solution and when nickel chloride (4 mM) was added to suppress channel-mediated calcium entry. Previous depletion of the ER calcium stores by cyclopiazonic acid abolished the HP-induced calcium level increase. The HP-induced increase persisted in cells exposed to xestospongin C, an inhibitor of IP3R-mediated calcium release. In contrast, ryanodine receptor (RyR) antagonist ruthenium red (10 μM) or dantrolene (25 μM) inhibited the HP-induced calcium increase. The HP-induced calcium increase was abolished when ryanodine-sensitive calcium stores were pre-depleted with caffeine (3 mM). HP caused ERK1/2 phosphorylation. The magnitude of the ERK1/2 phosphorylation response was reduced by ruthenium red and dantrolene. Conclusions. Increasing HP causes calcium release from a ryanodine-sensitive cytoplasmic store and subsequent ERK1/2 activation. Calcium store release appears to be a required early step in the initial astrocyte response to an HP increase. PMID:20071675

Helicobacter pylori HP1512 Is a Nickel-Responsive NikR-Regulated Outer Membrane Protein▿

PubMed Central

Davis, Gregg S.; Flannery, Erika L.; Mobley, Harry L. T.

2006-01-01

Helicobacter pylori is dependent upon the production of the highly abundant and active metalloenzyme urease for colonization of the human stomach. Thus, H. pylori has an absolute requirement for the transition metal nickel, a required cofactor for urease. To investigate the contribution of genes that are factors in this process, microarray analysis comparing the transcriptome of wild-type H. pylori 26695 cultured in brucella broth containing fetal calf serum (BBF) alone or supplemented with 100 μM NiCl2 suggested that HP1512 is repressed in the presence of 100 μM supplemental nickel. When measured by comparative real-time quantitative PCR (qPCR), HP1512 transcription was reduced 43-fold relative to the value for the wild type when cultured in BBF supplemented with 10 μM NiCl2. When grown in unsupplemented BBF, urease activity of an HP1512::cat mutant was significantly reduced compared to the wild type, 4.9 ± 0.5 μmol/min/mg of protein (n = 7) and 17.1 ± 4.9 μmol/min/mg of protein (n = 13), respectively (P < 0.0001). In silico analysis of the HP1511-HP1512 (HP1511-1512) intergenic region identified a putative NikR operator upstream of HP1512. Gel shift analysis with purified recombinant NikR verified nickel-dependent binding of H. pylori NikR to the HP1511-1512 intergenic region. Furthermore, comparative real-time qPCR of four nickel-related genes suggests that mutation of HP1512 results in reduced intracellular nickel concentration relative to wild-type H. pylori 26695. Taken together, these data suggest that HP1512 encodes a NikR-nickel-regulated outer membrane protein. PMID:17030579

Neonatal high protein intake enhances neonatal growth without significant adverse renal effects in spontaneous IUGR piglets.

PubMed

Boubred, Farid; Jamin, Agnes; Buffat, Christophe; Daniel, Laurent; Borel, Patrick; Boudry, Gaëlle; Le Huëron-Luron, Isabelle; Simeoni, Umberto

2017-05-01

In humans, early high protein (HP) intake has been recommended to prevent postnatal growth restriction and complications of intrauterine growth restriction (IUGR). However, the impact of such a strategy on the kidneys remains unknown, while significant renal hypertrophy, proteinuria, and glomerular sclerosis have been demonstrated in few experimental studies. The objective of this study was to evaluate the effects of a neonatal HP formula on renal structure in IUGR piglets. Spontaneous IUGR piglets were randomly allocated to normal protein (NP, n  = 10) formula or to HP formula (+50% protein content, n  = 10) up to day 28 after birth. Body weight, body composition, renal functions, and structure were assessed at the end of the neonatal period. While birth weights were similar, 28-day-old HP piglets were 18% heavier than NP piglets ( P  <   0.01). Carcass protein content was 22% higher in HP than in NP offspring ( P  <   0.01). Despite a HP intake, kidney weight and glomerular fibrosis were unaltered in HP piglets. Only a 20% increase in glomerular volume was noted in HP piglets ( P  < 0.05) and restricted to the inner cortical area nephrons ( P  =   0.03). Plasma urea/creatinine ratio and proteinuria were unchanged in HP piglets. In conclusion, neonatal HP feeding in IUGR piglets significantly enhanced neonatal growth and tissue protein deposition but mildly affected glomerular volume. It can be speculated that a sustained tissue protein anabolism in response to HP intake have limited single nephron glomerular hyperfiltration. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Impact of Helicobacter pylori Immunoglobulin G Levels and Atrophic Gastritis Status on Risk of Metabolic Syndrome.

PubMed

Takeoka, Atsushi; Tayama, Jun; Yamasaki, Hironori; Kobayashi, Masakazu; Ogawa, Sayaka; Saigo, Tatsuo; Hayashida, Masaki; Shirabe, Susumu

2016-01-01

Helicobacter pylori (HP) infection is implicated in gastric and extra-gastric diseases. While gastritis-related chronic inflammation represents a known trigger of metabolic disturbances, whether metabolic syndrome (MetS) is affected by gastritis status remains unclear. We aimed to clarify the effect of HP-related gastritis on the risk of MetS. We retrospectively enrolled patients undergoing screening for MetS between 2014 and 2015. Investigations included HP-specific immunoglobulin G (IgG) antibody assays to detect HP infection, and serum pepsinogen assays to evaluate atrophic gastritis status. The risk of MetS was evaluated via multiple logistic regression analyses with two covariates: serum HP infection status (IgG levels) and atrophic gastritis status (two criteria were applied; pepsinogen I/II ratio < 3 or both pepsinogen I levels ≤ 70 μg/L and pepsinogen I/II ratio < 3). Of 1,044 participants, 247 (23.7%) were HP seropositive, and 62 (6.0%) had MetS. HP seronegative and seropositive patients had similar risks of MetS. On the other hand, AG (defined in terms of serum PG I/II <3) was significant risk of MetS (OR of 2.52 [95% CI 1.05-7.52]). After stratification according to HP IgG concentration, patients with low HP infection status had the lowest MetS risk (defined as an odds ratio [OR] adjusted for age, sex, smoking, drinking and physical activity status). Taking this result as a reference, patients with negative, moderate, and high HP infection status had ORs (with 95% confidence intervals [CI]) of 2.15 (1.06-4.16), 3.69 (1.12-16.7), and 4.05 (1.05-26.8). HP-associated gastritis represents a risk factor for MetS. Research should determine why low and not negative HP infection status is associated with the lowest MetS risk.

Impact of Helicobacter pylori Immunoglobulin G Levels and Atrophic Gastritis Status on Risk of Metabolic Syndrome

PubMed Central

Takeoka, Atsushi; Tayama, Jun; Yamasaki, Hironori; Kobayashi, Masakazu; Ogawa, Sayaka; Saigo, Tatsuo; Hayashida, Masaki; Shirabe, Susumu

2016-01-01

Background Helicobacter pylori (HP) infection is implicated in gastric and extra-gastric diseases. While gastritis-related chronic inflammation represents a known trigger of metabolic disturbances, whether metabolic syndrome (MetS) is affected by gastritis status remains unclear. We aimed to clarify the effect of HP-related gastritis on the risk of MetS. Materials and Methods We retrospectively enrolled patients undergoing screening for MetS between 2014 and 2015. Investigations included HP-specific immunoglobulin G (IgG) antibody assays to detect HP infection, and serum pepsinogen assays to evaluate atrophic gastritis status. The risk of MetS was evaluated via multiple logistic regression analyses with two covariates: serum HP infection status (IgG levels) and atrophic gastritis status (two criteria were applied; pepsinogen I/II ratio < 3 or both pepsinogen I levels ≤ 70 μg/L and pepsinogen I/II ratio < 3). Results Of 1,044 participants, 247 (23.7%) were HP seropositive, and 62 (6.0%) had MetS. HP seronegative and seropositive patients had similar risks of MetS. On the other hand, AG (defined in terms of serum PG I/II <3) was significant risk of MetS (OR of 2.52 [95% CI 1.05–7.52]). After stratification according to HP IgG concentration, patients with low HP infection status had the lowest MetS risk (defined as an odds ratio [OR] adjusted for age, sex, smoking, drinking and physical activity status). Taking this result as a reference, patients with negative, moderate, and high HP infection status had ORs (with 95% confidence intervals [CI]) of 2.15 (1.06–4.16), 3.69 (1.12–16.7), and 4.05 (1.05–26.8). Conclusions HP-associated gastritis represents a risk factor for MetS. Research should determine why low and not negative HP infection status is associated with the lowest MetS risk. PMID:27851820

Conditional Self-Entropy and Conditional Joint Transfer Entropy in Heart Period Variability during Graded Postural Challenge.

PubMed

Porta, Alberto; Faes, Luca; Nollo, Giandomenico; Bari, Vlasta; Marchi, Andrea; De Maria, Beatrice; Takahashi, Anielle C M; Catai, Aparecida M

2015-01-01

Self-entropy (SE) and transfer entropy (TE) are widely utilized in biomedical signal processing to assess the information stored into a system and transferred from a source to a destination respectively. The study proposes a more specific definition of the SE, namely the conditional SE (CSE), and a more flexible definition of the TE based on joint TE (JTE), namely the conditional JTE (CJTE), for the analysis of information dynamics in multivariate time series. In a protocol evoking a gradual sympathetic activation and vagal withdrawal proportional to the magnitude of the orthostatic stimulus, such as the graded head-up tilt, we extracted the beat-to-beat spontaneous variability of heart period (HP), systolic arterial pressure (SAP) and respiratory activity (R) in 19 healthy subjects and we computed SE of HP, CSE of HP given SAP and R, JTE from SAP and R to HP, CJTE from SAP and R to HP given SAP and CJTE from SAP and R to HP given R. CSE of HP given SAP and R was significantly smaller than SE of HP and increased progressively with the amplitude of the stimulus, thus suggesting that dynamics internal to HP and unrelated to SAP and R, possibly linked to sympathetic activation evoked by head-up tilt, might play a role during the orthostatic challenge. While JTE from SAP and R to HP was independent of tilt table angle, CJTE from SAP and R to HP given R and from SAP and R to HP given SAP showed opposite trends with tilt table inclination, thus suggesting that the importance of the cardiac baroreflex increases and the relevance of the cardiopulmonary pathway decreases during head-up tilt. The study demonstrates the high specificity of CSE and the high flexibility of CJTE over real data and proves that they are particularly helpful in disentangling physiological mechanisms and in assessing their different contributions to the overall cardiovascular regulation.

Barriers and facilitators for the implementation of primary prevention and health promotion activities in primary care: a synthesis through meta-ethnography.

PubMed

Rubio-Valera, Maria; Pons-Vigués, Mariona; Martínez-Andrés, María; Moreno-Peral, Patricia; Berenguera, Anna; Fernández, Ana

2014-01-01

Evidence supports the implementation of primary prevention and health promotion (PP&HP) activities but primary care (PC) professionals show resistance to implementing these activities. The aim was to synthesize the available qualitative research on barriers and facilitators identified by PC physicians and nurses in the implementation of PP&HP in adults. A systematic search of three databases was conducted and supported by manual searches. The 35 articles included were translated into each other and a new interpretation of the concepts extracted was generated. The factors affecting the implementation of PP&HP activities in PC according to professionals were fitted into a five-level ecological model: intrapersonal factors, interpersonal processes, institutional factors, community factors and public policy. At the intrapersonal level we find professionals' beliefs about PP&HP, experiences, skills and knowledge, and selfconcept. The attitudes and behavior towards PP&HP of patients, specialists, practice managers and colleagues (interpersonal factors) affect the feasibility of implementing PP&HP. Institutional level: PC is perceived as well-placed to implement PP&HP but workload, lack of time and referral resources, and the predominance of the biomedical model (which prioritizes disease treatment) hamper the implementation of PP&HP. The effectiveness of financial incentives and tools such as guidelines and alarms/reminders is conditioned by professionals' attitudes to them. Community factors include patients' social and cultural characteristics (religion, financial resources, etc.), local referral resources, mass-media messages and pharmaceutical industry campaigns, and the importance given to PP&HP in the curriculum in university. Finally, policies affect the distribution of resources, thus affecting the implementation of PP&HP. Research on barriers and facilitators in the implementation of PP&HP activities in multirisk management is scarce. The conceptual overview provided by this synthesis resulted in the development of practical recommendations for the design of PP&HP in PC. However, the effectiveness of these recommendations needs to be demonstrated.

The Bifunctional Enzyme SpoT Is Involved in the Clarithromycin Tolerance of Helicobacter pylori by Upregulating the Transporters HP0939, HP1017, HP0497, and HP0471

PubMed Central

Geng, Xiwen; Li, Wen; Chen, Zhenghong; Gao, Sizhe; Hong, Wei; Ge, Xiaoran; Hou, Guihua; Hu, Zhekai; Zhou, Yabin; Zeng, Beini; Li, Wenjuan; Jia, Jihui

2017-01-01

ABSTRACT Clarithromycin (CLA) is a commonly recommended drug for Helicobacter pylori eradication. However, the prevalence of CLA-resistant H. pylori is increasing. Although point mutations in the 23S rRNA are key factors for CLA resistance, other factors, including efflux pumps and regulation genes, are also involved in the resistance of H. pylori to CLA. Guanosine 3′-diphosphate 5′-triphosphate and guanosine 3′,5′-bispyrophosphate [(p)ppGpp)], which are synthesized by the bifunctional enzyme SpoT in H. pylori, play an important role for some bacteria to adapt to antibiotic pressure. Nevertheless, no related research involving H. pylori has been reported. In addition, transporters have been found to be related to bacterial drug resistance. Therefore, this study investigated the function of SpoT in H. pylori resistance to CLA by examining the shifts in the expression of transporters and explored the role of transporters in the CLA resistance of H. pylori. A ΔspoT strain was constructed in this study, and it was shown that SpoT is involved in H. pylori tolerance of CLA by upregulating the transporters HP0939, HP1017, HP0497, and HP0471. This was assessed using a series of molecular and biochemical experiments and a cDNA microarray. Additionally, the knockout of genes hp0939, hp0471, and hp0497 in the resistant strains caused a reduction or loss (the latter in the Δhp0497 strain) of resistance to CLA. Furthermore, the average expression levels of these four transporters in clinical CLA-resistant strains were considerably higher than those in clinical CLA-sensitive strains. Taken together, our results revealed a novel molecular mechanism of H. pylori adaption to CLA stress. PMID:28242673

Evaluation of several clinical parameters after bleaching with hydrogen peroxide at different concentrations: A randomized clinical trial.

PubMed

Lima, Suellen Nogueira Linares; Ribeiro, Izabella Santos; Grisotto, Marcos Augusto; Fernandes, Elizabeth Soares; Hass, Viviane; de Jesus Tavarez, Rudys Rodolfo; Pinto, Shelon Cristina Souza; Lima, Darlon Martins; Loguercio, Alessandro D; Bandeca, Matheus Coelho

2018-01-01

This randomized double-blind clinical trial compared tooth sensitivity (TS), bleaching efficacy, and cytokine levels after applying in-office bleaching treatments containing 15% and 35% hydrogen peroxide (HP15% and HP35%, respectively). Twenty-five volunteers were randomly assigned to receive HP15% or HP35% treatment. The bleaching agent was applied in three 15-min applications per session. Two bleaching sessions were separated by a 1-week interval. The participants scored TS using a visual analog scale and numerical rating scale. Bleaching efficacy was determined by subjective and objective methods. Gingival crevicular fluid was collected from three jaws sites per patient for the analysis of fluid volume. Flow cytometry was used to analyze gingival crevicular fluid levels of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor, and interferon-gamma. All measurements were obtained before and after bleaching. All data were statistically analyzed (α=0.05). The absolute risk and intensity of TS was higher for HP35% than for HP15% (p>0.002). One month post-bleaching, HP35% produced more bleaching than HP15% (p=0.02). However patient perception (p=0.06) and patient satisfaction (p=0.53) with regard to bleaching were not significantly different. No significant differences existed in the gingival fluid volume (p>0.38) or in any cytokine level (p>0.05) for either HP concentration. Treatment: with HP35% is more effective than HP15%, but generates a greater risk and intensity of TS. No inflammatory changes occurred despite the difference in the HP concentrations. Hydrogen peroxide at a lower concentration (e.g., 15%) should be considered a good treatment alternative for in-office bleaching because the higher concentration for in-office bleaching generates a greater risk and intensity of TS for patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cancer in the crosshairs: targeting cancer metabolism with hyperpolarized carbon-13 MRI technology.

PubMed

von Morze, Cornelius; Merritt, Matthew E

2018-06-05

Magnetic resonance (MR)-based hyperpolarized (HP) 13 C metabolic imaging is under active pursuit as a new clinical diagnostic method for cancer detection, grading, and monitoring of therapeutic response. Following the tremendous success of metabolic imaging by positron emission tomography, which already plays major roles in clinical oncology, the added value of HP 13 C MRI is emerging. Aberrant glycolysis and central carbon metabolism is a hallmark of many forms of cancer. The chemical transformations associated with these pathways produce metabolites ranging in general from three to six carbons, and are dependent on the redox state and energy charge of the tissue. The significant changes in chemistry associated with flux through these pathways imply that HP imaging can take advantage of the underlying chemical shift information encoded into an MR experiment to produce images of the injected substrate as well as its metabolites. However, imaging of HP metabolites poses unique constraints on pulse sequence design related to detection of X-nuclei, decay of the HP magnetization due to T 1 , and the consumption of HP signal by the inspection pulses. Advancements in the field continue to depend critically on customization of MRI systems and pulse sequences for optimized detection of HP 13 C signals, focused largely on extracting the maximum amount of information during the short lifetime of the HP magnetization. From a clinical perspective, the success of HP 13 C MRI of cancer will largely depend upon the utility of HP pyruvate for the detection of lactate pools associated with the Warburg effect, though several other agents are also under investigation, with novel agents continually being formulated. In this review, the salient aspects of HP 13 C imaging will be highlighted, with an emphasis on both technological challenges and the biochemical aspects of HP experimental design. Copyright © 2018 John Wiley & Sons, Ltd.

Barriers and Facilitators for the Implementation of Primary Prevention and Health Promotion Activities in Primary Care: A Synthesis through Meta-Ethnography

PubMed Central

Rubio-Valera, Maria; Pons-Vigués, Mariona; Martínez-Andrés, María; Moreno-Peral, Patricia; Berenguera, Anna; Fernández, Ana

2014-01-01

Background Evidence supports the implementation of primary prevention and health promotion (PP&HP) activities but primary care (PC) professionals show resistance to implementing these activities. The aim was to synthesize the available qualitative research on barriers and facilitators identified by PC physicians and nurses in the implementation of PP&HP in adults. Methods and Findings A systematic search of three databases was conducted and supported by manual searches. The 35 articles included were translated into each other and a new interpretation of the concepts extracted was generated. The factors affecting the implementation of PP&HP activities in PC according to professionals were fitted into a five-level ecological model: intrapersonal factors, interpersonal processes, institutional factors, community factors and public policy. At the intrapersonal level we find professionals' beliefs about PP&HP, experiences, skills and knowledge, and selfconcept. The attitudes and behavior towards PP&HP of patients, specialists, practice managers and colleagues (interpersonal factors) affect the feasibility of implementing PP&HP. Institutional level: PC is perceived as well-placed to implement PP&HP but workload, lack of time and referral resources, and the predominance of the biomedical model (which prioritizes disease treatment) hamper the implementation of PP&HP. The effectiveness of financial incentives and tools such as guidelines and alarms/reminders is conditioned by professionals' attitudes to them. Community factors include patients' social and cultural characteristics (religion, financial resources, etc.), local referral resources, mass-media messages and pharmaceutical industry campaigns, and the importance given to PP&HP in the curriculum in university. Finally, policies affect the distribution of resources, thus affecting the implementation of PP&HP. Conclusions Research on barriers and facilitators in the implementation of PP&HP activities in multirisk management is scarce. The conceptual overview provided by this synthesis resulted in the development of practical recommendations for the design of PP&HP in PC. However, the effectiveness of these recommendations needs to be demonstrated. PMID:24586867

Enamel Mineral Content Changes After Bleaching With High and Low Hydrogen Peroxide Concentrations: Colorimetric Spectrophotometry and Total Reflection X-ray Fluorescence Analyses.

PubMed

Pinto, Avd; Bridi, E C; Amaral, Flb; França, Fmg; Turssi, C P; Pérez, C A; Martinez, E F; Flório, F M; Basting, R T

The purpose of this study was to evaluate the calcium (Ca) and phosphorous (P) content in enamel bleached with high and low concentrations of hydrogen peroxide (HP) using Total Reflection X-Ray Fluorescence (TXRF) and colorimetric spectrophotometry (SPEC). Forty-eight sound human third molars were used. Their roots were embedded in polystyrene resin and immersed for seven days in an artificial saliva solution. Then they were distributed into six groups to receive the bleaching treatments. The agents of high HP concentration (for in-office use) evaluated were Whiteness HP Maxx/FGM (35% HP), Whiteness HP Blue/FGM (35% HP, 2% calcium gluconate), Pola Office+/SDI (37.5% HP, 5% potassium nitrate), and Opalescence Boost/Ultradent (38% HP, 1.1% ion fluoride, 3% potassium nitrate); these agents were applied to enamel in three sessions. The agents of low HP concentration (for home use) evaluated were Pola Day/SDI (9.5% HP) and White Class 10%/FGM (10% HP, potassium nitrate, calcium, fluoride), and these agents were applied for 14 days. Enamel microbiopsies were evaluated by TXRF and SPEC analysis before the bleaching treatment (baseline), during the treatment, and 14 days after the end of the treatment. For TXRF, the Kruskal-Wallis test showed that Ca and P were not influenced by agent (p>0.05). For SPEC, Pola Office+, Opalescence Boost, Pola Day, and White Class 10% caused a decrease of Ca over time; there was a significant decrease of P over time to Pola Office+ and White Class 10%. The Spearman test showed no correlation between the Ca (p=0.987; r 2 =-0.020) and P (p=0.728, r 2 =0.038) obtained by SPEC and TXRF. For TXRF and SPEC, changes in Ca and P during bleaching occurred independently of the HP concentration used.

Reciprocal contribution of clinical studies and the HP10 antigen ELISA for the diagnosis of extraparenchymal neurocysticercosis.

PubMed

Parkhouse, R Michael E; Carpio, Arturo; Campoverde, Alfredo; Sastre, Patricia; Rojas, Glenda; Cortez, María Milagros

2018-02-01

To evaluate diagnosis of active neurocysticercosis, paired cerebral spinal fluid (CSF) and serum samples from 24 neurocysticercosis (NCC) patients and 17 control neurological patients were assayed in the HP10 Taenia antigen (Ag) ELISA. The CSF samples were also tested with an HP10 Lateral Flow Assay (LFA). The HP10 Ag was detected by ELISA in the CSF of 5/5 patients with Definitive extraparenchymal NCC, and in 4/5 of the corresponding sera. In the Definitive parenchymal group, on the other hand, the HP10 Ag was absent in 2/3 CSF (with a very low value in the one positive sample) and all the corresponding serum samples. Samples of CSF from 4/7 patients in the Probable parenchymal group, were also significantly HP10 Ag positive, suggesting the presence of extraparenchymal cysts not identified by the imaging studies. With the possible exception of one patient, the corresponding serum samples of the Probable parenchymal NCC group, were all HP10 Ag negative. Samples of CSF from 9 NCC patients diagnosed with Mixed parenchymal and extraparenchymal NCC were all significantly HP10 Ag positive, confirming the presence of extraparenchymal cysts, with only 7/9 of the corresponding serum samples being HP10 positive. Thus detection of the HP10 Ag indicates extraparenchymal and not parenchymal cyst localization and is more sensitive with CSF than serum. Three neurological patients clinically diagnosed as subarachnoid cyst, hydrocephalus and tuberculoma, respectively, were clearly positive for HP10 Ag. Of these, two were confirmed as NCC by subsequent imaging; the third died prior to further examination. Thus, a total of 8 patients had their clinical diagnosis questioned. Finally, there was good agreement between the HP10 Ag ELISA and LFA with CSF samples giving an optical density ≥0.4 in the ELISA assay. In conclusion, the HP10 Ag assay should provide a valuable and reciprocal tool in the clinical diagnosis and follow up of extraparenchymal NCC. Copyright © 2017 Elsevier B.V. All rights reserved.

Geometrical confinement of Gd(DOTA) molecules within mesoporous silicon nanoconstructs for MR imaging of cancer

PubMed Central

Gizzatov, Ayrat; Stigliano, Cinzia; Ananta, Jeyerama S.; Sethi, Richa; Xu, Rong; Guven, Adem; Ramirez, Maricela; Shen, Haifa; Sood, Anil; Ferrari, Mauro; Wilson, Lon J.; Liu, Xuewu; Decuzzi, Paolo

2015-01-01

Porous silicon has been used for the delivery of therapeutic and imaging agents in several biomedical applications. Here, mesoporous silicon nanoconstructs (SiMPs) with a discoidal shape and a sub-micrometer size (1,000 × 400 nm) have been conjugated with gadolinium-tetraazacyclododecane tetraacetic acid Gd(DOTA) molecules and proposed as contrast agents for Magnetic Resonance Imaging. The surface of the SiMPs with different porosities – small pore (SP: ~ 5 nm) and huge pore (HP: ~ 40 nm) – and of bulk, non-porous silica beads (1,000 nm in diameter) have been modified with covalently attached (3-aminopropyl)triethoxysilane (APTES) groups, conjugated with DOTA molecules, and reacted with an aqueous solution of GdCl3. The resulting Gd(DOTA) molecules confined within the small pores of the Gd-SiMPs achieve longitudinal relaxivities r1 of ~ 17 (mM·s)−1, which is 4 times greater than for free Gd(DOTA). This enhancement is ascribed to the confinement and stable chelation of Gd(DOTA) molecules within the SiMP mesoporous matrix. The resulting nanoconstructs possess no cytotoxicity and accumulate in ovarian tumors up to 2% of the injected dose per gram tissue, upon tail vein injection. All together this data suggests that Gd-SiMPs could be efficiently used for MR vascular imaging in cancer and other diseases. PMID:24931336

Geometrical confinement of Gd(DOTA) molecules within mesoporous silicon nanoconstructs for MR imaging of cancer.

PubMed

Gizzatov, Ayrat; Stigliano, Cinzia; Ananta, Jeyerama S; Sethi, Richa; Xu, Rong; Guven, Adem; Ramirez, Maricela; Shen, Haifa; Sood, Anil; Ferrari, Mauro; Wilson, Lon J; Liu, Xuewu; Decuzzi, Paolo

2014-09-28

Porous silicon has been used for the delivery of therapeutic and imaging agents in several biomedical applications. Here, mesoporous silicon nanoconstructs (SiMPs) with a discoidal shape and a sub-micrometer size (1000×400nm) have been conjugated with gadolinium-tetraazacyclododecane tetraacetic acid Gd(DOTA) molecules and proposed as contrast agents for Magnetic Resonance Imaging. The surface of the SiMPs with different porosities - small pore (SP: ∼5nm) and huge pore (HP: ∼40nm) - and of bulk, non-porous silica beads (1000nm in diameter) have been modified with covalently attached (3-aminopropyl)triethoxysilane (APTES) groups, conjugated with DOTA molecules, and reacted with an aqueous solution of GdCl3. The resulting Gd(DOTA) molecules confined within the small pores of the Gd-SiMPs achieve longitudinal relaxivities r1 of ∼17 (mMs)(-)(1), which is 4 times greater than for free Gd(DOTA). This enhancement is ascribed to the confinement and stable chelation of Gd(DOTA) molecules within the SiMP mesoporous matrix. The resulting nanoconstructs possess no cytotoxicity and accumulate in ovarian tumors up to 2% of the injected dose per gram tissue, upon tail vein injection. All together this data suggests that Gd-SiMPs could be efficiently used for MR vascular imaging in cancer and other diseases. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Characteristics of gastric cancer in peptic ulcer patients with Helicobacter pylori infection.

PubMed

Hwang, Jae Jin; Lee, Dong Ho; Lee, Ae-Ra; Yoon, Hyuk; Shin, Cheol Min; Park, Young Soo; Kim, Nayoung

2015-04-28

To evaluate the incidence and clinical characteristics of gastric cancer (GC) in peptic ulcer patients with Helicobacter pylori (H. pylori) infection. Between January 2003 and December 2013, the medical records of patients diagnosed with GC were retrospectively reviewed. Those with previous gastric ulcer (GU) and H. pylori infection were assigned to the HpGU-GC group (n = 86) and those with previous duodenal ulcer (DU) disease and H. pylori infection were assigned to the HpDU-GC group (n = 35). The incidence rates of GC in the HpGU-GC and HpDU-GC groups were analyzed. Data on demographics (age, gender, peptic ulcer complications and cancer treatment), GC clinical characteristics [location, pathological diagnosis, differentiation, T stage, Lauren's classification, atrophy of surrounding mucosa and intestinal metaplasia (IM)], outcome of eradication therapy for H. pylori infection, esophagogastroduodenoscopy number and the duration until GC onset were reviewed. Univariate and multivariate analyses were performed to identify factors influencing GC development. The relative risk of GC was evaluated using a Cox proportional hazards model. The incidence rates of GC were 3.60% (86/2387) in the HpGU-GC group and 1.66% (35/2098) in the HpDU-GC group. The annual incidence was 0.41% in the HpGU-GC group and 0.11% in the HpDU-GC group. The rates of moderate-to-severe atrophy of the surrounding mucosa and IM were higher in the HpGU-GC group than in the HpDU-GC group (86% vs 34.3%, respectively, and 61.6% vs 14.3%, respectively, P < 0.05). In the univariate analysis, atrophy of surrounding mucosa, IM and eradication therapy for H. pylori infection were significantly associated with the development of GC (P < 0.05). There was no significant difference in the prognosis of GC patients between the HpGU-GC and HpDU-GC groups (P = 0.347). The relative risk of GC development in the HpGU-GC group compared to that of the HpDU-GC group, after correction for age and gender, was 1.71 (95%CI: 1.09-2.70; P = 0.02). GU patients with H. pylori infection had higher GC incidence rates and relative risks. Atrophy of surrounding mucosa, IM and eradication therapy were associated with GC.

Effects of High Pressure on Bacillus licheniformis Spore Germination and Inactivation

PubMed Central

Borch-Pedersen, Kristina; Mellegård, Hilde; Reineke, Kai; Boysen, Preben; Sevenich, Robert; Lindbäck, Toril

2017-01-01

ABSTRACT Bacillus and Clostridium species form spores, which pose a challenge to the food industry due to their ubiquitous nature and extreme resistance. Pressurization at <300 MPa triggers spore germination by activating germination receptors (GRs), while pressurization at >300 MPa likely triggers germination by opening dipicolinic acid (DPA) channels present in the inner membrane of the spores. In this work, we expose spores of Bacillus licheniformis, a species associated with food spoilage and occasionally with food poisoning, to high pressure (HP) for holding times of up to 2 h. By using mutant spores lacking one or several GRs, we dissect the roles of the GerA, Ynd, and GerK GRs in moderately HP (mHP; 150 MPa)-induced spore germination. We show that Ynd alone is sufficient for efficient mHP-induced spore germination. GerK also triggers germination with mHP, although at a reduced germination rate compared to that of Ynd. GerA stimulates mHP-induced germination but only in the presence of either the intact GerK or Ynd GR. These results suggests that the effectiveness of the individual GRs in mHP-induced germination differs from their effectiveness in nutrient-induced germination, where GerA plays an essential role. In contrast to Bacillus subtilis spores, treatment with very HP (vHP) of 550 MPa at 37°C did not promote effective germination of B. licheniformis spores. However, treatment with vHP in combination with elevated temperatures (60°C) gave a synergistic effect on spore germination and inactivation. Together, these results provide novel insights into how HP affects B. licheniformis spore germination and inactivation and the role of individual GRs in this process. IMPORTANCE Bacterial spores are inherently resistant to food-processing regimes, such as high-temperature short-time pasteurization, and may therefore compromise food durability and safety. The induction of spore germination facilitates subsequent inactivation by gentler processing conditions that maintain the sensory and nutritional qualities of the food. High-pressure (HP) processing is a nonthermal food-processing technology used to eliminate microbes from food. The application of this technology for spore eradication in the food industry requires a better understanding of how HP affects the spores of different bacterial species. The present study provides novel insights into how HP affects Bacillus licheniformis spores, a species associated with food spoilage and occasionally food poisoning. We describe the roles of different germination receptors in HP-induced germination and the effects of two different pressure levels on the germination and inactivation of spores. This study will potentially contribute to the effort to implement HP technology for spore inactivation in the food industry. PMID:28476768

A Low-Complexity Euclidean Orthogonal LDPC Architecture for Low Power Applications

PubMed Central

Revathy, M.; Saravanan, R.

2015-01-01

Low-density parity-check (LDPC) codes have been implemented in latest digital video broadcasting, broadband wireless access (WiMax), and fourth generation of wireless standards. In this paper, we have proposed a high efficient low-density parity-check code (LDPC) decoder architecture for low power applications. This study also considers the design and analysis of check node and variable node units and Euclidean orthogonal generator in LDPC decoder architecture. The Euclidean orthogonal generator is used to reduce the error rate of the proposed LDPC architecture, which can be incorporated between check and variable node architecture. This proposed decoder design is synthesized on Xilinx 9.2i platform and simulated using Modelsim, which is targeted to 45 nm devices. Synthesis report proves that the proposed architecture greatly reduces the power consumption and hardware utilizations on comparing with different conventional architectures. PMID:26065017

Lipid nanoparticle vectorization of indocyanine green improves fluorescence imaging for tumor diagnosis and lymph node resection.

PubMed

Navarro, Fabrice P; Berger, Michel; Guillermet, Stéphanie; Josserand, Véronique; Guyon, Laurent; Neumann, Emmanuelle; Vinet, Françoise; Texier, Isabelle

2012-10-01

Fluorescence imaging is opening a new era in image-guided surgery and other medical applications. The only FDA approved contrast agent in the near infrared is IndoCyanine Green (ICG), which despites its low toxicity, displays poor chemical and optical properties for long-term and sensitive imaging applications in human. Lipid nanoparticles are investigated for improving ICG optical properties and in vivo fluorescence imaging sensitivity. 30 nm diameter lipid nanoparticles (LNP) are loaded with ICG. Their characterization and use for tumor and lymph node imaging are described. Nano-formulation benefits dye optical properties (6 times improved brightness) and chemical stability (>6 months at 4 degrees C in aqueous buffer). More importantly, LNP vectorization allows never reported sensitive and prolonged (>1 day) labeling of tumors and lymph nodes. Composed of human-use approved ingredients, this novel ICG nanometric formulation is foreseen to expand rapidly the field of clinical fluorescence imaging applications.

Demonstration of a roving-host wireless sensor network for rapid assessment monitoring of structural health

NASA Astrophysics Data System (ADS)

Mascarenas, David D. L.; Flynn, Eric; Lin, Kaisen; Farinholt, Kevin; Park, Gyuhae; Gupta, Rajesh; Todd, Michael; Farrar, Charles

2008-03-01

A major challenge impeding the deployment of wireless sensor networks for structural health monitoring (SHM) is developing means to supply power to the sensor nodes in a cost-effective manner. In this work an initial test of a roving-host wireless sensor network was performed on a bridge near Truth or Consequences, NM in August of 2007. The roving-host wireless sensor network features a radio controlled helicopter responsible for wirelessly delivering energy to sensor nodes on an "as-needed" basis. In addition, the helicopter also serves as a central data repository and processing center for the information collected by the sensor network. The sensor nodes used on the bridge were developed for measuring the peak displacement of the bridge, as well as measuring the preload of some of the bolted joints in the bridge. These sensors and sensor nodes were specifically designed to be able to operate from energy supplied wirelessly from the helicopter. The ultimate goal of this research is to ease the requirement for battery power supplies in wireless sensor networks.

Impact of line edge roughness on the performance of 14-nm FinFET: Device-circuit Co-design

NASA Astrophysics Data System (ADS)

Rathore, Rituraj Singh; Rana, Ashwani K.

2018-01-01

With the evolution of sub-20 nm FinFET technology, line edge roughness (LER) has been identified as a critical problem and may result in critical device parameter variation and performance limitation in the future VLSI circuit application. In the present work, an analytical model of fin-LER has been presented, which shows the impact of correlated and uncorrelated LER on FinFET structure. Further, the influence of correlated and uncorrelated fin- LER on all electrical performance parameters is thoroughly investigated using the three-dimensional (3-D) Technology Computer Aided Design (TCAD) simulations for 14-nm technology node. Moreover, the impact of all possible fin shapes on threshold voltage (VTH), drain induced barrier lowering (DIBL), on-current (ION), and off-current (IOFF) has been compared with the well calibrated rectangular FinFET structure. In addition, the influence of all possible fin geometries on the read stability of six-transistor (6-T) Static-Random-Access-Memory (SRAM) has been investigated. The study reveals that fin-LER plays a vital role as it directly governs the electrostatics of the FinFET structure. This has been found that there is a high degree of fluctuations in all performance parameters for uncorrelated fin-LER type FinFETs as compared to correlated fin-LER with respect to rectangular FinFET structure. This paper gives physical insight of FinFET design, especially in sub-20 nm technology nodes by concluding that the impact of LER on electrical parameters are minimum for correlated LER.

Actinic inspection of EUV reticles with arbitrary pattern design

NASA Astrophysics Data System (ADS)

Mochi, Iacopo; Helfenstein, Patrick; Rajeev, Rajendran; Fernandez, Sara; Kazazis, Dimitrios; Yoshitake, Shusuke; Ekinci, Yasin

2017-10-01

The re ective-mode EUV mask scanning lensless imaging microscope (RESCAN) is being developed to provide actinic mask inspection capabilities for defects and patterns with high resolution and high throughput, for 7 nm node and beyond. Here we, will report on our progress and present the results on programmed defect detection on random, logic-like patterns. The defects we investigated range from 200 nm to 50 nm size on the mask. We demonstrated the ability of RESCAN to detect these defects in die-to-die and die-to-database mode with a high signal to noise ratio. We also describe future plans for the upgrades to increase the resolution, the sensitivity, and the inspection speed of the demo tool.

Integration of Photo-Patternable Low-κ Material into Advanced Cu Back-End-Of-The-Line

NASA Astrophysics Data System (ADS)

Lin, Qinghuang; Nelson, Alshakim; Chen, Shyng-Tsong; Brock, Philip; Cohen, Stephan A.; Davis, Blake; Kaplan, Richard; Kwong, Ranee; Liniger, Eric; Neumayer, Debra; Patel, Jyotica; Shobha, Hosadurga; Sooriyakumaran, Ratnam; Purushothaman, Sampath; Miller, Robert; Spooner, Terry; Wisnieff, Robert

2010-05-01

We report herein the demonstration of a simple, low-cost Cu back-end-of-the-line (BEOL) dual-damascene integration using a novel photo-patternable low-κ dielectric material concept that dramatically reduces Cu BEOL integration complexity. This κ=2.7 photo-patternable low-κ material is based on the SiCOH-based material platform and has sub-200 nm resolution capability with 248 nm optical lithography. Cu/photo-patternable low-κ dual-damascene integration at 45 nm node BEOL fatwire levels has been demonstrated with very high electrical yields using the current manufacturing infrastructure. The photo-patternable low-κ concept is, therefore, a promising technology for highly efficient semiconductor Cu BEOL manufacturing.

Slow histidine H/D exchange protocol for thermodynamic analysis of protein folding and stability using mass spectrometry.

PubMed

Tran, Duc T; Banerjee, Sambuddha; Alayash, Abdu I; Crumbliss, Alvin L; Fitzgerald, Michael C

2012-02-07

Described here is a mass spectrometry-based protocol to study the thermodynamic stability of proteins and protein-ligand complexes using the chemical denaturant dependence of the slow H/D exchange reaction of the imidazole C(2) proton in histidine side chains. The protocol is developed using several model protein systems including: ribonuclease (Rnase) A, myoglobin, bovine carbonic anhydrase (BCA) II, hemoglobin (Hb), and the hemoglobin-haptoglobin (Hb-Hp) protein complex. Folding free energies consistent with those previously determined by other more conventional techniques were obtained for the two-state folding proteins, Rnase A and myoglobin. The protocol successfully detected a previously observed partially unfolded intermediate stabilized in the BCA II folding/unfolding reaction, and it could be used to generate a K(d) value of 0.24 nM for the Hb-Hp complex. The compatibility of the protocol with conventional mass spectrometry-based proteomic sample preparation and analysis methods was also demonstrated in an experiment in which the protocol was used to detect the binding of zinc to superoxide dismutase in the yeast cell lysate sample. The yeast cell sample analyses also helped define the scope of the technique, which requires the presence of globally protected histidine residues in a protein's three-dimensional structure for successful application. © 2011 American Chemical Society

HPLC determination and clinical significance of serum prednisone in patients with nephrotic syndrome

PubMed Central

Chen, Chun-Mei; Xia, Yun-Cheng; Zhang, Xu-Guang; Peng, Can-Hui; Liu, Fu-You; Peng, You-Ming; Sun, Lin

2014-01-01

Aim: A rapid protocol is necessary to determine the serum concentrations of prednisone. Methods: The HP1100 high-performance liquid chromatographic (HPLC) system was employed. The HP Lichrosphere C8 column (250 mm × 4 mm, i.d., 5 μm particle size) was used. The mobile phase was methanol, tetrahydrofuran and water in the ratio 25:25:50. The flow rate was 1.0 ml/min. The sample was monitored by UV absorbance at 240 nm. Acetanilide was used as the internal standard, and methanol was added into the serum for depositing the protein. Results: The chromatography was effective and was not interfered with by the serum components. Good linearity was observed, within the range of 10-500 μg/L for prednisone, and the detection limit was 5 μg/L. The serum concentrations of prednisone between the nephrotic syndrome (NS) group and the control group were significantly different (P < 0.05), while there was no significant difference between the females and males of the NS group (P > 0.05). The serum ncentration of prednisone in the steroid-resistant group was lower than that in the steroid-sensitive group (P < 0.05). Conclusions: HPLC is a practical and reliable method to determine the serum concentration of prednisone with high accuracy, precision, linearity and repeatability. PMID:25664064

Energy balance and hypothalamic effects of a high-protein/low-carbohydrate diet.

PubMed

Kinzig, Kimberly P; Hargrave, Sara L; Hyun, Jayson; Moran, Timothy H

2007-10-22

Diets high in fat or protein and extremely low in carbohydrate are frequently reported to result in weight loss in humans. We previously reported that rats maintained on a low-carbohydrate-high fat diet (LC-HF) consumed similar kcals/day as chow (CH)-fed rats and did not differ in body weight after 7 weeks. LC-HF rats had a 45% decrease in POMC expression in the ARC, decreased plasma insulin, and increased plasma leptin and ghrelin. In the present study we assessed the effects of a low-carbohydrate-high-protein diet (HP: 30% fat, 65% protein, and 5% CHO) on body weight, caloric intake, plasma hormone levels and hypothalamic gene expression. Male rats (n=16) were maintained on CH or HP for 4 weeks. HP rats gained significantly less weight than CH rats (73.4+/-9.4 and 125.0+/-8.2 g) and consumed significantly less kcals/day (94.8+/-1.5 and 123.6+/-1.1). Insulin was significantly reduced in HP rats (HP: 1.8+/-0.6 vs. CH: 4.12+/-0.8 ng/ml), there were no differences between groups in plasma leptin and plasma ghrelin was significantly elevated in HP rats (HP: 127.5+/-45 vs. CH: 76.9+/-8 pg/ml). Maintenance on HP resulted in significantly increased ARC POMC (HP: 121+/-10.0 vs. 100+/-5.9) and DMH NPY (HP: 297+/-82.1 vs. CH: 100+/-37.7) expression compared to CH controls. These data suggest that the macronutrient content of diets differentially influences hypothalamic gene expression in ways that can affect overall intake.

Antioxidant effects of rice bran oil mitigate repeated haloperidol-induced tardive dyskinesia in male rats.

PubMed

Samad, Noreen; Haleem, Darakhshan Jabeen

2017-08-01

Tardive dyskinesia (TD) is associated with the use of antipsychotic drugs such as D2 antagonist haloperidol (HP). The chronic use of HP is involved in the causation of free radicals and/or oxidative stress. In view of the nootropic, anti-anxiety, anti-inflammatory-like effects of rice bran oil (RBO) in a variety of investigations, we assessed the protective properties of RBO on HP-induced TD and neurochemical alteration. Rats treated with HP orally at a dose of 0.2 mg/kg/day for a period of 5 weeks developed VCMs which increased progressively as the treatment continued for 5 weeks. Co-administration of RBO by oral tubes at a dose of 0.4 ml/day prevented the induction of HP-induced VCMs. Repeated administration of HP increases the turnover of dopamine metabolism in the striatum. Conversely animals treated with HP + RBO decrease the metabolism of DA than water + HP treated animals. Striatal, malondieldehyde (MDA), hydrogen peroxide (H 2 O 2 ) and antioxidant enzyme superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were also determined. It is suggested that beneficial role of RBO in attenuation of HP-induced TD. The results therefore recommended that supplementation of RBO may be useful in the HP-induced TD. The findings have also potential implication in the treatment of schizophrenia and motor disorders.

Usefulness of Demarcation of Differentiated-Type Early Gastric Cancers after Helicobacter pylori Eradication by Magnifying Endoscopy with Narrow-Band Imaging.

PubMed

Akazawa, Yoichi; Ueyama, Hiroya; Yao, Takashi; Komori, Hiroyuki; Takeda, Tsutomu; Matsumoto, Kohei; Matsumoto, Kenshi; Asaoka, Daisuke; Hojo, Mariko; Watanabe, Sumio; Nagahara, Akihito

2018-06-05

Early gastric cancer after Helicobacter pylori (Hp) eradication is difficult to demarcate. We used the vessel plus surface classification system (VSCS) to determine whether magnifying endoscopy with narrow-band imaging (ME-NBI) could demarcate differentiated-type early gastric cancers after Hp eradication, and to identify causes of an unclear demarcation line (DL). Among 100 lesions of differentiated-type early gastric cancer resected endoscopically, 34 lesions in the Hp-eradicated group and 66 in the Hp-infected group were retrospectively compared. Clinicopathological factors and ME-NBI findings, including the presence or absence of the DL, were examined. Histopathologically, histological gastritis, the surface structure at the tumor border, well-differentiated adenocarcinoma with low-grade atypia (tub1-low), and non-neoplastic epithelium (NE) coverage rate on the tumor surface and at the tumor border were evaluated. DL (-) cases were more frequent in the Hp-eradicated group (11.8%, 4/34) than in the Hp-infected group (1.5%, 1/66; p < 0.05). The Hp-eradicated group had a higher NE coverage rate than the Hp-infected group (p < 0.05). All DL (-) cases had tub1-low or NE at the tumor border. ME-NBI with VSCS can identify the DL in most patients (88.2%) with differentiated-type early gastric cancer after Hp eradication. © 2018 S. Karger AG, Basel.

Increasing gastric juice pH level prior to anti-Helicobacter pylori therapy may be beneficial to the healing of duodenal ulcers.

PubMed

Fan, Hong-Yun; Wang, Juan; Yan, Guo-Chao; Huo, Xiao-Hui; Mu, Li-Juan; Chu, Jian-Kun; Niu, Wei-Wei; Duan, Zhi-Ying; Ma, Jin-Cheng; Wang, Jing; Wang, Zhi-Yu

2013-03-01

The aim of this study was to observe the efficacy of clarithromycin-based triple therapy for Helicobacter pylori (Hp)-infected duodenal ulcer when combined with different pH levels of gastric juices. A total of 160 patients with Hp-infected duodenal ulcers were randomly allocated into two groups. Patients in the treatment group (n=80) were administered a 20-mg dose of omeprazole twice daily for 1 week and then the treatment and control groups (n=80) received therapy for Hp infection and duodenal ulcers. We observed the ulcer healing stage, the content of anti-Hp IgA in gastric juice and the Hp eradication rate before and after proton pump inhibitor therapy in the two groups. Results revealed that the Hp eradication rate in the treatment group was 93% compared with 81% in the control group, and the difference was statistically significant (P<0.05). The ulcer healing rate in the treatment group was 93%, compared with 70% in the control group (P<0.05). A positive linear correlation was observed between gastric pH and the content of anti-Hp IgA in gastric juice (P<0.05). Increasing gastric pH prior to anti-Hp therapy may be beneficial to the eradication of Hp and for promoting the healing of duodenal ulcers.

A cost per live birth comparison of HMG and rFSH randomized trials.

PubMed

Connolly, Mark; De Vrieze, Kathleen; Ombelet, Willem; Schneider, Dirk; Currie, Craig

2008-12-01

To help inform healthcare treatment practices and funding decisions, an economic evaluation was conducted to compare the two leading gonadotrophins used for IVF in Belgium. Based on the results of a recently published meta-analysis, a simulated decision tree model was constructed with four states: (i) fresh cycle, (ii) cryopreserved cycle, (iii) live birth and (iv) treatment withdrawal. Gonadotrophin costs were based on highly purified human menopausal gonadotrophin (HP-HMG; Menopur) and recombinant FSH (rFSH) alpha (Gonal-F). After one fresh and one cryopreserved cycle the average treatment cost with HP-HMG was lower than with rFSH (HP-HMG euro3635; rFSH euro4103). The average cost saving per person started on HP-HMG when compared with rFSH was euro468. Additionally, the average costs per live birth of HP-HMG and rFSH were found to be significantly different: HP-HMG euro9996; rFSH euro13,009 (P < 0.0001). HP-HMG remained cost-saving even after key parameters in the model were varied in the probabilistic sensitivity analysis. Treatment with HP-HMG was found to be the dominant treatment strategy in IVF because of improved live birth rates and lower costs. Within a fixed healthcare budget, the cost-savings achieved using HP-HMG would allow for the delivery of additional IVF cycles.

Role of urease in megasome formation and Helicobacter pylori survival in macrophages

PubMed Central

Schwartz, Justin T.; Allen, Lee-Ann H.

2007-01-01

Previous studies have demonstrated that Helicobacter pylori (Hp) delays its entry into macrophages and persists inside megasomes, which are poorly acidified and accumulate early endosome autoantigen 1. Herein, we explored the role of Hp urease in bacterial survival in murine peritoneal macrophages and J774 cells. Plasmid-free mutagenesis was used to replace ureA and ureB with cat in Hp Strains 11637 and 11916. ureAB null Hp lacked detectable urease activity and did not express UreA or UreB as judged by immunoblotting. Deletion of ureAB had no effect on Hp binding to macrophages or the rate or extent of phagocytosis. However, intracellular survival of mutant organisms was impaired significantly. Immunofluorescence microscopy demonstrated that (in contrast to parental organisms) mutant Hp resided in single phagosomes, which were acidic and accumulated the lysosome marker lysosome-associated membrane protein-1 but not early endosome autoantigen 1. A similar phenotype was observed for spontaneous urease mutants derived from Hp Strain 60190. Treatment of macrophages with bafilomycin A1, NH4Cl, or chloroquine prevented acidification of phagosomes containing mutant Hp. However, only ammonium chloride enhanced bacterial viability significantly. Rescue of ureAB null organisms was also achieved by surface adsorption of active urease. Altogether, our data indicate a role for urease and urease-derived ammonia in megasome formation and Hp survival. PMID:16543403

78 FR 48867 - Nationwide Categorical Waivers Under the American Recovery and Reinvestment Act of 2009 (Recovery...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-12

... shaft (VHS) electric motors (less than 40 HP) to be utilized in Recovery Act projects funded by EERE...) vertical hollow shaft (VHS) electric motors (less than 40 HP) are not produced or manufactured in the...-horsepower (HP) vertical hollow shaft (VHS) electric motors (less than 40 HP) to be utilized in Recovery Act...

Hydrostatic pressure suppresses fibrotic changes via Akt/GSK-3 signaling in human cardiac fibroblasts.

PubMed

Tanaka, Ryo; Umemura, Masanari; Narikawa, Masatoshi; Fujita, Takayuki; Yokoyama, Utako; Ishigami, Tomoaki; Kimura, Kazuo; Tamura, Kouichi; Ishikawa, Yoshihiro

2018-05-01

Mechanical stresses play important roles in the process of constructing and modifying heart structure. It has been well established that stretch force acting on cardiac fibroblasts induces fibrosis. However, the effects of compressive force, that is, hydrostatic pressure (HP), have not been well elucidated. We thus evaluated the effects of HP using a pressure-loading apparatus in human cardiac fibroblasts (HCFs) in vitro. In this study, high HP (200 mmHg) resulted in significant phosphorylation of Akt in HCFs. HP then greatly inhibited glycogen synthase kinase 3 (GSK-3)α, which acts downstream of the PI3K/Akt pathway. Similarly, HP suppressed mRNA transcription of inflammatory cytokine-6, collagen I and III, and matrix metalloproteinase 1, compared with an atmospheric pressure condition. Furthermore, HP inhibited collagen matrix production in a three-dimensional HCF culture. Taken together, high HP suppressed the differentiation of fibroblasts into the myofibroblast phenotype. HP under certain conditions suppressed cardiac fibrosis via Akt/GSK-3 signaling in HCFs. These results might help to elucidate the pathology of some types of heart disease. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Development and analytical performance evaluation of FREND-SAA and FREND-Hp

NASA Astrophysics Data System (ADS)

Choi, Eunha; Seong, Jihyun; Lee, Seiyoung; Han, Sunmi

2017-07-01

The FREND System is a portable cartridge reader, quantifying analytes by measuring laser-induced fluorescence in a single-use reagent cartridge. The objective of this study was to evaluate FREND-SAA and FREND-Hp assays. The FREND-SAA and Hp assays were standardized to the WHO and IFCC reference materials. Analytical performance studies of Precision, Linearity, Limits of Detections, Interferences, and Method Comparisons for both assays were performed according to the CLSI guidelines. Both assays demonstrated acceptable imprecision of %CV in three different levels of samples. The linearity of the assays was found to be acceptable (SAA 5 150 mg/L, Hp 30 400 mg/dL). The detection limits were 3.8 mg/L (SAA) and 10.2 mg/dL (Hp). No significant interference and no significant deviation from linearity was found in the both comparison studies. In conclusion, NanoEnTek's FREND-SAA and Hp assays represent rapid, accurate and convenient means to quantify SAA and Hp in human serum on FREND system.

Downscaling ferroelectric field effect transistors by using ferroelectric Si-doped HfO2

NASA Astrophysics Data System (ADS)

Martin, Dominik; Yurchuk, Ekaterina; Müller, Stefan; Müller, Johannes; Paul, Jan; Sundquist, Jonas; Slesazeck, Stefan; Schlösser, Till; van Bentum, Ralf; Trentzsch, Martin; Schröder, Uwe; Mikolajick, Thomas

2013-10-01

Throughout the 22 nm technology node HfO2 is established as a reliable gate dielectric in contemporary complementary metal oxide semiconductor (CMOS) technology. The working principle of ferroelectric field effect transistors FeFET has also been demonstrated for some time for dielectric materials like Pb[ZrxTi1-x]O3 and SrBi2Ta2O9. However, integrating these into contemporary downscaled CMOS technology nodes is not trivial due to the necessity of an extremely thick gate stack. Recent developments have shown HfO2 to have ferroelectric properties, given the proper doping. Moreover, these doped HfO2 thin films only require layer thicknesses similar to the ones already in use in CMOS technology. This work will show how the incorporation of Si induces ferroelectricity in HfO2 based capacitor structures and finally demonstrate non-volatile storage in nFeFETs down to a gate length of 100 nm. A memory window of 0.41 V can be retained after 20,000 switching cycles. Retention can be extrapolated to 10 years.

Diffraction based overlay and image based overlay on production flow for advanced technology node

NASA Astrophysics Data System (ADS)

Blancquaert, Yoann; Dezauzier, Christophe

2013-04-01

One of the main challenges for lithography step is the overlay control. For the advanced technology node like 28nm and 14nm, the overlay budget becomes very tight. Two overlay techniques compete in our advanced semiconductor manufacturing: the Diffraction based Overlay (DBO) with the YieldStar S200 (ASML) and the Image Based Overlay (IBO) with ARCHER (KLA). In this paper we will compare these two methods through 3 critical production layers: Poly Gate, Contact and first metal layer. We will show the overlay results of the 2 techniques, explore the accuracy and compare the total measurement uncertainty (TMU) for the standard overlay targets of both techniques. We will see also the response and impact for the Image Based Overlay and Diffraction Based Overlay techniques through a process change like an additional Hardmask TEOS layer on the front-end stack. The importance of the target design is approached; we will propose more adapted design for image based targets. Finally we will present embedded targets in the 14 FDSOI with first results.

Dual-modality imaging with 99mTc and fluorescent indocyanine green using surface-modified silica nanoparticles for biopsy of the sentinel lymph node: an animal study

PubMed Central

2013-01-01

Background We propose a new approach to facilitate sentinel node biopsy examination by multimodality imaging in which radioactive and near-infrared (NIR) fluorescent nanoparticles depict deeply situated sentinel nodes and fluorescent nodes with anatomical resolution in the surgical field. For this purpose, we developed polyamidoamine (PAMAM)-coated silica nanoparticles loaded with technetium-99m (99mTc) and indocyanine green (ICG). Methods We conducted animal studies to test the feasibility and utility of this dual-modality imaging probe. The mean diameter of the PAMAM-coated silica nanoparticles was 30 to 50 nm, as evaluated from the images of transmission electron microscopy and scanning electron microscopy. The combined labeling with 99mTc and ICG was verified by thin-layer chromatography before each experiment. A volume of 0.1 ml of the nanoparticle solution (7.4 MBq, except for one rat that was injected with 3.7 MBq, and 1 μg of an ICG derivative [ICG-sulfo-OSu]) was injected submucosally into the tongue of six male Wistar rats. Results Scintigraphic images showed increased accumulation of 99mTc in the neck of four of the six rats. Nineteen lymph nodes were identified in the dissected neck of the six rats, and a contact radiographic study showed three nodes with a marked increase in uptake and three nodes with a weak uptake. NIR fluorescence imaging provided real-time clear fluorescent images of the lymph nodes in the neck with anatomical resolution. Six lymph nodes showed weak (+) to strong (+++) fluorescence, whereas other lymph nodes showed no fluorescence. Nodes showing increased radioactivity coincided with the fluorescent nodes. The radioactivity of 15 excised lymph nodes from the four rats was assayed using a gamma well counter. Comparisons of the levels of radioactivity revealed a large difference between the high-fluorescence-intensity group (four lymph nodes; mean, 0.109% ± 0.067%) and the low- or no-fluorescence-intensity group (11 lymph nodes; mean, 0.001% ± 0.000%, p < 0.05). Transmission electron microscopy revealed that small black granules were localized to and dispersed within the cytoplasm of macrophages in the lymph nodes. Conclusion Although further studies are needed to determine the appropriate dose of the dual-imaging nanoparticle probe for effective sensitivity and safety, the results of this animal study revealed a novel method for improved node detection by a dual-modality approach for sentinel lymph node biopsy. PMID:23618132

Addressing FinFET metrology challenges in 1X node using tilt-beam CD-SEM

NASA Astrophysics Data System (ADS)

Zhang, Xiaoxiao; Zhou, Hua; Ge, Zhenhua; Vaid, Alok; Konduparthi, Deepasree; Osorio, Carmen; Ventola, Stefano; Meir, Roi; Shoval, Ori; Kris, Roman; Adan, Ofer; Bar-Zvi, Maayan

2014-04-01

At 1X node, 3D FinFETS raise a number of new metrology challenges. Gate height and fin height are two of the most important parameters for process control. At present there is a metrology gap in inline in-die measurement of these parameters. In order to fill this metrology gap, in-column beam tilt has been developed and implemented on Applied Materials V4i+ top-down CD-SEM for height measurement. A low tilt (5°) beam and a high tilt (14°) beam have been calibrated to obtain two sets of images providing measurement of sidewall edge width to calculate height in the host. Evaluations are done with applications in both gate height and fin height. TEM correlation with R2 being 0.89 and precision of 0.81nm have been achieved on various in-die features in gate height application. Fin height measurement shows less accuracy (R2 being 0.77) and precision (1.49 nm) due to challenges brought by fin geometry, yet still promising as first attempt. Sensitivity to DOE offset, die-to-die and in-die variation is demonstrated in both gate height and fin height. Process defect is successfully captured from inline wafers with gate height measurement implemented in production. This is the first successful demonstration of inline in-die gate height measurement for 14nm FinFET process control.

Effects of ultra-thin Si-fin body widths upon SOI PMOS FinFETs

NASA Astrophysics Data System (ADS)

Liaw, Yue-Gie; Chen, Chii-Wen; Liao, Wen-Shiang; Wang, Mu-Chun; Zou, Xuecheng

2018-05-01

Nano-node tri-gate FinFET devices have been developed after integrating a 14 Å nitrided gate oxide upon the silicon-on-insulator (SOI) wafers established on an advanced CMOS logic platform. These vertical double gate (FinFET) devices with ultra-thin silicon fin (Si-fin) widths ranging from 27 nm to 17 nm and gate length down to 30 nm have been successfully developed with a 193 nm scanner lithography tool. Combining the cobalt fully silicidation and the CESL strain technology beneficial for PMOS FinFETs was incorporated into this work. Detailed analyses of Id-Vg characteristics, threshold voltage (Vt), and drain-induced barrier lowering (DIBL) illustrate that the thinnest 17 nm Si-fin width FinFET exhibits the best gate controllability due to its better suppression of short channel effect (SCE). However, higher source/drain resistance (RSD), channel mobility degradation due to dry etch steps, or “current crowding effect” will slightly limit its transconductance (Gm) and drive current.

Intact EAV-HP Endogenous Retrovirus in Sonnerat's Jungle Fowl

PubMed Central

Sacco, M. A.; Howes, K.; Venugopal, K.

2001-01-01

The EAV-HP group of chicken endogenous retrovirus elements was previously shown to be defective, with large deletions of the pol gene. In this report, we demonstrate that genomes of other Gallus species also maintain EAV-HP elements with similar deletions. The chicken EAV-HP1 locus was detected in both red (Gallus gallus gallus) and Sonnerat's (Gallus sonneratii) jungle fowl with identical integration sites, indicating that these elements had integrated before separation of the Gallus species. Furthermore, we demonstrate for the first time that the G. sonneratii genome carries EAV-HP elements with intact pol regions. PMID:11160706

Influence of source and micronization of soya bean meal on growth performance, nutrient digestibility and ileal mucosal morphology of Iberian piglets.

PubMed

Berrocoso, J D; Cámara, L; Rebollar, P G; Guzmán, P; Mateos, G G

2014-04-01

The effects of inclusion in the diet of different sources of soya bean meal (SBM) on growth performance, total tract apparent digestibility (TTAD) and apparent ileal digestibility (AID) of major dietary components and mucosal ileum morphology were studied in Iberian pigs weaned at 30 days of age. From 30 to 51 days of age (phase I), there was a control diet based on regular soya bean meal (R-SBM; 44% CP) of Argentina (ARG) origin and five extra diets in which a high-protein soya bean meal (HP-SBM; 49% CP) of the USA or ARG origin, either ground (990 μm) or micronized (60 μm), or a soya protein concentrate (SPC; 65% CP) substituted the R-SBM. From 51 to 61 days of age (phase II), all pigs were fed a common commercial diet in mash form. The following pre-planned orthogonal contrasts were conducted: (1) R-SBM v. all the other diets, (2) SPC v. all the HP-SBM diets, (3) micronized HP-SBM v. ground HP-SBM, (4) HP-SBM of ARG origin v. HP-SBM of US origin and (5) interaction between source and the degree of grinding of the HP-SBM. Dietary treatment did not affect growth performance of the pigs at any age but from 30 to 51 days of age, post weaning diarrhoea (PWD) was higher (P<0.001) and the TTAD and AID of all nutrients were lower for pigs fed the R-SBM diet than for pigs fed the HP-SBM or the SPC diets. However, no differences between the HP-SBM and the SPC containing diets were detected for any trait. The TTAD of organic matter (P=0.07) and gross energy (GE) (P=0.05) tended to be higher for the micronized HP-SBM than for the ground HP-SBM and that of GE was higher (P<0.05) for US meal than for the ARG meal. Pigs fed R-SBM had lower villus height (P<0.01) than pigs fed HP-SBM or SPC but no differences in ileal mucosal morphology were detected between SPC and HP-SBM containing diets. It is concluded that feeding the HP-SBM or SPC-reduced PWD and improved nutrient digestibility and ileal morphology as compared with feeding the R-SBM, but had no effect on pig performance. The inclusion in the diet of added value soya products (micronized SBM or SPC) in substitution of the R-SBM increased the TTAD of all nutrients and reduced PWD but had no advantage in terms of growth performance over the use of ground HP-SBM.

Advanced coatings for next generation lithography

NASA Astrophysics Data System (ADS)

Naujok, P.; Yulin, S.; Kaiser, N.; Tünnermann, A.

2015-03-01

Beyond EUV lithography at 6.X nm wavelength has a potential to extend EUVL beyond the 11 nm node. To implement B-based mirrors and to enable their industrial application in lithography tools, a reflectivity level of > 70% has to be reached in near future. The authors will prove that transition from conventional La/B4C to promising LaN/B4C multilayer coatings leads to enhanced optical properties. Currently a near normal-incidence reflectivity of 58.1% @ 6.65 nm is achieved by LaN/B4C multilayer mirrors. The introduction of ultrathin diffusion barriers into the multilayer design to reach the targeted reflectivity of 70% was also tested. The optimization of multilayer design and deposition process for interface-engineered La/C/B4C multilayer mirrors resulted in peak reflectivity of 56.8% at the wavelength of 6.66 nm. In addition, the thermal stability of several selected multilayers was investigated and will be discussed.

High-pressure high-temperature crystal growth of equiatomic rare earth stannides RENiSn and REPdSn

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

Heymann, Gunter; Heying, Birgit; Rodewald, Ute Ch.

2016-04-15

The two series of equiatomic rare earth (RE) stannides RENiSn and REPdSn were systematically studied with respect to high-pressure modifications. The normal-pressure (NP) low-temperature (LT) modifications were synthesized by arc-melting and subsequently treated under high-pressure (P{sub max}=11.5 GPa) and high-temperature (T{sub max}=1570 K) conditions in a Walker-type multi-anvil press. The pressure and temperature conditions were systematically varied in order to improve the crystallization conditions. The new ZrNiAl-type high-pressure modifications HP-RENiSn (RE=Sc, Y, La, Gd–Lu) and HP-REPdSn (RE=Y, Sm–Dy) were obtained in 80 mg quantities, several of them in X-ray pure form. Some of the REPdSn stannides with the heavy raremore » earth elements show high-temperature (HT) modifications. The structures of HP-ScNiSn, HP-GdNiSn, HP-DyNiSn (both ZrNiAl-type), NP-YbNiSn, and HT-ErPdSn (both TiNiSi-type) were refined from single crystal diffractometer data, indicating full ordering of the transition metal and tin sites. TiNiSi-type NP-EuPdSn transforms to MgZn{sub 2}-type HP-EuPdSn: P6{sub 3}/mmc, a=588.5(2), c=917.0(3) pm, wR2=0.0769, 211 F{sup 2} values, 11 variables. The structure refinement indicated statistical occupancy of the palladium and tin sites on the tetrahedral network. The X-ray pure high-pressure phases were studied with respect to their magnetic properties. HP-YPdSn is a Pauli paramagnet. The susceptibility data of HP-TbNiSn, HP-DyNiSn, HP-GdPdSn, and HP-TbPdSn show experimental magnetic moments close to the free ion values of RE{sup 3+} and antiferromagnetic ordering at low temperature with the highest Néel temperature of 15.8 K for HP-TbPdSn. HP-SmPdSn shows the typical Van Vleck type behavior along with antiferromagnetic ordering at T{sub N}=5.1 K. HP-EuPdSn shows divalent europium and antiferromagnetic ordering at 8.9 K followed by a spin reorientation at 5.7 K. - Graphical abstract: Packing of the polyhedra in the high-pressure phase of EuPdSn. - Highlights: • High-pressure phases of the stannides RENiSn and REPdSn. • Crystal growth conditions. • Pressure- and temperature-driven phase transitions. • Magnetic properties.« less

[Comparative diagnostic value of Helicobacter pylori infection testing methods].

PubMed

Girdalidze, A M; Elisabedashvili, G V; Sharvadze, L G; Dzhorbenadze, T A

2013-12-01

In 213 patients with gastric and duodenal pathology, including received surgery, comparative estimation of results of Helicobacter pylori (Hp) infection testing with invasive and noninvasive methods, were performed. Material for invasive endoscopic biopsy test (EBT), including rapid urease test (RUT) for rapid Hp identification by determination of urease activity, smear cytology and histology was extracted on endoscopy or intraoperationally. RUT was carried out with the help of URE-HP test kit. Serological test for Hp antibodies IgG and IgA class was performed by IFA using kit ELISA. 13С urea breath test (UBT) was made by determination of 13/12CO2 in breath samples on infrared spectroscope. Based on 5 different methods of Hp infection testing Hp positivity in 172 (80,8%) and Hp negativity in 41 (19,2%) from 213 examined patients was revealed. 13С-UBT revealed the highest diagnostic value (accuracy-97,5%, sensibility-97,0%, specificity-100%) in Hp infection diagnostics. In treatment efficiency control this parameters of 13С-UBT are also much high (96,7%, 90,0% and 100% respectively). In spite of high sensitivity of serological test (100%), it had comparative low specificity (71,0%) with high probability of false positive results in treated patients (antibodies titer to Hp after eradication retains for a long time). Thought, this test may be successfully used only in primary patients and in epidemiological studies. Among three methods of EBT, Hp infection detection with RUT revealed the best results (accuracy-94,8%, sensibility-95,0%, specificity-100%). Correlation of RUT and UBT results and much higher diagnostic value of UBT, necessitate RUT with histological study of stomach body mucosa to perform in patients over 45 year, with prolonged anamnesis and dangerous symptoms of disease. In Hp positive patients correlation of index DOB‰ of breath test with results of RUT was revealed. This can serve the index DOB‰ of 13С-UBT as a marker of Hp infection rate. The (accuracy, sensibility and specificity of breath test with local made 13С-urea (98,7%, 98,5% and 100% respectively) are the same as those for BT with standard 13С-urea (96,7%, 96,2% and 100% respectively). Above mentioned, 13С-UBT advantages (noninvasiveness, simplicity, rapidity, safety) and high diagnostic value exceeding same of other applied tests, give us opportunity to offer 13С-UBT as screening method of Hp infection diagnosis and a method of choise in control of Hp infection treatment efficiency.

Exploring the Potential Role of Chemopreventive Agent, Hesperetin Conjugated Pegylated Gold Nanoparticles in Diethylnitrosamine-Induced Hepatocellular Carcinoma in Male Wistar Albino Rats.

PubMed

Gokuladhas, Krishnan; Jayakumar, Subramaniyan; Rajan, Balan; Elamaran, Ramasamy; Pramila, Chengalvarayan Subramani; Gopikrishnan, Mani; Tamilarasi, Sasivarman; Devaki, Thiruvengadam

2016-04-01

Liver cancer is the fifth most common cancer and is still one of the leading causes of death world wide, due to food additives, alcohol, fungal toxins, air, toxic industrial chemicals, and water pollutants. Chemopreventive drugs play a potential role in liver cancer treatment. Obviously in the production of anticancer drugs, the factors like poor solubility, bioavailability, biocompatibility, limited chemical stability, large amount of dose etc., plays a major role. Against this backdrop, the idea of designing the chemopreventive nature of bio flavanoid hesperetin (HP) drug conjugated with pegylated gold nanoparticles to increasing the solubility, improve bioavailability and enhance the targeting capabilities of the drug during diethylnitrosamine (DEN) induced liver cancer in male wistar albino rats. The dose fixation studies and the toxicity of pure HP and HP conjugated gold nanoparticles (Au-mPEG(5000)-S-HP) were analysed. After concluded the dose fixation and toxicity studies the experimental design were segregated in six groups for the anticancer analysis of DEN induced HCC for 16 weeks. After the experimental period the body weight, relative liver weight, number of nodules and size of nodules, the levels of tumor markers like CEA, AFP and the level of lipid peroxidation, lipid hydroperoxides and the activities of antioxidant enzymes were assessed. The administration of DEN to rats resulted in increased relative liver weight and serum marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, and gamma glutamyl transpeptidase. The levels of lipid peroxides elevated (in both serum and tissue) with subsequent decrease in the final body weight and tissue antioxidants like superoxide dismutase, catalase, reduced glutathione, glutathione peroxidise, and glutathione reductase. HP supplementation (20 mg/kg b.wt) significantly attenuated these alterations, thereby showing potent anticancer effect in liver cancer and the HP loaded gold nanoparticels (Au-mPEG(5000)-S-HP) treated animals shows the better treatment than the pure HP due to the solubility of drug, bioavailability and the target drug delivery of the biodegradable polymer. Histological observations were also carried out, which added supports to the chemopreventive action of the pure HP and HP loaded gold nanoparticles (Au-mPEG(5000)-S-HP) against DEN induction during liver cancer progression. These findings suggest that HP loaded gold nanoparticels (Au-mPEG(5000)-S-HP) shows better efficacy than the pure HP against lipid peroxidation, hepatic cell damage and protects the antioxidant system in DEN induced hepatocellular carcinogenesis.

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Science.gov Websites

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Muscle strength gains during resistance exercise training are attenuated with soy compared with dairy or usual protein intake in older adults: A randomized controlled trial.

PubMed

Thomson, Rebecca L; Brinkworth, Grant D; Noakes, Manny; Buckley, Jonathan D

2016-02-01

Maintenance of muscle mass and strength into older age is critical to maintain health. The aim was to determine whether increased dairy or soy protein intake combined with resistance training enhanced strength gains in older adults. 179 healthy older adults (age 61.5 ± 7.4 yrs, BMI 27.6 ± 3.6 kg/m(2)) performed resistance training three times per week for 12 weeks and were randomized to one of three eucaloric dietary treatments which delivered >20 g of protein at each main meal or immediately after resistance training: high dairy protein (HP-D, >1.2 g of protein/kg body weight/d; ∼27 g/d dairy protein); high soy protein (HP-S, >1.2 g of protein/kg body weight/d; ∼27 g/d soy protein); usual protein intake (UP, <1.2 g of protein/kg body weight/d). Muscle strength, body composition, physical function and quality of life were assessed at baseline and 12 weeks. Treatments effects were analyzed using two-way ANOVA. 83 participants completed the intervention per protocol (HP-D = 34, HP-S = 26, UP = 23). Protein intake was higher in HP-D and HP-S compared with UP (HP-D 1.41 ± 0.14 g/kg/d, HP-S 1.42 ± 0.61 g/kg/d, UP 1.10 ± 0.10 g/kg/d; P < 0.001 treatment effect). Strength increased less in HP-S compared with HP-D and UP (HP-D 92.1 ± 40.8%, HP-S 63.0 ± 23.8%,UP 92.3 ± 35.4%; P = 0.002 treatment effect). Lean mass, physical function and mental health scores increased and fat mass decreased (P ≤ 0.006), with no treatment effect (P > 0.06). Increased soy protein intake attenuated gains in muscle strength during resistance training in older adults compared with increased intake of dairy protein or usual protein intake. ACTRN12612000177853 www.anzctr.org.au. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Size-dependent tissue kinetics of PEG-coated gold nanoparticles

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

Cho, Wan-Seob; Department of Toxicological Research, National Institute of Food and Drug Safety Evaluation, Korea Food and Drug Administration, Seoul 122-704; Cho, Minjung

2010-05-15

Gold nanoparticles (AuNPs) can be used in various biomedical applications, however, very little is known about their size-dependent in vivo kinetics. Here, we performed a kinetic study in mice with different sizes of PEG-coated AuNPs. Small AuNPs (4 or 13 nm) showed high levels in blood for 24 h and were cleared by 7 days, whereas large (100 nm) AuNPs were completely cleared by 24 h. All AuNPs in blood re-increased at 3 months, which correlated with organ levels. Levels of small AuNPs were peaked at 7 days in the liver and spleen and at 1 month in the mesentericmore » lymph node, and remained high until 6 months, with slow elimination. In contrast, large AuNPs were taken up rapidly (approx 30 min) into the liver, spleen, and mesenteric lymph nodes with less elimination phase. TEM showed that AuNPs were entrapped in cytoplasmic vesicles and lysosomes of Kupffer cells and macrophages of spleen and mesenteric lymph node. Small AuNPs transiently activated CYP1A1 and 2B, phase I metabolic enzymes, in liver tissues from 24 h to 7 days, which mirrored with elevated gold levels in the liver. Large AuNPs did not affect the metabolic enzymes. Thus, propensity to accumulate in the reticuloendothelial organs and activation of phase I metabolic enzymes, suggest that extensive further studies are needed for practical in vivo applications.« less

Two reaction pathways for transformation of high potential cytochrome b559 of PS II into the intermediate potential form.

PubMed

Kaminskaya, Olga; Shuvalov, Vladimir A; Renger, Gernot

2007-06-01

This study describes an analysis of different treatments that influence the relative content and the midpoint potential of HP Cyt b559 in PS II membrane fragments from higher plants. Two basically different types of irreversible modification effects are distinguished: the HP form of Cyt b559 is either predominantly affected when the heme group is oxidized ("O-type" effects) or when it is reduced ("R-type" effects). Transformation of HP Cyt b559 to lower potential redox forms (IP and LP forms) by the "O-type" mechanism is induced by high pH and detergent treatments. In this case the effects consist of a gradual decrease in the relative content of HP Cyt b559 while its midpoint potential remains unaffected. Transformation of HP Cyt b559 via an "R-type" mechanism is caused by a number of exogenous compounds denoted L: herbicides, ADRY reagents and tetraphenylboron. These compounds are postulated to bind to the PS II complex at a quinone binding site designated as Q(C) which interacts with Cyt b559 and is clearly not the Q(B) site. Binding of compounds L to the Q(C) site when HP Cyt b559 is oxidized gives rise to a gradual decrease in the E(m) of HP Cyt b559 with increasing concentration of L (up to 10 K(ox)(L) values) while the relative content of HP Cyt b559 is unaffected. Higher concentrations of compounds L required for their binding to Q(C) site when HP Cyt b559 is reduced (described by K(red)(L)) induce a conversion of HP Cyt b559 to lower potential redox forms ("R-type" transformation). Two reaction pathways for transitions of Cyt b559 between the different protein conformations that are responsible for the HP and IP/LP redox forms are proposed and new insights into the functional regulation of Cyt b559 via the Q(C) site are discussed.

Comparison of Spot Urine Protein to Creatinine Ratio to 24-Hour Proteinuria to Identify Important Change Over Time in Proteinuria in Lupus.

PubMed

Medina-Rosas, Jorge; Su, Jiandong; Cook, Richard J; Sabapathy, Arthy; Touma, Zahi

2017-09-01

The aim of this study was to determine whether spot urine protein-to-creatinine ratio (PCR) accurately measures the change in proteinuria compared with 24-hour proteinuria (24H-P). This was a retrospective analysis on patients' paired visits and paired urine samples for PCR and 24H-P. Patients with both abnormal 24H-P (>0.5 g/d) and PCR (>0.05 g/mmol) or both normal 24H-P (≤0.5 g/d) and PCR (≤0.05 g/mmol) at baseline visit were identified.The first follow-up visit with partial recovery (50% decrease in proteinuria) or complete recovery (≤0.5 g/d) was identified for those with abnormal baseline 24H-P, and new proteinuria (>0.5 g/d) was identified for those with normal 24H-P. Twenty-four-hour urine collection and PCR end-point frequencies were compared. Twenty-four-hour urine collection results were converted to 24H-PCR. Twenty-four-hour PCR and PCR were utilized to measure the magnitude of change (by standardized response mean [SRM]) in patients who achieved the end points. Of 230 patients, at baseline, 95 patients had abnormal and 109 had normal 24H-P and PCR. On follow-up, 57 achieved partial recovery, and 53 achieved complete recovery by 24H-P. Standardized response mean was -1.03 and -1.10 for 24H-PCR and PCR, respectively. By PCR, 53 patients had partial recovery, and 27 had complete recovery. Standardized response mean was -1.25 and -0.86 by 24H-PCR and PCR, respectively.For new proteinuria, 28 patients were identified by 24H-P and 21 by PCR. Twenty-four-hour PCR SRM was 0.80, and PCR SRM was 0.68. Protein-to-creatinine ratio does not have sufficient accuracy compared with 24H-P for improvement and worsening to be used in lieu of 24H-P.

Solid lipid nanoparticles for nose to brain delivery of haloperidol: in vitro drug release and pharmacokinetics evaluation

PubMed Central

Yasir, Mohd; Sara, Udai Vir Singh

2014-01-01

In the present study, haloperidol (HP)-loaded solid lipid nanoparticles (SLNs) were prepared to enhance the uptake of HP to brain via intranasal (i.n.) delivery. SLNs were prepared by a modified emulsification–diffusion technique and evaluated for particle size, zeta potential, drug entrapment efficiency, in vitro drug release, and stability. All parameters were found to be in an acceptable range. In vitro drug release was found to be 94.16±4.78% after 24 h and was fitted to the Higuchi model with a very high correlation coefficient (R2=0.9941). Pharmacokinetics studies were performed on albino Wistar rats and the concentration of HP in brain and blood was measured by high performance liquid chromatography. The brain/blood ratio at 0.5 h for HP-SLNs i.n., HP sol. i.n. and HP sol. i.v. was 1.61, 0.17 and 0.031, respectively, indicating direct nose-to-brain transport, bypassing the blood–brain barrier. The maximum concentration (Cmax) in brain achieved from i.n. administration of HP-SLNs (329.17±20.89 ng/mL, Tmax 2 h) was significantly higher than that achieved after i.v. (76.95±7.62 ng/mL, Tmax 1 h), and i.n. (90.13±6.28 ng/mL, Tmax 2 h) administration of HP sol. The highest drug-targeting efficiency (2362.43%) and direct transport percentage (95.77%) was found with HP-SLNs as compared to the other formulations. Higher DTE (%) and DTP (%) suggest that HP-SLNs have better brain targeting efficiency as compared to other formulations. PMID:26579417

Dynamic Hydrostatic Pressure Regulates Nucleus Pulposus Phenotypic Expression and Metabolism in a Cell Density-Dependent Manner.

PubMed

Shah, Bhranti S; Chahine, Nadeen O

2018-02-01

Dynamic hydrostatic pressure (HP) loading can modulate nucleus pulposus (NP) cell metabolism, extracellular matrix (ECM) composition, and induce transformation of notochordal NP cells into mature phenotype. However, the effects of varying cell density and dynamic HP magnitude on NP phenotype and metabolism are unknown. This study examined the effects of physiological magnitudes of HP loading applied to bovine NP cells encapsulated within three-dimensional (3D) alginate beads. Study 1: seeding density (1 M/mL versus 4 M/mL) was evaluated in unloaded and loaded (0.1 MPa, 0.1 Hz) conditions. Study 2: loading magnitude (0, 0.1, and 0.6 MPa) applied at 0.1 Hz to 1 M/mL for 7 days was evaluated. Study 1: 4 M/mL cell density had significantly lower adenosine triphosphate (ATP), glycosaminoglycan (GAG) and collagen content, and increased lactate dehydrogenase (LDH). HP loading significantly increased ATP levels, and expression of aggrecan, collagen I, keratin-19, and N-cadherin in HP loaded versus unloaded groups. Study 2: aggrecan expression increased in a dose dependent manner with HP magnitude, whereas N-cadherin and keratin-19 expression were greatest in low HP loading compared to unloaded. Overall, the findings of the current study indicate that cell seeding density within a 3D construct is a critical variable influencing the mechanobiological response of NP cells to HP loading. NP mechanobiology and phenotypic expression was also found to be dependent on the magnitude of HP loading. These findings suggest that HP loading and culture conditions of NP cells may require complex optimization for engineering an NP replacement tissue.

Increased plasma ghrelin suppresses insulin release in wethers fed with a high-protein diet.

PubMed

Takahashi, T; Sato, K; Kato, S; Yonezawa, T; Kobayashi, Y; Ohtani, Y; Ohwada, S; Aso, H; Yamaguchi, T; Roh, S G; Katoh, K

2014-06-01

Ghrelin is a multifunctional peptide that promotes an increase of food intake and stimulates GH secretion. Ghrelin secretion is regulated by nutritional status and nutrients. Although a high-protein (HP) diet increases plasma ghrelin secretion in mammals, the mechanisms and the roles of the elevated ghrelin concentrations due to a HP diet have not been fully established. To clarify the roles of elevated acylated ghrelin upon intake of a HP diet, we investigated the regulation of ghrelin concentrations in plasma and tissues in wethers fed with either the HP diet or the control (CNT) diet for 14 days, and examined the action of the elevated plasma ghrelin by using a ghrelin-receptor antagonist. The HP diet gradually increased the plasma acylated-ghrelin concentrations, but the CNT diet did not. Although the GH concentrations did not vary significantly across the groups, an injection of ghrelin-receptor antagonist enhanced insulin levels in circulation in the HP diet group. In the fundus region of the stomach, the ghrelin levels did not differ between the HP and CNT diet groups, whereas ghrelin O-acyltransferase mRNA levels were higher in the group fed with HP diet than those of the CNT diet group were. These results indicate that the HP diet elevated the plasma ghrelin levels by increasing its synthesis; this elevation strongly suppresses the appearance of insulin in the circulation of wethers, but it is not involved in GH secretion. Overall, our findings indicate a role of endogenous ghrelin action in secretion of insulin, which acts as a regulator after the consumption of a HP diet. © 2014 Society for Endocrinology.

Comparing Hp(3) evaluated from the conversion coefficients from air kerma to personal dose equivalent for eye lens dosimetry calibrated on a new cylindrical PMMA phantom

NASA Astrophysics Data System (ADS)

Esor, J.; Sudchai, W.; Monthonwattana, S.; Pungkun, V.; Intang, A.

2017-06-01

Based on a new occupational dose limit recommended by ICRP (2011), the annual dose limit for the lens of the eye for workers should be reduced from 150 mSv/y to 20 mSv/y averaged over 5 consecutive years in which no single year exceeding 50 mSv. This new dose limit directly affects radiologists and cardiologists whose work involves high radiation exposure over 20 mSv/y. Eye lens dosimetry (Hp(3)) has become increasingly important and should be evaluated directly based on dosimeters that are worn closely to the eye. Normally, Hp(3) dose algorithm was carried out by the combination of Hp(0.07) and Hp(10) values while dosimeters were calibrated on slab PMMA phantom. Recently, there were three reports from European Union that have shown the conversion coefficients from air kerma to Hp(3). These conversion coefficients carried out by ORAMED, PTB and CEA Saclay projects were performed by using a new cylindrical head phantom. In this study, various delivered doses were calculated using those three conversion coefficients while nanoDot, small OSL dosimeters, were used for Hp(3) measurement. These calibrations were performed with a standard X-ray generator at Secondary Standard Dosimetry Laboratory (SSDL). Delivered doses (Hp(3)) using those three conversion coefficients were compared with Hp(3) from nanoDot measurements. The results showed that percentage differences between delivered doses evaluated from the conversion coefficient of each project and Hp(3) doses evaluated from the nanoDots were found to be not exceeding -11.48 %, -8.85 % and -8.85 % for ORAMED, PTB and CEA Saclay project, respectively.

The Novel Helicobacter pylori CznABC Metal Efflux Pump Is Required for Cadmium, Zinc, and Nickel Resistance, Urease Modulation, and Gastric Colonization

PubMed Central

Stähler, Frank Nils; Odenbreit, Stefan; Haas, Rainer; Wilrich, Julia; Vliet, Arnoud H. M. Van; Kusters, Johannes G.; Kist, Manfred; Bereswill, Stefan

2006-01-01

Maintaining metal homeostasis is crucial for the adaptation of Helicobacter pylori to the gastric environment. Iron, copper, and nickel homeostasis has recently been demonstrated to be required for the establishment of H. pylori infection in animal models. Here we demonstrate that the HP0969-0971 gene cluster encoding the Czc-type metal export pump homologs HP0969, HP0970, and the H. pylori-specific protein HP0971 forms part of a novel H. pylori metal resistance determinant, which is required for gastric colonization and for the modulation of urease activity. Insertional mutagenesis of the HP0971, HP0970, or HP0969 genes in H. pylori reference strain 26695 resulted in increased sensitivity to cadmium, zinc, and nickel (czn), suggesting that the encoded proteins constitute a metal-specific export pump. Accordingly, the genes were designated cznC (HP0971), cznB (HP0970), and cznA (HP0969). The CznC and CznA proteins play a predominant role in nickel homeostasis, since only the cznC and cznA mutants but not the cznB mutant displayed an 8- to 10-fold increase in urease activity. Nickel-specific affinity chromatography demonstrated that recombinant versions of CznC and CznB can bind to nickel and that the purified CznB protein interacted with cadmium and zinc, since both metals competitively inhibited nickel binding. Finally, single cznA, cznB, and cznC mutants did not colonize the stomach in a Mongolian gerbil-based animal model. This demonstrates that the metal export functions of H. pylori cznABC are essential for gastric colonization and underlines the extraordinary importance of metal ion homeostasis for the survival of H. pylori in the gastric environment. PMID:16790756

Color alteration, hydrogen peroxide diffusion, and cytotoxicity caused by in-office bleaching protocols.

PubMed

de Almeida, Letícia Cunha Amaral Gonzaga; Soares, Diana Gabriela; Gallinari, Marjorie Oliveira; de Souza Costa, Carlos Alberto; Dos Santos, Paulo Henrique; Briso, André Luiz Fraga

2015-04-01

This study evaluated the color alteration, cytotoxicity, and hydrogen peroxide (HP) diffusion associated with different in-office bleaching protocols. Bovine enamel/dentin disks were subjected to three bleaching sessions with 35 % HP (three 15-min applications), 35 % HP (one 45-min application), or 20 % HP (one 45-min application). The control group was not bleached. Before bleaching, the disks were adapted to artificial pulp chambers positioned in compartments containing 1 ml of acetate buffer or medium, so that the dentin remained in contact with these substances. Immediately after bleaching, the HP that diffused through the disks was stabilized by acetate buffer and was quantified (two-way repeated measures ANOVA/Fisher's protected least significant difference (PLSD) test; α = 5 %). Cells of mouse dental papilla cell-23 (MDPC-23) were incubated in this culture media for 1 h, followed by analysis of cellular metabolism (methyl tetrazolium assay) (one-way ANOVA/Tukey test; α = 5 %) and morphology (scanning electron microscopy). The specimen color alteration (ΔE) was analyzed by reflection spectrophotometry (two-way repeated measures ANOVA/Fisher's PLSD test; α = 5 %). All protocols showed equal effectiveness at the end of the treatment. HP diffusion was significantly higher in the groups bleached with 35 % HP. Reapplication of 35 % HP resulted in increased diffusion only in the first session; however, the decrease in cell metabolism was similar for all studied protocols. Despite greater peroxide diffusion in the groups treated with 35 % HP, all protocols showed the same effectiveness and were cytotoxic to MDPC-23 cells. Bleaching protocols using high HP concentrations should be avoided because they exert aggressive actions on odontoblast-like cells.

Effect of Bleaching Gel Viscosity on Tooth Whitening Efficacy and Pulp Chamber Penetration: An In Vitro Study.

PubMed

Kwon, S R; Pallavi, Fnu; Shi, Y; Oyoyo, U; Mohraz, A; Li, Y

Whitening efficacy has been related to hydrogen peroxide (HP) diffusion into tooth structure. However, little information is available relating rheological properties to whitening efficacy. The purpose was to evaluate the whitening efficacy and HP penetration level of a 10% HP gel at three different viscosities and to compare them to a strip delivery system. Extracted molars (n=120) were randomly assigned into five groups (n=24/ group): NC_MED (negative control; median): medium viscosity gel without HP; LOW: 10% HP gel (low viscosity experimental gel, Ultradent Products Inc); MED: 10% HP gel (medium viscosity experimental gel, Ultradent); HIGH: 10% HP gel (high viscosity gel, Ultradent); and CWS: Crest 3D Whitestrips 1-Hour Express (Procter & Gamble). All teeth were subjected to five 60-minute whitening sessions. Instrumental color measurements were performed at baseline (T 0 ), and 1-day after each application (T 1 -T 5 ), and 1-month after whitening (T 6 ). HP penetration was estimated with leucocrystal violet and horseradish peroxidase. A Kruskal-Wallis test and post hoc Bonferroni test were performed to assess the difference in tooth color change and HP penetration among the groups (α=0.05). Hydrogen peroxide penetration levels and overall color changes at T 6 were 0.24 μg/mL / 2.80; 0.48 μg/mL / 8.48; 0.44 μg/mL / 7.72; 0.35 μg/mL / 8.49; 0.36 μg/mL / 7.30 for groups NC, LOW, MED, HIGH, and CWS, respectively. There was a significant difference for HP penetration, while there was no significant difference among the four experimental groups for tooth color change. Rheological properties should be considered when developing new whitening formulations.

Efficacy, safety and mechanism of HP-β-CD-PEI polymers as absorption enhancers on the intestinal absorption of poorly absorbable drugs in rats.

PubMed

Zhang, Hailong; Huang, Xiaoyan; Zhang, Yongjing; Gao, Yang

2017-03-01

Oral bioavailability of some hydrophilic therapeutic macromolecules was very poor, thus leading to their limited application in clinic. To investigate the efficacy, safety and mechanism of HP-β-CD-PEI polymers on the intestinal absorption of some poorly absorbable drugs in rats. Effects of HP-β-CD-PEI polymers on the intestinal absorptions of drugs were investigated by an in situ closed loop method in rats. The safety of HP-β-CD-PEI polymer was evaluated by measurement of lactate dehydrogenase (LDH) activity and amount of protein released from rat intestinal perfusate. The absorption enhancing mechanisms were explored by the measurement of zeta potential, transepithelial electrical resistance (TEER) and in vitro transport of FD4 (a paracellular marker) across rat intestinal membranes, respectively. HP-β-CD-PEI polymers, especially HP-β-CD-PEI 1800 , demonstrated excellent absorption enhancing effects on drug absorption in a concentration-dependent manner and the enhancing effect was more efficient in the small intestine than that in the large intestine. Five percent (w/v) HP-β-CD-PEI 1800 obviously decreased the TEER, accompanied with increase in the intestinal transport of FD4, indicating that absorption enhancing actions of HP-β-CD-PEI polymers were possibly performed by loosening tight junctions of intestinal epithelium cells, thereby increasing drug permeation via a paracellular pathway. A good liner relationship between absorption enhancing effects of HP-β-CD-PEI polymers and their zeta potentials suggested the contribution of positive charge on the surface of these polymers to their absorption enhancing effects. HP-β-CD-PEI polymers might be potential and safe absorption enhancers for improving oral delivery of poorly absorbable macromolecules including peptides and proteins.

Purification of bioactive phenolics from Phanerochaete chysosporium biomass extract on selected macroporous resins

NASA Astrophysics Data System (ADS)

Idris, Z. M.; Dzahir, M. I. H. M.; Jamal, P.; Barkat, A. A.; Xian, R. L. W.

2017-06-01

In this study, two different types of macroporous resins known as XAD-7HP and HP-20 were evaluated for the adsorption and desorption properties against bioactive phenolics extracted from Phanerochaete chrysosporium. From the previous static sorption studies, it was found that the adsorption capacity for both resins had has no significant difference. Then, the kinetic adsorption data were analyzed with both pseudo-first-order and pseudo-second-order equations and the later performed better. The adsorption isotherm data were fitted well by both Langmuir and Freundlich models. Meanwhile in desorption study, HP-20 and XAD-7HP gave 90.52% and 88.28% recoveries, respectively. Considering the desorption results of the macroporous resins, HP-20 and XAD-7HP were packed in chromatography column to further purify the phenolics. For dynamic adsorption, breakthrough capacity of HP-20 (0.522) was found to be higher than XAD-7HP (0.131). Different ethanol concentrations (30% to 50% (v/v)) were investigated at fixed flowrate (1 ml/min) on phenolics recovery from both types of resins. The highest recovery of bioactive phenolics was 94.3% using XAD-7HP resins at 50% (v/v) of ethanol. Only 77.1% of bioactive phenolics were recovered using HP-20 resin at the same experimental conditions. The purified extract subsequently was analyzed using HPLC. The results showed that three phenolics (gallic acid 3,4-dihydroxybenzoic acid and 4-hydroxybenzoic acid) were identified with higher concentrations as compared to non-purified extract. Finally, the purified extract was tested for scavenging activity against DPPH, and it showed that the activity increased significantly to 90.80% from 59.94% in non-purified extract.

Experimental study of {sup 99m}Tc-aluminum oxide use for sentinel lymph nodes detection

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

Chernov, V. I., E-mail: Chernov@oncology.tomsk.ru; Sinilkin, I. G.; Zelchan, R. V.

The purpose of the study was a comparative research in the possibility of using the radiopharmaceuticals {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis for visualizing sentinel lymph nodes. The measurement of the sizes of {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis colloidal particles was performed in seven series of radiopharmaceuticals. The pharmacokinetics of {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis was researched on 50 white male rats. The possibility of the use of {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis for lymphoscintigraphy was studied in the experiments on 12 white male rats. The average dynamic diameter of the sol particlemore » was 52–77 nm for {sup 99m}Tc-Al{sub 2}O{sub 3} and 16.7–24.5 nm for {sup 99m}Tc-Nanocis. Radiopharmaceuticals accumulated in the inguinal lymph node in 1 hour after administration; the average uptake of {sup 99}mTc-Al{sub 2}O{sub 3} was 8.6% in it, and the accumulation of {sup 99m}Tc-Nanocis was significantly lower—1.8% (p < 0.05). In all study points the average uptake of {sup 99m}Tc-Al{sub 2}O{sub 3} in the lymph node was significantly higher than {sup 99m}Tc-Nanocis accumulation. The results of dynamic scintigraphic studies in rats showed that {sup 99m}Tc-Al{sub 2}O{sub 3} and {sup 99m}Tc-Nanocis actively accumulated into the lymphatic system. By using {sup 99m}Tc-Al{sub 2}O{sub 3} inguinal lymph node was determined in 5 minutes after injection and clearly visualized in all the animals in the 15th minute, when the accumulation became more than 1% of the administered dose. Further observation indicated that the {sup 99m}Tc-Al{sub 2}O{sub 3} accumulation reached a plateau in a lymph node (average 10.5%) during 2-hour study and then its accumulation remained practically at the same level, slightly increasing to 12% in 24 hours. In case of {sup 99m}Tc-Nanocis inguinal lymph node was visualized in all animals for 15 min when it was accumulated on the average 1.03% of the administered dose. Plateau of {sup 99m}Tc-Nanocis accumulation in the lymph node (average 2.05%) occurred after 2 hours of the study and remained almost on the same level (in average 2.3%) for 24 hours. Thus, the experimental study of a new domestic radiopharmaceutical showed that the {sup 99m}Tc-Al{sub 2}O{sub 3} accumulates actively in the lymph nodes several times as compared to the imported analogue and its practical application will facilitate intraoperative identification of sentinel lymph nodes.« less

Development and validation of sensitive LC-MS/MS assays for quantification of HP-β-CD in human plasma and CSF

PubMed Central

Jiang, Hui; Sidhu, Rohini; Fujiwara, Hideji; De Meulder, Marc; de Vries, Ronald; Gong, Yong; Kao, Mark; Porter, Forbes D.; Yanjanin, Nicole M.; Carillo-Carasco, Nuria; Xu, Xin; Ottinger, Elizabeth; Woolery, Myra; Ory, Daniel S.; Jiang, Xuntian

2014-01-01

2-Hydroxypropyl-β-cyclodextrin (HP-β-CD), a widely used excipient for drug formulation, has emerged as an investigational new drug for the treatment of Niemann-Pick type C1 (NPC1) disease, a neurodegenerative cholesterol storage disorder. Development of a sensitive quantitative LC-MS/MS assay to monitor the pharmacokinetics (PKs) of HP-β-CD required for clinical trials has been challenging owing to the dispersity of the HP-β-CD. To support a phase 1 clinical trial for ICV delivery of HP-β-CD in NPC1 patients, novel methods for quantification of HP-β-CD in human plasma and cerebrospinal fluid (CSF) using LC-MS/MS were developed and validated: a 2D-LC-in-source fragmentation-MS/MS (2D-LC-IF-MS/MS) assay and a reversed phase ultra performance LC-MS/MS (RP-UPLC-MS/MS) assay. In both assays, protein precipitation and “dilute and shoot” procedures were used to process plasma and CSF, respectively. The assays were fully validated and in close agreement, and allowed determination of PK parameters for HP-β-CD. The LC-MS/MS methods are ∼100-fold more sensitive than the current HPLC assay, and were successfully employed to analyze HP-β-CD in human plasma and CSF samples to support the phase 1 clinical trial of HP-β-CD in NPC1 patients. PMID:24868096

Development and validation of sensitive LC-MS/MS assays for quantification of HP-β-CD in human plasma and CSF.

PubMed

Jiang, Hui; Sidhu, Rohini; Fujiwara, Hideji; De Meulder, Marc; de Vries, Ronald; Gong, Yong; Kao, Mark; Porter, Forbes D; Yanjanin, Nicole M; Carillo-Carasco, Nuria; Xu, Xin; Ottinger, Elizabeth; Woolery, Myra; Ory, Daniel S; Jiang, Xuntian

2014-07-01

2-Hydroxypropyl-β-cyclodextrin (HP-β-CD), a widely used excipient for drug formulation, has emerged as an investigational new drug for the treatment of Niemann-Pick type C1 (NPC1) disease, a neurodegenerative cholesterol storage disorder. Development of a sensitive quantitative LC-MS/MS assay to monitor the pharmacokinetics (PKs) of HP-β-CD required for clinical trials has been challenging owing to the dispersity of the HP-β-CD. To support a phase 1 clinical trial for ICV delivery of HP-β-CD in NPC1 patients, novel methods for quantification of HP-β-CD in human plasma and cerebrospinal fluid (CSF) using LC-MS/MS were developed and validated: a 2D-LC-in-source fragmentation-MS/MS (2D-LC-IF-MS/MS) assay and a reversed phase ultra performance LC-MS/MS (RP-UPLC-MS/MS) assay. In both assays, protein precipitation and "dilute and shoot" procedures were used to process plasma and CSF, respectively. The assays were fully validated and in close agreement, and allowed determination of PK parameters for HP-β-CD. The LC-MS/MS methods are ∼100-fold more sensitive than the current HPLC assay, and were successfully employed to analyze HP-β-CD in human plasma and CSF samples to support the phase 1 clinical trial of HP-β-CD in NPC1 patients. Copyright © 2014 by the American Society for Biochemistry and Molecular Biology, Inc.

Cost-effectiveness of a 12-dose regimen for treating latent tuberculous infection in the United States

PubMed Central

Shepardson, D.; Marks, S. M.; Chesson, H.; Kerrigan, A.; Holland, D. P.; Scott, N.; Tian, X.; Borisov, A. S.; Shang, N.; Heilig, C. M.; Sterling, T. R.; Villarino, M. E.; Mac Kenzie, W. R.

2017-01-01

SUMMARY SETTING A large randomized controlled trial recently showed that for treating latent tuberculous infection (LTBI) in persons at high risk of progression to tuberculosis (TB) disease, a 12-dose regimen of weekly rifapentine plus isoniazid (3HP) administered as directly observed treatment (DOT) can be as effective as 9 months of daily self-administered isoniazid (9H). OBJECTIVES To assess the cost-effectiveness of 3HP compared to 9H. DESIGN A computational model was designed to simulate individuals with LTBI treated with 9H or 3HP. Costs and health outcomes were estimated to determine the incremental costs per active TB case prevented and per quality-adjusted life year (QALY) gained by 3HP compared to 9H. RESULTS Over a 20-year period, treatment of LTBI with 3HP rather than 9H resulted in 5.2 fewer cases of TB and 25 fewer lost QALYs per 1000 individuals treated. From the health system and societal perspectives, 3HP would cost respectively US$21 525 and $4294 more per TB case prevented, and respectively $4565 and $911 more per QALY gained. CONCLUSIONS 3HP may be a cost-effective alternative to 9H, particularly if the cost of rifapentine decreases, the effectiveness of 3HP can be maintained without DOT, and 3HP treatment is limited to those with a high risk of progression to TB disease. PMID:24200264

dAdd1 and dXNP prevent genome instability by maintaining HP1a localization at Drosophila telomeres.

PubMed

Chavez, Joselyn; Murillo-Maldonado, Juan Manuel; Bahena, Vanessa; Cruz, Ana Karina; Castañeda-Sortibrán, América; Rodriguez-Arnaiz, Rosario; Zurita, Mario; Valadez-Graham, Viviana

2017-12-01

Telomeres are important contributors to genome stability, as they prevent linear chromosome end degradation and contribute to the avoidance of telomeric fusions. An important component of the telomeres is the heterochromatin protein 1a (HP1a). Mutations in Su(var)205, the gene encoding HP1a in Drosophila, result in telomeric fusions, retrotransposon regulation loss and larger telomeres, leading to chromosome instability. Previously, it was found that several proteins physically interact with HP1a, including dXNP and dAdd1 (orthologues to the mammalian ATRX gene). In this study, we found that mutations in the genes encoding the dXNP and dAdd1 proteins affect chromosome stability, causing chromosomal aberrations, including telomeric defects, similar to those observed in Su(var)205 mutants. In somatic cells, we observed that dXNP and dAdd1 participate in the silencing of the telomeric HTT array of retrotransposons, preventing anomalous retrotransposon transcription and integration. Furthermore, the lack of dAdd1 results in the loss of HP1a from the telomeric regions without affecting other chromosomal HP1a binding sites; mutations in dxnp also affected HP1a localization but not at all telomeres, suggesting a specialized role for dAdd1 and dXNP proteins in locating HP1a at the tips of the chromosomes. These results place dAdd1 as an essential regulator of HP1a localization and function in the telomere heterochromatic domain.

Mathematical modelling of the transport of hydroxypropyl-β-cyclodextrin inclusion complexes of ranitidine hydrochloride and furosemide loaded chitosan nanoparticles across a Caco-2 cell monolayer.

PubMed

Sadighi, Armin; Ostad, S N; Rezayat, S M; Foroutan, M; Faramarzi, M A; Dorkoosh, F A

2012-01-17

Chitosan nanoparticles (CS-NPs) have been used to enhance the permeability of furosemide and ranitidine hydrochloride (ranitidine HCl) which were selected as candidates for two different biopharmaceutical drug classes having low permeability across Caco-2 cell monolayers. Drugs loaded CS-NPs were prepared by ionic gelation of CS and pentasodium tripolyphosphate (TPP) which added to the drugs inclusion complexes with hydroxypropyl-β-cyclodextrin (HP-βCD). The stability constants for furosemide/HP-βCD and ranitidine HCl/HP-βCD were calculated as 335 M(-1) and 410 M(-1), whereas the association efficiencies (AE%) of the drugs/HP-βCD inclusion complexes with CS-NPs were determined to be 23.0 and 19.5%, respectively. Zetasizer and scanning electron microscopy (SEM) were used to characterise drugs/HP-βCD-NPs size and morphology. Transport of both nano and non-nano formulations of drugs/HP-βCD complexes across a Caco-2 cell monolayer was assessed and fitted to mathematical models. Furosemide/HP-βCD-NPs demonstrated transport kinetics best suited for the Higuchi model, whereas other drug formulations demonstrated power law transportation behaviour. Permeability experiments revealed that furosemide/HP-βCD and ranitidine HCl/HP-βCD nano formulations greatly induce the opening of tight junctions and enhance drug transition through Caco-2 monolayers. Copyright © 2011 Elsevier B.V. All rights reserved.

40 CFR Table 2b to Subpart Zzzz of... - Operating Limitations for New and Reconstructed 2SLB and Compression Ignition Stationary RICE...

Code of Federal Regulations, 2011 CFR

2011-07-01

... Reconstructed 2SLB and Compression Ignition Stationary RICE >500 HP Located at a Major Source of HAP Emissions, New and Reconstructed 4SLB Stationary RICE â¥250 HP Located at a Major Source of HAP Emissions, Existing Compression Ignition Stationary RICE >500 HP, and Existing 4SLB Stationary RICE >500 HP Located at...

Myocardial mechanics, energetics, and hemodynamics during intraaortic balloon and transvalvular axial flow hemopump support with a bovine model of ischemic cardiac dysfunction.

PubMed

Marks, J D; Pantalos, G M; Long, J W; Kinoshita, M; Everett, S D; Olsen, D B

1999-01-01

Unlike the mechanisms of intraaortic balloon pump (IABP) support, the mechanisms by which transvalvular axial flow Hemopump (HP) support benefit dysfunctional myocardium are less clearly understood. To help elucidate these mechanisms, hemodynamic, metabolic, and mechanical indexes of left ventricular function were measured during conditions of control, ischemic dysfunction, IABP support, and HP support. A large animal (calf) model of left ventricular dysfunction was created with multiple coronary ligations. Peak intraventricular pressure increased with HP support and decreased with IABP support. Intramyocardial pressure (an indicator of intramyocardial stress), time rate of pressure change (an indicator of contractility), and left ventricular myocardial oxygen consumption decreased with IABP and HP support. Left ventricular work decreased with HP support and increased with IABP support. During HP support, indexes of wall stress, work, and contractility, all primary determinants of oxygen consumption, were reduced. During IABP support, indexes of wall stress and contractility were reduced and external work increased. These changes were attributed primarily to changes in ventricular preload, and geometry for HP support, and to a reduction in afterload for IABP support. These findings support the hypothesis that both HP and IABP support reduce intramyocardial stress development and the corresponding oxygen consumption, although via different mechanisms.

Identification and characterization of a nuclear localization signal of TRIM28 that overlaps with the HP1 box

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

Moriyama, Tetsuji; Sangel, Percival; Yamaguchi, Hiroki

2015-07-03

Tripartite motif-containing 28 (TRIM28) is a transcription regulator, which forms a repressor complex containing heterochromatin protein 1 (HP1). Here, we report identification of a nuclear localization signal (NLS) within the 462-494 amino acid region of TRIM28 that overlaps with its HP1 binding site, HP1 box. GST-pulldown experiments revealed the interaction of the arginine-rich TRIM28 NLS with various importin α subtypes (α1, α2 and α4). In vitro transport assay demonstrated that nuclear localization of GFP-TRIM28 NLS is mediated by importin αs, in conjunction with importin β1 and Ran. Further, we demonstrated that HP1 and importin αs compete for binding to TRIM28. Together,more » our findings suggest that importin α has an essential role in the nuclear delivery and preferential HP1 interaction of TRIM28. - Highlights: • TRIM28 contains an NLS within the 462-494 amino acid region. • The nuclear import of TRIM28 is mediated by importin α/importin β1. • TRIM28 NLS overlaps with HP1 Box. • HP1 and importin α compete for binding to TRIM28.« less

Prevalence of Helicobacter pylori in the adolescent oral cavity: dependence on orthodontic therapy, oral flora and hygiene.

PubMed

Wichelhaus, Andrea; Brauchli, Lorenz; Song, Qunsheng; Adler, Guido; Bode, Günter

2011-07-01

Helicobacter pylori (HP) infection usually occurs in childhood. While there are various studies on the prevalence of HP in dental plaque, ours is the first to analyze its prevalence during orthodontic therapy and its interaction with competitive bacteria in adolescents. The prevalence of HP was examined before and during the first 12 weeks of orthodontic therapy with fixed appliances in 11 patients with a mean age of 12.7 years. A total of 93 plaque samples were analyzed using PCR. The data acquired at every consultation were the following: PCR analysis of dental plaque and (13)C urea breath tests for HP, quantitative analyses of saliva for Lactobacilli and Streptococcus mutans, the interproximal plaque index (API), and sulcus bleeding index (SBI). The prevalence of HP in plaque was 82% before orthodontic therapy, dropping to 54% during therapy (t test, p≤0.05). In contrast to HP's prevalence, the Lactobacilli count rose (p≤0.05). The number of Streptococcus mutans bacteria in saliva decreased during orthodontic therapy (p≤0.05). The prevalence of HP in dental plaque amounted to 82%. Orthodontic treatment did not reduce its prevalence. The prevalence of Lactobacilli was inversely proportional to that of HP.

High-pressure treatment for shelf-life extension and quality improvement of oysters cooked in a traditional Taiwanese oyster omelet.

PubMed

Lai, Kung-Ming; Chi, Hsin-Yi; Hsu, Kuo-Chiang

2010-01-01

Whole oysters were processed using high-pressure (HP) treatment at 250 and 300 MPa for 0 to 10 min and stored at 4 degrees Celsius for up to 28 days. HP-treated oysters and untreated oysters were evaluated for lipid oxidation, growth of microorganisms, and sensory characteristics after cooking at 160 degrees Celsius for 90 s. Microbial counts after HP treatment revealed that the bacterial load was initially reduced at all pressures. HP-treated oysters had significantly higher pH and moisture (P < 0.05) relative to control (untreated) oysters during storage. HP treatment increased lipid oxidation with unpleasant odor during storage compared with the control. HP treatment decreased redness but did not significantly affect the brightness and yellowness of cooked oysters. From tests of mechanical properties, 300 MPa-treated oysters after cooking had significantly increased toughness as measured by cutting force. HP-treated oysters after cooking received higher quality scores than did the control during the storage trial. Results indicated that 300 MPa for 2 min is the optimum HP treatment that results in oysters most acceptable for oyster omelets during storage at 4 degrees Celsius, and this treatment may extend the shelf life of these oysters to 21 days.

Chromatin Protein HP1α Interacts with the Mitotic Regulator Borealin Protein and Specifies the Centromere Localization of the Chromosomal Passenger Complex*

PubMed Central

Liu, Xing; Song, Zhenwei; Huo, Yuda; Zhang, Jiahai; Zhu, Tongge; Wang, Jianyu; Zhao, Xuannv; Aikhionbare, Felix; Zhang, Jiancun; Duan, Hequan; Wu, Jihui; Dou, Zhen; Shi, Yunyu; Yao, Xuebiao

2014-01-01

Accurate mitosis requires the chromosomal passenger protein complex (CPC) containing Aurora B kinase, borealin, INCENP, and survivin, which orchestrates chromosome dynamics. However, the chromatin factors that specify the CPC to the centromere remain elusive. Here we show that borealin interacts directly with heterochromatin protein 1α (HP1α) and that this interaction is mediated by an evolutionarily conserved PXVXL motif in the C-terminal borealin with the chromo shadow domain of HP1α. This borealin-HP1α interaction recruits the CPC to the centromere and governs an activation of Aurora B kinase judged by phosphorylation of Ser-7 in CENP-A, a substrate of Aurora B. Consistently, modulation of the motif PXVXL leads to defects in CPC centromere targeting and aberrant Aurora B activity. On the other hand, the localization of the CPC in the midzone is independent of the borealin-HP1α interaction, demonstrating the spatial requirement of HP1α in CPC localization to the centromere. These findings reveal a previously unrecognized but direct link between HP1α and CPC localization in the centromere and illustrate the critical role of borealin-HP1α interaction in orchestrating an accurate cell division. PMID:24917673

Disruption and reassociation of casein micelles under high pressure: influence of milk serum composition and casein micelle concentration.

PubMed

Huppertz, Thom; de Kruif, Cornelis G

2006-08-09

In this study, factors influencing the disruption and aggregation of casein micelles during high-pressure (HP) treatment at 250 MPa for 40 min were studied in situ in serum protein-free casein micelle suspensions. In control milk, light transmission increased with treatment time for approximately 15 min, after which a progressive partial reversal of the HP-induced increase in light transmission occurred, indicating initial HP-induced disruption of casein micelles, followed by reformation of casein aggregates from micellar fragments. The extent of HP-induced micellar disruption was negatively correlated with the concentration of casein micelles, milk pH, and levels of added ethanol, calcium chloride, or sodium chloride and positively correlated with the level of added sodium phosphate. The reformation of casein aggregates during prolonged HP treatment did not occur when HP-induced disruption of casein micelles was limited (<60%) or very extensive (>95%) and was promoted by a low initial milk pH or added sodium phosphate, sodium chloride, or ethanol. On the basis of these findings, a mechanism for HP-induced disruption of casein micelles and subsequent aggregation of micellar fragments is proposed, in which the main element appears to be HP-induced solubilization of micellar calcium phosphate.

Effects of high hydrostatic pressure on distribution dynamics of free amino acids in water soaked brown rice grain

NASA Astrophysics Data System (ADS)

Shigematsu, T.; Hayashi, M.; Nakajima, K.; Uno, Y.; Sakano, A.; Murakami, M.; Narahara, Y.; Ueno, S.; Fujii, T.

2010-03-01

High hydrostatic pressure (HP) with approximately below 400 MPa can induce a transformation of food materials to an alternative form, where membrane systems are damaged but certain enzymes are still active. HP treatment of water soaked brown rice grain could modify the mass transfer inside and apparent activities of enzymes, resulting in HP-dependent change of distribution of free amino acids. Thus, the distribution of free amino acids in brown rice grain during preservation after HP treatment was analyzed. Just after HP treatment at 200 MPa for 10 min, the distribution of free amino acids was not apparently different from that of untreated control. In contrast, after 1 to 4 days preservation at 25°C, amino acids, such as Ala, Glu, Gly, Asp and Val, showed higher concentrations than those in control. This result suggested that HP treatment induced proteolysis to produce free amino acids. However, Gln, Thr and Cys, showed no apparent difference, suggesting that conversion of certain amino acids produced by proteolysis occurred. Moreover, the concentration of γ-aminobutyric acid (GABA) in HP-treated sample was higher than that in untreated control. These results suggested that HP treatment induced alteration of distribution of free amino acids of rice grains via proteolysis and certain amino acids metabolism pathways.

Structure and ligand-binding site characteristics of the human P2Y11 nucleotide receptor deduced from computational modelling and mutational analysis

PubMed Central

Zylberg, Jacques; Ecke, Denise; Fischer, Bilha; Reiser, Georg

2007-01-01

The P2Y11-R (P2Y11 receptor) is a less explored drug target. We computed an hP2Y11-R (human P2Y11) homology model with two templates, bovine-rhodopsin (2.6 Å resolution; 1 Å=0.1 nm) and a hP2Y1–ATP complex model. The hP2Y11-R model was refined using molecular dynamics calculations and validated by virtual screening methods, with an enrichment factor of 5. Furthermore, mutational analyses of Arg106, Glu186, Arg268, Arg307 and Ala313 confirmed the adequacy of our hP2Y11-R model and the computed ligand recognition mode. The E186A and R268A mutants reduced the potency of ATP by one and three orders of magnitude respectively. The R106A and R307A mutants were functionally inactive. We propose that residues Arg106, Arg268, Arg307 and Glu186 are involved in ionic interactions with the phosphate moiety of ATP. Arg307 is possibly also H-bonded to N6 of ATP via the backbone carbonyl. Activity of ATP at the F109I mutant revealed that the proposed π-stacking of Phe109 with the adenine ring is a minor interaction. The mutation A313N, which is part of a hydrophobic pocket in the vicinity of the ATP C-2 position, partially explains the high activity of 2-MeS-ATP at P2Y1-R as compared with the negligible activity at the P2Y11-R. Inactivity of ATP at the Y261A mutant implies that Tyr261 acts as a molecular switch, as in other G-protein-coupled receptors. Moreover, analysis of cAMP responses seen with the mutants showed that the efficacy of coupling of the P2Y11-R with Gs is more variable than coupling with Gq. Our model also indicates that Ser206 forms an H-bond with Pγ (the γ-phosphate of the triphosphate chain of ATP) and Met310 interacts with the adenine moiety. PMID:17338680

Poly(3-Hydroxypropionate): a Promising Alternative to Fossil Fuel-Based Materials

PubMed Central

Andreeßen, Björn; Taylor, Nicolas

2014-01-01

Polyhydroxyalkanoates (PHAs) are storage compounds synthesized by numerous microorganisms and have attracted the interest of industry since they are biobased and biodegradable alternatives to fossil fuel-derived plastics. Among PHAs, poly(3-hydroxypropionate) [poly(3HP)] has outstanding material characteristics and exhibits a large variety of applications. As it is not brittle like, e.g., the best-studied PHA, poly(3-hydroxybutyrate) [poly(3HB)], it can be used as a plasticizer in blends to improve their properties. Furthermore, 3-hydroxypropionic acid (3HP) is considered likely to become one of the new industrial building blocks, and it can be obtained from poly(3HP) by simple hydrolysis. Unfortunately, no natural organism is known to accumulate poly(3HP) so far. Thus, several efforts have been made to engineer genetically modified organisms capable of synthesizing the homopolymer or copolymers containing 3HP. In this review, the achievements made so far in efforts to obtain biomass which has accumulated poly(3HP) or 3HP-containing copolymers, as well as the properties of these polyesters and their applications, are compiled and evaluated. PMID:25149521

Mesh wrapping for severe hepatic injury: a beneficial option in the trauma surgeon's armamentarium.

PubMed

Kennedy, Ryan; Brevard, Sidney B; Bosarge, Patrick; Simmons, Jon D; Frotan, Mohammed A; Baker, Jeremy A; Tuart, Lynda; Pritchett, Cindy; Gonzalez, Richard P

2015-03-01

The purpose of this study was to assess the efficacy of absorbable mesh wrapping (MW) versus perihepatic packing (HP) for severe hepatic injury. From January 2001 to December 2012, data were collected for MW patients with hepatic injury. Patients who underwent HP were matched with MW patients by injury mechanism, liver injury grade, Injury Severity Score, and age. Twenty-six MW and twenty-six HP patients were matched. Eighteen blunt and 8 penetrating injuries were present in each group. There were 9 (35%) mortalities in the MW group and 16 (62%) in the HP groups (P = .03). Average transfusions were 12.0 and 24.5 (P = .03) packed red blood cells in the MW and HP groups, respectively. Average laparotomies per survivors were 1.3 for the MW and 3.1 for the HP groups (P = .01). Average length of stay for survivors was 19 and 47 (P = .04) days in the MW and HP groups, respectively. MW for hepatic injuries can significantly decrease mortality, transfusions, laparotomies, and length of stay. Copyright © 2015 Elsevier Inc. All rights reserved.

The application of high-pressure treatment in the reduction of phosphate levels in breakfast sausages.

PubMed

O'Flynn, C C; Cruz-Romero, M C; Troy, D J; Mullen, A M; Kerry, J P

2014-01-01

This study investigated effects of high pressure (HP) treatment of pork meat at 150 or 300 MPa for 5 min before manufacturing sausages on the reduction of phosphate levels and compared to sausages manufactured with untreated pork meat (control sausages). Improvement in perceived saltiness, juiciness and overall flavour was observed in sausages manufactured using HP-treated meat at 150 MPa and 0% phosphate, compared to control sausages. Sausages manufactured using meat HP-treated at 150 MPa and 0.25% phosphate (P<0.05) improved hardness of sausages. HP-treated meat at 300 MPa and 0% phosphate decreased juiciness and adhesiveness, while at 0.25% phosphate, adversely affected emulsion stability and sensory attributes. HP treatment did not affect significantly the lightness of the sausages; however, elimination of phosphate reduced (P<0.05) the yellowness, while HP treatment at 150 MPa with 0.25 or 0.5% phosphate increased (P<0.05) redness. HP reatment at 150 MPa has potential for reducing phosphate levels in sausages without significant changes in their functionality and improved acceptability. © 2013.

Helicobacter pylori and micronutrients.

PubMed

Akcam, Mustafa

2010-02-01

Helicobacter pylori (HP) infection causes morbidity in several systems, especially in the gastrointestinal tract. The prevalence of disease is inversely related to social-economic and developmental status. It is more common in the developing than in developed countries. In the countries where social-economic status is low, not only HP infection, but also malnutrition and growth failure have a higher prevalence. According to these data, the relationship of nutrition and HP infection is still a question. Does HP infection affect nutritional status? On the contrary, does nutritional status affect HP infection? If so, how? This review was prepared after searching thoroughly almost all of the publications about relationship between HP infections and micronutrients, especially publications pertaining to childhood, from 1990 to 2009 in PubMed. Some valuable adult and experimental publications were also reviewed. These studies related H. pylori to iron, vitamin B12, vitamin C, vitamin A, vitamin E, folate, and selenium. Published studies reveal some evidence that HP has a negative effect on iron, vitamin B12 and vitamin C metabolism, but its influence on others is not clear.

Adrenal steroids in post-menopausal women: relation to obesity and to bone mineral content.

PubMed

Brody, S; Carlström, K; Lagrelius, A; Lunell, N O; Möllerström, G

1987-04-01

Basal levels and ACTH-induced increments of serum 17 alpha-hydroxyprogesterone (170HP), cortisol, 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA), and dehydroepiandrosterone sulphate (DHAS) were related to the degree of obesity and to trabecular bone mineral density in 29 postmenopausal women. The ACTH-induced increment of 170HP (delta 170HP) was negatively correlated to basal DHA and delta DHA. Positive correlations were found between obesity, expressed as Broca's index, and delta DHA and the delta DHA/delta 170HP ratio. Bone mineral density was positively correlated to basal DHAS, delta DHA, delta DHAS and the delta DHA/delta 170HP ratio, and negatively correlated to delta 170HP. DHA and 170HP represent a crossroad in adrenocortical steroid biosynthesis, leading to delta 5-androgens and glucocorticoids as main products. Besides age, obesity may also influence the intra-adrenal distribution between these two main steroidogenic pathways. The results suggest that differences at a very early stage of the adrenal steroidogenesis may influence calcium homeostasis in the post-menopausal woman.

Development of Genetically Stable Escherichia coli Strains for Poly(3-Hydroxypropionate) Production

PubMed Central

Gao, Yongqiang; Liu, Changshui; Ding, Yamei; Sun, Chao; Zhang, Rubing; Xian, Mo; Zhao, Guang

2014-01-01

Poly(3-hydroxypropionate) (P3HP) is a biodegradable and biocompatible thermoplastic. In our previous study, a pathway for P3HP production was constructed in recombinant Esecherichia coli. Seven exogenous genes in P3HP synthesis pathway were carried by two plasmid vectors. However, the P3HP production was severely suppressed by strain instability due to plasmid loss. In this paper, two strategies, chromosomal gene integration and plasmid addiction system (PAS) based on amino acid anabolism, were applied to construct a genetically stable strain. Finally, a combination of those two methods resulted in the best results. The resultant strain carried a portion of P3HP synthesis genes on chromosome and the others on plasmid, and also brought a tyrosine-auxotrophy based PAS. In aerobic fed-batch fermentation, this strain produced 25.7 g/L P3HP from glycerol, about 2.5-time higher than the previous strain with two plasmids. To the best of our knowledge, this is the highest P3HP production from inexpensive carbon sources. PMID:24837211

R&D 100 Awards | NREL

Science.gov Websites

a cost of about $.50/watt. Learn more HP Apollo 8000 System HP Apollo 8000 System Uses component Award - HP Apollo 8000 System - Steve Hammond and Team 2008 Editor's Choice Award - Hybrid CIGS (copper

Lost and Found

Science.gov Websites

Packard Operating Manual HP-IB System DC Power Supplies HP Models 6632A, 6633A, 6634A National Instruments LabView2 User Manual (Jan 1993 Edition) Hewlett Packard Operating and Service Manual HP-IB Isolated DAC

Passion and dependency in online shopping activities.

PubMed

Wang, Chih-Chien; Yang, Hui-Wen

2007-04-01

This study examines the influence of harmonious passion (HP) and obsessive passion (OP) to online shopping dependency. The results show that both HP and OP might lead to online shopping dependency and online shoppers with OP are more dependent on online shopping activities. In addition, this study also found out that HP and OP could be denoted as a sequence of different intensities of passion, where HP might be a necessity of OP.

Hydrostatic Pressure in Articular Cartilage Tissue Engineering: From Chondrocytes to Tissue Regeneration

PubMed Central

Elder, Benjamin D.

2009-01-01

Cartilage has a poor intrinsic healing response, and neither the innate healing response nor current clinical treatments can restore its function. Therefore, articular cartilage tissue engineering is a promising approach for the regeneration of damaged tissue. Because cartilage is exposed to mechanical forces during joint loading, many tissue engineering strategies use exogenous stimuli to enhance the biochemical or biomechanical properties of the engineered tissue. Hydrostatic pressure (HP) is emerging as arguably one of the most important mechanical stimuli for cartilage, although no optimal treatment has been established across all culture systems. Therefore, this review evaluates prior studies on articular cartilage involving the use of HP, with a particular emphasis on the treatments that appear promising for use in future studies. Additionally, this review addresses HP bioreactor design, chondroprotective effects of HP, the use of HP for chondrogenic differentiation, the effects of high pressures, and HP mechanotransduction. PMID:19196119

Hydrostatic pressure in articular cartilage tissue engineering: from chondrocytes to tissue regeneration.

PubMed

Elder, Benjamin D; Athanasiou, Kyriacos A

2009-03-01

Cartilage has a poor intrinsic healing response, and neither the innate healing response nor current clinical treatments can restore its function. Therefore, articular cartilage tissue engineering is a promising approach for the regeneration of damaged tissue. Because cartilage is exposed to mechanical forces during joint loading, many tissue engineering strategies use exogenous stimuli to enhance the biochemical or biomechanical properties of the engineered tissue. Hydrostatic pressure (HP) is emerging as arguably one of the most important mechanical stimuli for cartilage, although no optimal treatment has been established across all culture systems. Therefore, this review evaluates prior studies on articular cartilage involving the use of HP, with a particular emphasis on the treatments that appear promising for use in future studies. Additionally, this review addresses HP bioreactor design, chondroprotective effects of HP, the use of HP for chondrogenic differentiation, the effects of high pressures, and HP mechanotransduction.

Cleaning efficacy of hydroxypropyl-beta-cyclodextrin for biofouling reduction on reverse osmosis membranes.

PubMed

Alayande, Abayomi Babatunde; Kim, Lan Hee; Kim, In S

2016-01-01

In this study, an environmentally friendly compound, hydroxypropyl-beta-cyclodextrin (HP-β-CD) was applied to clean reverse osmosis (RO) membranes fouled by microorganisms. The cleaning with HP-β-CD removed the biofilm and resulted in a flux recovery ratio (FRR) of 102%. As cleaning efficiency is sometimes difficult to determine using flux recovery data alone, attached bacterial cells and extracellular polymeric substances (EPS) were quantified after cleaning the biofouled membrane with HP-β-CD. Membrane surface characterization using scanning electron microscopy (SEM), attenuated total reflectance Fourier transform infrared (ATR-FTIR) and atomic force microscopy (AFM) confirmed the effectiveness of HP-β-CD in removal of biofilm from the RO membrane surface. Finally, a comparative study was performed to investigate the competitiveness of HP-β-CD with other known cleaning agents such as sodium dodecyl sulfate (SDS), ethylenediaminetetraacetic acid (EDTA), Tween 20, rhamnolipid, nisin, and surfactin. In all cases, HP-β-CD was superior.

Preparation, characterization, and in vitro anti-inflammatory evaluation of novel water soluble kamebakaurin/hydroxypropyl-β-cyclodextrin inclusion complex

NASA Astrophysics Data System (ADS)

Raza, Aun; Sun, Huifang; Bano, Shumaila; Zhao, Yingying; Xu, Xiuquan; Tang, Jian

2017-02-01

To enhance the aqueous solubility of kamebakaurin (KA), it was complexed with hydroxypropyl-β-cyclodextrin (HP-β-CD). In this study, the interaction KA with HP-β-CD and their inclusion complex behavior were determined by different characterization techniques such as UV-vis, 1H NMR, FT-IR, PXRD and SEM. All the characterization information proved the development of inclusion complex KA/HP-β-CD, and this inclusion complex demonstrated discriminable spectroscopic characteristics and properties from free compound KA. The results demonstrated that the water solubility of KA was remarkably increased in the presence of HP-β-CD. Furthermore, in vitro anti-inflammatory study showed that inclusion complex KA/HP-β-CD maintained the anti-inflammatory effect of KA. These results demonstrate that HP-β-CD will be promisingly employed in the application of water-insoluble anti-inflammatory phytochemicals such as KA.

The effect of Helicobacter pylori on vitamin B 12 blood levels in chronic renal failure patients: a single blind control trial.

PubMed

Khedmat, Hossein; Amini, Mohsen; Karbasi, Ashraf; Azizi, Reza

2013-07-01

Helicobacter pylori (HP) is a common infection worldwide and has been associated with severe morbidity. The level of vitamin B 12 in HP-infected chronic kidney disease (CKD) patients is reported to be lower than in the general population. The present study has been designed to evaluate the vitamin B 12 level in HP-infected CKD patients. We assessed the serum levels of vitamin B 12 in 50 CKD patients with positive HP serology, one and three months after the eradication of HP infection. There were significant differences between the serum levels of vitamin B 12 in the study patients before (806.98 ± 466.82) and after (760.36 ± 433.93) eradication treatment (P <0.001). We conclude that our study suggests the correlation between vitamin B 12 deficiency in CKD patients and the HP infection status.

Biosynthesis and Biodegradation of 3-Hydroxypropionate- Containing Polyesters▿

PubMed Central

Andreeßen, Björn; Steinbüchel, Alexander

2010-01-01

3-Hydroxypropionate (3HP) is an important compound in the chemical industry, and the polymerized 3HP can be used as a bioplastic. In this review, we focus on polyesters consisting of 3HP monomers, including the homopolyester poly(3-hydroxypropionate) and copolyesters poly(3-hydroxybutyrate-co-3-hydroxypropionate), poly(3-hydroxypropionate-co-3-hydroxybutyrate-co-3-hydroxyhexanoate-co-3-hydroxyoctanoate), poly(4-hydroxybutyrate-co-3-hydroxypropionate-co-lactate), and poly(3-hydroxybutyrate-co-3-hydroxypropionate-co-4-hydroxybutyrate-co-lactate). Homopolyesters like poly(3-hydroxybutyrate) are often highly crystalline and brittle, which limits some of their applications. The incorporation of 3HP monomers reduces the glass transition temperature, the crystallinity, and also, at up to 60 to 70 mol% 3HP, the melting point of the copolymer. This review provides a survey of the synthesis and physical properties of different polyesters containing 3HP. PMID:20543057

Effectiveness of computer-assisted interactive videodisc instruction in teaching rheumatology to physical and occupational therapy students.

PubMed

Sanford, M K; Hazelwood, S E; Bridges, A J; Cutts, J H; Mitchell, J A; Reid, J C; Sharp, G

1996-01-01

A computer-assisted interactive videodisc instructional program, HP-RHEUM was designed to teach clinical findings in arthritis to occupational and physical therapy students. Using the Rheumatology Image Library videodisc produced by the National Library of Medicine, HP-RHEUM consists of instructional modules which employ advance organizers, examples/nonexamples, summaries, and immediate feedback. To see if HP-RHEUM would be as effective as traditional classroom instruction, control data were collected in 1991 from 52 OT and PT students. Treatment data were collected from 61 students in 1992 when HP-RHEUM entirely replaced lectures. Identical pre- and post-tests consisted of 70 multiple choice questions, with 24 matched to slides. On the slide questions the HP-RHEUM group had significantly higher scores. Otherwise, there was no significant difference in performance between groups. HP-RHEUM provided an independent learning method and enhanced visual comprehension of rheumatologic disease concepts.

[Micronuclei in mucose cells and colonization of human stomach epithelium with coccoid forms of Helicobacter pylori].

PubMed

Kitaeva, L V; Mikhaĭlova, I A; Semov, D; Proshin, S N; Kravtsov, V Iu

2008-01-01

International Agency for Research on Cancer recognized as sufficient the evidence of Helicobacter pylori (HP) infection carcinogenicity and placed it into the 1 st group of carcinogens. Micronucleus level in gastric epithelial cells of antral stomach region of patients with chronic non-atrophy gastritis (n = 62) was studied. 40 patients of 62 had HP-associated gastritis. The HP-bacterium exists in a spiral and coccoid form. Both morphological forms were examined using immunocytochemistry. Significantly increased micronucleus number was observed in the cells of HP-infected patients compared with non-infected person (P < 0.05). The frequency of stomach epithelium cells with micronuclei was enhanced considerably in the patients infected with the coccoid HP form. Therefore the patients with HP-associated chronic gastritis caused by the coccoid form with high degree of colonization must be considered as a group of enhanced risk of gastric carcinogenesis.

Compact 2D OPC modeling of a metal oxide EUV resist for a 7nm node BEOL layer

NASA Astrophysics Data System (ADS)

Lyons, Adam; Rio, David; Lee, Sook; Wallow, Thomas; Delorme, Maxence; Fumar-Pici, Anita; Kocsis, Michael; de Schepper, Peter; Greer, Michael; Stowers, Jason K.; Gillijns, Werner; De Simone, Danilo; Bekaert, Joost

2017-03-01

Inpria has developed a directly patternable metal oxide hard-mask as a high-resolution photoresist for EUV lithography1. In this contribution, we describe a Tachyon 2D OPC full-chip model for an Inpria resist as applied to an N7 BEOL block mask application.

Nanoelectronics and More-than-Moore at IMEC

NASA Astrophysics Data System (ADS)

Cartuyvels, Rudi; Biesemans, Serge; Vandervorst, Wilfried; De Boeck, Jo

2011-11-01

This paper presents an overview of imec's R&D addressing the challenges of CMOS scaling towards the 10 nm node and its outlook beyond. In addition to the relentless geometrical shrinks, opportunities to further increase nanoelectronic system functionality and performance by co-integration and chip stacking technologies combined with emerging MEMS and optoelectronic technologies will be presented.

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.

Rigorous assessment of patterning solution of metal layer in 7 nm technology node

NASA Astrophysics Data System (ADS)

Gao, Weimin; Ciofi, Ivan; Saad, Yves; Matagne, Philippe; Bachmann, Michael; Gillijns, Werner; Lucas, Kevin; Demmerle, Wolfgang; Schmoeller, Thomas

2016-01-01

In a 7 nm node (N7), the logic design requires a critical poly pitch of 42 to 45 nm and a metal 1 (M1) pitch of 28 to 32 nm. Such high-pattern density pushes the 193 immersion lithography solution toward its limit and also brings extremely complex patterning scenarios. The N7 M1 layer may require a self-aligned quadruple patterning (SAQP) with a triple litho-etch (LE3) block process. Therefore, the whole patterning process flow requires multiple exposure+etch+deposition processes and each step introduces a particular impact on the pattern profiles and the topography. In this study, we have successfully integrated a simulation tool that enables emulation of the whole patterning flow with realistic process-dependent three-dimensional (3-D) profile and topology. We use this tool to study the patterning process variations of the N7 M1 layer including the overlay control, the critical dimension uniformity budget, and the lithographic process window (PW). The resulting 3-D pattern structure can be used to optimize the process flow, verify design rules, extract parasitics, and most importantly, simulate the electric field, and identify hot spots for dielectric reliability. As an example application, the maximum electric field at M1 tip-to-tip, which is one of the most critical patterning locations, has been simulated and extracted. The approach helps to investigate the impact of process variations on dielectric reliability. We have also assessed the alternative M1 patterning flow with a single exposure block using extreme ultraviolet lithography (EUVL) and analyzed its advantages compared to the LE3 block approach.

Comparative analysis of the folding dynamics and kinetics of an engineered knotted protein and its variants derived from HP0242 of Helicobacter pylori

NASA Astrophysics Data System (ADS)

Wang, Liang-Wei; Liu, Yu-Nan; Lyu, Ping-Chiang; Jackson, Sophie E.; Hsu, Shang-Te Danny

2015-09-01

Understanding the mechanism by which a polypeptide chain thread itself spontaneously to attain a knotted conformation has been a major challenge in the field of protein folding. HP0242 is a homodimeric protein from Helicobacter pylori with intertwined helices to form a unique pseudo-knotted folding topology. A tandem HP0242 repeat has been constructed to become the first engineered trefoil-knotted protein. Its small size renders it a model system for computational analyses to examine its folding and knotting pathways. Here we report a multi-parametric study on the folding stability and kinetics of a library of HP0242 variants, including the trefoil-knotted tandem HP0242 repeat, using far-UV circular dichroism and fluorescence spectroscopy. Equilibrium chemical denaturation of HP0242 variants shows the presence of highly populated dimeric and structurally heterogeneous folding intermediates. Such equilibrium folding intermediates retain significant amount of helical structures except those at the N- and C-terminal regions in the native structure. Stopped-flow fluorescence measurements of HP0242 variants show that spontaneous refolding into knotted structures can be achieved within seconds, which is several orders of magnitude faster than previously observed for other knotted proteins. Nevertheless, the complex chevron plots indicate that HP0242 variants are prone to misfold into kinetic traps, leading to severely rolled-over refolding arms. The experimental observations are in general agreement with the previously reported molecular dynamics simulations. Based on our results, kinetic folding pathways are proposed to qualitatively describe the complex folding processes of HP0242 variants.

High phosphorus diet-induced changes in NaPi-IIb phosphate transporter expression in the rat kidney: DNA microarray analysis.

PubMed

Suyama, Tatsuya; Okada, Shinji; Ishijima, Tomoko; Iida, Kota; Abe, Keiko; Nakai, Yuji

2012-01-01

The mechanism by which phosphorus levels are maintained in the body was investigated by analyzing changes in gene expression in the rat kidney following administration of a high phosphorus (HP) diet. Male Wistar rats were divided into two groups and fed a diet containing 0.3% (control) or 1.2% (HP) phosphorous for 24 days. Phosphorous retention was not significantly increased in HP rats, but fractional excretion of phosphorus was significantly increased in the HP group compared to controls, with an excessive amount of the ingested phosphorus being passed through the body. DNA microarray analysis of kidney tissue from both groups revealed changes in gene expression profile induced by a HP diet. Among the genes that were upregulated, Gene Ontology (GO) terms related to ossification, collagen fibril organization, and inflammation and immune response were significantly enriched. In particular, there was significant upregulation of type IIb sodium-dependent phosphate transporter (NaPi-IIb) in the HP rat kidney compared to control rats. This upregulation was confirmed by in situ hybridization. Distinct signals for NaPi-IIb in both the cortex and medulla of the kidney were apparent in the HP group, while the corresponding signals were much weaker in the control group. Immunohistochemical analysis showed that NaPi-IIb localized to the basolateral side of kidney epithelial cells surrounding the urinary duct in HP rats but not in control animals. These data suggest that NaPi-IIb is upregulated in the kidney in response to the active excretion of phosphate in HP diet-fed rats.

Study of education program of in-hospital procurement transplant coordinators in Japan.

PubMed

Fukushima, N; Konaka, S; Yasuhira, M; Izawa, M

2014-01-01

As the number of donated organs is still extremely small in Japan compared with other developed countries, in-hospital procurement transplant coordinators (In-Hp PTC) may play an important role in increasing organ donation and making the procurement procedure smoother. In this study, our education program of In-Hp PTC is described. In May 2012, our department started the In-Hp PTC Education Program. In the first semester, a 2-hour lecture is provided every 2 weeks for 5 months to 15 In-Hp PTCs working near Osaka. In the second semester, 20 lectures were provided for 3 consecutive days to 31 In Hp PTCs, more than 80% of whom work far from Osaka. Lecture topics were the history and current status of organ donation in Japan, social regulation of organ donation, care of transplant recipients, overall procedures of organ donation, the role of In-Hp PTC, donor family care, donor indications, and donor assessment and management. Lectures also included simulations of the organ donation process. Participants were surveyed for their opinions after the program, Most participants were satisfied with the program, topics and duration. As most of them are not full-time In-Hp PTCs, they preferred to attend the 3-day program. Many participants are currently working as main In-Hp PTCs and establishing their own organ donation system in their hospital. In-Hp PTCs have an important role to play in establishing an organ procurement system and increasing organ donation in Japan. This program may help establish a systematic education program for this occupation in Japan. Copyright © 2014 Elsevier Inc. All rights reserved.

Helicobacter pylori related dyspepsia: prevalence and treatment outcomes at University Kebangsaan Malaysia-Primary Care Centre

PubMed Central

Abdul Aziz, Aznida Firzah; Hamzah, Zuhra; Tong, Seng Fah; Nadeson, Sukumar; Wan Puteh, Sharifa Ezat

2009-01-01

Background Optimum management of dyspepsia in primary care is a debatable subject. Testing for Helicobacter pylori (HP) has been recommended in primary care as this strategy will cure most underlying peptic ulcer disease and prevent future gastro duodenal disease. Methods A total of 98 patients completed Modified Glasgow Dyspepsia Severity Score Questionnaire (MGDSSQ) at initial presentation before undergoing the 13Carbon Urea Breath Test (UBT) for HP. Those with positive UBT received Eradication Therapy with oral Omeprazole 20 mg twice daily, Clarithromycin 500 mg daily and Amoxycillin 500 mg twice daily for one week followed by Omeprazole to be completed for another 4 to 6 weeks. Those with negative UBT received empirical treatment with oral Omeprazole 20 mg twice daily for 4 to 6 weeks. Patients were assessed again using the MGDSSQ at the completion of treatment and one month after stopping treatment. Results The prevalence of dyspepsia at Universiti Kebangsaan Malaysia-Primary Care Centre was 1.12% (124/11037), out of which 23.5% (23/98) was due to HP. Post treatment assessment in both HP (95.7%, 22/23) and non HP-related dyspepsia (86.7%, 65/75) groups showed complete or almost complete resolution of dyspepsia. Only about 4.3% (1/23) in the HP related dyspepsia and 13.3% (10/75) in the non HP group required endoscopy. Conclusion The prevalence of dyspepsia due to HP in this primary care centre was 23.5%. Detection of HP related dyspepsia yielded good treatment outcomes (95.7%). PMID:19435494

Gastritis in patients undergoing sleeve gastrectomy: Prevalence, ethnic distribution, and impact on glycemic.

PubMed

Rath-Wolfson, Lea; Varona, Roy; Bubis, Golan; Tatarov, Alexander; Koren, Rumelia; Ram, Edward

2017-04-01

Laparoscopic sleeve gastrectomy (LSG) is a therapeutic option in severely obese patients. The aim of this study was to evaluate the presence of Helicobacter pylori (HP) gastritis and non-Helicobacter gastritis in the gastrectomy specimens, and its association to other variables.One hundred six sleeve gastrectomy specimens were examined histopathologically for the presence of gastritis and its relation to other factors like ethnicity, glycemic control, and postoperative complications.Twelve patients had HP gastritis, 39 had non-HP gastritis, and 55 had normal mucosa. There was a statistical difference between the Arab and Jewish Israeli patients in our study. Twenty-eight of the Arab patients had HP gastritis and 48% had non-HP gastritis. In the Jewish population 6% had HP gastritis and 34% had non-HP gastritis. The preoperative glycemic control was worse in the gastritis group with a mean HbA1c of 8.344% while in the normal mucosa group the mean HbA1c was 6.55. After operation the glycemic control reverted to normal in most the diabetic patients. There were few postoperative complications however, they were not related to HP.There is a high incidence of gastritis in obese patients. The incidence of gastritis in the Arab population in our study was higher than that in the Jewish population. The glycemic control before surgery was worse in patients with gastritis than in the normal mucosa group. HP bares no risk for postoperative complications after LSG and does not affect weight loss. However a larger cohort of patients must be studied to arrive at conclusive results.

Gastritis in patients undergoing sleeve gastrectomy

PubMed Central

Rath-Wolfson, Lea; Varona, Roy; Bubis, Golan; Tatarov, Alexander; Koren, Rumelia; Ram, Edward

2017-01-01

Abstract Laparoscopic sleeve gastrectomy (LSG) is a therapeutic option in severely obese patients. The aim of this study was to evaluate the presence of Helicobacter pylori (HP) gastritis and non-Helicobacter gastritis in the gastrectomy specimens, and its association to other variables. One hundred six sleeve gastrectomy specimens were examined histopathologically for the presence of gastritis and its relation to other factors like ethnicity, glycemic control, and postoperative complications. Twelve patients had HP gastritis, 39 had non-HP gastritis, and 55 had normal mucosa. There was a statistical difference between the Arab and Jewish Israeli patients in our study. Twenty-eight of the Arab patients had HP gastritis and 48% had non-HP gastritis. In the Jewish population 6% had HP gastritis and 34% had non-HP gastritis. The preoperative glycemic control was worse in the gastritis group with a mean HbA1c of 8.344% while in the normal mucosa group the mean HbA1c was 6.55. After operation the glycemic control reverted to normal in most the diabetic patients. There were few postoperative complications however, they were not related to HP. There is a high incidence of gastritis in obese patients. The incidence of gastritis in the Arab population in our study was higher than that in the Jewish population. The glycemic control before surgery was worse in patients with gastritis than in the normal mucosa group. HP bares no risk for postoperative complications after LSG and does not affect weight loss. However a larger cohort of patients must be studied to arrive at conclusive results. PMID:28422853

Human cells derived from degenerate intervertebral discs respond differently to those derived from non-degenerate intervertebral discs following application of dynamic hydrostatic pressure.

PubMed

Le Maitre, Christine Lyn; Frain, Jennie; Fotheringham, Andrew P; Freemont, Anthony J; Hoyland, Judith Alison

2008-01-01

The intervertebral disc (IVD) is one of the body's most important load-bearing structures with the major mechanical force experienced in the nucleus pulposus (NP) being hydrostatic pressure (HP). Physiological levels of HP have an anabolic effect on IVD matrix metabolism in cells derived from non-degenerate animal and herniated IVD while excessive HP has a catabolic effect. However, no studies have investigated the response of non-degenerate and degenerate human disc cells derived from non-herniated discs to HP. Here we investigate the effect of physiological HP on such cells using a novel loading rig. Human IVD cells (both NP and AF) cultured in alginate were subjected to dynamic HP (0.8-1.7 MPa 0.5 Hz) for 2 h. Cell viability was assessed, RNA extracted and qRT-PCR for 18 s, c-fos, Sox-9, collagen type II, aggrecan and MMP-3 performed. Cell viability was unaffected by the loading regime. In non-degenerate NP cells, HP increased c-fos, aggrecan, Sox-9 and collagen type II (significantly so in the case of c-fos and aggrecan), but not MMP-3 gene expression. In contrast, application of HP to AF or degenerate NP cells had no effect on target gene expression. Our data shows that cells obtained from the healthy NP respond to dynamic HP by up-regulating genes indicative of healthy matrix homeostasis. However, responses differed in degenerate NP cells suggesting that an altered mechanotransduction pathway may be operational.

[Survey of Literature on the Development of an Evidence Database for Hospital-prepared Drugs in Japan].

PubMed

Momo, Kenji

2018-01-01

　Hospital-prepared drugs (HP), known as In'Naiseizai in Japan, are custom-prepared formulations which offer medical professionals an alternative administration pathway by changing the formulation of existing drugs according to a patients' needs. Preparing the HP is one of several roles of pharmacists in providing personalized medicine at hospitals in Japan. In 2012, the Japanese Society of Hospital Pharmacists provided guidelines for the appropriate use of "Hospital-prepared drugs". The following information was included in this guide: 1) documentation of the proper procedures, materials, prescription practices, etc., 2) required approval from the institutional review board of each HP on the risk-based classifications, and 3) to assess the stability, efficacy, and safety of each HP. However, several problems persist for pharmacists trying to prepare or use HP appropriately; the most common is insufficient manpower to both assess and prepare these drugs during routine hospital work. To resolve this problem, we are developing an evidence database for HP based on surveys of the current literature. This database has been developed for 109 drugs to date. Data-driven assessment of the stability of HP showed that 52 out of 109 drugs examined (47.7%). Notably, only 6 of the 109 HP (5.5%) in the database had all three characteristics of "stability", "safety", and "efficacy". In conclusion, the application of this database will save manpower hours for hospital pharmacists in the preparation of HP. In the near future, we will make this database available to the wider medical community via the web or through literature.

77 FR 31000 - Transcontinental Gas Pipe Line Company, LLC; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-24

... amend the authorized operation of its new 15,000 horsepower (HP) electric motor- driven compressor... the 15,000 HP electric compressor unit at a maximum of 9,000 HP. Transco now seeks authorization to...

High-Protein Exposure during Gestation or Lactation or after Weaning Has a Period-Specific Signature on Rat Pup Weight, Adiposity, Food Intake, and Glucose Homeostasis up to 6 Weeks of Age.

PubMed

Desclée de Maredsous, Caroline; Oozeer, Raish; Barbillon, Pierre; Mary-Huard, Tristan; Delteil, Corine; Blachier, François; Tomé, Daniel; van der Beek, Eline M; Davila, Anne-Marie

2016-01-01

Early-life nutrition has a programming effect on later metabolic health; however, the impact of exposure to a high-protein (HP) diet is still being investigated. This study evaluated the consequences on pup phenotype of an HP diet during gestation and lactation and after weaning. Wistar rat dams were separated into 2 groups fed an HP (55% protein) or normal protein (NP) (control; 20% protein) isocaloric diet during gestation, and each group subsequently was separated into 2 subgroups that were fed an HP or NP diet during lactation. After weaning, male and female pups from each mother subgroup were separated into 2 groups that were fed either an NP or HP diet until they were 6 wk old. Measurements included weight, food intake, body composition, blood glucose, insulin, glucagon, leptin, insulin-like growth factor I, and lipids. Feeding mothers the HP diet during gestation or lactation induced lower postweaning pup weight (gestation diet × time, P < 0.0001; lactation diet × time, P < 0.0001). Regardless of dams' diets, pups receiving HP compared with NP diet after weaning had 7% lower weight (NP, 135.0 ± 2.6 g; HP, 124.4 ± 2.5 g; P < 0.0001), 16% lower total energy intake (NP, 777 ± 14 kcal; HP, 649 ± 13 kcal; P < 0.0001) and 31% lower adiposity (P < 0.0001). Pups receiving HP compared with NP diet after weaning had increased blood glucose, insulin, and glucagon when food deprived (P < 0.0001 for all). The HP compared with the NP diet during gestation induced higher blood glucose in food-deprived rats (NP, 83.2 ± 2.1 mg/dL; HP, 91.2 ± 2.1 mg/dL; P = 0.046) and increased plasma insulin in fed pups receiving the postweaning NP diet (gestation diet × postweaning diet, P = 0.02). Increasing the protein concentration of the rat dams' diet during gestation, and to a lesser extent during lactation, and of the pups' diet after weaning influenced pup phenotype, including body weight, fat accumulation, food intake, and glucose tolerance at 6 wk of age. © 2016 American Society for Nutrition.

Performance of health product risk management and surveillance conducted by health personnel at sub-district health promotion hospitals in the northeast region of Thailand.

PubMed

Kanjanarach, Tipaporn; Jaisa-Ard, Raksaworn; Poonaovarat, Nantawan

2014-01-01

Health personnel at sub-district health promotion hospitals (SD-HPHs) are assigned to take responsibility for 15 activities related to health product risk management and surveillance (HP-RM&S). This cross-sectional survey aimed to identify factors that determined their job performance and to record their expressed needs to support HP-RM&S operation. In this study, job performance was defined as completion of all 15 activities. Self-administered postal questionnaires were used to collect data from 380 randomly selected health personnel who were in charge of HP-RM&S at SD-HPHs in the northeast of Thailand. Thirty-six point one percent (n=137) of the respondents were able to perform all 15 of the HP-RM&S activities assigned to SD-HPHs. A logistic regression model identified three factors that statistically significantly determined the completion of all 15 HP-RM&S activities. These were: receiving a high or very high level of support from the community (adjusted odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.5, 4.1), the responsible persons for HP-RM&S did not hold an administrative position (adjusted OR: 1.7; 95% CI: 1.1, 2.7), and having at least one training session related to HP-RM&S per year (adjusted OR: 1.7; 95% CI 1.1, 2.6). There were 1,536 expressed needs which can be classified into four major categories, ie, training needs (41.6%, n=639), resource support (28.3%, n=435), mechanisms that facilitate HP-RM&S operation (24.1%, n=370) and adjusting of the scope of HP-RM&S (6.0%, n=92). The topics most frequently referred to in training needs were drug law, food law, and cosmetics law. A strategy for improvement of the job performance in HP-RM&S of health personnel in SD-HPHs should target identifying schemes to encourage the community to proactively participate in HP-RM&S. The district health office as the organization directly controlling and supervising SD-HPHs should also regularly update knowledge base and skills necessary for HP-RM&S operation through training of the responsible health personnel.

Heterochromatin protein 1: don't judge the book by its cover!

PubMed

Hediger, Florence; Gasser, Susan M

2006-04-01

The name heterochromatin protein 1 (HP1) suggests that this small nuclear factor plays a role in forming heterochromatic domains. It was noticed years ago, however, that the distribution of HP1 on polytene chromosomes was not restricted to chromocenters or telomeres. HP1 was also found, reproducibly, along the euchromatic arms. A possible function in euchromatic gene regulation was postulated. Now, a large body of data has blurred the definition of HP1 as a structural component of heterochromatin, revealing its two-faced nature. Not only do HP1 isoforms have specific binding sites in both heterochromatic and euchromatic domains but they might also participate in the repression and activation of transcription in both compartments.

Effects of Hydroxylpropyl-β-Cyclodextrin on in Vitro Insulin Stability

PubMed Central

Zhang, Liefeng; Zhu, Wenjie; Song, Lingling; Wang, Yifan; Jiang, Hui; Xian, Suyun; Ren, Yong

2009-01-01

The objective of this study was to elucidate the effects of hydroxylpropyl-β-cyclodextrin (HP-β-CD) on the in vitro stability of insulin. It was found that HP-β-CD had positive effects on the stability of insulin in acid and base and under high temperature conditions. Furthermore, use of HP-β-CD could also increase the stability of disulfide bonds which are important to the conformation of insulin. Through 1H-NMR experiments it was found that the protective effect of HP-β-CD was due to complexation with insulin. The results suggest that the presence of HP-β-CD could improve the stability of insulin in different environments. PMID:19564937

Helium compressors for closed-cycle, 4.5-Kelvin refrigerators

NASA Technical Reports Server (NTRS)

Hanson, T. R.

1992-01-01

An improved helium compressor for traveling-wave maser and closed-cycle refrigerator systems was developed and is currently being supplied to the DSN. This new 5-hp compressor package is designed to replace the current 3-hp DSN compressors. The new compressor package was designed to retrofit into the existing 3-hp compressor frame and reuse many of the same components, therefore saving the cost of documenting and fabricating these components when implementing a new 5-hp compressor.

IPLIB (Image processing library) user's manual

NASA Technical Reports Server (NTRS)

Faulcon, N. D.; Monteith, J. H.; Miller, K.

1985-01-01

IPLIB is a collection of HP FORTRAN 77 subroutines and functions that facilitate the use of a COMTAL image processing system driven by an HP-1000 computer. It is intended for programmers who want to use the HP 1000 to drive the COMTAL Vision One/20 system. It is assumed that the programmer knows HP 1000 FORTRAN 77 or at least one FORTRAN dialect. It is also assumed that the programmer has some familiarity with the COMTAL Vision One/20 system.