Time-lapse evaluation of human embryo development in single versus sequential culture media--a sibling oocyte study.

PubMed

Ciray, Haydar Nadir; Aksoy, Turan; Goktas, Cihan; Ozturk, Bilgen; Bahceci, Mustafa

2012-09-01

To compare the dynamics of early development between embryos cultured in single and sequential media. Randomized, comparative study. Private IVF centre. A total of 446 metaphase II oocytes from 51 couples who underwent oocyte retrieval procedure for intracytoplasmic sperm injection. Forty-nine resulted in embryo transfer. Oocytes were split between single and sequential media produced by the same manufacturer and cultured in a time-lapse incubator. Morphokinetic parameters until the embryos reached the 5-cell stage (t5), utilization, clinical pregnancy and implantation rates. Embryos cultured in single media were advanced from the first mitosis cycle and reached 2- to 5-cell stages earlier. There was not any difference between the durations for cell cycle two (cc2 = t3-t2) and s2 (t4-t3). The utilization, clinical pregnancy and implantation rates did not differ between groups. The proportion of cryopreserved day 6 embryos to two pronuclei oocytes was significantly higher in sequential than in single media. Morphokinetics of embryo development vary between single and sequential culture media at least until the 5-cell stage. The overall clinical and embryological parameters remain similar regardless of the culture system.

Nanostructure Neutron Converter Layer Development

NASA Technical Reports Server (NTRS)

Park, Cheol (Inventor); Lowther, Sharon E. (Inventor); Kang, Jin Ho (Inventor); Thibeault, Sheila A. (Inventor); Sauti, Godfrey (Inventor); Bryant, Robert G. (Inventor)

2016-01-01

Methods for making a neutron converter layer are provided. The various embodiment methods enable the formation of a single layer neutron converter material. The single layer neutron converter material formed according to the various embodiments may have a high neutron absorption cross section, tailored resistivity providing a good electric field penetration with submicron particles, and a high secondary electron emission coefficient. In an embodiment method a neutron converter layer may be formed by sequential supercritical fluid metallization of a porous nanostructure aerogel or polyimide film. In another embodiment method a neutron converter layer may be formed by simultaneous supercritical fluid metallization of a porous nanostructure aerogel or polyimide film. In a further embodiment method a neutron converter layer may be formed by in-situ metalized aerogel nanostructure development.

Flat-plate solar array project process development area, process research of non-CZ silicon material

NASA Technical Reports Server (NTRS)

Campbell, R. B.

1984-01-01

The program is designed to investigate the fabrication of solar cells on N-type base material by a simultaneous diffusion of N-type and P-type dopants to form an P(+)NN(+) structure. The results of simultaneous diffusion experiments are being compared to cells fabricated using sequential diffusion of dopants into N-base material in the same resistivity range. The process used for the fabrication of the simultaneously diffused P(+)NN(+) cells follows the standard Westinghouse baseline sequence for P-base material except that the two diffusion processes (boron and phosphorus) are replaced by a single diffusion step. All experiments are carried out on N-type dendritic web grown in the Westinghouse pre-pilot facility. The resistivities vary from 0.5 (UC OMEGA)cm to 5 (UC OMEGA)cm. The dopant sources used for both the simultaneous and sequential diffusion experiments are commercial metallorganic solutions with phosphorus or boron components. After these liquids are applied to the web surface, they are baked to form a hard glass which acts as a diffusion source at elevated temperatures. In experiments performed thus far, cells produced in sequential diffusion tests have properties essentially equal to the baseline N(+)PP(+) cells. However, the simultaneous diffusions have produced cells with much lower IV characteristics mainly due to cross-doping of the sources at the diffusion temperature. This cross-doping is due to the high vapor pressure phosphorus (applied as a metallorganic to the back surface) diffusion through the SiO2 mask and then acting as a diffusant source for the front surface.

South Asia as a Reservoir for the Global Spread of Ciprofloxacin-Resistant Shigella sonnei: A Cross-Sectional Study.

PubMed

Chung The, Hao; Rabaa, Maia A; Pham Thanh, Duy; De Lappe, Niall; Cormican, Martin; Valcanis, Mary; Howden, Benjamin P; Wangchuk, Sonam; Bodhidatta, Ladaporn; Mason, Carl J; Nguyen Thi Nguyen, To; Vu Thuy, Duong; Thompson, Corinne N; Phu Huong Lan, Nguyen; Voong Vinh, Phat; Ha Thanh, Tuyen; Turner, Paul; Sar, Poda; Thwaites, Guy; Thomson, Nicholas R; Holt, Kathryn E; Baker, Stephen

2016-08-01

Antimicrobial resistance is a major issue in the Shigellae, particularly as a specific multidrug-resistant (MDR) lineage of Shigella sonnei (lineage III) is becoming globally dominant. Ciprofloxacin is a recommended treatment for Shigella infections. However, ciprofloxacin-resistant S. sonnei are being increasingly isolated in Asia and sporadically reported on other continents. We hypothesized that Asia is a primary hub for the recent international spread of ciprofloxacin-resistant S. sonnei. We performed whole-genome sequencing on a collection of 60 contemporaneous ciprofloxacin-resistant S. sonnei isolated in four countries within Asia (Vietnam, n = 11; Bhutan, n = 12; Thailand, n = 1; Cambodia, n = 1) and two outside of Asia (Australia, n = 19; Ireland, n = 16). We reconstructed the recent evolutionary history of these organisms and combined these data with their geographical location of isolation. Placing these sequences into a global phylogeny, we found that all ciprofloxacin-resistant S. sonnei formed a single clade within a Central Asian expansion of lineage III. Furthermore, our data show that resistance to ciprofloxacin within S. sonnei may be globally attributed to a single clonal emergence event, encompassing sequential gyrA-S83L, parC-S80I, and gyrA-D87G mutations. Geographical data predict that South Asia is the likely primary source of these organisms, which are being regularly exported across Asia and intercontinentally into Australia, the United States and Europe. Our analysis was limited by the number of S. sonnei sequences available from diverse geographical areas and time periods, and we cannot discount the potential existence of other unsampled reservoir populations of antimicrobial-resistant S. sonnei. This study suggests that a single clone, which is widespread in South Asia, is likely driving the current intercontinental surge of ciprofloxacin-resistant S. sonnei and is capable of establishing endemic transmission in new locations. Despite being limited in geographical scope, our work has major implications for understanding the international transfer of antimicrobial-resistant pathogens, with S. sonnei acting as a tractable model for studying how antimicrobial-resistant Gram-negative bacteria spread globally.

South Asia as a Reservoir for the Global Spread of Ciprofloxacin-Resistant Shigella sonnei: A Cross-Sectional Study

PubMed Central

Pham Thanh, Duy; De Lappe, Niall; Cormican, Martin; Howden, Benjamin P.; Wangchuk, Sonam; Bodhidatta, Ladaporn; Nguyen Thi Nguyen, To; Thompson, Corinne N.; Phu Huong Lan, Nguyen; Voong Vinh, Phat; Ha Thanh, Tuyen; Turner, Paul; Sar, Poda; Thwaites, Guy; Thomson, Nicholas R.; Holt, Kathryn E.; Baker, Stephen

2016-01-01

Background Antimicrobial resistance is a major issue in the Shigellae, particularly as a specific multidrug-resistant (MDR) lineage of Shigella sonnei (lineage III) is becoming globally dominant. Ciprofloxacin is a recommended treatment for Shigella infections. However, ciprofloxacin-resistant S. sonnei are being increasingly isolated in Asia and sporadically reported on other continents. We hypothesized that Asia is a primary hub for the recent international spread of ciprofloxacin-resistant S. sonnei. Methods and Findings We performed whole-genome sequencing on a collection of 60 contemporaneous ciprofloxacin-resistant S. sonnei isolated in four countries within Asia (Vietnam, n = 11; Bhutan, n = 12; Thailand, n = 1; Cambodia, n = 1) and two outside of Asia (Australia, n = 19; Ireland, n = 16). We reconstructed the recent evolutionary history of these organisms and combined these data with their geographical location of isolation. Placing these sequences into a global phylogeny, we found that all ciprofloxacin-resistant S. sonnei formed a single clade within a Central Asian expansion of lineage III. Furthermore, our data show that resistance to ciprofloxacin within S. sonnei may be globally attributed to a single clonal emergence event, encompassing sequential gyrA-S83L, parC-S80I, and gyrA-D87G mutations. Geographical data predict that South Asia is the likely primary source of these organisms, which are being regularly exported across Asia and intercontinentally into Australia, the United States and Europe. Our analysis was limited by the number of S. sonnei sequences available from diverse geographical areas and time periods, and we cannot discount the potential existence of other unsampled reservoir populations of antimicrobial-resistant S. sonnei. Conclusions This study suggests that a single clone, which is widespread in South Asia, is likely driving the current intercontinental surge of ciprofloxacin-resistant S. sonnei and is capable of establishing endemic transmission in new locations. Despite being limited in geographical scope, our work has major implications for understanding the international transfer of antimicrobial-resistant pathogens, with S. sonnei acting as a tractable model for studying how antimicrobial-resistant Gram-negative bacteria spread globally. PMID:27483136

Costs of achieving live birth from assisted reproductive technology: a comparison of sequential single and double embryo transfer approaches.

PubMed

Crawford, Sara; Boulet, Sheree L; Mneimneh, Allison S; Perkins, Kiran M; Jamieson, Denise J; Zhang, Yujia; Kissin, Dmitry M

2016-02-01

To assess treatment and pregnancy/infant-associated medical costs and birth outcomes for assisted reproductive technology (ART) cycles in a subset of patients using elective double embryo (ET) and to project the difference in costs and outcomes had the cycles instead been sequential single ETs (fresh followed by frozen if the fresh ET did not result in live birth). Retrospective cohort study using 2012 and 2013 data from the National ART Surveillance System. Infertility treatment centers. Fresh, autologous double ETs performed in 2012 among ART patients younger than 35 years of age with no prior ART use who cryopreserved at least one embryo. Sequential single and double ETs. Actual live birth rates and estimated ART treatment and pregnancy/infant-associated medical costs for double ET cycles started in 2012 and projected ART treatment and pregnancy/infant-associated medical costs if the double ET cycles had been performed as sequential single ETs. The estimated total ART treatment and pregnancy/infant-associated medical costs were $580.9 million for 10,001 double ETs started in 2012. If performed as sequential single ETs, estimated costs would have decreased by $195.0 million to $386.0 million, and live birth rates would have increased from 57.7%-68.0%. Sequential single ETs, when clinically appropriate, can reduce total ART treatment and pregnancy/infant-associated medical costs by reducing multiple births without lowering live birth rates. Published by Elsevier Inc.

Resisting distraction and response inhibition trigger similar enhancements of future performance.

PubMed

Bissett, Patrick G; Grant, Lauren D; Weissman, Daniel H

2017-10-01

Resisting distraction and response inhibition are crucial aspects of cognitive control. Interestingly, each of these abilities transiently improves just after it is utilized. Competing views differ, however, as to whether utilizing either of these abilities (e.g., resisting distraction) enhances future performance involving the other ability (e.g., response inhibition). To distinguish between these views, we combined a Stroop-like task that requires resisting distraction with a restraint variant of the stop-signal task that requires response inhibition. We observed similar sequential-trial effects (i.e., performance enhancements) following trials in which participants (a) resisted distraction (i.e., incongruent go trials) and (b) inhibited a response (i.e., congruent stop trials). First, the congruency effect in go trials, which indexes overall distractibility, was smaller after both incongruent go trials and congruent stop trials than it was after congruent go trials. Second, stop failures were less frequent after both incongruent go trials and congruent stop trials than after congruent go trials. A control experiment ruled out the possibility that perceptual conflict or surprise engendered by occasional stop signals triggers sequential-trial effects independent of stopping. Thus, our findings support a novel, integrated view in which resisting distraction and response inhibition trigger similar sequential enhancements of future performance. Copyright © 2017 Elsevier B.V. All rights reserved.

Sequential high intensity focused ultrasound (HIFU) ablation in the treatment of benign multinodular goitre: an observational retrospective study.

PubMed

Lang, Brian H H; Woo, Yu-Cho; Chiu, Keith Wan-Hang

2018-03-19

Assessing the efficacy and safety of sequential high-intensity focused ultrasound (HIFU) ablation in a multinodular goitre (MNG) by comparing them with single HIFU ablation. One hundred and four (84.6%) patients underwent single ablation of a single nodule (group I), while 19 (15.4%) underwent sequential ablation of two relatively-dominant nodules in a MNG (group II). Extent of shrinkage per nodule [by volume reduction ratio (VRR)], pain scores (by 0-10 visual analogue scale) during and after ablation, and rate of vocal cord palsy (VCP), skin burn and nausea/vomiting were compared between the two groups. All 19 (100%) sequential ablations completed successfully. The 3- and 6-month VRR of each nodule were comparable between the two groups (p > 0.05) and in group II, the 3- and 6-month VRR between the first and second nodules were comparable (p = 0.710 and p = 0.548, respectively). Pain score was significantly higher in group II in the morning after ablation (2.29 vs 1.15, p = 0.047) and nausea/vomiting occurred significantly more frequently in group II (15.8% vs 0.0%, p = 0.012). However, VCP and skin burn were comparable (p > 0.05). Sequential ablation had comparable efficacy and safety as single ablation. However, patients undergoing sequential ablation are at higher likelihood of pain in the following morning and nausea/vomiting after ablation. • Sequential HIFU ablation is well-tolerated in patients with two dominant thyroid nodules • More pain is experienced in the morning following sequential HIFU ablation • More nausea/vomiting is experienced following sequential HIFU ablation.

Compound mutations in BCR-ABL1 are not major drivers of primary or secondary resistance to ponatinib in CP-CML patients

PubMed Central

Hodgson, J. Graeme; Shah, Neil P.; Cortes, Jorge E.; Kim, Dong-Wook; Nicolini, Franck E.; Talpaz, Moshe; Baccarani, Michele; Müller, Martin C.; Li, Jin; Parker, Wendy T.; Lustgarten, Stephanie; Clackson, Tim; Haluska, Frank G.; Guilhot, Francois; Kantarjian, Hagop M.; Soverini, Simona; Hochhaus, Andreas; Hughes, Timothy P.; Rivera, Victor M.; Branford, Susan

2016-01-01

BCR-ABL1 kinase domain mutations can confer resistance to first- and second-generation tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). In preclinical studies, clinically achievable concentrations of the third-generation BCR-ABL1 TKI ponatinib inhibit T315I and all other single BCR-ABL1 mutants except T315M, which generates a single amino acid exchange, but requires 2 sequential nucleotide exchanges. In addition, certain compound mutants (containing ≥2 mutations in cis) confer resistance. Initial analyses based largely on conventional Sanger sequencing (SS) have suggested that the preclinical relationship between BCR-ABL1 mutation status and ponatinib efficacy is generally recapitulated in patients receiving therapy. Thus far, however, such analyses have been limited by the inability of SS to definitively identify compound mutations or mutations representing less than ∼20% of total alleles (referred to as “low-level mutations”), as well as limited patient follow-up. Here we used next-generation sequencing (NGS) to define the baseline BCR-ABL1 mutation status of 267 heavily pretreated chronic phase (CP)-CML patients from the PACE trial, and used SS to identify clonally dominant mutants that may have developed on ponatinib therapy (30.1 months median follow-up). Durable cytogenetic and molecular responses were observed irrespective of baseline mutation status and included patients with compound mutations. No single or compound mutation was identified that consistently conferred primary and/or secondary resistance to ponatinib in CP-CML patients. Ponatinib is effective in CP-CML irrespective of baseline mutation status. PMID:26603839

A brief review of the management of platinum-resistant-platinum-refractory ovarian cancer.

PubMed

Oronsky, Bryan; Ray, Carolyn M; Spira, Alexander I; Trepel, Jane B; Carter, Corey A; Cottrill, Hope M

2017-06-01

Ovarian cancer, which ranks fifth in cancer deaths among women, is the most lethal gynecologic malignancy. Epithelial ovarian cancer (EOC) is the most common histologic type, with the 5-year survival for all stages estimated at 45.6%. This rate increases to more than 70% in the minority of patients who are diagnosed at an early stage, but declines to 35% in the vast majority of patients diagnosed at advanced stage. Recurrent EOC is incurable. Platinum sensitivity (or lack thereof) is a major determinant of prognosis. The current standard treatment is primary surgery followed by platinum-based chemotherapy. In recurrent platinum-resistant/platinum-refractory EOC, sequential single-agent salvage chemotherapy is superior to multiagent chemotherapy. Multiagent regimens increase toxicity without clear benefit; however, no preferred sequence of single agents is recommended. The impact of targeted therapies and immunotherapies on progression-free survival and overall survival, which remains dismal, is under active investigation. Currently, clinical trials offer the best hope for the development of a new treatment paradigm in this recalcitrant disease.

Effect of electron irradiation on superconductivity in single crystals of Ba ( Fe 1 – x Ru x ) 2 As 2 ( x = 0.24 )

DOE PAGES

Prozorov, R.; Kończykowski, M.; Tanatar, M. A.; ...

2014-11-18

A single crystal of isovalently substituted Ba(Fe 1-xRu x) 2As 2 (x=0.24) is sequentially irradiated with 2.5 MeV electrons up to a maximum dose of 2.1×10 19 e -/cm 2. The electrical resistivity is measured in situ at T=22 K during the irradiation and ex situ as a function of temperature between subsequent irradiation runs. Upon irradiation, the superconducting transition temperature T c decreases and the residual resistivity ρ0 increases. We find that electron irradiation leads to the fastest suppression of T c compared to other types of artificially introduced disorder, probably due to the strong short-range potential of themore » pointlike irradiation defects. As a result, a more detailed analysis within a multiband scenario with variable scattering potential strength shows that the observed T c versus ρ 0 is fully compatible with s ± pairing, in contrast to earlier claims that this model leads to a too rapid suppression of T c with scattering.« less

Polymeric microchip for the simultaneous determination of anions and cations by hydrodynamic injection using a dual-channel sequential injection microchip electrophoresis system.

PubMed

Gaudry, Adam J; Nai, Yi Heng; Guijt, Rosanne M; Breadmore, Michael C

2014-04-01

A dual-channel sequential injection microchip capillary electrophoresis system with pressure-driven injection is demonstrated for simultaneous separations of anions and cations from a single sample. The poly(methyl methacrylate) (PMMA) microchips feature integral in-plane contactless conductivity detection electrodes. A novel, hydrodynamic "split-injection" method utilizes background electrolyte (BGE) sheathing to gate the sample flows, while control over the injection volume is achieved by balancing hydrodynamic resistances using external hydrodynamic resistors. Injection is realized by a unique flow-through interface, allowing for automated, continuous sampling for sequential injection analysis by microchip electrophoresis. The developed system was very robust, with individual microchips used for up to 2000 analyses with lifetimes limited by irreversible blockages of the microchannels. The unique dual-channel geometry was demonstrated by the simultaneous separation of three cations and three anions in individual microchannels in under 40 s with limits of detection (LODs) ranging from 1.5 to 24 μM. From a series of 100 sequential injections the %RSDs were determined for every fifth run, resulting in %RSDs for migration times that ranged from 0.3 to 0.7 (n = 20) and 2.3 to 4.5 for peak area (n = 20). This system offers low LODs and a high degree of reproducibility and robustness while the hydrodynamic injection eliminates electrokinetic bias during injection, making it attractive for a wide range of rapid, sensitive, and quantitative online analytical applications.

[Sequential prescriptions: Arguments for a change of therapeutic patterns in treatment resistant depressions].

PubMed

Allouche, G

2016-02-01

Among the therapeutic strategies in treatment of resistant depression, the use of sequential prescriptions is discussed here. A number of observations, initially quite isolated and few controlled studies, some large-scale, have been reported, which showed a definite therapeutic effect of certain requirements in sequential treatment of depression. The Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D) is up to now the largest clinical trial exploring treatment strategies in non psychotic resistant depression in real-life conditions with an algorithm of sequential decision. The main conclusions of this study are the following: after two unsuccessful attempts, the chance of remission decreases considerably. A 12-months follow-up showed that the higher the use of the processing steps were high, the more common the relapses were during this period. The pharmacological differences between psychotropic did not cause clinically significant difference. The positive effect of lithium in combination with antidepressants has been known since the work of De Montigny. Antidepressants allow readjustment of physiological sequence involving different monoaminergic systems together. Studies with tricyclic antidepressant-thyroid hormone T3: in depression, decreased norepinephrine at the synaptic receptors believed to cause hypersensitivity of these receptors. Thyroid hormones modulate the activity of adrenergic receptors. There would be a balance of activity between alpha and beta-adrenergic receptors, depending on the bioavailability of thyroid hormones. ECT may in some cases promote pharmacological response in case of previous resistance, or be effective in preventing relapse. Cognitive therapy and antidepressant medications likely have an effect on different types of depression. We can consider the interest of cognitive therapy in a sequential pattern after effective treatment with an antidepressant effect for treatment of residual symptoms, preventing relapses and recurrences, in antidepressant maintenance. These data support the interest of therapeutic strategies based on evolutionary criteria. Sequential models inspired by statistical methods may incorporate the effects of a future treatment by measuring the current one. Copyright © 2015 L’Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Measuring Incompatible Observables by Exploiting Sequential Weak Values.

PubMed

Piacentini, F; Avella, A; Levi, M P; Gramegna, M; Brida, G; Degiovanni, I P; Cohen, E; Lussana, R; Villa, F; Tosi, A; Zappa, F; Genovese, M

2016-10-21

One of the most intriguing aspects of quantum mechanics is the impossibility of measuring at the same time observables corresponding to noncommuting operators, because of quantum uncertainty. This impossibility can be partially relaxed when considering joint or sequential weak value evaluation. Indeed, weak value measurements have been a real breakthrough in the quantum measurement framework that is of the utmost interest from both a fundamental and an applicative point of view. In this Letter, we show how we realized for the first time a sequential weak value evaluation of two incompatible observables using a genuine single-photon experiment. These (sometimes anomalous) sequential weak values revealed the single-operator weak values, as well as the local correlation between them.

Measuring Incompatible Observables by Exploiting Sequential Weak Values

NASA Astrophysics Data System (ADS)

Piacentini, F.; Avella, A.; Levi, M. P.; Gramegna, M.; Brida, G.; Degiovanni, I. P.; Cohen, E.; Lussana, R.; Villa, F.; Tosi, A.; Zappa, F.; Genovese, M.

2016-10-01

One of the most intriguing aspects of quantum mechanics is the impossibility of measuring at the same time observables corresponding to noncommuting operators, because of quantum uncertainty. This impossibility can be partially relaxed when considering joint or sequential weak value evaluation. Indeed, weak value measurements have been a real breakthrough in the quantum measurement framework that is of the utmost interest from both a fundamental and an applicative point of view. In this Letter, we show how we realized for the first time a sequential weak value evaluation of two incompatible observables using a genuine single-photon experiment. These (sometimes anomalous) sequential weak values revealed the single-operator weak values, as well as the local correlation between them.

Sequential infiltration synthesis for enhancing multiple-patterning lithography

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

Darling, Seth B.; Elam, Jeffrey W.; Tseng, Yu-Chih

Simplified methods of multiple-patterning photolithography using sequential infiltration synthesis to modify the photoresist such that it withstands plasma etching better than unmodified resist and replaces one or more hard masks and/or a freezing step in MPL processes including litho-etch-litho-etch photolithography or litho-freeze-litho-etch photolithography.

Active and Inactive Leg Hemodynamics during Sequential Single-Leg Interval Cycling.

PubMed

Gordon, Nicole; Abbiss, Chris R; Ihsan, Mohammed; Maiorana, Andrew J; Peiffer, Jeremiah J

2018-06-01

Leg order during sequential single-leg cycling (i.e., exercising both legs independently within a single session) may affect local muscular responses potentially influencing adaptations. This study examined the cardiovascular and skeletal muscle hemodynamic responses during double-leg and sequential single-leg cycling. Ten young healthy adults (28 ± 6 yr) completed six 1-min double-leg intervals interspersed with 1 min of passive recovery and, on a separate occasion, 12 (six with one leg followed by six with the other leg) 1-min single-leg intervals interspersed with 1 min of passive recovery. Oxygen consumption, heart rate, blood pressure, muscle oxygenation, muscle blood volume, and power output were measured throughout each session. Oxygen consumption, heart rate, and power output were not different between sets of single-leg intervals, but the average of both sets was lower than the double-leg intervals. Mean arterial pressure was higher during double-leg compared with sequential single-leg intervals (115 ± 9 vs 104 ± 9 mm Hg, P < 0.05) and higher during the initial compared with second set of single-leg intervals (108 ± 10 vs 101 ± 10 mm Hg, P < 0.05). The increase in muscle blood volume from baseline was similar between the active single leg and the double leg (267 ± 150 vs 214 ± 169 μM·cm, P = 0.26). The pattern of change in muscle blood volume from the initial to second set of intervals was significantly different (P < 0.05) when the leg was active in the initial (-52.3% ± 111.6%) compared with second set (65.1% ± 152.9%). These data indicate that the order in which each leg performs sequential single-leg cycling influences the local hemodynamic responses, with the inactive muscle influencing the stimulus experienced by the contralateral leg.

Spatiotemporally and Sequentially-Controlled Drug Release from Polymer Gatekeeper-Hollow Silica Nanoparticles

NASA Astrophysics Data System (ADS)

Palanikumar, L.; Jeena, M. T.; Kim, Kibeom; Yong Oh, Jun; Kim, Chaekyu; Park, Myoung-Hwan; Ryu, Ja-Hyoung

2017-04-01

Combination chemotherapy has become the primary strategy against cancer multidrug resistance; however, accomplishing optimal pharmacokinetic delivery of multiple drugs is still challenging. Herein, we report a sequential combination drug delivery strategy exploiting a pH-triggerable and redox switch to release cargos from hollow silica nanoparticles in a spatiotemporal manner. This versatile system further enables a large loading efficiency for both hydrophobic and hydrophilic drugs inside the nanoparticles, followed by self-crosslinking with disulfide and diisopropylamine-functionalized polymers. In acidic tumour environments, the positive charge generated by the protonation of the diisopropylamine moiety facilitated the cellular uptake of the particles. Upon internalization, the acidic endosomal pH condition and intracellular glutathione regulated the sequential release of the drugs in a time-dependent manner, providing a promising therapeutic approach to overcoming drug resistance during cancer treatment.

Elemental depth profiles and plasma etching rates of positive-tone electron beam resists after sequential infiltration synthesis of alumina

NASA Astrophysics Data System (ADS)

Ozaki, Yuki; Ito, Shunya; Hiroshiba, Nobuya; Nakamura, Takahiro; Nakagawa, Masaru

2018-06-01

By scanning transmission electron microscopy and energy dispersive X-ray spectroscopy (STEM–EDS), we investigated the elemental depth profiles of organic electron beam resist films after the sequential infiltration synthesis (SIS) of inorganic alumina. Although a 40-nm-thick poly(methyl methacrylate) (PMMA) film was entirely hybridized with alumina, an uneven distribution was observed near the interface between the substrate and the resist as well as near the resist surface. The uneven distribution was observed around the center of a 100-nm-thick PMMA film. The thicknesses of the PMMA and CSAR62 resist films decreased almost linearly as functions of plasma etching period. The comparison of etching rate among oxygen reactive ion etching, C3F8 reactive ion beam etching (RIBE), and Ar ion beam milling suggested that the SIS treatment enhanced the etching resistance of the electron beam resists to chemical reactions rather than to ion collisions. We proposed oxygen- and Ar-assisted C3F8 RIBE for the fabrication of silica imprint molds by electron beam lithography.

Insecticide resistance resulting from sequential selection of houseflies in the field by organophosphorus compounds*

PubMed Central

Georghiou, George P.; Hawley, Marilyn K.

1971-01-01

Although cross-resistance in houseflies to the organophosphates has eliminated numerous potentially useful compounds from field use, the ”subgroup” specificity of this phenomenon has permitted housefly control to be carried out for nearly a quarter of a century by changing from one toxicant to another within this class of insecticides. A question of considerable importance in insect control is whether the development of resistance to one subgroup of organophosphates will be at the expense of resistance to a subgroup applied previously. The development over several years of resistance in a field population selected sequentially by a number of organophosphates was studied. It was observed that the resistance spectrum expanded progressively to include, finally, organophosphates originally thought to belong to more than one subgroup—namely, malathion (resistance greater than 100 times), fenchlorphos (114 times), diazinon (163 times), coumaphos (greater than 100 times), Ciodrin (greater than 100 times), fenthion (18 times) and naled (9.3 times). Resistance to each compound continued to rise to levels considerably higher than those achieved at the time when the field use of the compound ended. The possible coexistence of subgroup cross-resistance in a population is discussed in the light of these results. PMID:5316852

Comparison of two commercial embryo culture media (SAGE-1 step single medium vs. G1-PLUSTM/G2-PLUSTM sequential media): Influence on in vitro fertilization outcomes and human embryo quality.

PubMed

López-Pelayo, Iratxe; Gutiérrez-Romero, Javier María; Armada, Ana Isabel Mangano; Calero-Ruiz, María Mercedes; Acevedo-Yagüe, Pablo Javier Moreno de

2018-04-26

To compare embryo quality, fertilization, implantation, miscarriage and clinical pregnancy rates for embryos cultured in two different commercial culture media until D-2 or D-3. In this retrospective study, we analyzed 189 cycles performed in 2016. Metaphase II oocytes were microinjected and allocated into single medium (SAGE 1-STEP, Origio) until transferred, frozen or discarded; or, if sequential media were used, the oocytes were cultured in G1-PLUSTM (Vitrolife) up to D-2 or D-3 and in G2-PLUSTM (Vitrolife) to transfer. On the following day, the oocytes were checked for normal fertilization and on D-2 and D-3 for morphological classification. Statistical analysis was performed using the chi-square and Mann-Whitney tests in PASW Statistics 18.0. The fertilization rates were 70.07% for single and 69.11% for sequential media (p=0.736). The mean number of embryos with high morphological quality (class A/B) was higher in the single medium than in the sequential media: D-2 [class A (190 vs. 107, p<0.001), B (133 vs. 118, p=0.018)]; D-3 [class A (40 vs. 19, p=0.048) but without differences in class B (40 vs. 49)]. Consequently, a higher number of embryos cultured in single medium were frozen: 197 (21.00%) vs. sequential: 102 (11.00%), p<0.001. No differences were found in implantation rates (30.16% vs. 25.57%, p=0.520), clinical pregnancy rates (55.88% vs. 41.05%, p=0.213), or miscarriage rates (14.29% vs. 9.52%, p=0.472). Embryo culture in single medium yields greater efficiency per cycle than in sequential media. Higher embryo quality and quantity were achieved, resulting in more frozen embryos. There were no differences in clinical pregnancy rates.

THRESHOLD LOGIC SYNTHESIS OF SEQUENTIAL MACHINES.

DTIC Science & Technology

The application of threshold logic to the design of sequential machines is the subject of this research. A single layer of threshold logic units in...advantages of fewer components because of the use of threshold logic, along with very high-speed operation resulting from the use of only a single layer of...logic. In some instances, namely for asynchronous machines, the only delay need be the natural delay of the single layer of threshold elements. It is

Sequential Delivery of Cyclopeptide RA-V and Doxorubicin for Combination Therapy on Resistant Tumor and In Situ Monitoring of Cytochrome c Release

PubMed Central

Chen, Huachao; Wang, Yurong; Yao, Yongrong; Qiao, Shenglin; Wang, Hao; Tan, Ninghua

2017-01-01

A programmed drug delivery system that can achieve sequential release of multiple therapeutics under different stimulus holds great promise to enhance the treatment efficacy and overcome multi-drug resistance (MDR) in tumor. Herein, multi-organelle-targeted and pH/ cytochrome c (Cyt c) dual-responsive nanoparticles were designed for combination therapy on resistant tumor. In this system (designated DGLipo NPs), doxorubicin (Dox) was intercalated into the DNA duplex containing a Cyt c aptamer, which subsequently loaded in the dendrigraftpoly-L-lysines (DGL) cores of DGLipo NPs, while cyclopeptide RA-V was doped into the pH-sensitive liposomal shells. After dual modification with c(RGDfK) and mitochondria-penetrating peptide (MPP), DGLipo NPs could successively deliver the two drugs into lysosome and mitochondria of cancer cells, and achieve sequential drug release in virtue of the unique characteristic of these two organelles. The organelle-specific and spatiotemporally controlled release of Dox and RA-V led to enhanced therapeutic outcomes in MDR tumor. More significantly, the DGLipo NPs were successfully applied to monitor Cyt c release during mitochondria-mediated apoptotic process. This work represents a versatile strategy for precise combination therapy against resistant tumor with spatiotemporal control, and provides a potential tool for Cyt c-related apoptotic studies. PMID:29109776

Trial Sequential Methods for Meta-Analysis

ERIC Educational Resources Information Center

Kulinskaya, Elena; Wood, John

2014-01-01

Statistical methods for sequential meta-analysis have applications also for the design of new trials. Existing methods are based on group sequential methods developed for single trials and start with the calculation of a required information size. This works satisfactorily within the framework of fixed effects meta-analysis, but conceptual…

Advanced electric-field scanning probe lithography on molecular resist using active cantilever

NASA Astrophysics Data System (ADS)

Kaestner, Marcus; Aydogan, Cemal; Lipowicz, Hubert-Seweryn; Ivanov, Tzvetan; Lenk, Steve; Ahmad, Ahmad; Angelov, Tihomir; Reum, Alexander; Ishchuk, Valentyn; Atanasov, Ivaylo; Krivoshapkina, Yana; Hofer, Manuel; Holz, Mathias; Rangelow, Ivo W.

2015-03-01

The routine "on demand" fabrication of features smaller than 10 nm opens up new possibilities for the realization of many novel nanoelectronic, NEMS, optical and bio-nanotechnology-based devices. Based on the thermally actuated, piezoresistive cantilever technology we have developed a first prototype of a scanning probe lithography (SPL) platform able to image, inspect, align and pattern features down to single digit nano regime. The direct, mask-less patterning of molecular resists using active scanning probes represents a promising path circumventing the problems in today's radiation-based lithography. Here, we present examples of practical applications of the previously published electric field based, current-controlled scanning probe lithography on molecular glass resist calixarene by using the developed tabletop SPL system. We demonstrate the application of a step-and-repeat scanning probe lithography scheme including optical as well as AFM based alignment and navigation. In addition, sequential read-write cycle patterning combining positive and negative tone lithography is shown. We are presenting patterning over larger areas (80 x 80 μm) and feature the practical applicability of the lithographic processes.

Long-term colonization with single and multiple strains of Helicobacter pylori assessed by DNA fingerprinting.

PubMed Central

Taylor, N S; Fox, J G; Akopyants, N S; Berg, D E; Thompson, N; Shames, B; Yan, L; Fontham, E; Janney, F; Hunter, F M

1995-01-01

The gastric pathogen Helicobacter pylori establishes long-term chronic infections that can lead to gastritis, peptic ulcers, and cancer. The species is so diverse that distinctly different strains are generally recovered from each patient. To better understand the dynamics of long-term carriage, we characterized H. pylori isolates from initial and follow-up biopsy specimens from a patient population at high risk of H. pylori infection and gastric cancer. Eighty-five isolates were obtained from 23 patients and were analyzed by genomic restriction enzyme analysis, arbitrarily primed PCR fingerprinting, (random amplified polymorphic DNA analysis), and/or restriction of specific PCR-amplified genes (restriction fragment length polymorphism analysis). A single strain was found in sequential biopsy specimens from 12 of 15 patients (80%) receiving sucralfate. In the remaining three patients treated with sucralfate, two strains were identified in two patients and three strains were identified in the third patient. In contrast, a single strain was found in sequential biopsy specimens from only three of eight patients (37%) receiving bismuth, metronidazole, and nitrofurantoin. Two strains were identified in five other patients receiving bismuth-antibiotic (63%). Immunoglobulin G antibodies to H. pylori were present in the sera of all patients. Thus, H. pylori colonization can persist for long periods (up to at least 4 years), despite high titers of immunoglobulin G antibodies in serum. Resistance to metronidazole was noted in some strains before and/or after treatment, but all strains remained susceptible to amoxicillin, tetracycline, and nitrofurantoin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7790461

Sequential accelerated tests: Improving the correlation of accelerated tests to module performance in the field

NASA Astrophysics Data System (ADS)

Felder, Thomas; Gambogi, William; Stika, Katherine; Yu, Bao-Ling; Bradley, Alex; Hu, Hongjie; Garreau-Iles, Lucie; Trout, T. John

2016-09-01

DuPont has been working steadily to develop accelerated backsheet tests that correlate with solar panels observations in the field. This report updates efforts in sequential testing. Single exposure tests are more commonly used and can be completed more quickly, and certain tests provide helpful predictions of certain backsheet failure modes. DuPont recommendations for single exposure tests are based on 25-year exposure levels for UV and humidity/temperature, and form a good basis for sequential test development. We recommend a sequential exposure of damp heat followed by UV then repetitions of thermal cycling and UVA. This sequence preserves 25-year exposure levels for humidity/temperature and UV, and correlates well with a large body of field observations. Measurements can be taken at intervals in the test, although the full test runs 10 months. A second, shorter sequential test based on damp heat and thermal cycling tests mechanical durability and correlates with loss of mechanical properties seen in the field. Ongoing work is directed toward shorter sequential tests that preserve good correlation to field data.

Networked Workstations and Parallel Processing Utilizing Functional Languages

DTIC Science & Technology

1993-03-01

program . This frees the programmer to concentrate on what the program is to do, not how the program is...traditional ’von Neumann’ architecture uses a timer based (e.g., the program counter), sequentially pro- grammed, single processor approach to problem...traditional ’von Neumann’ architecture uses a timer based (e.g., the program counter), sequentially programmed , single processor approach to

Automated single-slide staining device

NASA Technical Reports Server (NTRS)

Wilkins, J. R.; Mills, S. M. (Inventor)

1977-01-01

A simple apparatus and method is disclosed for making individual single Gram stains on bacteria inoculated slides to assist in classifying bacteria in the laboratory as Gram-positive or Gram-negative. The apparatus involves positioning a single inoculated slide in a stationary position and thereafter automatically and sequentially flooding the slide with increments of a primary stain, a mordant, a decolorizer, a counterstain and a wash solution in a sequential manner without the individual lab technician touching the slide and with minimum danger of contamination thereof from other slides.

Hemodynamic analysis of sequential graft from right coronary system to left coronary system.

PubMed

Wang, Wenxin; Mao, Boyan; Wang, Haoran; Geng, Xueying; Zhao, Xi; Zhang, Huixia; Xie, Jinsheng; Zhao, Zhou; Lian, Bo; Liu, Youjun

2016-12-28

Sequential and single grafting are two surgical procedures of coronary artery bypass grafting. However, it remains unclear if the sequential graft can be used between the right and left coronary artery system. The purpose of this paper is to clarify the possibility of right coronary artery system anastomosis to left coronary system. A patient-specific 3D model was first reconstructed based on coronary computed tomography angiography (CCTA) images. Two different grafts, the normal multi-graft (Model 1) and the novel multi-graft (Model 2), were then implemented on this patient-specific model using virtual surgery techniques. In Model 1, the single graft was anastomosed to right coronary artery (RCA) and the sequential graft was adopted to anastomose left anterior descending (LAD) and left circumflex artery (LCX). While in Model 2, the single graft was anastomosed to LAD and the sequential graft was adopted to anastomose RCA and LCX. A zero-dimensional/three-dimensional (0D/3D) coupling method was used to realize the multi-scale simulation of both the pre-operative and two post-operative models. Flow rates in the coronary artery and grafts were obtained. The hemodynamic parameters were also showed, including wall shear stress (WSS) and oscillatory shear index (OSI). The area of low WSS and OSI in Model 1 was much less than that in Model 2. Model 1 shows optimistic hemodynamic modifications which may enhance the long-term patency of grafts. The anterior segments of sequential graft have better long-term patency than the posterior segments. With rational spatial position of the heart vessels, the last anastomosis of sequential graft should be connected to the main branch.

Sequential lineup laps and eyewitness accuracy.

PubMed

Steblay, Nancy K; Dietrich, Hannah L; Ryan, Shannon L; Raczynski, Jeanette L; James, Kali A

2011-08-01

Police practice of double-blind sequential lineups prompts a question about the efficacy of repeated viewings (laps) of the sequential lineup. Two laboratory experiments confirmed the presence of a sequential lap effect: an increase in witness lineup picks from first to second lap, when the culprit was a stranger. The second lap produced more errors than correct identifications. In Experiment 2, lineup diagnosticity was significantly higher for sequential lineup procedures that employed a single versus double laps. Witnesses who elected to view a second lap made significantly more errors than witnesses who chose to stop after one lap or those who were required to view two laps. Witnesses with prior exposure to the culprit did not exhibit a sequential lap effect.

Simultaneous Versus Sequential Ptosis and Strabismus Surgery in Children.

PubMed

Revere, Karen E; Binenbaum, Gil; Li, Jonathan; Mills, Monte D; Katowitz, William R; Katowitz, James A

The authors sought to compare the clinical outcomes of simultaneous versus sequential ptosis and strabismus surgery in children. Retrospective, single-center cohort study of children requiring both ptosis and strabismus surgery on the same eye. Simultaneous surgeries were performed during a single anesthetic event; sequential surgeries were performed at least 7 weeks apart. Outcomes were ptosis surgery success (margin reflex distance 1 ≥ 2 mm, good eyelid contour, and good eyelid crease); strabismus surgery success (ocular alignment within 10 prism diopters of orthophoria and/or improved head position); surgical complications; and reoperations. Fifty-six children were studied, 38 had simultaneous surgery and 18 sequential. Strabismus surgery was performed first in 38/38 simultaneous and 6/18 sequential cases. Mean age at first surgery was 64 months, with mean follow up 27 months. A total of 75% of children had congenital ptosis; 64% had comitant strabismus. A majority of ptosis surgeries were frontalis sling (59%) or Fasanella-Servat (30%) procedures. There were no significant differences between simultaneous and sequential groups with regards to surgical success rates, complications, or reoperations (all p > 0.28). In the first comparative study of simultaneous versus sequential ptosis and strabismus surgery, no advantage for sequential surgery was seen. Despite a theoretical risk of postoperative eyelid malposition or complications when surgeries were performed in a combined manner, the rate of such outcomes was not increased with simultaneous surgeries. Performing ptosis and strabismus surgery together appears to be clinically effective and safe, and reduces anesthesia exposure during childhood.

Elimination of the last reactions in ergosterol biosynthesis alters the resistance of Saccharomyces cerevisiae to multiple stresses.

PubMed

Liu, Guodong; Chen, Yun; Færgeman, Nils J; Nielsen, Jens

2017-09-01

The sterol composition of membranes is known to influence many phenotypes of yeast. However, a systematic study of the relationship between sterol composition and stress resistances has not been conducted. Here, we therefore constructed single or double gene deletion mutants of the last four enzymes in ergosterol biosynthesis in a prototrophic genetic background of Saccharomyces cerevisiae. Identification of the sterol composition of these mutants revealed a high flexibility of the sterol-processing steps instead of the previously proposed sequential conversion. Compared with the wild type, the mutants showed altered resistances to different exogenous stresses regarding the specific growth rate and duration of lag phase. The erg5 deletion mutant whose sterol has a saturated side chain exhibited overall robust growth under the tested stress conditions. The thermotolerant phenotype of erg5 deletion mutant was reproduced in filamentous fungus Penicillium oxalicum. These results highlight the important role of sterols in the response of yeast cells to environmental stresses, and suggest the possibility of improving the robustness of industrial yeast strains by engineering their sterol composition. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Sequential treatment with aurora B inhibitors enhances cisplatin-mediated apoptosis via c-Myc.

PubMed

Ma, Yaxi; Cao, Handi; Lou, Siyue; Shao, Xuejing; Lv, Wen; Qi, Xiaotian; Liu, Yujia; Ying, Meidan; He, Qiaojun; Yang, Xiaochun

2015-04-01

Platinum compound such as cisplatin is the first-line chemotherapy of choice in most patients with ovarian carcinoma. However, patients with inherent or acquired cisplatin resistance often experience relapse. Therefore, novel therapies are urgently required to treat drug-resistant ovarian carcinoma. Here, we showed that compared to the non-functional traditional simultaneous treatment, sequential combination of Aurora B inhibitors followed by cisplatin synergistically enhanced apoptotic response in cisplatin-resistant OVCAR-8 cells. This effect was accompanied by the induction of polyploidy in a c-Myc-dependent manner, as c-Myc knockdown reduced the efficacy of the combination by suppressing the expression of Aurora B and impairing cellular response to Aurora B inhibitor, as indicated by the decreased polyploidy and hyperphosphorylation of histone H1. In c-Myc-deficient SKOV3 cells, c-Myc overexpression restored Aurora B expression, induced polyploidy after inhibition of Aurora B, and sensitized cells to this combination therapy. Thus, our report reveals for the first time that sequential treatment of Aurora B inhibitors and cisplatin is essential to inhibit ovarian carcinoma by inducing polyploidy and downregulating c-Myc and that c-Myc is identified as a predictive biomarker to select cells responsive to chemotherapeutical combinations targeting Aurora B. Collectively, these studies provide novel approaches to overcoming cisplatin chemotherapy resistance in ovarian cancer. Pretreatment of Aurora B inhibitors augment apoptotic effects of cisplatin. The synergy of Aurora B inhibitor with cisplatin is dependent on c-Myc expression. c-Myc-dependent induction of polyploidy sensitizes cells to cisplatin.

Sequential Linker Installation: Precise Placement of Functional Groups in Multivariate Metal-Organic Frameworks

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

Yuan, S; Lu, WG; Chen, YP

2015-03-11

A unique strategy, sequential linker installation (SLI), has been developed to construct multivariate MOFs with functional groups precisely positioned. PCN-700, a Zr-MOF with eight-connected Zr6O4(OH)(8)(H2O)(4) clusters, has been judiciously designed; the Zr-6 clusters in this MOF are arranged in such a fashion that, by replacement of terminal OH-/H2O ligands, subsequent insertion of linear dicarboxylate linkers is achieved. We demonstrate that linkers with distinct lengths and functionalities can be sequentially installed into PCN-700. Single-crystal to single-crystal transformation is realized so that the positions of the subsequently installed linkers are pinpointed via single-crystal X-ray diffraction analyses. This methodology provides a powerful toolmore » to construct multivariate MOFs with precisely positioned functionalities in the desired proximity, which would otherwise be difficult to achieve.« less

Antitumor efficacy of triple monoclonal antibody inhibition of epidermal growth factor receptor (EGFR) with MM151 in EGFR-dependent and in cetuximab-resistant human colorectal cancer cells

PubMed Central

Napolitano, Stefania; Martini, Giulia; Martinelli, Erika; Della Corte, Carminia Maria; Morgillo, Floriana; Belli, Valentina; Cardone, Claudia; Matrone, Nunzia; Ciardiello, Fortunato; Troiani, Teresa

2017-01-01

Purpose We investigated the effect of triple monoclonal antibody inhibition of EGFR to overcome acquired resistance to first generation of anti-EGFR inhibitors. Experimental design MM151 is a mixture of three different monoclonal IgG1 antibodies directed toward three different, non-overlapping, epitopes of the EGFR. We performed an in vivo study by using human CRC cell lines (SW48, LIM 1215 and CACO2) which are sensitive to EGFR inhibitors, in order to evaluate the activity of MM151 as compared to standard anti-EGFR mAbs, such as cetuximab, as single agent or in a sequential strategy of combination MM151 with irinotecan (induction therapy) followed by MM151 with a selective MEK1/2 inhibitor (MEKi) (maintenance therapy). Furthermore, the ability of MM151 to overcome acquired resistance to cetuximab has been also evaluated in cetuximab-refractory CRC models. Results MM151 shown stronger antitumor activity as compared to cetuximab. The maintenance treatment with MM151 plus MEKi resulted the most effective therapeutic modality. In fact, this combination caused an almost complete suppression of tumor growth in SW48, LIM 1215 and CACO2 xenografts model at 30 week. Moreover, in this treatment group, mice with no evidence of tumor were more than double as compared to single agent treated mice. Its superior activity has also been demonstrated, in cetuximab-refractory CRC models. Conclusions These results provide experimental evidence that more efficient and complete EGFR blockade may determine better antitumor activity and could contribute to prevent and/or overcome acquired resistance to EGFR inhibitors. PMID:29137301

The Estrous Cycle of the Ewe Is Resistant to Disruption by Repeated, Acute Psychosocial Stress1

PubMed Central

Wagenmaker, Elizabeth R.; Breen, Kellie M.; Oakley, Amy E.; Tilbrook, Alan J.; Karsch, Fred J.

2010-01-01

Five experiments were conducted to test the hypothesis that psychosocial stress interferes with the estrous cycle of sheep. In experiment 1, ewes were repeatedly isolated during the follicular phase. Timing, amplitude, and duration of the preovulatory luteinizing hormone (LH) surge were not affected. In experiment 2, follicular-phase ewes were subjected twice to a “layered stress” paradigm consisting of sequential, hourly application of isolation, restraint, blindfold, and predator cues. This reduced the LH pulse amplitude but did not affect the LH surge. In experiment 3, different acute stressors were given sequentially within the follicular phase: food denial plus unfamiliar noises and forced exercise, layered stress, exercise around midnight, and transportation. This, too, did not affect the LH surge. In experiment 4, variable acute psychosocial stress was given every 1–2 days for two entire estrous cycles; this did not disrupt any parameter of the cycle monitored. Lastly, experiment 5 examined whether the psychosocial stress paradigms of experiment 4 would disrupt the cycle and estrous behavior if sheep were metabolically stressed by chronic food restriction. Thirty percent of the food-restricted ewes exhibited deterioration of estrous cycle parameters followed by cessation of cycles and failure to express estrous behavior. However, disruption was not more evident in ewes that also encountered psychosocial stress. Collectively, these findings indicate the estrous cycle of sheep is remarkably resistant to disruption by acute bouts of psychosocial stress applied intermittently during either a single follicular phase or repeatedly over two estrous cycles. PMID:20164438

Resistant Hypertension On Treatment (ResHypOT): sequential nephron blockade compared to dual blockade of the renin-angiotensin-aldosterone system plus bisoprolol in the treatment of resistant arterial hypertension - study protocol for a randomized controlled trial.

PubMed

Cestário, Elizabeth do Espirito Santo; Fernandes, Letícia Aparecida Barufi; Giollo-Júnior, Luiz Tadeu; Uyemura, Jéssica Rodrigues Roma; Matarucco, Camila Suemi Sato; Landim, Manoel Idelfonso Paz; Cosenso-Martin, Luciana Neves; Tácito, Lúcia Helena Bonalume; Moreno, Heitor; Vilela-Martin, José Fernando; Yugar-Toledo, Juan Carlos

2018-02-12

Resistant hypertension is characterized when the blood pressure (BP) remains above the recommended goal after taking three antihypertensive drugs with synergistic actions at their maximum recommended tolerated doses, preferably including a diuretic. Identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether acting on the control of intravascular volume or sodium balance, or acting on the effects of the renin-angiotensin-aldosterone system (RAAS) on the kidney. This is a randomized, open-label, clinical trial is designed to compare sequential nephron blockade and its contribution to the intravascular volume component with dual blockade of the RAAS plus bisoprolol and the importance of serum renin in maintaining BP levels. The trial has two arms: sequential nephron blockade versus dual blockade of the RAAS (with an angiotensin converting enzyme (ACE) inhibitor plus a beta-blocker) both added-on to a thiazide diuretic, a calcium-channel blocker and an angiotensin receptor-1 blocker (ARB). Sequential nephron blockade consists in a progressive increase in sodium depletion using a thiazide diuretic, an aldosterone-receptor blocker, furosemide and, finally, amiloride. On the other hand, the dual blockade of the RAAS consists of the progressive addition of an ACE inhibitor until the maximum dose and then the administration of a beta-blocker until the maximum dose. The primary outcomes will be reductions in the systolic BP, diastolic BP, mean BP and pulse pressure (PP) after 20 weeks of treatment. The secondary outcomes will evaluate treatment safety and tolerability, biochemical changes, evaluation of renal function and recognition of hypotension (ambulatory BP monitoring (ABPM)). The sample size was calculated assuming an alpha error of 5% to reject the null hypothesis with a statistical power of 80% giving a total of 40 individuals per group. In recent years, the cost of resistant hypertension (RH) treatment has increased. Thus, identifying the contribution of intravascular volume and serum renin in maintaining BP levels could help tailor more effective hypertension treatment, whether by acting on the control of intravascular volume or sodium balance, or by acting on the effects of the RAAS on the kidney. Sequential Nephron Blockade vs. Dual Blockade Renin-angiotensin System + Bisoprolol in Resistant Arterial Hypertension (ResHypOT). ClinicalTrials.gov, ID: NCT02832973 . Registered on 14 July 2016. First received: 12 June 2016. Last updated: 18 July 2016.

Bioerodible System for Sequential Release of Multiple Drugs

PubMed Central

Sundararaj, Sharath C.; Thomas, Mark V.; Dziubla, Thomas D.; Puleo, David A.

2013-01-01

Because many complex physiological processes are controlled by multiple biomolecules, comprehensive treatment of certain disease conditions may be more effectively achieved by administration of more than one type of drug. Thus, the objective of the present research was to develop a multilayered, polymer-based system for sequential delivery of multiple drugs. The polymers used were cellulose acetate phthalate (CAP) complexed with Pluronic F-127 (P). After evaluating morphology of the resulting CAPP system, in vitro release of small molecule drugs and a model protein was studied from both single and multilayered devices. Drug release from single-layered CAPP films followed zero-order kinetics related to surface erosion of the association polymer. Release studies from multilayered CAPP devices showed the possibility of achieving intermittent release of one type of drug as well as sequential release of more than one type of drug. Mathematical modeling accurately predicted the release profiles for both single layer and multilayered devices. The present CAPP association polymer-based multilayer devices can be used for localized, sequential delivery of multiple drugs for the possible treatment of complex disease conditions, and perhaps for tissue engineering applications, that require delivery of more than one type of biomolecule. PMID:24096151

Effects of Temperature and Supply Voltage on SEU- and SET-Induced Errors in Bulk 40-nm Sequential Circuits

NASA Astrophysics Data System (ADS)

Chen, R. M.; Diggins, Z. J.; Mahatme, N. N.; Wang, L.; Zhang, E. X.; Chen, Y. P.; Zhang, H.; Liu, Y. N.; Narasimham, B.; Witulski, A. F.; Bhuva, B. L.; Fleetwood, D. M.

2017-08-01

The single-event sensitivity of bulk 40-nm sequential circuits is investigated as a function of temperature and supply voltage. An overall increase in SEU cross section versus temperature is observed at relatively high supply voltages. However, at low supply voltages, there is a threshold temperature beyond which the SEU cross section decreases with further increases in temperature. Single-event transient induced errors in flip-flops also increase versus temperature at relatively high supply voltages and are more sensitive to temperature variation than those caused by single-event upsets.

A single molecule assay to probe monovalent and multivalent bonds between hyaluronan and its key leukocyte receptor CD44 under force

NASA Astrophysics Data System (ADS)

Bano, Fouzia; Banerji, Suneale; Howarth, Mark; Jackson, David G.; Richter, Ralf P.

2016-09-01

Glycosaminoglycans (GAGs), a category of linear, anionic polysaccharides, are ubiquitous in the extracellular space, and important extrinsic regulators of cell function. Despite the recognized significance of mechanical stimuli in cellular communication, however, only few single molecule methods are currently available to study how monovalent and multivalent GAG·protein bonds respond to directed mechanical forces. Here, we have devised such a method, by combining purpose-designed surfaces that afford immobilization of GAGs and receptors at controlled nanoscale organizations with single molecule force spectroscopy (SMFS). We apply the method to study the interaction of the GAG polymer hyaluronan (HA) with CD44, its receptor in vascular endothelium. Individual bonds between HA and CD44 are remarkably resistant to rupture under force in comparison to their low binding affinity. Multiple bonds along a single HA chain rupture sequentially and independently under load. We also demonstrate how strong non-covalent bonds, which are versatile for controlled protein and GAG immobilization, can be effectively used as molecular anchors in SMFS. We thus establish a versatile method for analyzing the nanomechanics of GAG·protein interactions at the level of single GAG chains, which provides new molecular-level insight into the role of mechanical forces in the assembly and function of GAG-rich extracellular matrices.

An open-pattern droplet-in-oil planar array for single cell analysis based on sequential inkjet printing technology.

PubMed

Wang, Chenyu; Liu, Wenwen; Tan, Manqing; Sun, Hongbo; Yu, Yude

2017-07-01

Cellular heterogeneity represents a fundamental principle of cell biology for which a readily available single-cell research tool is urgently required. Here, we present a novel method combining cell-sized well arrays with sequential inkjet printing. Briefly, K562 cells with phosphate buffer saline buffer were captured at high efficiency (74.5%) in a cell-sized well as a "primary droplet" and sealed using fluorinated oil. Then, piezoelectric inkjet printing technology was adapted to precisely inject the cell lysis buffer and the fluorogenic substrate, fluorescein-di-β-D-galactopyranoside, as a "secondary droplet" to penetrate the sealing oil and fuse with the "primary droplet." We thereby successfully measured the intracellular β-galactosidase activity of K562 cells at the single-cell level. Our method allows, for the first time, the ability to simultaneously accommodate the high occupancy rate of single cells and sequential addition of reagents while retaining an open structure. We believe that the feasibility and flexibility of our method will enhance its use as a universal single-cell research tool as well as accelerate the adoption of inkjet printing in the study of cellular heterogeneity.

Sequential interactions-in which one player plays first and another responds-promote cooperation in evolutionary-dynamical simulations of single-shot Prisoner's Dilemma and Snowdrift games.

PubMed

Laird, Robert A

2018-09-07

Cooperation is a central topic in evolutionary biology because (a) it is difficult to reconcile why individuals would act in a way that benefits others if such action is costly to themselves, and (b) it underpins many of the 'major transitions of evolution', making it essential for explaining the origins of successively higher levels of biological organization. Within evolutionary game theory, the Prisoner's Dilemma and Snowdrift games are the main theoretical constructs used to study the evolution of cooperation in dyadic interactions. In single-shot versions of these games, wherein individuals play each other only once, players typically act simultaneously rather than sequentially. Allowing one player to respond to the actions of its co-player-in the absence of any possibility of the responder being rewarded for cooperation or punished for defection, as in simultaneous or sequential iterated games-may seem to invite more incentive for exploitation and retaliation in single-shot games, compared to when interactions occur simultaneously, thereby reducing the likelihood that cooperative strategies can thrive. To the contrary, I use lattice-based, evolutionary-dynamical simulation models of single-shot games to demonstrate that under many conditions, sequential interactions have the potential to enhance unilaterally or mutually cooperative outcomes and increase the average payoff of populations, relative to simultaneous interactions-benefits that are especially prevalent in a spatially explicit context. This surprising result is attributable to the presence of conditional strategies that emerge in sequential games that can't occur in the corresponding simultaneous versions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Noninferiority, randomized, controlled trial comparing embryo development using media developed for sequential or undisturbed culture in a time-lapse setup.

PubMed

Hardarson, Thorir; Bungum, Mona; Conaghan, Joe; Meintjes, Marius; Chantilis, Samuel J; Molnar, Laszlo; Gunnarsson, Kristina; Wikland, Matts

2015-12-01

To study whether a culture medium that allows undisturbed culture supports human embryo development to the blastocyst stage equivalently to a well-established sequential media. Randomized, double-blinded sibling trial. Independent in vitro fertilization (IVF) clinics. One hundred twenty-eight patients, with 1,356 zygotes randomized into two study arms. Embryos randomly allocated into two study arms to compare embryo development on a time-lapse system using a single-step medium or sequential media. Percentage of good-quality blastocysts on day 5. Percentage of day 5 good-quality blastocysts was 21.1% (standard deviation [SD] ± 21.6%) and 22.2% (SD ± 22.1%) in the single-step time-lapse medium (G-TL) and the sequential media (G-1/G-2) groups, respectively. The mean difference (-1.2; 95% CI, -6.0; 3.6) between the two media systems for the primary end point was less than the noninferiority margin of -8%. There was a statistically significantly lower number of good-quality embryos on day 3 in the G-TL group [50.7% (SD ± 30.6%) vs. 60.8% (SD ± 30.7%)]. Four out of the 11 measured morphokinetic parameters were statistically significantly different for the two media used. The mean levels of ammonium concentration in the media at the end of the culture period was statistically significantly lower in the G-TL group as compared with the G-2 group. We have shown that a single-step culture medium supports blastocyst development equivalently to established sequential media. The ammonium concentrations were lower in the single-step media, and the measured morphokinetic parameters were modified somewhat. NCT01939626. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Improved Murine Blastocyst Quality and Development in a Single Culture Medium Compared to Sequential Culture Media

PubMed Central

Hennings, Justin M.; Zimmer, Randall L.; Nabli, Henda; Davis, J. Wade; Sutovsky, Peter; Sutovsky, Miriam; Sharpe-Timms, Kathy L.

2015-01-01

Objective: Validate single versus sequential culture media for murine embryo development. Design: Prospective laboratory experiment. Setting: Assisted Reproduction Laboratory. Animals: Murine embryos. Interventions: Thawed murine zygotes cultured for 3 or 5 days (d3 or d5) in single or sequential embryo culture media developed for human in vitro fertilization. Main Outcome Measures: On d3, zygotes developing to the 8 cell (8C) stage or greater were quantified using 4’,6-diamidino-2-phenylindole (DAPI), and quality was assessed by morphological analysis. On d5, the number of embryos reaching the blastocyst stage was counted. DAPI was used to quantify total nuclei and inner cell mass nuclei. Localization of ubiquitin C-terminal hydrolase L1 (UCHL1) and ubiquitin C-terminal hydrolase L3 (UCHL3) was reference points for evaluating cell quality. Results: Comparing outcomes in single versus to sequential media, the odds of embryos developing to the 8C stage on d3 were 2.34 time greater (P = .06). On d5, more embryos reached the blastocyst stage (P = <.0001), hatched, and had significantly more trophoblast cells (P = .005) contributing to the increased total cell number. Also at d5, localization of distinct cytoplasmic UCHL1 and nuclear UCHL3 was found in high-quality hatching blastocysts. Localization of UCHL1 and UCHL3 was diffuse and inappropriately dispersed throughout the cytoplasm in low-quality nonhatching blastocysts. Conclusions: Single medium yields greater cell numbers, an increased growth rate, and more hatching of murine embryos. Cytoplasmic UCHL1 and nuclear UHCL3 localization patterns were indicative of embryo quality. Our conclusions are limited to murine embryos but one might speculate that single medium may also be more beneficial for human embryo culture. Human embryo studies are needed. PMID:26668049

Improved Murine Blastocyst Quality and Development in a Single Culture Medium Compared to Sequential Culture Media.

PubMed

Hennings, Justin M; Zimmer, Randall L; Nabli, Henda; Davis, J Wade; Sutovsky, Peter; Sutovsky, Miriam; Sharpe-Timms, Kathy L

2016-03-01

Validate single versus sequential culture media for murine embryo development. Prospective laboratory experiment. Assisted Reproduction Laboratory. Murine embryos. Thawed murine zygotes cultured for 3 or 5 days (d3 or d5) in single or sequential embryo culture media developed for human in vitro fertilization. On d3, zygotes developing to the 8 cell (8C) stage or greater were quantified using 4',6-diamidino-2-phenylindole (DAPI), and quality was assessed by morphological analysis. On d5, the number of embryos reaching the blastocyst stage was counted. DAPI was used to quantify total nuclei and inner cell mass nuclei. Localization of ubiquitin C-terminal hydrolase L1 (UCHL1) and ubiquitin C-terminal hydrolase L3 (UCHL3) was reference points for evaluating cell quality. Comparing outcomes in single versus to sequential media, the odds of embryos developing to the 8C stage on d3 were 2.34 time greater (P = .06). On d5, more embryos reached the blastocyst stage (P = <.0001), hatched, and had significantly more trophoblast cells (P = .005) contributing to the increased total cell number. Also at d5, localization of distinct cytoplasmic UCHL1 and nuclear UCHL3 was found in high-quality hatching blastocysts. Localization of UCHL1 and UCHL3 was diffuse and inappropriately dispersed throughout the cytoplasm in low-quality nonhatching blastocysts. Single medium yields greater cell numbers, an increased growth rate, and more hatching of murine embryos. Cytoplasmic UCHL1 and nuclear UHCL3 localization patterns were indicative of embryo quality. Our conclusions are limited to murine embryos but one might speculate that single medium may also be more beneficial for human embryo culture. Human embryo studies are needed. © The Author(s) 2015.

Optical and structural properties of cobalt-permalloy slanted columnar heterostructure thin films

NASA Astrophysics Data System (ADS)

Sekora, Derek; Briley, Chad; Schubert, Mathias; Schubert, Eva

2017-11-01

Optical and structural properties of sequential Co-column-NiFe-column slanted columnar heterostructure thin films with an Al2O3 passivation coating are reported. Electron-beam evaporated glancing angle deposition is utilized to deposit the sequential multiple-material slanted columnar heterostructure thin films. Mueller matrix generalized spectroscopic ellipsometry data is analyzed with a best-match model approach employing the anisotropic Bruggeman effective medium approximation formalism to determine bulk-like and anisotropic optical and structural properties of the individual Co and NiFe slanted columnar material sub-layers. Scanning electron microscopy is applied to image the Co-NiFe sequential growth properties and to verify the results of the ellipsometric analysis. Comparisons to single-material slanted columnar thin films and optically bulk solid thin films are presented and discussed. We find that the optical and structural properties of each material sub-layer of the sequential slanted columnar heterostructure film are distinct from each other and resemble those of their respective single-material counterparts.

Sequential Anaerobic/Aerobic Digestion for Enhanced Carbon/Nitrogen Removal and Cake Odor Reduction.

PubMed

Ahmad, Muneer; Denee, Marco Abel; Jiang, Hao; Eskicioglu, Cigdem; Kadota, Paul; Gregonia, Theresa

2016-12-01

  Anaerobic digestion (AD) has been proven to be an effective process for the treatment of wastewater sludge. However, it produces high levels of ammonia in the digester effluent, which may jeopardize meeting stringent nutrient discharge limits. In this study, the effect of a sequential anaerobic/aerobic (AN/AERO) digestion and a single-stage conventional AN digestion (as control) was investigated on mixed (primary + secondary) sludge generated by the Annacis Island wastewater treatment plant (WWTP) (BC, Canada). An overall sludge retention time (SRT) of 22.5 days under three different scenarios was chosen based on the current operational SRT of the digesters at the Annacis Island WWTP. The steady state results have shown that sequential AN/AERO digestion configurations achieved up to 11% higher volatile solids (VS) removal and 72% lower ammonia generation over single-stage conventional AN digestion. Furthermore, sequential AN/AERO system also showed enhanced dewaterability, improved fecal coliform destruction and reduced digested cake odors over control digesters.

Electricity generation and brewery wastewater treatment from sequential anode-cathode microbial fuel cell.

PubMed

Wen, Qing; Wu, Ying; Zhao, Li-xin; Sun, Qian; Kong, Fan-ying

2010-02-01

A sequential anode-cathode double-chamber microbial fuel cell (MFC), in which the effluent of anode chamber was used as a continuous feed for an aerated cathode chamber, was constructed in this experiment to investigate the performance of brewery wastewater treatment in conjugation with electricity generation. Carbon fiber was used as anode and plain carbon felt with biofilm as cathode. When hydraulic retention time (HRT) was 14.7 h, a relatively high chemical oxygen demand (COD) removal efficiency of 91.7%-95.7% was achieved under long-term stable operation. The MFC displayed an open circuit voltage of 0.434 V and a maximum power density of 830 mW/m(3) at an external resistance of 300 Omega. To estimate the electrochemical performance of the MFC, electrochemical measurements were carried out and showed that polarization resistance of anode was the major limiting factor in the MFC. Since a high COD removal efficiency was achieved, we conclude that the sequential anode-cathode MFC constructed with bio-cathode in this experiment could provide a new approach for brewery wastewater treatment.

Electricity generation and brewery wastewater treatment from sequential anode-cathode microbial fuel cell*

PubMed Central

Wen, Qing; Wu, Ying; Zhao, Li-xin; Sun, Qian; Kong, Fan-ying

2010-01-01

A sequential anode-cathode double-chamber microbial fuel cell (MFC), in which the effluent of anode chamber was used as a continuous feed for an aerated cathode chamber, was constructed in this experiment to investigate the performance of brewery wastewater treatment in conjugation with electricity generation. Carbon fiber was used as anode and plain carbon felt with biofilm as cathode. When hydraulic retention time (HRT) was 14.7 h, a relatively high chemical oxygen demand (COD) removal efficiency of 91.7%–95.7% was achieved under long-term stable operation. The MFC displayed an open circuit voltage of 0.434 V and a maximum power density of 830 mW/m3 at an external resistance of 300 Ω. To estimate the electrochemical performance of the MFC, electrochemical measurements were carried out and showed that polarization resistance of anode was the major limiting factor in the MFC. Since a high COD removal efficiency was achieved, we conclude that the sequential anode-cathode MFC constructed with bio-cathode in this experiment could provide a new approach for brewery wastewater treatment. PMID:20104642

Electromagnetic-induction logging to monitor changing chloride concentrations

USGS Publications Warehouse

Metzger, Loren F.; Izbicki, John A.

2013-01-01

Water from the San Joaquin Delta, having chloride concentrations up to 3590 mg/L, has intruded fresh water aquifers underlying Stockton, California. Changes in chloride concentrations at depth within these aquifers were evaluated using sequential electromagnetic (EM) induction logs collected during 2004 through 2007 at seven multiple-well sites as deep as 268 m. Sequential EM logging is useful for identifying changes in groundwater quality through polyvinyl chloride-cased wells in intervals not screened by wells. These unscreened intervals represent more than 90% of the aquifer at the sites studied. Sequential EM logging suggested degrading groundwater quality in numerous thin intervals, typically between 1 and 7 m in thickness, especially in the northern part of the study area. Some of these intervals were unscreened by wells, and would not have been identified by traditional groundwater sample collection. Sequential logging also identified intervals with improving water quality—possibly due to groundwater management practices that have limited pumping and promoted artificial recharge. EM resistivity was correlated with chloride concentrations in sampled wells and in water from core material. Natural gamma log data were used to account for the effect of aquifer lithology on EM resistivity. Results of this study show that a sequential EM logging is useful for identifying and monitoring the movement of high-chloride water, having lower salinities and chloride concentrations than sea water, in aquifer intervals not screened by wells, and that increases in chloride in water from wells in the area are consistent with high-chloride water originating from the San Joaquin Delta rather than from the underlying saline aquifer.

Changes in protein domains outside the catalytic site of the bacteriophage Qβ replicase reduce the mutagenic effect of 5-azacytidine.

PubMed

Cabanillas, Laura; Sanjuán, Rafael; Lázaro, Ester

2014-09-01

The high genetic heterogeneity and great adaptability of RNA viruses are ultimately caused by the low replication fidelity of their polymerases. However, single amino acid substitutions that modify replication fidelity can evolve in response to mutagenic treatments with nucleoside analogues. Here, we investigated how two independent mutants of the bacteriophage Qβ replicase (Thr210Ala and Tyr410His) reduce sensitivity to the nucleoside analogue 5-azacytidine (AZC). Despite being located outside the catalytic site, both mutants reduced the mutation frequency in the presence of the drug. However, they did not modify the type of AZC-induced substitutions, which was mediated mainly by ambiguous base pairing of the analogue with purines. Furthermore, the Thr210Ala and Tyr410His substitutions had little or no effect on replication fidelity in untreated viruses. Also, both substitutions were costly in the absence of AZC or when the action of the drug was suppressed by adding an excess of natural pyrimidines (uridine or cytosine). Overall, the phenotypic properties of these two mutants were highly convergent, despite the mutations being located in different domains of the Qβ replicase. This suggests that treatment with a given nucleoside analogue tends to select for a unique functional response in the viral replicase. In the last years, artificial increase of the replication error rate has been proposed as an antiviral therapy. In this study, we investigated the mechanisms by which two substitutions in the Qβ replicase confer partial resistance to the mutagenic nucleoside analogue AZC. As opposed to previous work with animal viruses, where different mutations selected sequentially conferred nucleoside analogue resistance through different mechanisms, our results suggest that there are few or no alternative AZC resistance phenotypes in Qβ. Also, despite resistance mutations being highly costly in the absence of the drug, there was no sequential fixation of secondary mutations. Bacteriophage Qβ is the virus with the highest reported mutation rate, which should make it particularly sensitive to nucleoside analogue treatments, probably favoring resistance mutations even if they incur high costs. The results are also relevant for understanding the possible pathways by which fidelity of the replication machinery can be modified. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Changes in thermo-tolerance and survival under simulated gastrointestinal conditions of Salmonella Enteritidis PT4 and Salmonella Typhimurium PT4 in chicken breast meat after exposure to sequential stresses.

PubMed

Melo, Adma Nadja Ferreira de; Souza, Geany Targino de; Schaffner, Donald; Oliveira, Tereza C Moreira de; Maciel, Janeeyre Ferreira; Souza, Evandro Leite de; Magnani, Marciane

2017-06-19

This study assessed changes in thermo-tolerance and capability to survive to simulated gastrointestinal conditions of Salmonella Enteritidis PT4 and Salmonella Typhimurium PT4 inoculated in chicken breast meat following exposure to stresses (cold, acid and osmotic) commonly imposed during food processing. The effects of the stress imposed by exposure to oregano (Origanum vulgare L.) essential oil (OVEO) on thermo-tolerance were also assessed. After exposure to cold stress (5°C for 5h) in chicken breast meat the test strains were sequentially exposed to the different stressing substances (lactic acid, NaCl or OVEO) at sub-lethal amounts, which were defined considering previously determined minimum inhibitory concentrations, and finally to thermal treatment (55°C for 30min). Resistant cells from distinct sequential treatments were exposed to simulated gastrointestinal conditions. The exposure to cold stress did not result in increased tolerance to acid stress (lactic acid: 5 and 2.5μL/g) for both strains. Cells of S. Typhimurium PT4 and S. Enteritidis PT4 previously exposed to acid stress showed higher (p<0.05) tolerance to osmotic stress (NaCl: 75 or 37.5mg/g) compared to non-acid-exposed cells. Exposure to osmotic stress without previous exposure to acid stress caused a salt-concentration dependent decrease in counts for both strains. Exposure to OVEO (1.25 and 0.62μL/g) decreased the acid and osmotic tolerance of both S. Enteritidis PT4 and S. Typhimurium PT4. Sequential exposure to acid and osmotic stress conditions after cold exposure increased (p<0.05) the thermo-tolerance in both strains. The cells that survived the sequential stress exposure (resistant) showed higher tolerance (p<0.05) to acidic conditions during continuous exposure (182min) to simulated gastrointestinal conditions. Resistant cells of S. Enteritidis PT4 and S. Typhimurium PT4 showed higher survival rates (p<0.05) than control cells at the end of the in vitro digestion. These results show that sequential exposure to multiple sub-lethal stresses may increase the thermo-tolerance and enhance the survival under gastrointestinal conditions of S. Enteritidis PT4 and S. Typhimurium PT4. Copyright © 2017 Elsevier B.V. All rights reserved.

Evolution of a double amino acid substitution in the 5-enolpyruvylshikimate-3-phosphate synthase in Eleusine indica conferring high-level glyphosate resistance.

PubMed

Yu, Qin; Jalaludin, Adam; Han, Heping; Chen, Ming; Sammons, R Douglas; Powles, Stephen B

2015-04-01

Glyphosate is the most important and widely used herbicide in world agriculture. Intensive glyphosate selection has resulted in the widespread evolution of glyphosate-resistant weed populations, threatening the sustainability of this valuable once-in-a-century agrochemical. Field-evolved glyphosate resistance due to known resistance mechanisms is generally low to modest. Here, working with a highly glyphosate-resistant Eleusine indica population, we identified a double amino acid substitution (T102I+P106S [TIPS]) in the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene in glyphosate-resistant individuals. This TIPS mutation recreates the biotechnology-engineered commercial first generation glyphosate-tolerant EPSPS in corn (Zea mays) and now in other crops. In E. indica, the naturally evolved TIPS mutants are highly (more than 180-fold) resistant to glyphosate compared with the wild type and more resistant (more than 32-fold) than the previously known P106S mutants. The E. indica TIPS EPSPS showed very high-level (2,647-fold) in vitro resistance to glyphosate relative to the wild type and is more resistant (600-fold) than the P106S variant. The evolution of the TIPS mutation in crop fields under glyphosate selection is likely a sequential event, with the P106S mutation being selected first and fixed, followed by the T102I mutation to create the highly resistant TIPS EPSPS. The sequential evolution of the TIPS mutation endowing high-level glyphosate resistance is an important mechanism by which plants adapt to intense herbicide selection and a dramatic example of evolution in action. © 2015 American Society of Plant Biologists. All Rights Reserved.

Evolution of a Double Amino Acid Substitution in the 5-Enolpyruvylshikimate-3-Phosphate Synthase in Eleusine indica Conferring High-Level Glyphosate Resistance1

PubMed Central

Yu, Qin; Jalaludin, Adam; Han, Heping; Chen, Ming; Sammons, R. Douglas; Powles, Stephen B.

2015-01-01

Glyphosate is the most important and widely used herbicide in world agriculture. Intensive glyphosate selection has resulted in the widespread evolution of glyphosate-resistant weed populations, threatening the sustainability of this valuable once-in-a-century agrochemical. Field-evolved glyphosate resistance due to known resistance mechanisms is generally low to modest. Here, working with a highly glyphosate-resistant Eleusine indica population, we identified a double amino acid substitution (T102I + P106S [TIPS]) in the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene in glyphosate-resistant individuals. This TIPS mutation recreates the biotechnology-engineered commercial first generation glyphosate-tolerant EPSPS in corn (Zea mays) and now in other crops. In E. indica, the naturally evolved TIPS mutants are highly (more than 180-fold) resistant to glyphosate compared with the wild type and more resistant (more than 32-fold) than the previously known P106S mutants. The E. indica TIPS EPSPS showed very high-level (2,647-fold) in vitro resistance to glyphosate relative to the wild type and is more resistant (600-fold) than the P106S variant. The evolution of the TIPS mutation in crop fields under glyphosate selection is likely a sequential event, with the P106S mutation being selected first and fixed, followed by the T102I mutation to create the highly resistant TIPS EPSPS. The sequential evolution of the TIPS mutation endowing high-level glyphosate resistance is an important mechanism by which plants adapt to intense herbicide selection and a dramatic example of evolution in action. PMID:25717039

Turning EGFR mutation-positive non-small-cell lung cancer into a chronic disease: optimal sequential therapy with EGFR tyrosine kinase inhibitors

PubMed Central

Hirsh, Vera

2018-01-01

Four epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), erlotinib, gefitinib, afatinib and osimertinib, are currently available for the management of EGFR mutation-positive non-small-cell lung cancer (NSCLC), with others in development. Although tumors are exquisitely sensitive to these agents, acquired resistance is inevitable. Furthermore, emerging data indicate that first- (erlotinib and gefitinib), second- (afatinib) and third-generation (osimertinib) EGFR TKIs differ in terms of efficacy and tolerability profiles. Therefore, there is a strong imperative to optimize the sequence of TKIs in order to maximize their clinical benefit. Osimertinib has demonstrated striking efficacy as a second-line treatment option in patients with T790M-positive tumors, and also confers efficacy and tolerability advantages over first-generation TKIs in the first-line setting. However, while accrual of T790M is the most predominant mechanism of resistance to erlotinib, gefitinib and afatinib, resistance mechanisms to osimertinib have not been clearly elucidated, meaning that possible therapy options after osimertinib failure are not clear. At present, few data comparing sequential regimens in patients with EGFR mutation-positive NSCLC are available and prospective clinical trials are required. This article reviews the similarities and differences between EGFR TKIs, and discusses key considerations when assessing optimal sequential therapy with these agents for the treatment of EGFR mutation-positive NSCLC. PMID:29383041

[Anesthesia in single and bilateral sequential lung transplantation. Lung Transplantation Group].

PubMed

Della Rocca, G; Coccia, C; Pugliese, F; Pompei, L; Ruberto, F; Costa, M G; Venuta, F; Rendina, E A; De Giacomo, T; Pietropaoli, P; Gasparetto, A

2000-04-01

Anesthesia for lung transplantation: intraoperative complications and long term results. 52 patients were scheduled for 16 single lung transplantations (SLT) (9 fibrosis and 7 emphysema) and 36 bilateral sequential lung transplantations (DLT) (4 bronchiectasis, 6 emphysema, 3 fibrosis, 22 cystic fibrosis and 1 pulmonary hypertension). Anesthesia was induced with propofol or midazolam, and fentanyl or alfentanil. As muscle relaxant vecuronium bromide was used. Anesthesia was maintained with isoflurane, fentanyl in boluses or sufentanil continuous infusion in O2 100%. Prostaglandin E1 (20-300 ng/kg/min), inhaled nitric oxide (10-40 ppm), dobutamine (5-15 mcg/kg/min), norepinephrine (0.05-3 mcg/kg/min) and ephedrine (5-10 mg per bolus) were used for hemodynamic management. In 2 patients inhaled areosolized prostacyclin were administered. Mean pulmonary arterial pressure (mPA) and pulmonary vascular resistance (PVRI) increased after pulmonary artery clamping during first lung (mPA: 3347 nel DLT, 3643 nel SLT; PVRI; 375488 nel DLT, 377420 nel SLT) and second lung implantation (mPA: 3746; PVRI: 263553) and decreased after reperfusion of the first (mPA: 4737 nel DLT, 4329 nel SLT; PVRI: 488263 nel DLT, 420233 nel SLT) and the second lung (mPA: 4629; PVRI: 553260). Only in 9 cases (7 DLT and 2 SLT) C-P bypass was used. With a strong drug support with pulmonary vasodilators, positive inotropic and systemic vasoconstrictor drugs, in most patients we transplanted C-P bypass can be avoided. Intraoperative deaths were not observed. Two years actuarial survival is 65% for DLT and 60% for SLT.

Resistance of various shiga toxin-producing Escherichia coli to electrolyzed oxidizing water

USDA-ARS?s Scientific Manuscript database

The resistance of thirty two strains of Escherichia coli O157:H7 and six major serotypes of non-O157 Shiga toxin- producing E. coli (STEC) plus E. coli O104 was tested against Electrolyzed oxidizing (EO) water using two different methods; modified AOAC 955.16 sequential inoculation method and minim...

A retrospective study on sequential desensitization-rechallenge for antituberculosis drug allergy

PubMed Central

Chia, Faith Li-Ann; Tan, Sze-Chin; Tan, Teck-Choon; Leong, Khai-Pang; Tan, Justina Wei-Lyn; Tang, Chwee-Ying; Hou, Jin-Feng; Chan, Grace Yin-Lai; Chng, Hiok-Hee

2014-01-01

Background Antituberculosis (anti-TB) drug allergy often involves multiple concurrently administered drugs which subsequently need to be reinitiated as no better alternatives exist. Objective To describe the results of tailored sequential desensitization-rechallenge (D-R) for anti-TB drug allergy. Methods Consecutive patients who had undergone D-R to anti-TB drugs between 1 September 1997 and 31 January 2012 were recruited. Following resolution of the acute reaction, anti-TB drug was restarted at 1:6,000 to 1:3 of the final daily dose (FDD), with gradual single or multiple step daily dose escalation to the FDD. Subsequent drugs were sequentially added ≥3 days later when the preceding drug was tolerated. Full blood count and liver function tests were monitored prior to addition of each new drug. Results There were 11 patients of whom 10 were male, predominantly Chinese (8 patients). Regimens comprised at least 3 drugs: isoniazid (INH), rifampicin (RIF), ethambutol (EMB), pyrazinamide (PZA), or streptomycin. All patients had nonimmediate reactions, with cutaneous eruptions, where maculopapular exanthema (MPE) was the most common (8 patients). Drug-induced hypersensitivity syndrome (DIHS) occurred in 6 patients, and Stevens Johnson syndrome (SJS) in 2 patients. D-R to INH was successful in 7/9 patients (77.8%) and to RIF/EMB/PZA/streptomycin in all. Of the 2 patients who failed INH D-R, 1 developed fever and MPE on day 3, the other MPE on day 8. D-R with INH and RIF respectively was successful in 2 patients with SJS. Among DIHS patients, 1 failed D-R with INH (fever and MPE on day 3). There were 23/25 (92%) successful D-R among the 11 patients. All patients completed TB treatment of ≥5 months' duration with no cases of drug-resistant TB. Conclusion Tailored sequential TB drug D-R is successful where no better alternative therapies are available, with careful dose escalation and close monitoring, and after a careful risk-benefit assessment. PMID:25097851

Sequential Requests and the Problem of Message Sampling.

ERIC Educational Resources Information Center

Cantrill, James Gerard

S. Jackson and S. Jacobs's criticism of "single message" designs in communication research served as a framework for a study that examined the differences between various sequential request paradigms. The study sought to answer the following questions: (1) What were the most naturalistic request sequences assured to replicate…

The role of fibers in the femoral attachment of the anterior cruciate ligament in resisting tibial displacement.

PubMed

Kawaguchi, Yasuyuki; Kondo, Eiji; Takeda, Ryo; Akita, Keiichi; Yasuda, Kazunori; Amis, Andrew A

2015-03-01

The purpose was to clarify the load-bearing functions of the fibers of the femoral anterior cruciate ligament (ACL) attachment in resisting tibial anterior drawer and rotation. A sequential cutting study was performed on 8 fresh-frozen human knees. The femoral attachment of the ACL was divided into a central area that had dense fibers inserting directly into the femur and anterior and posterior fan-like extension areas. The ACL fibers were cut sequentially from the bone: the posterior fan-like area in 2 stages, the central dense area in 4 stages, and then the anterior fan-like area in 2 stages. Each knee was mounted in a robotic joint testing system that applied tibial anteroposterior 6-mm translations and 10° or 15° of internal rotation at 0° to 90° of flexion. The reduction of restraining force or moment was measured after each cut. The central area resisted 82% to 90% of the anterior drawer force; the anterior fan-like area, 2% to 3%; and the posterior fan-like area, 11% to 15%. Among the 4 central areas, most load was carried close to the roof of the intercondylar notch: the anteromedial bundle resisted 66% to 84% of the force and the posterolateral bundle resisted 16% to 9% from 0° to 90° of flexion. There was no clear pattern for tibial internal rotation, with the load shared among the posterodistal and central areas near extension and mostly the central areas in flexion. Under the experimental conditions described, 66% to 84% of the resistance to tibial anterior drawer arose from the ACL fibers at the central-proximal area of the femoral attachment, corresponding to the anteromedial bundle; the fan-like extension fibers contributed very little. This work did not support moving a single-bundle ACL graft to the side wall of the notch or attempting to cover the whole attachment area if the intention was to mimic how the natural ACL resists tibial displacements. There is ongoing debate about how best to reconstruct the ACL to restore normal knee function, including where is the best place for ACL graft tunnels. This study found that the most important area on the femur, in terms of resisting displacement of the tibia, was in the central-anterior part of the femoral ACL attachment, near the roof of the intercondylar notch. The testing protocol did not lead to data that would support using a large ACL graft tunnel that attempts to cover the whole natural femoral attachment area. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

The Role of Fibers in the Femoral Attachment of the Anterior Cruciate Ligament in Resisting Tibial Displacement

PubMed Central

Kawaguchi, Yasuyuki; Kondo, Eiji; Takeda, Ryo; Akita, Keiichi; Yasuda, Kazunori; Amis, Andrew A.

2015-01-01

Purpose The purpose was to clarify the load-bearing functions of the fibers of the femoral anterior cruciate ligament (ACL) attachment in resisting tibial anterior drawer and rotation. Methods A sequential cutting study was performed on 8 fresh-frozen human knees. The femoral attachment of the ACL was divided into a central area that had dense fibers inserting directly into the femur and anterior and posterior fan-like extension areas. The ACL fibers were cut sequentially from the bone: the posterior fan-like area in 2 stages, the central dense area in 4 stages, and then the anterior fan-like area in 2 stages. Each knee was mounted in a robotic joint testing system that applied tibial anteroposterior 6-mm translations and 10° or 15° of internal rotation at 0° to 90° of flexion. The reduction of restraining force or moment was measured after each cut. Results The central area resisted 82% to 90% of the anterior drawer force; the anterior fan-like area, 2% to 3%; and the posterior fan-like area, 11% to 15%. Among the 4 central areas, most load was carried close to the roof of the intercondylar notch: the anteromedial bundle resisted 66% to 84% of the force and the posterolateral bundle resisted 16% to 9% from 0° to 90° of flexion. There was no clear pattern for tibial internal rotation, with the load shared among the posterodistal and central areas near extension and mostly the central areas in flexion. Conclusions Under the experimental conditions described, 66% to 84% of the resistance to tibial anterior drawer arose from the ACL fibers at the central-proximal area of the femoral attachment, corresponding to the anteromedial bundle; the fan-like extension fibers contributed very little. This work did not support moving a single-bundle ACL graft to the side wall of the notch or attempting to cover the whole attachment area if the intention was to mimic how the natural ACL resists tibial displacements. Clinical Relevance There is ongoing debate about how best to reconstruct the ACL to restore normal knee function, including where is the best place for ACL graft tunnels. This study found that the most important area on the femur, in terms of resisting displacement of the tibia, was in the central-anterior part of the femoral ACL attachment, near the roof of the intercondylar notch. The testing protocol did not lead to data that would support using a large ACL graft tunnel that attempts to cover the whole natural femoral attachment area. PMID:25530509

Blastocyst culture using single versus sequential media in clinical IVF: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Sfontouris, Ioannis A; Martins, Wellington P; Nastri, Carolina O; Viana, Iara G R; Navarro, Paula A; Raine-Fenning, Nick; van der Poel, Sheryl; Rienzi, Laura; Racowsky, Catherine

2016-10-01

The purpose of this study was to undertake a review of the available evidence comparing the use of a single medium versus sequential media for embryo culture to the blastocyst stage in clinical IVF. We searched the Cochrane Central, PubMed, Scopus, ClinicalTrials.gov, Current Controlled Trials and WHO International Clinical Trials Registry Platform to identify randomized controlled trials comparing single versus sequential media for blastocyst culture and ongoing pregnancy rate. Included studies randomized either oocytes/zygotes or women. Eligible oocyte/zygote studies were analyzed to assess the risk difference (RD) and 95 % confidence intervals (CI) between the two media systems; eligible woman-based studies were analyzed to assess the risk ratio (RR) and 95 % CI for clinical pregnancy rate. No differences were observed between single and sequential media for either ongoing pregnancy per randomized woman (relative risk (RR) = 0.9, 95 % CI = 0.7 to 1.3, two studies including 246 women, I 2  = 0 %) or clinical pregnancy per randomized woman (RR = 1.0, 95 % CI = 0.7 to 1.4, one study including 100 women); or miscarriage per clinical pregnancy: RR = 1.3, 95 % CI = 0.4 to 4.3, two studies including 246 participants, I 2  = 0 %). Single media use was associated with an increase blastocyst formation per randomized oocyte/zygote (relative distribution (RD) = +0.06, 95 % CI = +0.01 to +0.12, ten studies including 7455 oocytes/zygotes, I 2  = 83 %) but not top/high blastocyst formation (RD = +0.05, 95 % CI = -0.01 to +0.11, five studies including 3879 oocytes/zygotes, I 2  = 93 %). The overall quality of the evidence was very low for all these four outcomes. Although using a single medium for extended culture has some practical advantages and blastocyst formation rates appear to be higher, there is insufficient evidence to recommend either sequential or single-step media as being superior for the culture of embryos to days 5/6. Future studies comparing these two media systems in well-designed trials should be performed.

Finite element modeling of borehole heat exchanger systems. Part 1. Fundamentals

NASA Astrophysics Data System (ADS)

Diersch, H.-J. G.; Bauer, D.; Heidemann, W.; Rühaak, W.; Schätzl, P.

2011-08-01

Single borehole heat exchanger (BHE) and arrays of BHE are modeled by using the finite element method. The first part of the paper derives the fundamental equations for BHE systems and their finite element representations, where the thermal exchange between the borehole components is modeled via thermal transfer relations. For this purpose improved relationships for thermal resistances and capacities of BHE are introduced. Pipe-to-grout thermal transfer possesses multiple grout points for double U-shape and single U-shape BHE to attain a more accurate modeling. The numerical solution of the final 3D problems is performed via a widely non-sequential (essentially non-iterative) coupling strategy for the BHE and porous medium discretization. Four types of vertical BHE are supported: double U-shape (2U) pipe, single U-shape (1U) pipe, coaxial pipe with annular (CXA) and centred (CXC) inlet. Two computational strategies are used: (1) The analytical BHE method based on Eskilson and Claesson's (1988) solution, (2) numerical BHE method based on Al-Khoury et al.'s (2005) solution. The second part of the paper focusses on BHE meshing aspects, the validation of BHE solutions and practical applications for borehole thermal energy store systems.

Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias

PubMed Central

Weisberg, Ellen; Catley, Laurie; Wright, Renee D.; Moreno, Daisy; Banerji, Lolita; Ray, Arghya; Manley, Paul W.; Mestan, Juergen; Fabbro, Doriano; Jiang, Jingrui; Hall-Meyers, Elizabeth; Callahan, Linda; DellaGatta, Jamie L.; Kung, Andrew L.

2007-01-01

Drug resistance resulting from emergence of imatinib-resistant BCR-ABL point mutations is a significant problem in advanced-stage chronic myelogenous leukemia (CML). The BCR-ABL inhibitor, nilotinib (AMN107), is significantly more potent against BCR-ABL than imatinib, and is active against many imatinib-resistant BCR-ABL mutants. Phase 1/2 clinical trials show that nilotinib can induce remissions in patients who have previously failed imatinib, indicating that sequential therapy with these 2 agents has clinical value. However, simultaneous, rather than sequential, administration of 2 BCR-ABL kinase inhibitors is attractive for many reasons, including the theoretical possibility that this could reduce emergence of drug-resistant clones. Here, we show that exposure of a variety of BCR-ABL+ cell lines to imatinib and nilotinib results in additive or synergistic cytotoxicity, including testing of a large panel of cells expressing BCR-ABL point mutations causing resistance to imatinib in patients. Further, using a highly quantifiable bioluminescent in vivo model, drug combinations were at least additive in antileukemic activity, compared with each drug alone. These results suggest that despite binding to the same site in the same target kinase, the combination of imatinib and nilotinib is highly efficacious in these models, indicating that clinical testing of combinations of BCR-ABL kinase inhibitors is warranted. PMID:17068153

High- and Low-Load Resistance Training: Interpretation and Practical Application of Current Research Findings.

PubMed

Fisher, James; Steele, James; Smith, Dave

2017-03-01

Our current state of knowledge regarding the load (lighter or heavier) lifted in resistance training programmes that will result in 'optimal' strength and hypertrophic adaptations is unclear. Despite this, position stands and recommendations are made based on, we propose, limited evidence to lift heavier weights. Here we discuss the state of evidence on the impact of load and how it, as a single variable, stimulates adaptations to take place and whether evidence for recommending heavier loads is available, well-defined, currently correctly interpreted or has been overlooked. Areas of discussion include electromyography amplitude, in vivo and in vitro methods of measuring hypertrophy, and motor schema and skill acquisition. The present piece clarifies to trainers and trainees the impact of these variables by discussing interpretation of synchronous and sequential motor unit recruitment and revisiting the size principle, poor agreement between whole-muscle cross-sectional area (CSA) and biopsy-determined changes in myofibril CSA, and neural adaptations around task specificity. Our opinion is that the practical implications of being able to self-select external load include reducing the need for specific facility memberships, motivating older persons or those who might be less confident using heavy loads, and allowing people to undertake home- or field-based resistance training intervention strategies that might ultimately improve exercise adherence.

Glucose-6-phosphate dehydrogenase deficiency and the risk of malaria: A meta-analysis and trial sequential analysis

NASA Astrophysics Data System (ADS)

Sun, Fengmei; Zhang, Juan; Pu, Yuepu

2017-10-01

This study is designed to perform a meta-analysis and trial sequential analysis (TSA) to investigate whether people with G6PD deficiency suffered less malarial infection. We searched from PubMed, Science Direct, Springer Link, CNKI, and Wan Fang databases for case-control study, cohort study or cross section study until April 2017. TSA was used to determine the state of evidence and calculate the required sample size. Eight case-control studies and five cross-sectional studies (30,683participants) were included in this meta-analysis. Compared with normal control group, we found significant protection from severe malaria (OR 0.644, 95% CI [0.493-0.842]; P=0.001) among people with decreasing G6PD activity. People with variations of G6PD gene at nucleotide 202(G6PD A-) were also found to be associated with resistance on severe malaria pooled (OR 0.851, 95% CI [0.779-0.930]; P =0.0001). Sex-stratified test suggested that protection of severe malaria is conferred to both G6PD A-males and heterozygous females (with a single copy of the variant). In conclusion, our study found a significant protection from severe malaria among G6PD deficient people compared to the

Variations in the technique for autologous limbal transplantation.

PubMed

Mataix, B; Alcántara, A; Caro, M; Montero, J; Ponte, B; Rodríguez de la Rúa, E

2016-10-01

To present the results on the use of a single block limbal autograft, combined with amniotic membrane transplantation and sectoral sequential postoperative epitheliectomy of the conjunctiva in 2 patients with unilateral total limbal stem cell deficiency. A single block limbal autograft combined with amniotic membrane transplantation may be sufficient to restore a stable corneal surface, but sometimes sequential sectoral conjunctival epitheliectomy may be required to treat anomalous epithelial remnants. Copyright © 2016 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

A translational study of resistance emergence using sequential direct-acting antiviral agents for hepatitis C using ultra-deep sequencing.

PubMed

Abe, Hiromi; Hayes, C Nelson; Hiraga, Nobuhiko; Imamura, Michio; Tsuge, Masataka; Miki, Daiki; Takahashi, Shoichi; Ochi, Hidenori; Chayama, Kazuaki

2013-09-01

Direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) have recently been developed and are ultimately hoped to replace interferon-based therapy. However, DAA monotherapy results in rapid emergence of resistant strains and DAAs must be used in combinations that present a high genetic barrier to resistance, although viral kinetics of multidrug-resistant strains remain poorly characterized. The aim of this study is to track the emergence and fitness of resistance using combinations of telaprevir and NS5A or NS5B inhibitors with genotype 1b clones. HCV-infected chimeric mice were treated with DAAs, and resistance was monitored using direct and ultra-deep sequencing. Combination therapy with telaprevir and BMS-788329 (NS5A inhibitor) reduced serum HCV RNA to undetectable levels. The presence of an NS3-V36A telaprevir resistance mutation resulted in poor response to telaprevir monotherapy but showed significant HCV reduction when telaprevir was combined with BMS-788329. However, a BMS-788329-resistant strain emerged at low frequency. Infection with a BMS-788329-resistant NS5A-L31V mutation rapidly resulted in gain of an additional NS5A-Y93A mutation that conferred telaprevir resistance during combination therapy. Infection with dual NS5AL31V/NS5AY93H mutations resulted in poor response to combination therapy and development of telaprevir resistance. Although HCV RNA became undetectable soon after the beginning of combination therapy with BMS-788329 and BMS-821095 (NS5B inhibitor), rebound with emergence of resistance against all three drugs occurred. Triple resistance also occurred following infection with the NS3V36A/NS5AL31V/NS5AY93H triple mutation. Resistant strains easily develop from cloned virus strains. Sequential use of DAAs should be avoided to prevent emergence of multidrug-resistant strains.

Conceptual scoring of receptive and expressive vocabulary measures in simultaneous and sequential bilingual children.

PubMed

Gross, Megan; Buac, Milijana; Kaushanskaya, Margarita

2014-11-01

The authors examined the effects of conceptual scoring on the performance of simultaneous and sequential bilinguals on standardized receptive and expressive vocabulary measures in English and Spanish. Participants included 40 English-speaking monolingual children, 39 simultaneous Spanish-English bilingual children, and 19 sequential bilingual children, ages 5-7. The children completed standardized receptive and expressive vocabulary measures in English and also in Spanish for those who were bilingual. After the standardized administration, bilingual children were given the opportunity to respond to missed items in their other language to obtain a conceptual score. Controlling for group differences in socioeconomic status (SES), both simultaneous and sequential bilingual children scored significantly below monolingual children on single-language measures of English receptive and expressive vocabulary. Conceptual scoring removed the significant difference between monolingual and simultaneous bilingual children in the receptive modality but not in the expressive modality; differences remained between monolingual and sequential bilingual children in both modalities. However, in both bilingual groups, conceptual scoring increased the proportion of children with vocabulary scores within the average range. Conceptual scoring does not fully ameliorate the bias inherent in single-language standardized vocabulary measures for bilingual children, but the procedures employed here may assist in ruling out vocabulary deficits, particularly in typically developing simultaneous bilingual children.

Conceptual scoring of receptive and expressive vocabulary measures in simultaneous and sequential bilingual children

PubMed Central

Gross, Megan; Buac, Milijana; Kaushanskaya, Margarita

2014-01-01

Purpose This study examined the effects of conceptual scoring on the performance of simultaneous and sequential bilinguals on standardized receptive and expressive vocabulary measures in English and Spanish. Method Participants included 40 English-speaking monolingual children, 39 simultaneous Spanish-English bilingual children, and 19 sequential bilinguals, ages 5–7. The children completed standardized receptive and expressive vocabulary measures in English and also in Spanish for bilinguals. After the standardized administration, bilinguals were given the opportunity to respond to missed items in their other language to obtain a conceptual score. Results Controlling for group differences in socioeconomic status (SES), both simultaneous and sequential bilinguals scored significantly below monolinguals on single-language measures of English receptive and expressive vocabulary. Conceptual scoring removed the significant difference between monolinguals and simultaneous bilinguals in the receptive modality, but not in the expressive modality; differences remained between monolinguals and sequential bilinguals in both modalities. However, in both bilingual groups conceptual scoring increased the proportion of children with vocabulary scores within the average range. Conclusions Conceptual scoring does not fully ameliorate the bias inherent in single-language standardized vocabulary measures for bilinguals, but the procedures employed here may assist in ruling out vocabulary deficits, particularly in typically-developing simultaneous bilingual children. PMID:24811415

Investigating Stage-Sequential Growth Mixture Models with Multiphase Longitudinal Data

ERIC Educational Resources Information Center

Kim, Su-Young; Kim, Jee-Seon

2012-01-01

This article investigates three types of stage-sequential growth mixture models in the structural equation modeling framework for the analysis of multiple-phase longitudinal data. These models can be important tools for situations in which a single-phase growth mixture model produces distorted results and can allow researchers to better understand…

Proportion Congruent Effects in the Absence of Sequential Congruent Effects

ERIC Educational Resources Information Center

Torres-Quesada, Maryem; Milliken, Bruce; Lupiáñez, Juan; Funes, María Jesús

2014-01-01

A debated question in the cognitive control field is whether cognitive control is best conceptualized as a collection of distinct control mechanisms or a single general purpose mechanism. In an attempt to answer this question, previous studies have dissociated two well-known effects related to cognitive control: sequential congruence and…

Metal fractionation in olive oil and urban sewage sludges using the three-stage BCR sequential extraction method and microwave single extractions.

PubMed

Pérez Cid, B; Fernández Alborés, A; Fernández Gómez, E; Faliqé López, E

2001-08-01

The conventional three-stage BCR sequential extraction method was employed for the fractionation of heavy metals in sewage sludge samples from an urban wastewater treatment plant and from an olive oil factory. The results obtained for Cu, Cr, Ni, Pb and Zn in these samples were compared with those attained by a simplified extraction procedure based on microwave single extractions and using the same reagents as employed in each individual BCR fraction. The microwave operating conditions in the single extractions (heating time and power) were optimized for all the metals studied in order to achieve an extraction efficiency similar to that of the conventional BCR procedure. The measurement of metals in the extracts was carried out by flame atomic absorption spectrometry. The results obtained in the first and third fractions by the proposed procedure were, for all metals, in good agreement with those obtained using the BCR sequential method. Although in the reducible fraction the extraction efficiency of the accelerated procedure was inferior to that of the conventional method, the overall metals leached by both microwave single and sequential extractions were basically the same (recoveries between 90.09 and 103.7%), except for Zn in urban sewage sludges where an extraction efficiency of 87% was achieved. Chemometric analysis showed a good correlation between the results given by the two extraction methodologies compared. The application of the proposed approach to a certified reference material (CRM-601) also provided satisfactory results in the first and third fractions, as it was observed for the sludge samples analysed.

Sequential glycan profiling at single cell level with the microfluidic lab-in-a-trench platform: a new era in experimental cell biology.

PubMed

O'Connell, Tríona M; King, Damien; Dixit, Chandra K; O'Connor, Brendan; Walls, Dermot; Ducrée, Jens

2014-09-21

It is now widely recognised that the earliest changes that occur on a cell when it is stressed or becoming diseased are alterations in its surface glycosylation. Current state-of-the-art technologies in glycoanalysis include mass spectrometry, protein microarray formats, techniques in cytometry and more recently, glyco-quantitative polymerase chain reaction (Glyco-qPCR). Techniques for the glycoprofiling of the surfaces of single cells are either limited to the analysis of large cell populations or are unable to handle multiple and/or sequential probing. Here, we report a novel approach of single live cell glycoprofiling enabled by the microfluidic "Lab-in-a-Trench" (LiaT) platform for performing capture and retention of cells, along with shear-free reagent loading and washing. The significant technical improvement on state-of-the-art is the demonstration of consecutive, spatio-temporally profiling of glycans on a single cell by sequential elution of the previous lectin probe using their corresponding free sugar. We have qualitatively analysed glycan density on the surface of individual cells. This has allowed us to qualitatively co-localise the observed glycans. This approach enables exhaustive glycoprofiling and glycan mapping on the surface of individual live cells with multiple lectins. The possibility of sequentially profiling glycans on cells will be a powerful new tool to add to current glycoanalytical techniques. The LiaT platform will enable cell biologists to perform many high sensitivity assays and also will also make a significant impact on biomarker research.

Single-visit or multiple-visit root canal treatment: systematic review, meta-analysis and trial sequential analysis

PubMed Central

Schwendicke, Falk; Göstemeyer, Gerd

2017-01-01

Objectives Single-visit root canal treatment has some advantages over conventional multivisit treatment, but might increase the risk of complications. We systematically evaluated the risk of complications after single-visit or multiple-visit root canal treatment using meta-analysis and trial-sequential analysis. Data Controlled trials comparing single-visit versus multiple-visit root canal treatment of permanent teeth were included. Trials needed to assess the risk of long-term complications (pain, infection, new/persisting/increasing periapical lesions ≥1 year after treatment), short-term pain or flare-up (acute exacerbation of initiation or continuation of root canal treatment). Sources Electronic databases (PubMed, EMBASE, Cochrane Central) were screened, random-effects meta-analyses performed and trial-sequential analysis used to control for risk of random errors. Evidence was graded according to GRADE. Study selection 29 trials (4341 patients) were included, all but 6 showing high risk of bias. Based on 10 trials (1257 teeth), risk of complications was not significantly different in single-visit versus multiple-visit treatment (risk ratio (RR) 1.00 (95% CI 0.75 to 1.35); weak evidence). Based on 20 studies (3008 teeth), risk of pain did not significantly differ between treatments (RR 0.99 (95% CI 0.76 to 1.30); moderate evidence). Risk of flare-up was recorded by 8 studies (1110 teeth) and was significantly higher after single-visit versus multiple-visit treatment (RR 2.13 (95% CI 1.16 to 3.89); very weak evidence). Trial-sequential analysis revealed that firm evidence for benefit, harm or futility was not reached for any of the outcomes. Conclusions There is insufficient evidence to rule out whether important differences between both strategies exist. Clinical significance Dentists can provide root canal treatment in 1 or multiple visits. Given the possibly increased risk of flare-ups, multiple-visit treatment might be preferred for certain teeth (eg, those with periapical lesions). PMID:28148534

Sequential liquid biopsies reveal dynamic alterations of EGFR driver mutations and indicate EGFR amplification as a new mechanism of resistance to osimertinib in NSCLC.

PubMed

Knebel, Franciele H; Bettoni, Fabiana; Shimada, Andrea K; Cruz, Manoel; Alessi, João Victor; Negrão, Marcelo V; Reis, Luiz Fernando L; Katz, Artur; Camargo, Anamaria A

2017-06-01

Osimertinib is an EGFR-T790M-specific TKI, which has demonstrated impressive response rates in NSCLC, after failure to first-line anti-EGFR TKIs. However, acquired resistance to osimertinib is also observed and the molecular mechanisms of resistance are not yet fully understood. Monitoring and managing NSCLC patients who progressed on osimertinib is, therefore, emerging as an important clinical challenge. Sequential liquid biopsies were used to monitor a patient with EGFR-exon19del positive NSCLC, who received erlotinib and progressed through the acquisition of the EGFR-T790M mutation. Erlotinib was discontinued and osimertinib was initiated. Blood samples were collected at erlotinib progression and during osimertinib treatment for the detection of the activating (EGFR-exon19del) and resistance mutations (EGFR-T790M, EGFR-C797S, BRAF-V600E, METamp and ERBB2amp) in the plasma DNA using digital droplet PCR. Plasma levels of the activating EGFR-exon19del accurately paralleled the clinical and radiological progression of disease and allowed early detection of AR to osimertinib. Resistance to osimertinib coincided with the emergence of a small tumor cell subpopulation carrying the known EGFR-C797S resistance mutation and an additional subpopulation carrying amplified copies of EGFR-exon19del. Given the existence of multiple AR mechanisms, quantification of the original EGFR activation mutation, instead of the resistance mutations, can be efficiently used to monitor response to osimertinib, allowing early detection of AR. Absolute quantification of both activation and resistance mutations can provide important information on tumor clonal evolution upon progression to osimertinib. Selective amplification of the EGFR-exon19del allele may represent a novel resistance mechanism to osimertinib. Copyright © 2017 Elsevier B.V. All rights reserved.

Tissue Inhibitor of Metalloproteinase 1 Expression Associated with Gene Demethylation Confers Anoikis Resistance in Early Phases of Melanocyte Malignant Transformation1

PubMed Central

Ricca, Tatiana I; Liang, Gangning; Suenaga, Ana Paula M; Han, Sang W; Jones, Peter A; Jasiulionis, Miriam G

2009-01-01

Although anoikis resistance has been considered a hallmark of malignant phenotype, the causal relation between neoplastic transformation and anchorage-independent growth remains undefined. We developed an experimental model of murine melanocyte malignant transformation, where a melanocyte lineage (melan-a) was submitted to sequential cycles of anchorage blockade, resulting in progressive morphologic alterations, and malignant transformation. Throughout this process, cells corresponding to premalignant melanocytes and melanoma cell lines were established and show progressive anoikis resistance and increased expression of Timp1. In melan-a melanocytes, Timp1 expression is suppressed by DNA methylation as indicated by its reexpression after 5-aza-2′-deoxycytidine treatment. Methylation-sensitive single-nucleotide primer extension analysis showed increased demethylation in Timp1 in parallel with its expression along malignant transformation. Interestingly, TIMP1 expression has already been related with negative prognosis in some human cancers. Although described as a MMP inhibitor, this protein has been associated with apoptosis resistance in different cell types. Melan-a cells overexpressing Timp1 showed increased survival in suspension but were unable to form tumors in vivo, whereas Timp1-overexpressing melanoma cells showed reduced latency time for tumor appearance and increased metastatic potential. Here, we demonstrated for the first time an increment in Timp1 expression since the early phases of melanocyte malignant transformation, associated to a progressive gene demethylation, which confers anoikis resistance. In this way, Timp1 might be considered as a valued marker for melanocyte malignant transformation. PMID:19956395

Genome Engineering in Bacillus anthracis Using Cre Recombinase

PubMed Central

Pomerantsev, Andrei P.; Sitaraman, Ramakrishnan; Galloway, Craig R.; Kivovich, Violetta; Leppla, Stephen H.

2006-01-01

Genome engineering is a powerful method for the study of bacterial virulence. With the availability of the complete genomic sequence of Bacillus anthracis, it is now possible to inactivate or delete selected genes of interest. However, many current methods for disrupting or deleting more than one gene require use of multiple antibiotic resistance determinants. In this report we used an approach that temporarily inserts an antibiotic resistance marker into a selected region of the genome and subsequently removes it, leaving the target region (a single gene or a larger genomic segment) permanently mutated. For this purpose, a spectinomycin resistance cassette flanked by bacteriophage P1 loxP sites oriented as direct repeats was inserted within a selected gene. After identification of strains having the spectinomycin cassette inserted by a double-crossover event, a thermo-sensitive plasmid expressing Cre recombinase was introduced at the permissive temperature. Cre recombinase action at the loxP sites excised the spectinomycin marker, leaving a single loxP site within the targeted gene or genomic segment. The Cre-expressing plasmid was then removed by growth at the restrictive temperature. The procedure could then be repeated to mutate additional genes. In this way, we sequentially mutated two pairs of genes: pepM and spo0A, and mcrB and mrr. Furthermore, loxP sites introduced at distant genes could be recombined by Cre recombinase to cause deletion of large intervening regions. In this way, we deleted the capBCAD region of the pXO2 plasmid and the entire 30 kb of chromosomal DNA between the mcrB and mrr genes, and in the latter case we found that the 32 intervening open reading frames were not essential to growth. PMID:16369025

Development of a Markerless Genetic Exchange System in Desulfovibrio vulgaris Hildenborough and Its Use in Generating a Strain with Increased Transformation Efficiency

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

Keller, Kimberly L.; Bender, Kelly S.; Wall, Judy D.

2009-07-21

In recent years, the genetic manipulation of the sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough has seen enormous progress. In spite of this progress, the current marker exchange deletion method does not allow for easy selection of multiple sequential gene deletions in a single strain because of the limited number of selectable markers available in D. vulgaris. To broaden the repertoire of genetic tools for manipulation, an in-frame, markerless deletion system has been developed. The counterselectable marker that makes this deletion system possible is the pyrimidine salvage enzyme, uracil phosphoribosyltransferase, encoded by upp. In wild-type D. vulgaris, growth was shown to bemore » inhibited by the toxic pyrimidine analog 5-fluorouracil (5-FU); whereas, a mutant bearing a deletion of the upp gene was resistant to 5-FU. When a plasmid containing the wild-type upp gene expressed constitutively from the aph(3')-II promoter (promoter for the kanamycin resistance gene in Tn5) was introduced into the upp deletion strain, sensitivity to 5-FU was restored. This observation allowed us to develop a two-step integration and excision strategy for the deletion of genes of interest. Since this inframe deletion strategy does not retain an antibiotic cassette, multiple deletions can be generated in a single strain without the accumulation of genes conferring antibiotic resistances. We used this strategy to generate a deletion strain lacking the endonuclease (hsdR, DVU1703) of a type I restriction-modification system, that we designated JW7035. The transformation efficiency of the JW7035 strain was found to be 100 to 1000 times greater than that of the wild-type strain when stable plasmids were introduced via electroporation.« less

Mitigation of substrate defects in reflective reticles using sequential coating and annealing

DOEpatents

Mirkanimi, Paul B.

2002-01-01

A buffer-layer to minimize the size of defects on a reticle substrate prior to deposition of a reflective coating on the substrate. The buffer-layer is formed by either a multilayer deposited on the substrate or by a plurality of sequentially deposited and annealed coatings deposited on the substrate. The plurality of sequentially deposited and annealed coating may comprise multilayer and single layer coatings. The multilayer deposited and annealed buffer layer coatings may be of the same or different material than the reflecting coating thereafter deposited on the buffer-layer.

Gold-catalyzed sequential annulations towards 3,4-fused bi/tri-cyclic furans involving a [3+2+2]-cycloaddition.

PubMed

Liu, Suna; Yang, Pu; Peng, Shiyong; Zhu, Chenghao; Cao, Shengyu; Li, Jian; Sun, Jiangtao

2017-01-17

A gold-catalyzed sequential annulation reaction to prepare 3,4-fused bicyclic furan compounds has been realized by employing 2-(1-alkynyl)-2-alken-1-ones and 1,3,5-triazines as the starting materials under mild reaction conditions. This protocol features multiple bond formation in a single operation with the incorporation of two nitrogen and two carbon atoms into the final products. A mechanistic investigation reveals that the sequential annulations involved an unprecedented stepwise [3+2+2]-cycloaddition.

Single-wall carbon nanotube-based proton exchange membrane assembly for hydrogen fuel cells.

PubMed

Girishkumar, G; Rettker, Matthew; Underhile, Robert; Binz, David; Vinodgopal, K; McGinn, Paul; Kamat, Prashant

2005-08-30

A membrane electrode assembly (MEA) for hydrogen fuel cells has been fabricated using single-walled carbon nanotubes (SWCNTs) support and platinum catalyst. Films of SWCNTs and commercial platinum (Pt) black were sequentially cast on a carbon fiber electrode (CFE) using a simple electrophoretic deposition procedure. Scanning electron microscopy and Raman spectroscopy showed that the nanotubes and the platinum retained their nanostructure morphology on the carbon fiber surface. Electrochemical impedance spectroscopy (EIS) revealed that the carbon nanotube-based electrodes exhibited an order of magnitude lower charge-transfer reaction resistance (R(ct)) for the hydrogen evolution reaction (HER) than did the commercial carbon black (CB)-based electrodes. The proton exchange membrane (PEM) assembly fabricated using the CFE/SWCNT/Pt electrodes was evaluated using a fuel cell testing unit operating with H(2) and O(2) as input fuels at 25 and 60 degrees C. The maximum power density obtained using CFE/SWCNT/Pt electrodes as both the anode and the cathode was approximately 20% better than that using the CFE/CB/Pt electrodes.

A perspective on diuretic resistance in chronic congestive heart failure.

PubMed

Shah, Niel; Madanieh, Raef; Alkan, Mehmet; Dogar, Muhammad U; Kosmas, Constantine E; Vittorio, Timothy J

2017-10-01

Chronic congestive heart failure (CHF) is a complex disorder characterized by inability of the heart to keep up the demands on it, followed by the progressive pump failure and fluid accumulation. Although the loop diuretics are widely used in heart failure (HF) patients, both pharmacodynamic and pharmacokinetic alterations are thought to be responsible for diuretic resistance in these patients. Strategies to overcome diuretic resistance include sodium intake restriction, changes in diuretic dose and route of administration and sequential nephron diuretic therapy. In this review, we discuss the definition, prevalence, mechanism of development and management strategies of diuretic resistance in HF patients.

Joint Inversion of 3d Mt/gravity/magnetic at Pisagua Fault.

NASA Astrophysics Data System (ADS)

Bascur, J.; Saez, P.; Tapia, R.; Humpire, M.

2017-12-01

This work shows the results of a joint inversion at Pisagua Fault using 3D Magnetotellurics (MT), gravity and regional magnetic data. The MT survey has a poor coverage of study area with only 21 stations; however, it allows to detect a low resistivity zone aligned with the Pisagua Fault trace that it is interpreted as a damage zone. The integration of gravity and magnetic data, which have more dense sampling and coverage, adds more detail and resolution to the detected low resistivity structure and helps to improve the structure interpretation using the resulted models (density, magnetic-susceptibility and electrical resistivity). The joint inversion process minimizes a multiple target function which includes the data misfit, model roughness and coupling norms (crossgradient and direct relations) for all geophysical methods considered (MT, gravity and magnetic). This process is solved iteratively using the Gauss-Newton method which updates the model of each geophysical method improving its individual data misfit, model roughness and the coupling with the other geophysical models. For solving the model updates of magnetic and gravity methods were developed dedicated 3D inversion software codes which include the coupling norms with additionals geophysical parameters. The model update of the 3D MT is calculated using an iterative method which sequentially filters the priority model and the output model of a single 3D MT inversion process for obtaining the resistivity model coupled solution with the gravity and magnetic methods.

SIMPLE: a sequential immunoperoxidase labeling and erasing method.

PubMed

Glass, George; Papin, Jason A; Mandell, James W

2009-10-01

The ability to simultaneously visualize expression of multiple antigens in cells and tissues can provide powerful insights into cellular and organismal biology. However, standard methods are limited to the use of just two or three simultaneous probes and have not been widely adopted for routine use in paraffin-embedded tissue. We have developed a novel approach called sequential immunoperoxidase labeling and erasing (SIMPLE) that enables the simultaneous visualization of at least five markers within a single tissue section. Utilizing the alcohol-soluble peroxidase substrate 3-amino-9-ethylcarbazole, combined with a rapid non-destructive method for antibody-antigen dissociation, we demonstrate the ability to erase the results of a single immunohistochemical stain while preserving tissue antigenicity for repeated rounds of labeling. SIMPLE is greatly facilitated by the use of a whole-slide scanner, which can capture the results of each sequential stain without any information loss.

Reduction of display artifacts by random sampling

NASA Technical Reports Server (NTRS)

Ahumada, A. J., Jr.; Nagel, D. C.; Watson, A. B.; Yellott, J. I., Jr.

1983-01-01

The application of random-sampling techniques to remove visible artifacts (such as flicker, moire patterns, and paradoxical motion) introduced in TV-type displays by discrete sequential scanning is discussed and demonstrated. Sequential-scanning artifacts are described; the window of visibility defined in spatiotemporal frequency space by Watson and Ahumada (1982 and 1983) and Watson et al. (1983) is explained; the basic principles of random sampling are reviewed and illustrated by the case of the human retina; and it is proposed that the sampling artifacts can be replaced by random noise, which can then be shifted to frequency-space regions outside the window of visibility. Vertical sequential, single-random-sequence, and continuously renewed random-sequence plotting displays generating 128 points at update rates up to 130 Hz are applied to images of stationary and moving lines, and best results are obtained with the single random sequence for the stationary lines and with the renewed random sequence for the moving lines.

Sequential x-ray diffraction topography at 1-BM x-ray optics testing beamline at the advanced photon source

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

Stoupin, Stanislav, E-mail: sstoupin@aps.anl.gov; Shvyd’ko, Yuri; Trakhtenberg, Emil

2016-07-27

We report progress on implementation and commissioning of sequential X-ray diffraction topography at 1-BM Optics Testing Beamline of the Advanced Photon Source to accommodate growing needs of strain characterization in diffractive crystal optics and other semiconductor single crystals. The setup enables evaluation of strain in single crystals in the nearly-nondispersive double-crystal geometry. Si asymmetric collimator crystals of different crystallographic orientations were designed, fabricated and characterized using in-house capabilities. Imaging the exit beam using digital area detectors permits rapid sequential acquisition of X-ray topographs at different angular positions on the rocking curve of a crystal under investigation. Results on sensitivity andmore » spatial resolution are reported based on experiments with high-quality Si and diamond crystals. The new setup complements laboratory-based X-ray topography capabilities of the Optics group at the Advanced Photon Source.« less

Anomalous weak values and the violation of a multiple-measurement Leggett-Garg inequality

NASA Astrophysics Data System (ADS)

Avella, Alessio; Piacentini, Fabrizio; Borsarelli, Michelangelo; Barbieri, Marco; Gramegna, Marco; Lussana, Rudi; Villa, Federica; Tosi, Alberto; Degiovanni, Ivo Pietro; Genovese, Marco

2017-11-01

Quantum mechanics presents peculiar properties that, on the one hand, have been the subject of several theoretical and experimental studies about its very foundations and, on the other hand, provide tools for developing new technologies, the so-called quantum technologies. The nonclassicality pointed out by Leggett-Garg inequalities has represented, with Bell inequalities, one of the most investigated subjects. In this article we study the connection of Leggett-Garg inequalities with a new emerging field of quantum measurement, the weak values in the case of a series of sequential measurements on a single object. In detail, we perform an experimental study of the four-time-correlator Leggett-Garg test, by exploiting single and sequential weak measurements performed on heralded single photons.

Violation of the Wiedemann-Franz law in a single-electron transistor.

PubMed

Kubala, Björn; König, Jürgen; Pekola, Jukka

2008-02-15

We study the influence of Coulomb interaction on the thermoelectric transport coefficients for a metallic single-electron transistor. By performing a perturbation expansion up to second order in the tunnel-barrier conductance, we include sequential and cotunneling processes as well as quantum fluctuations that renormalize the charging energy and the tunnel conductance. We find that Coulomb interaction leads to a strong violation of the Wiedemann-Franz law: the Lorenz ratio becomes gate-voltage dependent for sequential tunneling, and is increased by a factor 9/5 in the cotunneling regime. Finally, we suggest a measurement scheme for an experimental realization.

In-situ measurement system

DOEpatents

Lord, David E.

1983-01-01

A multipurpose in situ underground measurement system comprising a plurality of long electrical resistance elements in the form of rigid reinforcing bars, each having an open loop "hairpin" configuration of shorter length than the other resistance elements. The resistance elements are arranged in pairs in a unitized structure, and grouted in place in the underground volume. The electrical resistance of each element and the difference in electrical resistance of the paired elements are obtained, which difference values may be used in analytical methods involving resistance as a function of temperature. A scanner sequentially connects the resistance-measuring apparatus to each individual pair of elements. A source of heating current is also selectively connectable for heating the elements to an initial predetermined temperature prior to electrical resistance measurements when used as an anemometer.

Students' conceptual performance on synthesis physics problems with varying mathematical complexity

NASA Astrophysics Data System (ADS)

Ibrahim, Bashirah; Ding, Lin; Heckler, Andrew F.; White, Daniel R.; Badeau, Ryan

2017-06-01

A body of research on physics problem solving has focused on single-concept problems. In this study we use "synthesis problems" that involve multiple concepts typically taught in different chapters. We use two types of synthesis problems, sequential and simultaneous synthesis tasks. Sequential problems require a consecutive application of fundamental principles, and simultaneous problems require a concurrent application of pertinent concepts. We explore students' conceptual performance when they solve quantitative synthesis problems with varying mathematical complexity. Conceptual performance refers to the identification, follow-up, and correct application of the pertinent concepts. Mathematical complexity is determined by the type and the number of equations to be manipulated concurrently due to the number of unknowns in each equation. Data were collected from written tasks and individual interviews administered to physics major students (N =179 ) enrolled in a second year mechanics course. The results indicate that mathematical complexity does not impact students' conceptual performance on the sequential tasks. In contrast, for the simultaneous problems, mathematical complexity negatively influences the students' conceptual performance. This difference may be explained by the students' familiarity with and confidence in particular concepts coupled with cognitive load associated with manipulating complex quantitative equations. Another explanation pertains to the type of synthesis problems, either sequential or simultaneous task. The students split the situation presented in the sequential synthesis tasks into segments but treated the situation in the simultaneous synthesis tasks as a single event.

Sequential segmental terminal lenticular side-cut dissection for safe and effective small-incision lenticule extraction in thin lenticules.

PubMed

Jacob, Soosan; Agarwal, Amar; Mazzotta, Cosimo; Agarwal, Athiya; Raj, John Michael

2017-04-01

Small-incision lenticule extraction may be associated with complications such as partial lenticular dissection, torn lenticule, lenticular adherence to cap, torn cap, and sub-cap epithelial ingrowth, some of which are more likely to occur during low-myopia corrections. We describe sequential segmental terminal lenticular side-cut dissection to facilitate minimally traumatic and smooth lenticular extraction. Anterior lamellar dissection is followed by central posterior lamellar dissection, leaving a thin peripheral rim and avoiding the lenticular side cut. This is followed by sequential segmental dissection of the lenticular side cut in a manner that fixates the lenticule and provides sufficient resistance for smooth and complete dissection of the posterior lamellar cut without undesired movements of the lenticule. The technique is advantageous in thin lenticules, where the risk for complications is high, but can also be used in thick lenticular dissection using wider sweeps to separate the lenticular side cut sequentially. Copyright © 2017 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Multidrug Resistance among New Tuberculosis Cases: Detecting Local Variation through Lot Quality-Assurance Sampling

PubMed Central

Lynn Hedt, Bethany; van Leth, Frank; Zignol, Matteo; Cobelens, Frank; van Gemert, Wayne; Viet Nhung, Nguyen; Lyepshina, Svitlana; Egwaga, Saidi; Cohen, Ted

2012-01-01

Background Current methodology for multidrug-resistant TB (MDR TB) surveys endorsed by the World Health Organization provides estimates of MDR TB prevalence among new cases at the national level. On the aggregate, local variation in the burden of MDR TB may be masked. This paper investigates the utility of applying lot quality-assurance sampling to identify geographic heterogeneity in the proportion of new cases with multidrug resistance. Methods We simulated the performance of lot quality-assurance sampling by applying these classification-based approaches to data collected in the most recent TB drug-resistance surveys in Ukraine, Vietnam, and Tanzania. We explored three classification systems—two-way static, three-way static, and three-way truncated sequential sampling—at two sets of thresholds: low MDR TB = 2%, high MDR TB = 10%, and low MDR TB = 5%, high MDR TB = 20%. Results The lot quality-assurance sampling systems identified local variability in the prevalence of multidrug resistance in both high-resistance (Ukraine) and low-resistance settings (Vietnam). In Tanzania, prevalence was uniformly low, and the lot quality-assurance sampling approach did not reveal variability. The three-way classification systems provide additional information, but sample sizes may not be obtainable in some settings. New rapid drug-sensitivity testing methods may allow truncated sequential sampling designs and early stopping within static designs, producing even greater efficiency gains. Conclusions Lot quality-assurance sampling study designs may offer an efficient approach for collecting critical information on local variability in the burden of multidrug-resistant TB. Before this methodology is adopted, programs must determine appropriate classification thresholds, the most useful classification system, and appropriate weighting if unbiased national estimates are also desired. PMID:22249242

Multidrug resistance among new tuberculosis cases: detecting local variation through lot quality-assurance sampling.

PubMed

Hedt, Bethany Lynn; van Leth, Frank; Zignol, Matteo; Cobelens, Frank; van Gemert, Wayne; Nhung, Nguyen Viet; Lyepshina, Svitlana; Egwaga, Saidi; Cohen, Ted

2012-03-01

Current methodology for multidrug-resistant tuberculosis (MDR TB) surveys endorsed by the World Health Organization provides estimates of MDR TB prevalence among new cases at the national level. On the aggregate, local variation in the burden of MDR TB may be masked. This paper investigates the utility of applying lot quality-assurance sampling to identify geographic heterogeneity in the proportion of new cases with multidrug resistance. We simulated the performance of lot quality-assurance sampling by applying these classification-based approaches to data collected in the most recent TB drug-resistance surveys in Ukraine, Vietnam, and Tanzania. We explored 3 classification systems- two-way static, three-way static, and three-way truncated sequential sampling-at 2 sets of thresholds: low MDR TB = 2%, high MDR TB = 10%, and low MDR TB = 5%, high MDR TB = 20%. The lot quality-assurance sampling systems identified local variability in the prevalence of multidrug resistance in both high-resistance (Ukraine) and low-resistance settings (Vietnam). In Tanzania, prevalence was uniformly low, and the lot quality-assurance sampling approach did not reveal variability. The three-way classification systems provide additional information, but sample sizes may not be obtainable in some settings. New rapid drug-sensitivity testing methods may allow truncated sequential sampling designs and early stopping within static designs, producing even greater efficiency gains. Lot quality-assurance sampling study designs may offer an efficient approach for collecting critical information on local variability in the burden of multidrug-resistant TB. Before this methodology is adopted, programs must determine appropriate classification thresholds, the most useful classification system, and appropriate weighting if unbiased national estimates are also desired.

Nonvolatile reconfigurable sequential logic in a HfO2 resistive random access memory array.

PubMed

Zhou, Ya-Xiong; Li, Yi; Su, Yu-Ting; Wang, Zhuo-Rui; Shih, Ling-Yi; Chang, Ting-Chang; Chang, Kuan-Chang; Long, Shi-Bing; Sze, Simon M; Miao, Xiang-Shui

2017-05-25

Resistive random access memory (RRAM) based reconfigurable logic provides a temporal programmable dimension to realize Boolean logic functions and is regarded as a promising route to build non-von Neumann computing architecture. In this work, a reconfigurable operation method is proposed to perform nonvolatile sequential logic in a HfO 2 -based RRAM array. Eight kinds of Boolean logic functions can be implemented within the same hardware fabrics. During the logic computing processes, the RRAM devices in an array are flexibly configured in a bipolar or complementary structure. The validity was demonstrated by experimentally implemented NAND and XOR logic functions and a theoretically designed 1-bit full adder. With the trade-off between temporal and spatial computing complexity, our method makes better use of limited computing resources, thus provides an attractive scheme for the construction of logic-in-memory systems.

Physical activity in England: who is meeting the recommended level of participation through sports and exercise?

PubMed

Anokye, Nana Kwame; Pokhrel, Subhash; Buxton, Martin; Fox-Rushby, Julia

2013-06-01

Little is known about the correlates of meeting recommended levels of participation in physical activity (PA) and how this understanding informs public health policies on behaviour change. To analyse who meets the recommended level of participation in PA in males and females separately by applying 'process' modelling frameworks (single vs. sequential 2-step process). Using the Health Survey for England 2006, (n = 14 142; ≥ 16 years), gender-specific regression models were estimated using bivariate probit with selectivity correction and single probit models. A 'sequential, 2-step process' modelled participation and meeting the recommended level separately, whereas the 'single process' considered both participation and level together. In females, meeting the recommended level was associated with degree holders [Marginal effect (ME) = 0.013] and age (ME = -0.001), whereas in males, age was a significant correlate (ME = -0.003 to -0.004). The order of importance of correlates was similar across genders, with ethnicity being the most important correlate in both males (ME = -0.060) and females (ME = -0.133). In females, the 'sequential, 2-step process' performed better (ρ = -0.364, P < 0.001) than that in males (ρ = 0.154). The degree to which people undertake the recommended level of PA through vigorous activity varies between males and females, and the process that best predicts such decisions, i.e. whether it is a sequential, 2-step process or a single-step choice, is also different for males and females. Understanding this should help to identify subgroups that are less likely to meet the recommended level of PA (and hence more likely to benefit from any PA promotion intervention).

Sequential roles of primary somatosensory cortex and posterior parietal cortex in tactile-visual cross-modal working memory: a single-pulse transcranial magnetic stimulation (spTMS) study.

PubMed

Ku, Yixuan; Zhao, Di; Hao, Ning; Hu, Yi; Bodner, Mark; Zhou, Yong-Di

2015-01-01

Both monkey neurophysiological and human EEG studies have shown that association cortices, as well as primary sensory cortical areas, play an essential role in sequential neural processes underlying cross-modal working memory. The present study aims to further examine causal and sequential roles of the primary sensory cortex and association cortex in cross-modal working memory. Individual MRI-based single-pulse transcranial magnetic stimulation (spTMS) was applied to bilateral primary somatosensory cortices (SI) and the contralateral posterior parietal cortex (PPC), while participants were performing a tactile-visual cross-modal delayed matching-to-sample task. Time points of spTMS were 300 ms, 600 ms, 900 ms after the onset of the tactile sample stimulus in the task. The accuracy of task performance and reaction time were significantly impaired when spTMS was applied to the contralateral SI at 300 ms. Significant impairment on performance accuracy was also observed when the contralateral PPC was stimulated at 600 ms. SI and PPC play sequential and distinct roles in neural processes of cross-modal associations and working memory. Copyright © 2015 Elsevier Inc. All rights reserved.

Challenges and Opportunities in Gen3 Embedded Cooling with High-Quality Microgap Flow

NASA Technical Reports Server (NTRS)

Bar-Cohen, Avram; Robinson, Franklin L.; Deisenroth, David C.

2018-01-01

Gen3, Embedded Cooling, promises to revolutionize thermal management of advanced microelectronic systems by eliminating the sequential conductive and interfacial thermal resistances which dominate the present 'remote cooling' paradigm. Single-phase interchip microfluidic flow with high thermal conductivity chips and substrates has been used successfully to cool single transistors dissipating more than 40kW/sq cm, but efficient heat removal from transistor arrays, larger chips, and chip stacks operating at these prodigious heat fluxes would require the use of high vapor fraction (quality), two-phase cooling in intra- and inter-chip microgap channels. The motivation, as well as the challenges and opportunities associated with evaporative embedded cooling in realistic form factors, is the focus of this paper. The paper will begin with a brief review of the history of thermal packaging, reflecting the 70-year 'inward migration' of cooling technology from the computer-room, to the rack, and then to the single chip and multichip module with 'remote' or attached air- and liquid-cooled coldplates. Discussion of the limitations of this approach and recent results from single-phase embedded cooling will follow. This will set the stage for discussion of the development challenges associated with application of this Gen3 thermal management paradigm to commercial semiconductor hardware, including dealing with the effects of channel length, orientation, and manifold-driven centrifugal acceleration on the governing behavior.

Chemical system biology based molecular interactions to identify inhibitors against Q151M mutant of HIV-1 reverse transcriptase.

PubMed

Pandey, Rajan Kumar; Sharma, Drista; Ojha, Rupal; Bhatt, Tarun Kumar; Prajapati, Vijay Kumar

2018-05-09

The emergence of mutations leading to drug resistance is the main cause of therapeutic failure in the human HIV infection. Chemical system biology approach has drawn great attention to discover new antiretroviral hits with high efficacy and negligible toxicity, which can be used as a prerequisite for HIV drug resistance global action plan 2017-21. To discover potential hits, we docked 49 antiretroviral analogs (n = 6294) against HIV-1 reverse transcriptase Q151M mutant & its wild-type form and narrow downed their number in three sequential modes of docking using Schrödinger suite. Later on, 80 ligands having better docking score than reference ligands (tenofovir and lamivudine) were screened for ADME, toxicity prediction, and binding energy estimation. Simultaneously, the area under the curve (AUC) was estimated using receiver operating characteristics (ROC) curve analysis to validate docking protocols. Finally, single point energy and molecular dynamics simulation approaches were performed for best two ligands (L3 and L14). This study reveals the antiretroviral efficacy of obtained two best ligands and delivers the hits against HIV-1 reverse transcriptase Q151M mutant. Copyright © 2018 Elsevier B.V. All rights reserved.

Self-Assembled Core-Satellite Gold Nanoparticle Networks for Ultrasensitive Detection of Chiral Molecules by Recognition Tunneling Current.

PubMed

Zhang, Yuanchao; Liu, Jingquan; Li, Da; Dai, Xing; Yan, Fuhua; Conlan, Xavier A; Zhou, Ruhong; Barrow, Colin J; He, Jin; Wang, Xin; Yang, Wenrong

2016-05-24

Chirality sensing is a very challenging task. Here, we report a method for ultrasensitive detection of chiral molecule l/d-carnitine based on changes in the recognition tunneling current across self-assembled core-satellite gold nanoparticle (GNP) networks. The recognition tunneling technique has been demonstrated to work at the single molecule level where the binding between the reader molecules and the analytes in a nanojunction. This process was observed to generate a unique and sensitive change in tunneling current, which can be used to identify the analytes of interest. The molecular recognition mechanism between amino acid l-cysteine and l/d-carnitine has been studied with the aid of SERS. The different binding strength between homo- or heterochiral pairs can be effectively probed by the copper ion replacement fracture. The device resistance was measured before and after the sequential exposures to l/d-carnitine and copper ions. The normalized resistance change was found to be extremely sensitive to the chirality of carnitine molecule. The results suggested that a GNP networks device optimized for recognition tunneling was successfully built and that such a device can be used for ultrasensitive detection of chiral molecules.

Evaluating specificity of sequential extraction for chemical forms of lead in artificially-contaminated and field-contaminated soils.

PubMed

Tai, Yiping; McBride, Murray B; Li, Zhian

2013-03-30

In the present study, we evaluated a commonly employed modified Bureau Communautaire de Référence (BCR test) 3-step sequential extraction procedure for its ability to distinguish forms of solid-phase Pb in soils with different sources and histories of contamination. When the modified BCR test was applied to mineral soils spiked with three forms of Pb (pyromorphite, hydrocerussite and nitrate salt), the added Pb was highly susceptible to dissolution in the operationally-defined "reducible" or "oxide" fraction regardless of form. When three different materials (mineral soil, organic soil and goethite) were spiked with soluble Pb nitrate, the BCR sequential extraction profiles revealed that soil organic matter was capable of retaining Pb in more stable and acid-resistant forms than silicate clay minerals or goethite. However, the BCR sequential extraction for field-collected soils with known and different sources of Pb contamination was not sufficiently discriminatory in the dissolution of soil Pb phases to allow soil Pb forms to be "fingerprinted" by this method. It is concluded that standard sequential extraction procedures are probably not very useful in predicting lability and bioavailability of Pb in contaminated soils. Copyright © 2013 Elsevier B.V. All rights reserved.

Development, Characterization, and Resultant Properties of a Carbon, Boron, and Chromium Ternary Diffusion System

NASA Astrophysics Data System (ADS)

Domec, Brennan S.

In today's industry, engineering materials are continuously pushed to the limits. Often, the application only demands high-specification properties in a narrowly-defined region of the material, such as the outermost surface. This, in combination with the economic benefits, makes case hardening an attractive solution to meet industry demands. While case hardening has been in use for decades, applications demanding high hardness, deep case depth, and high corrosion resistance are often under-served by this process. Instead, new solutions are required. The goal of this study is to develop and characterize a new borochromizing process applied to a pre-carburized AISI 8620 alloy steel. The process was successfully developed using a combination of computational simulations, calculations, and experimental testing. Process kinetics were studied by fitting case depth measurement data to Fick's Second Law of Diffusion and an Arrhenius equation. Results indicate that the kinetics of the co-diffusion method are unaffected by the addition of chromium to the powder pack. The results also show that significant structural degradation of the case occurs when chromizing is applied sequentially to an existing boronized case. The amount of degradation is proportional to the chromizing parameters. Microstructural evolution was studied using metallographic methods, simulation and computational calculations, and analytical techniques. While the co-diffusion process failed to enrich the substrate with chromium, significant enrichment is obtained with the sequential diffusion process. The amount of enrichment is directly proportional to the chromizing parameters with higher parameters resulting in more enrichment. The case consists of M7C3 and M23C6 carbides nearest the surface, minor amounts of CrB, and a balance of M2B. Corrosion resistance was measured with salt spray and electrochemical methods. These methods confirm the benefit of surface enrichment by chromium in the sequential diffusion method with corrosion resistance increasing directly with chromium concentration. The results also confirm the deleterious effect of surface-breaking case defects and the need to reduce or eliminate them. The best combination of microstructural integrity, mean surface hardness, effective case depth, and corrosion resistance is obtained in samples sequentially boronized and chromized at 870°C for 6hrs. Additional work is required to further optimize process parameters and case properties.

Mechanism of the reset process in bipolar-resistance-switching Ta/TaOx/Pt capacitors based on observation of the capacitance and resistance

NASA Astrophysics Data System (ADS)

Na, Sang-Chul; Kim, Jae-Jun; Chul Chun, Min; Hee Jin, Da; Ahn, Seung-Eon; Soo Kang, Bo

2014-03-01

The capacitance (C) and the resistance (R) were measured at various states as the reset process progressed in bipolar-resistance-switching Ta/TaOx/Pt thin film capacitors. The reset process was found to undergo three sequential stages where C and R showed different behavior: increasing C and constant R before an abrupt reset transition, the rapid increase of both C and R upon transition, and saturated C thereafter. These behaviors can be explained in terms of the annihilation of the oxygen vacancies followed by rupture of the conducting channels.

A perspective on diuretic resistance in chronic congestive heart failure

PubMed Central

Shah, Niel; Madanieh, Raef; Alkan, Mehmet; Dogar, Muhammad U.; Kosmas, Constantine E.; Vittorio, Timothy J.

2017-01-01

Chronic congestive heart failure (CHF) is a complex disorder characterized by inability of the heart to keep up the demands on it, followed by the progressive pump failure and fluid accumulation. Although the loop diuretics are widely used in heart failure (HF) patients, both pharmacodynamic and pharmacokinetic alterations are thought to be responsible for diuretic resistance in these patients. Strategies to overcome diuretic resistance include sodium intake restriction, changes in diuretic dose and route of administration and sequential nephron diuretic therapy. In this review, we discuss the definition, prevalence, mechanism of development and management strategies of diuretic resistance in HF patients. PMID:28728476

Localization of Mobile Robots Using Odometry and an External Vision Sensor

PubMed Central

Pizarro, Daniel; Mazo, Manuel; Santiso, Enrique; Marron, Marta; Jimenez, David; Cobreces, Santiago; Losada, Cristina

2010-01-01

This paper presents a sensor system for robot localization based on the information obtained from a single camera attached in a fixed place external to the robot. Our approach firstly obtains the 3D geometrical model of the robot based on the projection of its natural appearance in the camera while the robot performs an initialization trajectory. This paper proposes a structure-from-motion solution that uses the odometry sensors inside the robot as a metric reference. Secondly, an online localization method based on a sequential Bayesian inference is proposed, which uses the geometrical model of the robot as a link between image measurements and pose estimation. The online approach is resistant to hard occlusions and the experimental setup proposed in this paper shows its effectiveness in real situations. The proposed approach has many applications in both the industrial and service robot fields. PMID:22319318

Localization of mobile robots using odometry and an external vision sensor.

PubMed

Pizarro, Daniel; Mazo, Manuel; Santiso, Enrique; Marron, Marta; Jimenez, David; Cobreces, Santiago; Losada, Cristina

2010-01-01

This paper presents a sensor system for robot localization based on the information obtained from a single camera attached in a fixed place external to the robot. Our approach firstly obtains the 3D geometrical model of the robot based on the projection of its natural appearance in the camera while the robot performs an initialization trajectory. This paper proposes a structure-from-motion solution that uses the odometry sensors inside the robot as a metric reference. Secondly, an online localization method based on a sequential Bayesian inference is proposed, which uses the geometrical model of the robot as a link between image measurements and pose estimation. The online approach is resistant to hard occlusions and the experimental setup proposed in this paper shows its effectiveness in real situations. The proposed approach has many applications in both the industrial and service robot fields.

Update in pulmonary arterial hypertension.

PubMed

Mejía Chew, C R; Alcolea Batres, S; Ríos Blanco, J J

2016-11-01

Pulmonary arterial hypertension is a rare and progressive disease that mainly affects the pulmonary arterioles (precapillary), regardless of the triggering aetiology. The prevalence of pulmonary hypertension and pulmonary arterial hypertension in Spain is estimated at 19.2 and 16 cases per million inhabitants, respectively. The diagnosis of pulmonary arterial hypertension is based on haemodynamic criteria (mean pulmonary artery pressure ≥25mmHg, pulmonary capillary wedge pressure ≤15mmHg and pulmonary vascular resistance >3 Wood units) and therefore requires the implementation of right cardiac catheterisation. Sequential therapy with a single drug has been used in clinical practice. However, recent European guidelines recommend combined initial therapy in some situations. This review conducts a critical update of our knowledge of this disease according to the latest guidelines and recommendations. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

CRISPR/Cas9 mediated sequential editing of genes critical for ookinete motility in Plasmodium yoelii.

PubMed

Zhang, Cui; Gao, Han; Yang, Zhenke; Jiang, Yuanyuan; Li, Zhenkui; Wang, Xu; Xiao, Bo; Su, Xin-Zhuan; Cui, Huiting; Yuan, Jing

2017-03-01

CRISPR/Cas9 has been successfully adapted for gene editing in malaria parasites including Plasmodium falciparum and Plasmodium yoelii. However, the reported methods were limited to editing one gene at a time. In practice, it is often desired to modify multiple genetic loci in a parasite genome. Here we describe a CRISPR/Cas9 mediated genome editing method that allows successive modification of more than one gene in the genome of P. yoelii using an improved single-vector system (pYCm) we developed previously. Drug resistant genes encoding human dihydrofolate reductase (hDHFR) and a yeast bifunctional protein (yFCU), with cytosine deaminase (CD) and uridyl phosphoribosyl transferase (UPRT) activities in the plasmid, allowed sequential positive (pyrimethamine, Pyr) and negative (5-fluorocytosine, 5FC) selections and generation of transgenic parasites free of the episomal plasmid after genetic modification. Using this system, we were able to efficiently tag a gene of interest (Pyp28) and subsequently disrupted two genes (Pyctrp and Pycdpk3) that are individually critical for ookinete motility. Disruption of the genes either eliminated (Pyctrp) or greatly reduced (Pycdpk3) ookinete forward motility in matrigel in vitro and completely blocked oocyst development in mosquito midgut. The method will greatly facilitate studies of parasite gene function, development, and disease pathogenesis. Copyright © 2016 Elsevier B.V. All rights reserved.

In situ measurement system

DOEpatents

Lord, D.E.

1980-11-24

A multipurpose in situ underground measurement system comprising a plurality of long electrical resistance elements in the form of rigid reinforcing bars, each having an open loop hairpin configuration of shorter length than the other resistance elements. The resistance elements are arranged in pairs in a unitized structure, and grouted in place in the underground volume. Measurement means are provided for obtaining for each pair the electrical resistance of each element and the difference in electrical resistance of the paired elements, which difference values may be used in analytical methods involving resistance as a function of temperature. A scanner means sequentially connects the resistance-measuring apparatus to each individual pair of elements. A source of heating current is also selectively connectable for heating the elements to an initial predetermined temperature prior to electrical resistance measurements when used as an anemometer.

Modulation of Limbic and Prefrontal Connectivity by Electroconvulsive Therapy in Treatment-resistant Depression: A Preliminary Study.

PubMed

Cano, Marta; Cardoner, Narcís; Urretavizcaya, Mikel; Martínez-Zalacaín, Ignacio; Goldberg, Ximena; Via, Esther; Contreras-Rodríguez, Oren; Camprodon, Joan; de Arriba-Arnau, Aida; Hernández-Ribas, Rosa; Pujol, Jesús; Soriano-Mas, Carles; Menchón, José M

2016-01-01

Although current models of depression suggest that a sequential modulation of limbic and prefrontal connectivity is needed for illness recovery, neuroimaging studies of electroconvulsive therapy (ECT) have focused on assessing functional connectivity (FC) before and after an ECT course, without characterizing functional changes occurring at early treatment phases. To assess sequential changes in limbic and prefrontal FC during the course of ECT and their impact on clinical response. Longitudinal intralimbic and limbic-prefrontal networks connectivity study. We assessed 15 patients with treatment-resistant depression at four different time-points throughout the entire course of an ECT protocol and 10 healthy participants at two functional neuroimaging examinations. Furthermore, a path analysis to test direct and indirect predictive effects of limbic and prefrontal FC changes on clinical response measured with the Hamilton Rating Scale for Depression was also performed. An early significant intralimbic FC decrease significantly predicted a later increase in limbic-prefrontal FC, which in turn significantly predicted clinical improvement at the end of an ECT course. Our data support that treatment response involves sequential changes in FC within regions of the intralimbic and limbic-prefrontal networks. This approach may help in identifying potential early biomarkers of treatment response. Copyright © 2015 Elsevier Inc. All rights reserved.

Sequential analysis as a tool for detection of amikacin ototoxicity in the treatment of multidrug-resistant tuberculosis.

PubMed

Vasconcelos, Karla Anacleto de; Frota, Silvana Maria Monte Coelho; Ruffino-Netto, Antonio; Kritski, Afrânio Lineu

2018-04-01

To investigate early detection of amikacin-induced ototoxicity in a population treated for multidrug-resistant tuberculosis (MDR-TB), by means of three different tests: pure-tone audiometry (PTA); high-frequency audiometry (HFA); and distortion-product otoacoustic emission (DPOAE) testing. This was a longitudinal prospective cohort study involving patients aged 18-69 years with a diagnosis of MDR-TB who had to receive amikacin for six months as part of their antituberculosis drug regimen for the first time. Hearing was assessed before treatment initiation and at two and six months after treatment initiation. Sequential statistics were used to analyze the results. We included 61 patients, but the final population consisted of 10 patients (7 men and 3 women) because of sequential analysis. Comparison of the test results obtained at two and six months after treatment initiation with those obtained at baseline revealed that HFA at two months and PTA at six months detected hearing threshold shifts consistent with ototoxicity. However, DPOAE testing did not detect such shifts. The statistical method used in this study makes it possible to conclude that, over the six-month period, amikacin-associated hearing threshold shifts were detected by HFA and PTA, and that DPOAE testing was not efficient in detecting such shifts.

Validation of a motion-robust 2D sequential technique for quantification of hepatic proton density fat fraction during free breathing.

PubMed

Pooler, B Dustin; Hernando, Diego; Ruby, Jeannine A; Ishii, Hiroshi; Shimakawa, Ann; Reeder, Scott B

2018-04-17

Current chemical-shift-encoded (CSE) MRI techniques for measuring hepatic proton density fat fraction (PDFF) are sensitive to motion artifacts. Initial validation of a motion-robust 2D-sequential CSE-MRI technique for quantification of hepatic PDFF. Phantom study and prospective in vivo cohort. Fifty adult patients (27 women, 23 men, mean age 57.2 years). 3D, 2D-interleaved, and 2D-sequential CSE-MRI acquisitions at 1.5T. Three CSE-MRI techniques (3D, 2D-interleaved, 2D-sequential) were performed in a PDFF phantom and in vivo. Reference standards were 3D CSE-MRI PDFF measurements for the phantom study and single-voxel MR spectroscopy hepatic PDFF measurements (MRS-PDFF) in vivo. In vivo hepatic MRI-PDFF measurements were performed during a single breath-hold (BH) and free breathing (FB), and were repeated by a second reader for the FB 2D-sequential sequence to assess interreader variability. Correlation plots to validate the 2D-sequential CSE-MRI against the phantom and in vivo reference standards. Bland-Altman analysis of FB versus BH CSE-MRI acquisitions to evaluate robustness to motion. Bland-Altman analysis to assess interreader variability. Phantom 2D-sequential CSE-MRI PDFF measurements demonstrated excellent agreement and correlation (R 2 > 0.99) with 3D CSE-MRI. In vivo, the mean (±SD) hepatic PDFF was 8.8 ± 8.7% (range 0.6-28.5%). Compared with BH acquisitions, FB hepatic PDFF measurements demonstrated bias of +0.15% for 2D-sequential compared with + 0.53% for 3D and +0.94% for 2D-interleaved. 95% limits of agreement (LOA) were narrower for 2D-sequential (±0.99%), compared with 3D (±3.72%) and 2D-interleaved (±3.10%). All CSE-MRI techniques had excellent correlation with MRS (R 2 > 0.97). The FB 2D-sequential acquisition demonstrated little interreader variability, with mean bias of +0.07% and 95% LOA of ± 1.53%. This motion-robust 2D-sequential CSE-MRI can accurately measure hepatic PDFF during free breathing in a patient population with a range of PDFF values of 0.6-28.5%, permitting accurate quantification of liver fat content without the need for suspended respiration. 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Enantioselective Cobalt-Catalyzed Sequential Nazarov Cyclization/Electrophilic Fluorination: Access to Chiral α-Fluorocyclopentenones.

PubMed

Zhang, Heyi; Cheng, Biao; Lu, Zhan

2018-06-20

A newly designed thiazoline iminopyridine ligand for enantioselective cobalt-catalyzed sequential Nazarov cyclization/electrophilic fluorination was developed. Various chiral α-fluorocyclopentenones were prepared with good yields and diastereo- and enantioselectivities. Further derivatizations could be easily carried out to provide chiral cyclopentenols with three contiguous stereocenters. Furthermore, a direct deesterification of fluorinated products could afford chiral α-single fluorine-substituted cyclopentenones.

Preemptive Isolation Precautions of Patients at High Risk for Methicillin-Resistant Staphylococcus aureus in Combination With Ultrarapid Polymerase Chain Reaction Screening as an Effective Tool for Infection Control.

PubMed

Hallak, Ghias; Neuner, Bruno; Schefold, Joerg C; Gorzelniak, Kerstin; Rapsch, Brigitte; Pfüller, Roland; Stengel, Dirk; Wellmann, Jürgen; Ekkernkamp, Axel; Walter, Michael

2016-12-01

This sequential nonrandomized intervention study investigated the role of preemptive isolation precautions plus ultrarapid polymerase chain reaction screening for methicillin-resistant Staphylococcus aureus (MRSA). Compared with no prophylactic isolation plus conventional microbiology MRSA screening, nosocomial MRSA colonization and total MRSA incidence per 10,000 patient days significantly decreased. Infect Control Hosp Epidemiol 2016;1489-1491.

Multi-point objective-oriented sequential sampling strategy for constrained robust design

NASA Astrophysics Data System (ADS)

Zhu, Ping; Zhang, Siliang; Chen, Wei

2015-03-01

Metamodelling techniques are widely used to approximate system responses of expensive simulation models. In association with the use of metamodels, objective-oriented sequential sampling methods have been demonstrated to be effective in balancing the need for searching an optimal solution versus reducing the metamodelling uncertainty. However, existing infilling criteria are developed for deterministic problems and restricted to one sampling point in one iteration. To exploit the use of multiple samples and identify the true robust solution in fewer iterations, a multi-point objective-oriented sequential sampling strategy is proposed for constrained robust design problems. In this article, earlier development of objective-oriented sequential sampling strategy for unconstrained robust design is first extended to constrained problems. Next, a double-loop multi-point sequential sampling strategy is developed. The proposed methods are validated using two mathematical examples followed by a highly nonlinear automotive crashworthiness design example. The results show that the proposed method can mitigate the effect of both metamodelling uncertainty and design uncertainty, and identify the robust design solution more efficiently than the single-point sequential sampling approach.

Options for the management of antiviral resistance during hepatitis B therapy: reflections on battles over a decade

PubMed Central

2013-01-01

Although much advancement has been achieved in the treatment of chronic hepatitis B, antiviral resistance is still a challenging issue. Previous generation antiviral agents have already developed resistance in a number of patients, and it is still being used especially in resource limited countries. Once antiviral resistance occurs, it predisposes to subsequent resistance, resulting in multidrug resistance. Therefore, prevention of initial antiviral resistance is the most important strategy, and appropriate choice and modification of therapy would be the cornerstone in avoiding treatment failures. Until now, management of antiviral resistance has been evolving from sequential therapy to combination therapy. In the era of tenofovir, the paradigm shifts again, and we have to decide when to switch and when to combine on the basis of newly emerging clinical data. We expect future eradication of chronic hepatitis B virus infection by proper prevention and optimal management of antiviral resistance. PMID:24133659

Single-visit or multiple-visit root canal treatment: systematic review, meta-analysis and trial sequential analysis.

PubMed

Schwendicke, Falk; Göstemeyer, Gerd

2017-02-01

Single-visit root canal treatment has some advantages over conventional multivisit treatment, but might increase the risk of complications. We systematically evaluated the risk of complications after single-visit or multiple-visit root canal treatment using meta-analysis and trial-sequential analysis. Controlled trials comparing single-visit versus multiple-visit root canal treatment of permanent teeth were included. Trials needed to assess the risk of long-term complications (pain, infection, new/persisting/increasing periapical lesions ≥1 year after treatment), short-term pain or flare-up (acute exacerbation of initiation or continuation of root canal treatment). Electronic databases (PubMed, EMBASE, Cochrane Central) were screened, random-effects meta-analyses performed and trial-sequential analysis used to control for risk of random errors. Evidence was graded according to GRADE. 29 trials (4341 patients) were included, all but 6 showing high risk of bias. Based on 10 trials (1257 teeth), risk of complications was not significantly different in single-visit versus multiple-visit treatment (risk ratio (RR) 1.00 (95% CI 0.75 to 1.35); weak evidence). Based on 20 studies (3008 teeth), risk of pain did not significantly differ between treatments (RR 0.99 (95% CI 0.76 to 1.30); moderate evidence). Risk of flare-up was recorded by 8 studies (1110 teeth) and was significantly higher after single-visit versus multiple-visit treatment (RR 2.13 (95% CI 1.16 to 3.89); very weak evidence). Trial-sequential analysis revealed that firm evidence for benefit, harm or futility was not reached for any of the outcomes. There is insufficient evidence to rule out whether important differences between both strategies exist. Dentists can provide root canal treatment in 1 or multiple visits. Given the possibly increased risk of flare-ups, multiple-visit treatment might be preferred for certain teeth (eg, those with periapical lesions). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Leveraging Hypoxia-Activated Prodrugs to Prevent Drug Resistance in Solid Tumors.

PubMed

Lindsay, Danika; Garvey, Colleen M; Mumenthaler, Shannon M; Foo, Jasmine

2016-08-01

Experimental studies have shown that one key factor in driving the emergence of drug resistance in solid tumors is tumor hypoxia, which leads to the formation of localized environmental niches where drug-resistant cell populations can evolve and survive. Hypoxia-activated prodrugs (HAPs) are compounds designed to penetrate to hypoxic regions of a tumor and release cytotoxic or cytostatic agents; several of these HAPs are currently in clinical trial. However, preliminary results have not shown a survival benefit in several of these trials. We hypothesize that the efficacy of treatments involving these prodrugs depends heavily on identifying the correct treatment schedule, and that mathematical modeling can be used to help design potential therapeutic strategies combining HAPs with standard therapies to achieve long-term tumor control or eradication. We develop this framework in the specific context of EGFR-driven non-small cell lung cancer, which is commonly treated with the tyrosine kinase inhibitor erlotinib. We develop a stochastic mathematical model, parametrized using clinical and experimental data, to explore a spectrum of treatment regimens combining a HAP, evofosfamide, with erlotinib. We design combination toxicity constraint models and optimize treatment strategies over the space of tolerated schedules to identify specific combination schedules that lead to optimal tumor control. We find that (i) combining these therapies delays resistance longer than any monotherapy schedule with either evofosfamide or erlotinib alone, (ii) sequentially alternating single doses of each drug leads to minimal tumor burden and maximal reduction in probability of developing resistance, and (iii) strategies minimizing the length of time after an evofosfamide dose and before erlotinib confer further benefits in reduction of tumor burden. These results provide insights into how hypoxia-activated prodrugs may be used to enhance therapeutic effectiveness in the clinic.

Emergence of dalbavancin non-susceptible, vancomycin-intermediate Staphylococcus aureus (VISA) after treatment of MRSA central line-associated bloodstream infection with a dalbavancin- and vancomycin-containing regimen.

PubMed

Werth, B J; Jain, R; Hahn, A; Cummings, L; Weaver, T; Waalkes, A; Sengupta, D; Salipante, S J; Rakita, R M; Butler-Wu, S M

2018-04-01

Dalbavancin is a long-acting lipoglycopeptide with activity against gram-positives, including methicillin-resistant Staphylococcus aureus (MRSA). The potential for lipoglycopeptides, with half-lives greater than 1 week, to select for resistance is unknown. Here we explore a case of MRSA central line-associated bloodstream infection in which dalbavancin and vancomycin non-susceptibility emerged in a urine isolate collected after the patient was treated with vancomycin and dalbavancin sequentially. Isolates from blood and urine underwent susceptibility testing, and whole genome sequencing (WGS). The blood isolate was subjected to successive passage in vitro in the presence of escalating dalbavancin concentrations and the emergent isolate was subjected to repeat susceptibility testing and WGS. The blood isolate was fully susceptible to vancomycin; however, MICs of the urine isolate to dalbavancin, vancomycin, telavancin, and daptomycin were at least fourfold higher than the blood-derived strain. Both strains were indistinguishable by spa and variable number tandem repeat (VNTR) typing, and WGS revealed only seven variants, indicating clonality. Four variants affected genes, including a 3bp in-frame deletion in yvqF, a gene which has been implicated in glycopeptide resistance. Vancomycin and dalbavancin non-susceptibility emerged in the blood isolate after successive passage in vitro in the presence of dalbavancin, and WGS identified a single non-synonymous variant in yvqF. This is the first case in which VISA has emerged in the context of a dalbavancin-containing regimen. The selection for cross-resistance to vancomycin in vitro by dalbavancin exposure alone is troubling. Clinicians should be aware of the possibility for emergence of dalbavancin non-susceptibility and glycopeptide cross-resistance arising following therapy. Copyright © 2017. Published by Elsevier Ltd.

Effect of different cements on the biomechanical behavior of teeth restored with cast dowel-and-cores-in vitro and FEA analysis.

PubMed

Soares, Carlos José; Raposo, Luís Henrique Araújo; Soares, Paulo Vinícius; Santos-Filho, Paulo César Freitas; Menezes, Murilo Sousa; Soares, Priscilla Barbosa Ferreira; Magalhães, Denildo

2010-02-01

To test the hypothesis that the type of cement used for fixation of cast dowel-and-cores might influence fracture resistance, fracture mode, and stress distribution of single-rooted teeth restored with this class of metallic dowels. The coronal portion was removed from 40 bovine incisors, leaving a 15 mm root. After endodontic treatment and standardized root canal relief at 10 mm, specimens were embedded in polystyrene resin, and the periodontal ligament was simulated with polyether impression material. The specimens were randomly divided into four groups (n = 10), and restored with Cu-Al cast dowel-and-cores cemented with one of four options: conventional glass ionomer cement (GI); resin-modified glass ionomer cement (GR); dual-cure resin cement (RC); or zinc-phosphate cement (ZP). Sequentially, fracture resistance of the specimens was tested with a tangential load at a 135 degrees angle with a 0.5 mm/min crosshead speed. Data were analyzed using one-way analysis of variance (ANOVA) and the Fisher test. Two-dimensional finite element analysis (2D-FEA) was then performed with representative models of each group simulating a 100 microm cement layer. Results were analyzed based on von Mises stress distribution criteria. The mean fracture resistance values were (in N): RC, 838.2 +/- 135.9; GI, 772.4 +/- 169.8; GR, 613.4 +/- 157.5; ZP, 643.6 +/- 106.7. FEA revealed that RC and GR presented lower stress values than ZP and GI. The higher stress concentration was coincident with more catastrophic failures, and consequently, with lower fracture resistance values. The type of cement influenced fracture resistance, failure mode, and stress distribution on teeth restored with cast dowel-and-cores.

Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized study.

PubMed

Nasa, Mukesh; Choksey, Ajay; Phadke, Aniruddha; Sawant, Prabha

2013-11-01

Antimicrobial resistance has decreased eradication rates for Helicobacter pylori infection worldwide. A sequential treatment schedule has been reported to be effective, but studies published to date were performed in Italy. We undertook this study to determine whether these results could be replicated in India. A randomized, open-labeled, prospective controlled trial comparing sequential vs. standard triple-drug therapy was carried out at Lokmanya Tilak Municipal General Hospital, Mumbai. Two hundred and thirty-one patients with dyspepsia were randomized to a 10-day sequential regimen (40 mg of pantoprazole, 1 g of amoxicillin, each administered twice daily for the first 5 days, followed by 40 mg of pantoprazole, 500 mg of clarithromycin, and 500 mg of tinidazole, each administered twice daily for the remaining 5 days) or to standard 14-day therapy (40 mg of pantoprazole, 500 mg of clarithromycin, and 1 g of amoxicillin, each administered twice daily). The eradication rate achieved with the sequential regimen was significantly greater than that obtained with the triple therapy. Per-protocol eradication rate of sequential therapy was 92.4% (95% CI 85.8-96.1%) vs. 81.8% (95% CI 73.9-87.8%) (p = 0.027) for standard drug therapy. Intention-to-treat eradication rates were 88.2% (95% CI 80.9-93.0%) vs. 79.1% (95% CI 71.1-85.4%), p = 0.029, respectively. The incidence of major and minor side effects between therapy groups was not significantly different (14.6% in the triple therapy group vs. 23.5% in sequential group, p = 0.12). Follow up was incomplete in 3.3% and 4.7% patients in standard and sequential therapy groups, respectively. Sequential therapy includes one additional antibiotic (tinidazole) that is not contained in standard therapy. Sequential therapy was significantly better than standard therapy for eradicating H. pylori infection.

The Aggregation of Single-Case Results Using Hierarchical Linear Models

ERIC Educational Resources Information Center

Van den Noortgate, Wim; Onghena, Patrick

2007-01-01

To investigate the generalizability of the results of single-case experimental studies, evaluating the effect of one or more treatments, in applied research various simultaneous and sequential replication strategies are used. We discuss one approach for aggregating the results for single-cases: the use of hierarchical linear models. This approach…

Location Prediction Based on Transition Probability Matrices Constructing from Sequential Rules for Spatial-Temporal K-Anonymity Dataset

PubMed Central

Liu, Zhao; Zhu, Yunhong; Wu, Chenxue

2016-01-01

Spatial-temporal k-anonymity has become a mainstream approach among techniques for protection of users’ privacy in location-based services (LBS) applications, and has been applied to several variants such as LBS snapshot queries and continuous queries. Analyzing large-scale spatial-temporal anonymity sets may benefit several LBS applications. In this paper, we propose two location prediction methods based on transition probability matrices constructing from sequential rules for spatial-temporal k-anonymity dataset. First, we define single-step sequential rules mined from sequential spatial-temporal k-anonymity datasets generated from continuous LBS queries for multiple users. We then construct transition probability matrices from mined single-step sequential rules, and normalize the transition probabilities in the transition matrices. Next, we regard a mobility model for an LBS requester as a stationary stochastic process and compute the n-step transition probability matrices by raising the normalized transition probability matrices to the power n. Furthermore, we propose two location prediction methods: rough prediction and accurate prediction. The former achieves the probabilities of arriving at target locations along simple paths those include only current locations, target locations and transition steps. By iteratively combining the probabilities for simple paths with n steps and the probabilities for detailed paths with n-1 steps, the latter method calculates transition probabilities for detailed paths with n steps from current locations to target locations. Finally, we conduct extensive experiments, and correctness and flexibility of our proposed algorithm have been verified. PMID:27508502

The effects of 595- and 1,064-nm lasers on rooster comb blood vessels using dual-wavelength and multipulse techniques.

PubMed

Li, Guang; Sun, Jianfang; Shao, Xuebao; Sang, Honggui; Zhou, Zhanchao

2011-10-01

After laser irradiation, hemoglobin can transform into methemoglobin and coagulum, which have high absorptivity of near-infrared light. Sequential irradiation with 595 nm and 1,064 nm may be more effective than single wavelength to decrease residual vessel number in rooster combs. Six protocols (single pulse with 595 nm, double pulse with 595 nm, single pulse with 1,064 nm, double pulse with 1,064 nm, sequential irradiation with 595 nm and 1,064 nm (multiplex), and a blank control group) were used to compare the effects of sequential and single-wavelength irradiation on reducing residual vessel number, as well as the epidermal side effects, in the rooster comb. Different treatment techniques were applied to the same comb, at the same time. The treated areas of the epidermis and the residual vessels were observed using an optical microscope. All five techniques were effective in decreasing the number of residual vessels in the comb, and the side effects on the epidermis were similar for all. Considering the selectivity of the 595-nm laser and the rich melanin in the human epidermis, the dual-wavelength laser has a distinct advantage in treating vascular lesions. The authors have indicated no significant interest with commercial supporters. © 2011 by the American Society for Dermatologic Surgery, Inc.

Sequential single shot X-ray photon correlation spectroscopy at the SACLA free electron laser

DOE PAGES

Lehmkühler, Felix; Kwaśniewski, Paweł; Roseker, Wojciech; ...

2015-11-27

In this study, hard X-ray free electron lasers allow for the first time to access dynamics of condensed matter samples ranging from femtoseconds to several hundred seconds. In particular, the exceptional large transverse coherence of the X-ray pulses and the high time-averaged flux promises to reach time and length scales that have not been accessible up to now with storage ring based sources. However, due to the fluctuations originating from the stochastic nature of the self-amplified spontaneous emission (SASE) process the application of well established techniques such as X-ray photon correlation spectroscopy (XPCS) is challenging. Here we demonstrate a single-shotmore » based sequential XPCS study on a colloidal suspension with a relaxation time comparable to the SACLA free-electron laser pulse repetition rate. High quality correlation functions could be extracted without any indications for sample damage. This opens the way for systematic sequential XPCS experiments at FEL sources.« less

Sequential single shot X-ray photon correlation spectroscopy at the SACLA free electron laser

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

Lehmkühler, Felix; Kwaśniewski, Paweł; Roseker, Wojciech

In this study, hard X-ray free electron lasers allow for the first time to access dynamics of condensed matter samples ranging from femtoseconds to several hundred seconds. In particular, the exceptional large transverse coherence of the X-ray pulses and the high time-averaged flux promises to reach time and length scales that have not been accessible up to now with storage ring based sources. However, due to the fluctuations originating from the stochastic nature of the self-amplified spontaneous emission (SASE) process the application of well established techniques such as X-ray photon correlation spectroscopy (XPCS) is challenging. Here we demonstrate a single-shotmore » based sequential XPCS study on a colloidal suspension with a relaxation time comparable to the SACLA free-electron laser pulse repetition rate. High quality correlation functions could be extracted without any indications for sample damage. This opens the way for systematic sequential XPCS experiments at FEL sources.« less

Crystal Growth and Dissolution of Methylammonium Lead Iodide Perovskite in Sequential Deposition: Correlation between Morphology Evolution and Photovoltaic Performance.

PubMed

Hsieh, Tsung-Yu; Huang, Chi-Kai; Su, Tzu-Sen; Hong, Cheng-You; Wei, Tzu-Chien

2017-03-15

Crystal morphology and structure are important for improving the organic-inorganic lead halide perovskite semiconductor property in optoelectronic, electronic, and photovoltaic devices. In particular, crystal growth and dissolution are two major phenomena in determining the morphology of methylammonium lead iodide perovskite in the sequential deposition method for fabricating a perovskite solar cell. In this report, the effect of immersion time in the second step, i.e., methlyammonium iodide immersion in the morphological, structural, optical, and photovoltaic evolution, is extensively investigated. Supported by experimental evidence, a five-staged, time-dependent evolution of the morphology of methylammonium lead iodide perovskite crystals is established and is well connected to the photovoltaic performance. This result is beneficial for engineering optimal time for methylammonium iodide immersion and converging the solar cell performance in the sequential deposition route. Meanwhile, our result suggests that large, well-faceted methylammonium lead iodide perovskite single crystal may be incubated by solution process. This offers a low cost route for synthesizing perovskite single crystal.

Remote sensing of freeze-thaw transitions in Arctic soils using the complex resistivity method

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

Wu, Yuxin; Hubbard, Susan S; Ulrich, Craig

2013-01-01

Our ability to monitor freeze - thaw transitions is critical to developing a predictive understanding of biogeochemical transitions and carbon dynamics in high latitude environments. In this study, we conducted laboratory column experiments to explore the potential of the complex resistivity method for monitoring the freeze - thaw transitions of the arctic permafrost soils. Samples for the experiment were collected from the upper active layer of Gelisol soils at the Barrow Environmental Observatory, Barrow Alaska. Freeze - thaw transitions were induced through exposing the soil column to controlled temperature environments at 4 C and -20 C. Complex resistivity and temperaturemore » measurements were collected regularly during the freeze - thaw transitions using electrodes and temperature sensors installed along the column. During the experiments, over two orders of magnitude of resistivity variations were observed when the temperature was increased or decreased between -20 C and 0 C. Smaller resistivity variations were also observed during the isothermal thawing or freezing processes that occurred near 0 C. Single frequency electrical phase response and imaginary conductivity at 1 Hz were found to be exclusively related to the unfrozen water in the soil matrix, suggesting that these geophysical 24 attributes can be used as a proxy for the monitoring of the onset and progression of the freeze - thaw transitions. Spectral electrical responses and fitted Cole Cole parameters contained additional information about the freeze - thaw transition affected by the soil grain size distribution. Specifically, a shift of the observed spectral response to lower frequency was observed during isothermal thawing process, which we interpret to be due to sequential thawing, first from fine then to coarse particles within the soil matrix. Our study demonstrates the potential of the complex resistivity method for remote monitoring of freeze - thaw transitions in arctic soils. Although conducted at the laboratory scale, this study provides the foundation for exploring the potential of the complex resistivity signals for monitoring spatiotemporal variations of freeze - thaw transitions over field-relevant scales.« less

Tumor resistance to vascular disrupting agents: mechanisms, imaging, and solutions

PubMed Central

Liang, Wenjie; Ni, Yicheng; Chen, Feng

2016-01-01

The emergence of vascular disrupting agents (VDAs) is a significant advance in the treatment of solid tumors. VDAs induce rapid and selective shutdown of tumor blood flow resulting in massive necrosis. However, a viable marginal tumor rim always remains after VDA treatment and is a major cause of recurrence. In this review, we discuss the mechanisms involved in the resistance of solid tumors to VDAs. Hypoxia, tumor-associated macrophages, and bone marrow-derived circulating endothelial progenitor cells all may contribute to resistance. Resistance can be monitored using magnetic resonance imaging markers. The various solutions proposed to manage tumor resistance to VDAs emphasize combining these agents with other approaches including antiangiogenic agents, chemotherapy, radiotherapy, radioimmunotherapy, and sequential dual-targeting internal radiotherapy. PMID:26812886

Integrated molecular analysis of tumor biopsies on sequential CTLA-4 and PD-1 blockade reveals markers of response and resistance

PubMed Central

Roh, Whijae; Chen, Pei-Ling; Reuben, Alexandre; Spencer, Christine N.; Prieto, Peter A.; Miller, John P.; Gopalakrishnan, Vancheswaran; Wang, Feng; Cooper, Zachary A.; Reddy, Sangeetha M.; Gumbs, Curtis; Little, Latasha; Chang, Qing; Chen, Wei-Shen; Wani, Khalida; Petaccia De Macedo, Mariana; Chen, Eveline; Austin-Breneman, Jacob L.; Jiang, Hong; Roszik, Jason; Tetzlaff, Michael T.; Davies, Michael A.; Gershenwald, Jeffrey E.; Tawbi, Hussein; Lazar, Alexander J.; Hwu, Patrick; Hwu, Wen-Jen; Diab, Adi; Glitza, Isabella C.; Patel, Sapna P.; Woodman, Scott E.; Amaria, Rodabe N.; Prieto, Victor G.; Hu, Jianhua; Sharma, Padmanee; Allison, James P.; Chin, Lynda; Zhang, Jianhua; Wargo, Jennifer A.; Futreal, P. Andrew

2018-01-01

Immune checkpoint blockade produces clinical benefit in many patients. However better biomarkers of response are still needed, and mechanisms of resistance remain incompletely understood. To address this, we recently studied a cohort of melanoma patients treated with sequential checkpoint blockade against cytotoxic T lymphocyte antigen-4 (CTLA-4) followed by programmed death receptor-1 (PD-1), and identified immune markers of response and resistance. Building on these studies, we performed deep molecular profiling including T-cell receptor sequencing (TCR-seq) and whole exome sequencing (WES) within the same cohort, and demonstrated that a more clonal T cell repertoire was predictive of response to PD-1 but not CTLA-4 blockade. Analysis of copy number alterations identified a higher burden of copy number loss in non-responders to CTLA-4 and PD-1 blockade and found that it was associated with decreased expression of genes in immune-related pathways. The effect of mutational load and burden of copy number loss on response was non-redundant, suggesting the potential utility of a combinatorial biomarker to optimize patient care with checkpoint blockade therapy. PMID:28251903

A path-level exact parallelization strategy for sequential simulation

NASA Astrophysics Data System (ADS)

Peredo, Oscar F.; Baeza, Daniel; Ortiz, Julián M.; Herrero, José R.

2018-01-01

Sequential Simulation is a well known method in geostatistical modelling. Following the Bayesian approach for simulation of conditionally dependent random events, Sequential Indicator Simulation (SIS) method draws simulated values for K categories (categorical case) or classes defined by K different thresholds (continuous case). Similarly, Sequential Gaussian Simulation (SGS) method draws simulated values from a multivariate Gaussian field. In this work, a path-level approach to parallelize SIS and SGS methods is presented. A first stage of re-arrangement of the simulation path is performed, followed by a second stage of parallel simulation for non-conflicting nodes. A key advantage of the proposed parallelization method is to generate identical realizations as with the original non-parallelized methods. Case studies are presented using two sequential simulation codes from GSLIB: SISIM and SGSIM. Execution time and speedup results are shown for large-scale domains, with many categories and maximum kriging neighbours in each case, achieving high speedup results in the best scenarios using 16 threads of execution in a single machine.

Sequential continuous flow processes for the oxidation of amines and azides by using HOF·MeCN.

PubMed

McPake, Christopher B; Murray, Christopher B; Sandford, Graham

2012-02-13

The generation and use of the highly potent oxidising agent HOF·MeCN in a controlled single continuous flow process is described. Oxidations of amines and azides to corresponding nitrated systems by using fluorine gas, water and acetonitrile by sequential gas-liquid/liquid-liquid continuous flow procedures are reported. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparative efficacy of simultaneous versus sequential multiple health behavior change interventions among adults: A systematic review of randomised trials.

PubMed

James, Erica; Freund, Megan; Booth, Angela; Duncan, Mitch J; Johnson, Natalie; Short, Camille E; Wolfenden, Luke; Stacey, Fiona G; Kay-Lambkin, Frances; Vandelanotte, Corneel

2016-08-01

Growing evidence points to the benefits of addressing multiple health behaviors rather than single behaviors. This review evaluates the relative effectiveness of simultaneous and sequentially delivered multiple health behavior change (MHBC) interventions. Secondary aims were to identify: a) the most effective spacing of sequentially delivered components; b) differences in efficacy of MHBC interventions for adoption/cessation behaviors and lifestyle/addictive behaviors, and; c) differences in trial retention between simultaneously and sequentially delivered interventions. MHBC intervention trials published up to October 2015 were identified through a systematic search. Eligible trials were randomised controlled trials that directly compared simultaneous and sequential delivery of a MHBC intervention. A narrative synthesis was undertaken. Six trials met the inclusion criteria and across these trials the behaviors targeted were smoking, diet, physical activity, and alcohol consumption. Three trials reported a difference in intervention effect between a sequential and simultaneous approach in at least one behavioral outcome. Of these, two trials favoured a sequential approach on smoking. One trial favoured a simultaneous approach on fat intake. There was no difference in retention between sequential and simultaneous approaches. There is limited evidence regarding the relative effectiveness of sequential and simultaneous approaches. Given only three of the six trials observed a difference in intervention effectiveness for one health behavior outcome, and the relatively consistent finding that the sequential and simultaneous approaches were more effective than a usual/minimal care control condition, it appears that both approaches should be considered equally efficacious. PROSPERO registration number: CRD42015027876. Copyright © 2016 Elsevier Inc. All rights reserved.

Impact of Temporal Masking of Flip-Flop Upsets on Soft Error Rates of Sequential Circuits

NASA Astrophysics Data System (ADS)

Chen, R. M.; Mahatme, N. N.; Diggins, Z. J.; Wang, L.; Zhang, E. X.; Chen, Y. P.; Liu, Y. N.; Narasimham, B.; Witulski, A. F.; Bhuva, B. L.; Fleetwood, D. M.

2017-08-01

Reductions in single-event (SE) upset (SEU) rates for sequential circuits due to temporal masking effects are evaluated. The impacts of supply voltage, combinational-logic delay, flip-flop (FF) SEU performance, and particle linear energy transfer (LET) values are analyzed for SE cross sections of sequential circuits. Alpha particles and heavy ions with different LET values are used to characterize the circuits fabricated at the 40-nm bulk CMOS technology node. Experimental results show that increasing the delay of the logic circuit present between FFs and decreasing the supply voltage are two effective ways of reducing SE error rates for sequential circuits for particles with low LET values due to temporal masking. SEU-hardened FFs benefit less from temporal masking than conventional FFs. Circuit hardening implications for SEU-hardened and unhardened FFs are discussed.

[In vitro study of shaping ability of single-file techniques in curved canals].

PubMed

Zeng, Yajie; Gu, Lisha; Cai, Yanling; Chen, Dian; Wei, Xi

2014-11-01

To compare the shaping quality in curved canals of two single-file technique systems with other two traditional full-sequential systems. Eighty mature molar canals with the curvature between 20 and 45 degrees were randomly divided into four groups. Specimens in each group were prepared to size 25 at working length using A (Reciproc), B (OneShape), C (MTwo) and D (Revo S), respectively. Each canal was scanned by micro-computed tomography before and after preparation. Parameters including changes in dentine volume, percentage of uninstrumented area, degree and tendency of transportation were analyzed. The operating time was also recorded. In full canal length, there was no difference in canal dentine removal, instrumented percentage and transportation degree among four groups (P > 0.05). In the apical 4 mm region, group A removed more dentine [(2.14±0.76) mm(2) of canal surface area and (0.38 ± 0.15) mm(3) of canal volume] than groups B and C(P < 0.05). At 1 mm level, median of transportation degree of group A was 0.05 (0.03)mm, which was smaller than other groups (P < 0.05). Groups A and B took (86.3±24.6) s and (85.9±21.3) s, while groups C and D took (147.4±28.3) s and (126.3±27.7) s srespectively to finish preparation. Single file techniques were significantly faster than the two full-sequential systems (P < 0.01). Compared with the continuous rotary systems, the reciprocating single-file system A showed better apical shaping ability. Both single-file techniques were more efficient than full-sequential systems for curved canal preparation. Single-file techniques appear to be the effective and efficient method for curved canal preparation.

Safety of three sequential whole bladder photodynamic therapy (WBPDT) treatments in the management of resistant bladder cancer

NASA Astrophysics Data System (ADS)

Mejia, Maria C.; Nseyo, Unyime O.

2009-02-01

INTRODUCTION: WBPDT has been used to treat resistant superficial bladder cancer, with clinical benefits and associated dose-dependent side effects. OBJECTIVE: The objective of this study was to assess the safety of three sequential WBPDT treatments in patients with resistant non-muscle invasive (NMI) bladder cancer. MATERIALS AND METHODS: 12 males and one female provided written informed consent in this Phase II study. Each patient received intravenous injection of Photofrin® (AXCAN Parma Inc, Canada) at 1.5 mg/kg two days prior to whole bladder laser (630nm) treatment. Assessment of safety and efficacy included weekly urinary symptoms; cystoscopy, biopsy and cytology; and measurement of bladder volume quarterly after each treatment at baseline, six and 12 months. Treatment #2 and/or #3 occurred only in the absence of bladder contracture, and/or disease progression. RESULTS: 13 patients: 12 males and one female have been enrolled and average age of enrollees is 67.1(52 - 87) years. Four patients had Ta-T1/Grade I-III tumors; two patients had CIS associated with T1/GI-III; and seven patients had carcinoma in situ (CIS) only. Three patients received 3/3 treatments, and are evaluable for toxicity; three patients received two treatments only; and seven patients received one treatment only. There was no bladder contracture; transient mild to moderate bladder irritative voiding symptoms of dysuria, urinary frequency, nocturia and urgency occurred in all patients. The three evaluable patients were without evidence of disease at average of 13.1 (7-20) months. CONCLUSION: Three sequential WBPDT treatments might have a favorable toxicity profile in the management of recurrent/ refractory non-muscle invasive bladder cancer.

Optical fiber switch

DOEpatents

Early, James W.; Lester, Charles S.

2002-01-01

Optical fiber switches operated by electrical activation of at least one laser light modulator through which laser light is directed into at least one polarizer are used for the sequential transport of laser light from a single laser into a plurality of optical fibers. In one embodiment of the invention, laser light from a single excitation laser is sequentially transported to a plurality of optical fibers which in turn transport the laser light to separate individual remotely located laser fuel ignitors. The invention can be operated electro-optically with no need for any mechanical or moving parts, or, alternatively, can be operated electro-mechanically. The invention can be used to switch either pulsed or continuous wave laser light.

Unfolding of titin immunoglobulin domains by steered molecular dynamics simulation.

PubMed

Lu, H; Isralewitz, B; Krammer, A; Vogel, V; Schulten, K

1998-08-01

Titin, a 1-microm-long protein found in striated muscle myofibrils, possesses unique elastic and extensibility properties in its I-band region, which is largely composed of a PEVK region (70% proline, glutamic acid, valine, and lysine residue) and seven-strand beta-sandwich immunoglobulin-like (Ig) domains. The behavior of titin as a multistage entropic spring has been shown in atomic force microscope and optical tweezer experiments to partially depend on the reversible unfolding of individual Ig domains. We performed steered molecular dynamics simulations to stretch single titin Ig domains in solution with pulling speeds of 0.5 and 1.0 A/ps. Resulting force-extension profiles exhibit a single dominant peak for each Ig domain unfolding, consistent with the experimentally observed sequential, as opposed to concerted, unfolding of Ig domains under external stretching forces. This force peak can be attributed to an initial burst of backbone hydrogen bonds, which takes place between antiparallel beta-strands A and B and between parallel beta-strands A' and G. Additional features of the simulations, including the position of the force peak and relative unfolding resistance of different Ig domains, can be related to experimental observations.

Flexible storage medium for write-once optical tape

NASA Technical Reports Server (NTRS)

Strandjord, Andrew J. G.; Webb, Steven P.; Perettie, Donald J.; Cipriano, Robert A.

1993-01-01

A write-once data storage media was developed which is suitable for optical tape applications. The media is manufactured using a continuous film process to deposit a ternary alloy of tin, bismuth, and copper. This laser sensitive layer is sputter deposited onto commercial plastic web as a single-layer thin film. A second layer is sequentially deposited on top of the alloy to enhance the media performance and act as an abrasion resistant hard overcoat. The media was observed to have laser write sensitivities of less than 2.0 njoules/bit, carrier-to-noise levels of greater than 50dB's, modulation depths of approximately 100 percent, read-margins of greater than 35, uniform grain sizes of less than 200 Angstroms, and a media lifetime that exceeds 10 years. Prototype tape media was produced for use in the CREO drive system. The active and overcoat materials are first sputter deposited onto three mil PET film in a single pass through the vacuum coating system, and then converted down into multiple reels of 35mm x 880m tape. One mil PET film was also coated in this manner and then slit and packaged into 3480 tape cartridges.

Single step sequential polydimethylsiloxane wet etching to fabricate a microfluidic channel with various cross-sectional geometries

NASA Astrophysics Data System (ADS)

Wang, C.-K.; Liao, W.-H.; Wu, H.-M.; Lo, Y.-H.; Lin, T.-R.; Tung, Y.-C.

2017-11-01

Polydimethylsiloxane (PDMS) has become a widely used material to construct microfluidic devices for various biomedical and chemical applications due to its desirable material properties and manufacturability. PDMS microfluidic devices are usually fabricated using soft lithography replica molding methods with master molds made of photolithogrpahy patterned photoresist layers on silicon wafers. The fabricated microfluidic channels often have rectangular cross-sectional geometries with single or multiple heights. In this paper, we develop a single step sequential PDMS wet etching process that can be used to fabricate microfluidic channels with various cross-sectional geometries from single-layer PDMS microfluidic channels. The cross-sections of the fabricated channel can be non-rectangular, and varied along the flow direction. Furthermore, the fabricated cross-sectional geometries can be numerically simulated beforehand. In the experiments, we fabricate microfluidic channels with various cross-sectional geometries using the developed technique. In addition, we fabricate a microfluidic mixer with alternative mirrored cross-sectional geometries along the flow direction to demonstrate the practical usage of the developed technique.

Simultaneous and Sequential MS/MS Scan Combinations and Permutations in a Linear Quadrupole Ion Trap.

PubMed

Snyder, Dalton T; Szalwinski, Lucas J; Cooks, R Graham

2017-10-17

Methods of performing precursor ion scans as well as neutral loss scans in a single linear quadrupole ion trap have recently been described. In this paper we report methodology for performing permutations of MS/MS scan modes, that is, ordered combinations of precursor, product, and neutral loss scans following a single ion injection event. Only particular permutations are allowed; the sequences demonstrated here are (1) multiple precursor ion scans, (2) precursor ion scans followed by a single neutral loss scan, (3) precursor ion scans followed by product ion scans, and (4) segmented neutral loss scans. (5) The common product ion scan can be performed earlier in these sequences, under certain conditions. Simultaneous scans can also be performed. These include multiple precursor ion scans, precursor ion scans with an accompanying neutral loss scan, and multiple neutral loss scans. We argue that the new capability to perform complex simultaneous and sequential MS n operations on single ion populations represents a significant step in increasing the selectivity of mass spectrometry.

Clinically significant borderline resistance of sequential clinical isolates of Klebsiella pneumoniae.

PubMed

Wagenlehner, F M E; Heisig, P; Irtenkauf, C; Notka, F; Decker, J; Lehn, N; Linde, H

2003-10-01

Two sequential clinical isolates of Klebsiella pneumoniae (Kpn) were isolated from bronchoalveolar lavage fluid (Kpn#1) and sputum (Kpn#2) of a patient with pneumonia, complicated by anatomical and immunosuppressive problems due to Wegener's granulomatosis. Despite 4 weeks of systemic treatment with ciprofloxacin (CIP) Kpn#2 was isolated thereafter. A fluoroquinolone-resistant mutant (Kpn#1-SEL) was derived from Kpn#1 in vitro by selecting on agar plates supplemented with ofloxacin. Kpn#1, Kpn#1-SEL and Kpn#2 had an identical pattern in PFGE. CIP MICs were 0.25, 2 and 4 mg/l for Kpn#1, Kpn#2 and Kpn#1-SEL, respectively. Kpn ATCC 10031 (CIP MIC 0.002 mg/l) served as control. We analyzed mechanisms of fluoroquinolone resistance by determining antibiotic susceptibility, organic solvent tolerance, accumulation of fluoroquinolones, dominance testing with wild-type topoisomerase genes (gyrA/B, parC/E), sequencing of the quinolone resistance determining regions of gyrA/B, parC/E and marR and Northern blotting of marR and acrAB genes. Compared with Kpn ATCC 10031, elevated MICs to fluoroquinolones and unrelated antibiotics in Kpn#1 was presumably due to a primary efflux pump other than AcrAB and increased the CIP MIC 125-fold. Although Kpn#1 tested sensitive according to NCCLS breakpoints, the elevated CIP MIC of 0.25 mg/l presumably rendered this isolate clinically resistant and lead to therapeutic failure in this case. Further increase of MIC to fluoroquinolones in vivo and in vitro was distinct. Kpn#1-SEL, selected in vitro, acquired a GyrA target mutation, whereas in Kpn#2 no known resistance mechanism could be detected.

Cable tester

NASA Astrophysics Data System (ADS)

Rammage, Robert L.

1990-10-01

A device for sequentially testing the plurality of connectors in a wiring harness is disclosed. The harness is attached to the tester by means of adapter cables and a rotary switch is used to sequentially, individually test the connectors by passing a current through the connector. If the connector is unbroken, a light will flash to show it is electrically sound. The adapters allow a large number of cable configurations to be tested using a single tester configuration.

"Sequential" boron neutron capture therapy (BNCT): a novel approach to BNCT for the treatment of oral cancer in the hamster cheek pouch model.

PubMed

Molinari, Ana J; Pozzi, Emiliano C C; Monti Hughes, Andrea; Heber, Elisa M; Garabalino, Marcela A; Thorp, Silvia I; Miller, Marcelo; Itoiz, Maria E; Aromando, Romina F; Nigg, David W; Quintana, Jorge; Santa Cruz, Gustavo A; Trivillin, Verónica A; Schwint, Amanda E

2011-04-01

In the present study the therapeutic effect and potential toxicity of the novel "Sequential" boron neutron capture therapy (Seq-BNCT) for the treatment of oral cancer was evaluated in the hamster cheek pouch model at the RA-3 Nuclear Reactor. Two groups of animals were treated with "Sequential" BNCT, i.e., BNCT mediated by boronophenylalanine (BPA) followed by BNCT mediated by sodium decahydrodecaborate (GB-10) either 24 h (Seq-24h-BNCT) or 48 h (Seq-48h-BNCT) later. In an additional group of animals, BPA and GB-10 were administered concomitantly [(BPA + GB-10)-BNCT]. The single-application BNCT was to the same total physical tumor dose as the "Sequential" BNCT treatments. At 28 days post-treatment, Seq-24h-BNCT and Seq-48h-BNCT induced, respectively, overall tumor responses of 95 ± 2% and 91 ± 3%, with no statistically significant differences between protocols. Overall response for the single treatment with (BPA + GB-10)-BNCT was 75 ± 5%, significantly lower than for Seq-BNCT. Both Seq-BNCT protocols and (BPA + GB-10)-BNCT induced reversible mucositis in the dose-limiting precancerous tissue around treated tumors, reaching Grade 3/4 mucositis in 47 ± 12% and 60 ± 22% of the animals, respectively. No normal tissue toxicity was associated with tumor response for any of the protocols. "Sequential" BNCT enhanced tumor response without an increase in mucositis in dose-limiting precancerous tissue. © 2011 by Radiation Research Society

Outcomes of resistance-guided sequential treatment of Mycoplasma genitalium infections: a prospective evaluation.

PubMed

Read, T R H; Fairley, C K; Murray, G L; Jensen, J S; Danielewski, J; Worthington, K; Doyle, M; Mokany, E; Tan, L; Chow, E P F; Garland, S M; Bradshaw, C S

2018-06-05

Rising macrolide and quinolone resistance in Mycoplasma genitalium necessitate new treatment approaches. We evaluated outcomes of sequential antimicrobial therapy for M.genitalium guided by a macrolide-resistance assay. In mid-2016 Melbourne Sexual Health Centre switched from azithromycin to doxycycline (100mg twice daily,7 days) for non-gonococcal urethritis/cervicitis/proctitis. Cases were tested for M. genitalium and macrolide-resistance mutations (MRM) by polymerase chain reaction (PCR). Directly after doxycycline, MRM-negative infections received 2.5g azithromycin (1g then 500mg daily for 3 days), and MRM-positive infections received sitafloxacin (100mg twice daily, 7 days). Assessment of test-of-cure and reinfection risk, occurred 14-90 days after the second antibiotic. Those reporting condomless sex with incompletely treated partners were excluded. Of 244 evaluable M. genitalium infections (52 women, 68 heterosexual men, 124 men who have sex with men) diagnosed from 20 June 2016 to 15 May 2017, MRM were detected in 167 [68.4% (95%confidence interval(CI):62.2%, 74.2%)]. Treatment with doxycycline decreased bacterial load by a mean 2.60 log10 (n=56, p<0.0001). Microbiologic cure occurred in: 73/77 MRM-negative infections [94.8% (95%CI:87.2%, 98.6%)] and in 154/167 MRM-positive infections [92.2% (95%CI:87.1%, 95.8%)]. Selection of macrolide-resistance occurred in only 2 [2.6% (95%CI: 0.3%, 9.2%)] of 76 macrolide-susceptible infections. Proportions reporting no missed doses and no adverse events, respectively, were: doxycycline 89.9% and 86.6%, sitafloxacin 90.8% and 80.5%, azithromycin 100% and 91.4%. In the context of high levels of antimicrobial resistance, switching from azithromycin to doxycycline for presumptive treatment of M. genitalium, followed by resistance-guided therapy, cured ≥92% of infections, with infrequent selection of macrolide resistance.

Structural characterization of polysaccharides from bamboo

NASA Astrophysics Data System (ADS)

Kamil, Ruzaimah Nik Mohamad; Yusuf, Nur'aini Raman; Yunus, Normawati M.; Yusup, Suzana

2014-10-01

The alkaline and water soluble polysaccharides were isolate by sequential extractions with distilled water, 60% ethanol containing 1%, 5% and 8% NaOH. The samples were prepared at 60 °C for 3 h from local bamboo. The functional group of the sample were examined using FTIR analysis. The most precipitate obtained is from using 60% ethanol containing 8% NaOH with yield of 2.6%. The former 3 residues isolated by sequential extractions with distilled water, 60% ethanol containing 1% and 5% NaOH are barely visible after filtering with cellulose filter paper. The FTIR result showed that the water-soluble polysaccharides consisted mainly of OH group, CH group, CO indicates the carbohydrate and sugar chain. The sample weight loss was slightly decreased with increasing of temperature.

Pathophysiology of resistant hypertension in chronic kidney disease.

PubMed

Campese, Vito M

2014-01-01

Hypertension associated with chronic kidney diseases often is resistant to drug treatment. This review deals with two main aspects of the management of CKD patients with hypertension: the role of sodium/volume and the need for dietary salt restriction, as well as appropriate use of diuretics and what currently is called sequential nephron blockade; the second aspect that is addressed extensively in this review is the role of the sympathetic nervous system and the possible clinical use of renal denervation.

Deficits in sequential processing manifest in motor and linguistic tasks in a multigenerational family with childhood apraxia of speech

PubMed Central

PETER, BEATE; BUTTON, LE; STOEL-GAMMON, CAROL; CHAPMAN, KATHY; RASKIND, WENDY H.

2013-01-01

The purpose of this study was to evaluate a global deficit in sequential processing as candidate endophenotypein a family with familial childhood apraxia of speech (CAS). Of 10 adults and 13 children in a three-generational family with speech sound disorder (SSD) consistent with CAS, 3 adults and 6 children had past or present SSD diagnoses. Two preschoolers with unremediated CAS showed a high number of sequencing errors during single-word production. Performance on tasks with high sequential processing loads differentiated between the affected and unaffected family members, whereas there were no group differences in tasks with low processing loads. Adults with a history of SSD produced more sequencing errors during nonword and multisyllabic real word imitation, compared to those without such a history. Results are consistent with a global deficit in sequential processing that influences speech development as well as cognitive and linguistic processing. PMID:23339324

Visual short-term memory for sequential arrays.

PubMed

Kumar, Arjun; Jiang, Yuhong

2005-04-01

The capacity of visual short-term memory (VSTM) for a single visual display has been investigated in past research, but VSTM for multiple sequential arrays has been explored only recently. In this study, we investigate the capacity of VSTM across two sequential arrays separated by a variable stimulus onset asynchrony (SOA). VSTM for spatial locations (Experiment 1), colors (Experiments 2-4), orientations (Experiments 3 and 4), and conjunction of color and orientation (Experiment 4) were tested, with the SOA across the two sequential arrays varying from 100 to 1,500 msec. We find that VSTM for the trailing array is much better than VSTM for the leading array, but when averaged across the two arrays VSTM has a constant capacity independent of the SOA. We suggest that multiple displays compete for retention in VSTM and that separating information into two temporally discrete groups does not enhance the overall capacity of VSTM.

A Process Improvement Evaluation of Sequential Compression Device Compliance and Effects of Provider Intervention.

PubMed

Beachler, Jason A; Krueger, Chad A; Johnson, Anthony E

This process improvement study sought to evaluate the compliance in orthopaedic patients with sequential compression devices and to monitor any improvement in compliance following an educational intervention. All non-intensive care unit orthopaedic primary patients were evaluated at random times and their compliance with sequential compression devices was monitored and recorded. Following a 2-week period of data collection, an educational flyer was displayed in every patient's room and nursing staff held an in-service training event focusing on the importance of sequential compression device use in the surgical patient. Patients were then monitored, again at random, and compliance was recorded. With the addition of a simple flyer and a single in-service on the importance of mechanical compression in the surgical patient, a significant improvement in compliance was documented at the authors' institution from 28% to 59% (p < .0001).

Diffusion barrier properties of single- and multilayered quasi-amorphous tantalum nitride thin films against copper penetration

NASA Astrophysics Data System (ADS)

Chen, G. S.; Chen, S. T.

2000-06-01

Tantalum-related thin films containing different amounts of nitrogen are sputter deposited at different argon-to-nitrogen flow rate ratios on (100) silicon substrates. Using x-ray diffractometry, transmission electron microscopy, composition and resistivity analyses, and bending-beam stress measurement technique, this work examines the impact of varying the nitrogen flow rate, particularly on the crystal structure, composition, resistivity, and residual intrinsic stress of the deposited Ta2N thin films. With an adequate amount of controlled, reactive nitrogen in the sputtering gas, thin films of the tantalum nitride of nominal formula Ta2N are predominantly amorphous and can exist over a range of nitrogen concentrations slightly deviated from stoichiometry. The single-layered quasi-amorphous Ta2N (a-Ta2N) thin films yield intrinsic compressive stresses in the range 3-5 GPa. In addition, the use of the 40-nm-thick a-Ta2N thin films with different nitrogen atomic concentrations (33% and 36%) and layering designs as diffusion barriers between silicon and copper are also evaluated. When subjected to high-temperature annealing, the single-layered a-Ta2N barrier layers degrade primarily by an amorphous-to-crystalline transition of the barrier layers. Crystallization of the single-layered stoichiometric a-Ta2N (Ta67N33) diffusion barriers occurs at temperatures as low as 450 °C. Doing so allows copper to preferentially penetrate through the grain boundaries or thermal-induced microcracks of the crystallized barriers and react with silicon, sequentially forming {111}-facetted pyramidal Cu3Si precipitates and TaSi2 Overdoping nitrogen into the amorphous matrix can dramatically increase the crystallization temperature to 600 °C. This temperature increase slows down the inward diffusion of copper and delays the formation of both silicides. The nitrogen overdoped Ta2N (Ta64N36) diffusion barriers can thus be significantly enhanced so as to yield a failure temperature 100 °C greater than that of the Ta67N33 diffusion barriers. Moreover, multilayered films, formed by alternately stacking the Ta67N33 and Ta64N36 layers with an optimized bilayer thickness (λ) of 10 nm, can dramatically reduce the intrinsic compressive stress to only 0.7 GPa and undergo high-temperature annealing without crystallization. Therefore, the Ta67N33/Ta64N36 multilayered films exhibit a much better barrier performance than the highly crystallization-resistant Ta64N36 single-layered films.

Role of Pseudomonas aeruginosa low-molecular-mass penicillin-binding proteins in AmpC expression, β-lactam resistance, and peptidoglycan structure.

PubMed

Ropy, Alaa; Cabot, Gabriel; Sánchez-Diener, Irina; Aguilera, Cristian; Moya, Bartolome; Ayala, Juan A; Oliver, Antonio

2015-07-01

This study aimed to characterize the role of Pseudomonas aeruginosa low-molecular-mass penicillin-binding proteins (LMM PBPs), namely, PBP4 (DacB), PBP5 (DacC), and PBP7 (PbpG), in peptidoglycan composition, β-lactam resistance, and ampC regulation. For this purpose, we constructed all single and multiple mutants of dacB, dacC, pbpG, and ampC from the wild-type P. aeruginosa PAO1 strain. Peptidoglycan composition was determined by high-performance liquid chromatography (HPLC), ampC expression by reverse transcription-PCR (RT-PCR), PBP patterns by a Bocillin FL-binding test, and antimicrobial susceptibility by MIC testing for a panel of β-lactams. Microscopy and growth rate analyses revealed no apparent major morphological changes for any of the mutants compared to the wild-type PAO1 strain. Of the single mutants, only dacC mutation led to significantly increased pentapeptide levels, showing that PBP5 is the major dd-carboxypeptidase in P. aeruginosa. Moreover, our results indicate that PBP4 and PBP7 play a significant role as dd-carboxypeptidase only if PBP5 is absent, and their dd-endopeptidase activity is also inferred. As expected, the inactivation of PBP4 led to a significant increase in ampC expression (around 50-fold), but, remarkably, the sequential inactivation of the three LMM PBPs produced a much greater increase (1,000-fold), which correlated with peptidoglycan pentapeptide levels. Finally, the β-lactam susceptibility profiles of the LMM PBP mutants correlated well with the ampC expression data. However, the inactivation of ampC in these mutants also evidenced a role of LMM PBPs, especially PBP5, in intrinsic β-lactam resistance. In summary, in addition to assessing the effect of P. aeruginosa LMM PBPs on peptidoglycan structure for the first time, we obtained results that represent a step forward in understanding the impact of these PBPs on β-lactam resistance, apparently driven by the interplay between their roles in AmpC induction, β-lactam trapping, and dd-carboxypeptidase/β-lactamase activity. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Robust inference for group sequential trials.

PubMed

Ganju, Jitendra; Lin, Yunzhi; Zhou, Kefei

2017-03-01

For ethical reasons, group sequential trials were introduced to allow trials to stop early in the event of extreme results. Endpoints in such trials are usually mortality or irreversible morbidity. For a given endpoint, the norm is to use a single test statistic and to use that same statistic for each analysis. This approach is risky because the test statistic has to be specified before the study is unblinded, and there is loss in power if the assumptions that ensure optimality for each analysis are not met. To minimize the risk of moderate to substantial loss in power due to a suboptimal choice of a statistic, a robust method was developed for nonsequential trials. The concept is analogous to diversification of financial investments to minimize risk. The method is based on combining P values from multiple test statistics for formal inference while controlling the type I error rate at its designated value.This article evaluates the performance of 2 P value combining methods for group sequential trials. The emphasis is on time to event trials although results from less complex trials are also included. The gain or loss in power with the combination method relative to a single statistic is asymmetric in its favor. Depending on the power of each individual test, the combination method can give more power than any single test or give power that is closer to the test with the most power. The versatility of the method is that it can combine P values from different test statistics for analysis at different times. The robustness of results suggests that inference from group sequential trials can be strengthened with the use of combined tests. Copyright © 2017 John Wiley & Sons, Ltd.

Cascade catalysis in membranes with enzyme immobilization for multi-enzymatic conversion of CO2 to methanol.

PubMed

Luo, Jianquan; Meyer, Anne S; Mateiu, R V; Pinelo, Manuel

2015-05-25

Facile co-immobilization of enzymes is highly desirable for bioconversion methods involving multi-enzymatic cascade reactions. Here we show for the first time that three enzymes can be immobilized in flat-sheet polymeric membranes simultaneously or separately by simple pressure-driven filtration (i.e. by directing membrane fouling formation), without any addition of organic solvent. Such co-immobilization and sequential immobilization systems were examined for the production of methanol from CO2 with formate dehydrogenase (FDH), formaldehyde dehydrogenase (FaldDH) and alcohol dehydrogenase (ADH). Enzyme activity was fully retained by this non-covalent immobilization strategy. The two immobilization systems had similar catalytic efficiencies because the second reaction (formic acid→formaldehyde) catalyzed by FaldDH was found to be the cascade bottleneck (a threshold substrate concentration was required). Moreover, the trade-off between the mitigation of product inhibition and low substrate concentration for the adjacent enzymes probably made the co-immobilization meaningless. Thus, sequential immobilization could be used for multi-enzymatic cascade reactions, as it allowed the operational conditions for each single step to be optimized, not only during the enzyme immobilization but also during the reaction process, and the pressure-driven mass transfer (flow-through mode) could overcome the diffusion resistance between enzymes. This study not only offers a green and facile immobilization method for multi-enzymatic cascade systems, but also reveals the reaction bottleneck and provides possible solutions for the bioconversion of CO2 to methanol. Copyright © 2015 Elsevier B.V. All rights reserved.

Successful Combination of Sequential Gene Therapy and Rescue Allo-HSCT in Two Children with X-CGD - Importance of Timing.

PubMed

Siler, Ulrich; Paruzynski, Anna; Holtgreve-Grez, Heidi; Kuzmenko, Elena; Koehl, Ulrike; Renner, Eleonore D; Alhan, Canan; de Loosdrecht, Arjan A van; Schwäble, Joachim; Pfluger, Thomas; Tchinda, Joelle; Schmugge, Markus; Jauch, Anna; Naundorf, Sonja; Kühlcke, Klaus; Notheis, Gundula; Güngor, Tayfun; Kalle, Christof V; Schmidt, Manfred; Grez, Manuel; Seger, Reinhard; Reichenbach, Janine

2015-01-01

We report on a series of sequential events leading to long-term survival and cure of pediatric X-linked chronic granulomatous disease (X-CGD) patients after gamma-retroviral gene therapy (GT) and rescue HSCT. Due to therapyrefractory life-threatening infections requiring hematopoietic stem cell transplantation (HSCT) but absence of HLAidentical donors, we treated 2 boys with X-CGD by GT. Following GT both children completely resolved invasive Aspergillus nidulans infections. However, one child developed dual insertional activation of ecotropic viral integration site 1 (EVI1) and signal transducer and activator of transcription 3 (STAT3) genes, leading to myelodysplastic syndrome (MDS) with monosomy 7. Despite resistance to mismatched allo-HSCT with standard myeloablative conditioning, secondary intensified rescue allo-HSCT resulted in 100 % donor chimerism and disappearance of MDS. The other child did not develop MDS despite expansion of a clone with a single insertion in the myelodysplasia syndrome 1 (MDS1) gene and was cured by early standard allo-HSCT. The slowly developing dominance of clones harboring integrations in MDS1-EVI1 may guide clinical intervention strategies, i.e. early rescue allo-HSCT, prior to malignant transformation. GT was essential for both children to survive and to clear therapy-refractory infections, and future GT with safer lentiviral self-inactivated (SIN) vectors may offer a therapeutic alternative for X-CGD patients suffering from life-threatening infections and lacking HLA-identical HSC donors.

Functional Investigation of NCI-H460-Inducible Myofibroblasts on the Chemoresistance to VP-16 with a Microfluidic 3D Co-Culture Device

PubMed Central

He, Jiarui; Guo, Zhe; Ying, Li; Xu, Zhiyun; Zhang, Jianing; Lu, Jianxin; Wang, Qi

2013-01-01

Fibroblasts, the major cell type in tumor stroma, are essential for tumor growth and survival, and represent an important therapeutic target for cancers. Here we presented a microfluidic co-culture device in which the three-dimensional (3D) matrix was employed to reconstruct an in vivo-like fibroblast-tumor cell microenvironment for investigation of the role of myofibroblasts induced by lung cancer cells in the chemoresistance to VP-16. Composed of a double-layer chip and an injection pump, the device houses fibroblasts and lung cancer cells co-cultured in 3D matrix and 2D mode to induce fibroblasts to become myofibroblasts with the supplement of the medium continuously. With this device, we verified that the cytokines secreted by lung cancer cells could effectively transform the fibroblasts into myofibroblasts. Moreover, compared to fibroblasts, the myofibroblasts showed higher resistance to anticancer drug VP-16. We also demonstrated that this kind of acquired resistance in myofibroblasts was associated with the expression of Glucose-regulated protein 78 (GP78). We concluded that this device allows for the assay to characterize various cellular events in a single device sequentially, facilitating a better understanding of the interactions among heterotypic cells in a sophisticated microenvironment. PMID:23613925

The finite state projection approach to analyze dynamics of heterogeneous populations

NASA Astrophysics Data System (ADS)

Johnson, Rob; Munsky, Brian

2017-06-01

Population modeling aims to capture and predict the dynamics of cell populations in constant or fluctuating environments. At the elementary level, population growth proceeds through sequential divisions of individual cells. Due to stochastic effects, populations of cells are inherently heterogeneous in phenotype, and some phenotypic variables have an effect on division or survival rates, as can be seen in partial drug resistance. Therefore, when modeling population dynamics where the control of growth and division is phenotype dependent, the corresponding model must take account of the underlying cellular heterogeneity. The finite state projection (FSP) approach has often been used to analyze the statistics of independent cells. Here, we extend the FSP analysis to explore the coupling of cell dynamics and biomolecule dynamics within a population. This extension allows a general framework with which to model the state occupations of a heterogeneous, isogenic population of dividing and expiring cells. The method is demonstrated with a simple model of cell-cycle progression, which we use to explore possible dynamics of drug resistance phenotypes in dividing cells. We use this method to show how stochastic single-cell behaviors affect population level efficacy of drug treatments, and we illustrate how slight modifications to treatment regimens may have dramatic effects on drug efficacy.

Bridging the qualitative-quantitative divide: Experiences from conducting a mixed methods evaluation in the RUCAS programme.

PubMed

Makrakis, Vassilios; Kostoulas-Makrakis, Nelly

2016-02-01

Quantitative and qualitative approaches to planning and evaluation in education for sustainable development have often been treated by practitioners from a single research paradigm. This paper discusses the utility of mixed method evaluation designs which integrate qualitative and quantitative data through a sequential transformative process. Sequential mixed method data collection strategies involve collecting data in an iterative process whereby data collected in one phase contribute to data collected in the next. This is done through examples from a programme addressing the 'Reorientation of University Curricula to Address Sustainability (RUCAS): A European Commission Tempus-funded Programme'. It is argued that the two approaches are complementary and that there are significant gains from combining both. Using methods from both research paradigms does not, however, mean that the inherent differences among epistemologies and methodologies should be neglected. Based on this experience, it is recommended that using a sequential transformative mixed method evaluation can produce more robust results than could be accomplished using a single approach in programme planning and evaluation focussed on education for sustainable development. Copyright © 2015 Elsevier Ltd. All rights reserved.

Resistance to minor groove binders.

PubMed

Colmegna, Benedetta; Uboldi, Sarah; Erba, Eugenio; D'Incalci, Maurizio

2014-03-01

In this paper multiple resistance mechanisms to minor groove binders (MGBs) are overviewed. MGBs with antitumor properties are natural products or their derivatives and, as expected, they are all substrates of P-glycoprotein (P-gp). However, a moderate expression of P-gp does not appear to reduce the sensitivity to trabectedin, the only MGB so far approved for clinical use. Resistance to this drug is often related to transcriptional mechanisms and to DNA repair pathways, particularly defects in transcription-coupled nucleotide excision repair (TC-NER). Therefore tumors resistant to trabectedin may become hypersensitive to UV rays and other DNA damaging agents acting in the major groove, such as Platinum (Pt) complexes. If this is confirmed in clinic, that will provide the rationale to combine trabectedin sequentially with Pt derivates.

Revascularization of Left Coronary System Using a Skeletonized Left Internal Mammary Artery　- Sequential vs. Separate Grafting.

PubMed

Ji, Qiang; Shi, YunQing; Xia, LiMin; Ma, RunHua; Shen, JinQiang; Lai, Hao; Ding, WenJun; Wang, ChunSheng

2017-12-25

To evaluate in-hospital and mid-term outcomes of sequential vs. separate grafting of in situ skeletonized left internal mammary artery (LIMA) to the left coronary system in a single-center, propensity-matched study.Methods and Results:After propensity score-matching, 120 pairs of patients undergoing first scheduled isolated coronary artery bypass grafting (CABG) with in situ skeletonized LIMA grafting to the left anterior descending artery (LAD) territory were entered into a sequential group (sequential grafting of LIMA to the diagonal artery and then to the LAD) or a control group (separate grafting of LIMA to the LAD). The in-hospital and follow-up clinical outcomes and follow-up LIMA graft patency were compared. Both propensity score-matched groups had similar in-hospital and follow-up clinical outcomes. Sequential LIMA grafting was not found to be an independent predictor of adverse events. During a follow-up period of 27.0±7.3 months, 99.1% patency for the diagonal site and 98.3% for the LAD site were determined by coronary computed tomographic angiography after sequential LIMA grafting, both of which were similar with graft patency of separate grafting of in situ skeletonized LIMA to the LAD. Revascularization of the left coronary system using a skeletonized LIMA resulted in excellent in-hospital and mid-term clinical outcomes and graft patency using sequential grafting.

A Strategy to Design High-Density Nanoscale Devices utilizing Vapor Deposition of Metal Halide Perovskite Materials.

PubMed

Hwang, Bohee; Lee, Jang-Sik

2017-08-01

The demand for high memory density has increased due to increasing needs of information storage, such as big data processing and the Internet of Things. Organic-inorganic perovskite materials that show nonvolatile resistive switching memory properties have potential applications as the resistive switching layer for next-generation memory devices, but, for practical applications, these materials should be utilized in high-density data-storage devices. Here, nanoscale memory devices are fabricated by sequential vapor deposition of organolead halide perovskite (OHP) CH 3 NH 3 PbI 3 layers on wafers perforated with 250 nm via-holes. These devices have bipolar resistive switching properties, and show low-voltage operation, fast switching speed (200 ns), good endurance, and data-retention time >10 5 s. Moreover, the use of sequential vapor deposition is extended to deposit CH 3 NH 3 PbI 3 as the memory element in a cross-point array structure. This method to fabricate high-density memory devices could be used for memory cells that occupy large areas, and to overcome the scaling limit of existing methods; it also presents a way to use OHPs to increase memory storage capacity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Selection history and epistatic interactions impact dynamics of adaptation to novel environmental stresses.

PubMed

Lagator, Mato; Colegrave, Nick; Neve, Paul

2014-11-07

In rapidly changing environments, selection history may impact the dynamics of adaptation. Mutations selected in one environment may result in pleiotropic fitness trade-offs in subsequent novel environments, slowing the rates of adaptation. Epistatic interactions between mutations selected in sequential stressful environments may slow or accelerate subsequent rates of adaptation, depending on the nature of that interaction. We explored the dynamics of adaptation during sequential exposure to herbicides with different modes of action in Chlamydomonas reinhardtii. Evolution of resistance to two of the herbicides was largely independent of selection history. For carbetamide, previous adaptation to other herbicide modes of action positively impacted the likelihood of adaptation to this herbicide. Furthermore, while adaptation to all individual herbicides was associated with pleiotropic fitness costs in stress-free environments, we observed that accumulation of resistance mechanisms was accompanied by a reduction in overall fitness costs. We suggest that antagonistic epistasis may be a driving mechanism that enables populations to more readily adapt in novel environments. These findings highlight the potential for sequences of xenobiotics to facilitate the rapid evolution of multiple-drug and -pesticide resistance, as well as the potential for epistatic interactions between adaptive mutations to facilitate evolutionary rescue in rapidly changing environments. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Deficit irrigation practices may alter Vitis vinifera L. resistance to cold injury: Empirical evidence from the field

USDA-ARS?s Scientific Manuscript database

Deficit irrigation reduces seasonal carbohydrate supply and decreases starch concentrations in vegetative tissues. The specific role of starch metabolism in conferring tolerance to cold is still poorly understood. A decrease in cold tolerance after sequential years of deficit irrigation would limit ...

Use of Grasp Force Focus Positioning to Enhance the Torque Resistance Capability of Robotic Grasps

DTIC Science & Technology

1990-12-13

8217SEQUENTIAL’, 124 1 FORM=’FORMATTED’) 125 OPEN(18,FILE=’CNTCTS’//RUN//’. DkT ’ ,STATUS=’NEW’, 126 1 ACCESS=’SEqtJENTIAL’, 127 1 FO’FOMTED’) 128 OPEN(19,FILE

Souldrama[R]: Spirituality in Action

ERIC Educational Resources Information Center

Miller, Connie

2008-01-01

Souldrama[R] is a therapeutic, psychospiritual group action model that leads participants through seven sequential stages of spiritual development with the goal of accessing their spiritual intelligence. It can help group members move past resistance and recognize and move on to their higher purpose. Psychodramatically based, it is intended to be…

Detailed imaging and genetic analysis reveal a secondary BRAF(L505H) resistance mutation and extensive intrapatient heterogeneity in metastatic BRAF mutant melanoma patients treated with vemurafenib.

PubMed

Hoogstraat, Marlous; Gadellaa-van Hooijdonk, Christa G; Ubink, Inge; Besselink, Nicolle J M; Pieterse, Mark; Veldhuis, Wouter; van Stralen, Marijn; Meijer, Eelco F J; Willems, Stefan M; Hadders, Michael A; Kuilman, Thomas; Krijgsman, Oscar; Peeper, Daniel S; Koudijs, Marco J; Cuppen, Edwin; Voest, Emile E; Lolkema, Martijn P

2015-05-01

Resistance to treatment is the main problem of targeted treatment for cancer. We followed ten patients during treatment with vemurafenib, by three-dimensional imaging. In all patients, only a subset of lesions progressed. Next-generation DNA sequencing was performed on sequential biopsies in four patients to uncover mechanisms of resistance. In two patients, we identified mutations that explained resistance to vemurafenib; one of these patients had a secondary BRAF L505H mutation. This is the first observation of a secondary BRAF mutation in a vemurafenib-resistant patient-derived melanoma sample, which confirms the potential importance of the BRAF L505H mutation in the development of therapy resistance. Moreover, this study hints toward an important role for tumor heterogeneity in determining the outcome of targeted treatments. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Two Novel Point Mutations in Clinical Staphylococcus aureus Reduce Linezolid Susceptibility and Switch on the Stringent Response to Promote Persistent Infection

PubMed Central

Gao, Wei; Chua, Kyra; Davies, John K.; Newton, Hayley J.; Seemann, Torsten; Harrison, Paul F.; Holmes, Natasha E.; Rhee, Hyun-Woo; Hong, Jong-In; Hartland, Elizabeth L.; Stinear, Timothy P.; Howden, Benjamin P.

2010-01-01

Staphylococcus aureus frequently invades the human bloodstream, leading to life threatening bacteremia and often secondary foci of infection. Failure of antibiotic therapy to eradicate infection is frequently described; in some cases associated with altered S. aureus antimicrobial resistance or the small colony variant (SCV) phenotype. Newer antimicrobials, such as linezolid, remain the last available therapy for some patients with multi-resistant S. aureus infections. Using comparative and functional genomics we investigated the molecular determinants of resistance and SCV formation in sequential S. aureus isolates from a patient who had a persistent and recurrent S. aureus infection, after failed therapy with multiple antimicrobials, including linezolid. Two point mutations in key staphylococcal genes dramatically affected clinical behaviour of the bacterium, altering virulence and antimicrobial resistance. Most strikingly, a single nucleotide substitution in relA (SACOL1689) reduced RelA hydrolase activity and caused accumulation of the intracellular signalling molecule guanosine 3′, 5′-bis(diphosphate) (ppGpp) and permanent activation of the stringent response, which has not previously been reported in S. aureus. Using the clinical isolate and a defined mutant with an identical relA mutation, we demonstrate for the first time the impact of an active stringent response in S. aureus, which was associated with reduced growth, and attenuated virulence in the Galleria mellonella model. In addition, a mutation in rlmN (SACOL1230), encoding a ribosomal methyltransferase that methylates 23S rRNA at position A2503, caused a reduction in linezolid susceptibility. These results reinforce the exquisite adaptability of S. aureus and show how subtle molecular changes cause major alterations in bacterial behaviour, as well as highlighting potential weaknesses of current antibiotic treatment regimens. PMID:20548948

Single nanoparticle tracking spectroscopic microscope

DOEpatents

Yang, Haw [Moraga, CA; Cang, Hu [Berkeley, CA; Xu, Cangshan [Berkeley, CA; Wong, Chung M [San Gabriel, CA

2011-07-19

A system that can maintain and track the position of a single nanoparticle in three dimensions for a prolonged period has been disclosed. The system allows for continuously imaging the particle to observe any interactions it may have. The system also enables the acquisition of real-time sequential spectroscopic information from the particle. The apparatus holds great promise in performing single molecule spectroscopy and imaging on a non-stationary target.

Comparison of Image Quality and Radiation Dose of Coronary Computed Tomography Angiography Between Conventional Helical Scanning and a Strategy Incorporating Sequential Scanning

PubMed Central

Einstein, Andrew J.; Wolff, Steven D.; Manheimer, Eric D.; Thompson, James; Terry, Sylvia; Uretsky, Seth; Pilip, Adalbert; Peters, M. Robert

2009-01-01

Radiation dose from coronary computed tomography angiography may be reduced using a sequential scanning protocol rather than a conventional helical scanning protocol. Here we compare radiation dose and image quality from coronary computed tomography angiography in a single center between an initial period during which helical scanning with electrocardiographically-controlled tube current modulation was used for all patients (n=138) and after adoption of a strategy incorporating sequential scanning whenever appropriate (n=261). Using the sequential-if-appropriate strategy, sequential scanning was employed in 86.2% of patients. Compared to the helical-only strategy, this strategy was associated with a 65.1% dose reduction (mean dose-length product of 305.2 vs. 875.1 and mean effective dose of 14.9 mSv vs. 5.2 mSv, respectively), with no significant change in overall image quality, step artifacts, motion artifacts, or perceived image noise. For the 225 patients undergoing sequential scanning, the dose-length product was 201.9 ± 90.0 mGy·cm, while for patients undergoing helical scanning under either strategy, the dose-length product was 890.9 ± 293.3 mGy·cm (p<0.0001), corresponding to mean effective doses of 3.4 mSv and 15.1 mSv, respectively, a 77.5% reduction. Image quality was significantly greater for the sequential studies, reflecting the poorer image quality in patients undergoing helical scanning in the sequential-if-appropriate strategy. In conclusion, a sequential-if-appropriate diagnostic strategy reduces dose markedly compared to a helical-only strategy, with no significant difference in image quality. PMID:19892048

Comparison of Radiation Dose and Image Quality of Triple-Rule-Out Computed Tomography Angiography Between Conventional Helical Scanning and a Strategy Incorporating Sequential Scanning

PubMed Central

Manheimer, Eric D.; Peters, M. Robert; Wolff, Steven D.; Qureshi, Mehreen A.; Atluri, Prashanth; Pearson, Gregory D.N.; Einstein, Andrew J.

2011-01-01

Triple-rule-out computed tomography angiography (TRO CTA), performed to evaluate the coronary arteries, pulmonary arteries, and thoracic aorta, has been associated with high radiation exposure. Utilization of sequential scanning for coronary computed tomography angiography (CCTA) reduces radiation dose. The application of sequential scanning to TRO CTA is much less well defined. We analyzed radiation dose and image quality from TRO CTA performed in a single outpatient center, comparing scans from a period during which helical scanning with electrocardiographically controlled tube current modulation was used for all patients (n=35) and after adoption of a strategy incorporating sequential scanning whenever appropriate (n=35). Sequential scanning was able to be employed in 86% of cases. The sequential-if-appropriate strategy, compared to the helical-only strategy, was associated with a 61.6% dose decrease (mean dose-length product [DLP] of 439 mGy×cm vs 1144 mGy×cm and mean effective dose of 7.5 mSv vs 19.4 mSv, respectively, p<0.0001). Similarly, there was a 71.5% dose reduction among 30 patients scanned with the sequential protocol compared to 40 patients scanned with the helical protocol under either strategy (326 mGy×cm vs 1141 mGy×cm and 5.5 mSv vs 19.4 mSv, respectively, p<0.0001). Although image quality did not differ between strategies, there was a non-statistically significant trend towards better quality in the sequential protocol compared to the helical protocol. In conclusion, approaching TRO CTA with a diagnostic strategy of sequential scanning as appropriate offers a marked reduction in radiation dose while maintaining image quality. PMID:21306693

Suppressing correlations in massively parallel simulations of lattice models

NASA Astrophysics Data System (ADS)

Kelling, Jeffrey; Ódor, Géza; Gemming, Sibylle

2017-11-01

For lattice Monte Carlo simulations parallelization is crucial to make studies of large systems and long simulation time feasible, while sequential simulations remain the gold-standard for correlation-free dynamics. Here, various domain decomposition schemes are compared, concluding with one which delivers virtually correlation-free simulations on GPUs. Extensive simulations of the octahedron model for 2 + 1 dimensional Kardar-Parisi-Zhang surface growth, which is very sensitive to correlation in the site-selection dynamics, were performed to show self-consistency of the parallel runs and agreement with the sequential algorithm. We present a GPU implementation providing a speedup of about 30 × over a parallel CPU implementation on a single socket and at least 180 × with respect to the sequential reference.

Optimization, formulation, and characterization of multiflavonoids-loaded flavanosome by bulk or sequential technique

PubMed Central

Karthivashan, Govindarajan; Masarudin, Mas Jaffri; Kura, Aminu Umar; Abas, Faridah; Fakurazi, Sharida

2016-01-01

This study involves adaptation of bulk or sequential technique to load multiple flavonoids in a single phytosome, which can be termed as “flavonosome”. Three widely established and therapeutically valuable flavonoids, such as quercetin (Q), kaempferol (K), and apigenin (A), were quantified in the ethyl acetate fraction of Moringa oleifera leaves extract and were commercially obtained and incorporated in a single flavonosome (QKA–phosphatidylcholine) through four different methods of synthesis – bulk (M1) and serialized (M2) co-sonication and bulk (M3) and sequential (M4) co-loading. The study also established an optimal formulation method based on screening the synthesized flavonosomes with respect to their size, charge, polydispersity index, morphology, drug–carrier interaction, antioxidant potential through in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics, and cytotoxicity evaluation against human hepatoma cell line (HepaRG). Furthermore, entrapment and loading efficiency of flavonoids in the optimal flavonosome have been identified. Among the four synthesis methods, sequential loading technique has been optimized as the best method for the synthesis of QKA–phosphatidylcholine flavonosome, which revealed an average diameter of 375.93±33.61 nm, with a zeta potential of −39.07±3.55 mV, and the entrapment efficiency was >98% for all the flavonoids, whereas the drug-loading capacity of Q, K, and A was 31.63%±0.17%, 34.51%±2.07%, and 31.79%±0.01%, respectively. The in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics of the flavonoids indirectly depicts the release kinetic behavior of the flavonoids from the carrier. The QKA-loaded flavonosome had no indication of toxicity toward human hepatoma cell line as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide result, wherein even at the higher concentration of 200 µg/mL, the flavonosomes exert >85% of cell viability. These results suggest that sequential loading technique may be a promising nanodrug delivery system for loading multiflavonoids in a single entity with sustained activity as an antioxidant, hepatoprotective, and hepatosupplement candidate. PMID:27555765

Optimization, formulation, and characterization of multiflavonoids-loaded flavanosome by bulk or sequential technique.

PubMed

Karthivashan, Govindarajan; Masarudin, Mas Jaffri; Kura, Aminu Umar; Abas, Faridah; Fakurazi, Sharida

2016-01-01

This study involves adaptation of bulk or sequential technique to load multiple flavonoids in a single phytosome, which can be termed as "flavonosome". Three widely established and therapeutically valuable flavonoids, such as quercetin (Q), kaempferol (K), and apigenin (A), were quantified in the ethyl acetate fraction of Moringa oleifera leaves extract and were commercially obtained and incorporated in a single flavonosome (QKA-phosphatidylcholine) through four different methods of synthesis - bulk (M1) and serialized (M2) co-sonication and bulk (M3) and sequential (M4) co-loading. The study also established an optimal formulation method based on screening the synthesized flavonosomes with respect to their size, charge, polydispersity index, morphology, drug-carrier interaction, antioxidant potential through in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics, and cytotoxicity evaluation against human hepatoma cell line (HepaRG). Furthermore, entrapment and loading efficiency of flavonoids in the optimal flavonosome have been identified. Among the four synthesis methods, sequential loading technique has been optimized as the best method for the synthesis of QKA-phosphatidylcholine flavonosome, which revealed an average diameter of 375.93±33.61 nm, with a zeta potential of -39.07±3.55 mV, and the entrapment efficiency was >98% for all the flavonoids, whereas the drug-loading capacity of Q, K, and A was 31.63%±0.17%, 34.51%±2.07%, and 31.79%±0.01%, respectively. The in vitro 1,1-diphenyl-2-picrylhydrazyl kinetics of the flavonoids indirectly depicts the release kinetic behavior of the flavonoids from the carrier. The QKA-loaded flavonosome had no indication of toxicity toward human hepatoma cell line as shown by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide result, wherein even at the higher concentration of 200 µg/mL, the flavonosomes exert >85% of cell viability. These results suggest that sequential loading technique may be a promising nanodrug delivery system for loading multiflavonoids in a single entity with sustained activity as an antioxidant, hepatoprotective, and hepatosupplement candidate.

Towards new therapeutic approaches for malignant melanoma.

PubMed

Pacheco, Ivan; Buzea, Cristina; Tron, Victor

2011-11-01

Recent progress in understanding the molecular mechanisms of the initiation and progression of melanoma has created new opportunities for developing novel therapeutic modalities to manage this potentially lethal disease. Although at first glance, melanoma carcinogenesis appears to be a chaotic system, it is indeed, arguably, a deterministic multistep process involving sequential alterations of proto-oncogenes, tumour suppressors and miRNA genes. The scope of this article is to discuss the most recent and significant advances in melanoma molecular therapeutics. It is apparent that using single agents targeting solely individual melanoma pathways might be insufficient for long-term survival. However, the outstanding results on melanoma survival observed with novel selective inhibitors of B-RAF, such as PLX4032 give hope that melanoma can be cured. The fact that melanoma develops acquired resistance to PLX4032 emphasises the importance of simultaneously targeting several pathways. Because the most striking feature of melanoma is its unsurpassed ability to metastasise, it is important to implement newer systems for drug delivery adapted from research on stem cells and nanotechnology.

Blastocyst Development in a Single Medium Compared to Sequential Media: A Prospective Study With Sibling Oocytes.

PubMed

Sfontouris, Ioannis A; Kolibianakis, Efstratios M; Lainas, George T; Petsas, George K; Tarlatzis, Basil C; Lainas, Trifon G

2017-09-01

The aim of the present study was to compare blastocyst formation rates after embryo culture in a single medium (Global) as compared to sequential media (ISM1/BlastAssist). In this prospective trial with sibling oocytes, 542 metaphase II (ΜΙΙ) oocytes from 31 women were randomly and equally divided to be fertilized and cultured to the blastocyst stage in either sequential media (ISM1/BlastAssist; n = 271 MII oocytes) or a single medium (Global; n = 271 MII oocytes). In both groups, embryos were cultured in an interrupted fashion with media changes on day 3. Embryo transfer was performed on day 5. Blastocyst formation rates on day 5 (61.7% ± 19.9% vs 37.0% ± 25.5%, P < .001) were significantly higher following culture in Global as compared to ISM1/BlastAssist, respectively. Fertilization rates, cleavage rates, and percentage of good quality embryos on day 3 were similar between Global and ISM1/BlastAssist, respectively. The percentages of good quality blastocysts (63.0% ± 24.8% vs 32.1% ± 37.2%, P < .001), blastocysts selected for transfer (27.8% ± 19.2% vs 11.1% ± 14.4%, P = .005), and utilization rates (62.5% ± 24.8% vs 39.0% ± 25.2%, P < .001) were significantly higher in Global as compared to ISM1/BlastAssist, respectively. In conclusion, culture in Global was associated with higher blastocyst formation rates compared to ISM1/BlastAssist, suggesting that the single medium may provide better support to the developing embryo.

Accurate Reading with Sequential Presentation of Single Letters

PubMed Central

Price, Nicholas S. C.; Edwards, Gemma L.

2012-01-01

Rapid, accurate reading is possible when isolated, single words from a sentence are sequentially presented at a fixed spatial location. We investigated if reading of words and sentences is possible when single letters are rapidly presented at the fovea under user-controlled or automatically controlled rates. When tested with complete sentences, trained participants achieved reading rates of over 60 wpm and accuracies of over 90% with the single letter reading (SLR) method and naive participants achieved average reading rates over 30 wpm with greater than 90% accuracy. Accuracy declined as individual letters were presented for shorter periods of time, even when the overall reading rate was maintained by increasing the duration of spaces between words. Words in the lexicon that occur more frequently were identified with higher accuracy and more quickly, demonstrating that trained participants have lexical access. In combination, our data strongly suggest that comprehension is possible and that SLR is a practicable form of reading under conditions in which normal scanning of text is not possible, or for scenarios with limited spatial and temporal resolution such as patients with low vision or prostheses. PMID:23115548

High Information Capacity Quantum Imaging

DTIC Science & Technology

2014-09-19

single-pixel camera [41, 75]. An object is imaged onto a Digital Micromirror device ( DMD ), a 2D binary array of individually-addressable mirrors that...reflect light either to a single detector or a dump. Rows of the sensing matrix A consist of random, binary patterns placed sequentially on the DMD ...The single-pixel camera concept naturally adapts to imaging correlations by adding a second detector. Consider placing separate DMDs in the near-field

Empagliflozin/linagliptin single-pill combination therapy for patients with type 2 diabetes mellitus.

PubMed

Jain, Rajeev Kumar

2017-04-01

Type 2 diabetes mellitus (T2DM) is typically progressive, with sequential addition of therapies often needed to address increasing hyperglycemia over the disease course. Using treatments in combination may be preferred to sequential addition, as a means of providing a more rapid clinical response and potentially avoiding clinical inertia. In such cases, a single-pill combination can help to reduce pill burden. Although various single-pill combinations of oral glucose-lowering agents are available, empagliflozin/linagliptin was the first approved combination of a sodium glucose co-transporter 2 (SGLT2) inhibitor with a dipeptidyl peptidase 4 (DPP-4) inhibitor in the United States. Areas covered: Two publications of the clinical trial investigating the efficacy and safety of single-pill combinations of empagliflozin/linagliptin in treatment-naive or metformin-treated patients with T2DM (NCT01422876) are reviewed, and their potential impact on clinical practice is discussed. Expert opinion: The study discussed provides evidence for the efficacy and safety of empagliflozin/linagliptin single pills. Addition of an empagliflozin/linagliptin single pill may be considered in patients with inadequate glycemic control on metformin, or as an alternative to first-line treatment with empagliflozin or linagliptin when metformin is not suitable, particularly in patients with very poor glycemic control, or those who need to achieve target more quickly.

48. VIEW LOOKING NORTHEAST AT EXCITER RESISTANCE GRIDS LOCATED UNDER ...

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

48. VIEW LOOKING NORTHEAST AT EXCITER RESISTANCE GRIDS LOCATED UNDER THE CONTROL ROOM ON SOUTH SIDE OF TURBINE HALL. THE GRIDS WERE AN ESSENTIAL PART OF THE CONTROL SYSTEM THAT MAINTAINED CONSTANT VOLTAGE ON THE RAILROAD POWER LINES. TIRRILL VOLTAGE REGULATORS (SEE CT-142A-100) SENSED VOLTAGE VARIATIONS AND INITIATED SWITCHING SEQUENCES TO REGULATE THE VOLTAGE AND MAINTAIN A SYSTEM STANDARD VOLTAGE. THE RESISTANCE GRIDS WERE SEQUENTIALLY ADDED TO OR REMOVED FROM THE GENERATOR FIELD COIL CIRCUITS. THIS RESISTANCE LOAD DISSIPATED EXCITIR GENERATOR POWER AS HEAT. THIS IN TURN WOULD VARY THE STRENGTH OF THE FIELD MAGNET AND CONSEQUENTLY RAISE OR LOWER THE OUTPUT VOLTAGE FROM THE MAIN GENERATOR ARMATURE. - New York, New Haven & Hartford Railroad, Cos Cob Power Plant, Sound Shore Drive, Greenwich, Fairfield County, CT

Effects of native vegetation on invasion success of Chinese tallow in a floating marsh ecosystem

Treesearch

L.L. Battaglia; J.S. Denslow; J.R. Inczauskis; S.G. Baer

2009-01-01

Interactions between resident and exotic species have been shown to control the biotic resistance of communities to invasion. With different life stages of the exotic species, each sequential interaction may dampen or strengthen previous ones, thereby influencing invasion success.We assessed the effects of resident vegetation type on...

Smoking and Health. A Guide for School Action Grades 1-12.

ERIC Educational Resources Information Center

Ohio State Dept. of Health, Columbus.

Enabling teachers to present a detailed unit on smoking is an objective of this curriculum guide. It organizes information which, if made a relevant part of the student's experience, attempts to help him effectively resist the pressures to begin smoking. Seventeen units, arranged in sequential order, cover cardiovascular and respiratory systems,…

Sequentially evaporated thin Y-Ba-Cu-O superconductor films: Composition and processing effects

NASA Technical Reports Server (NTRS)

Valco, George J.; Rohrer, Norman J.; Warner, Joseph D.; Bhasin, Kul B.

1988-01-01

Thin films of YBa2Cu3O(7-beta) have been grown by sequential evaporation of Cu, Y, and BaF2 on SrTiO3 and MgO substrates. The onset temperatures were as high as 93 K while T sub c was 85 K. The Ba/Y ratio was varied from 1.9 to 4.0. The Cu/Y ratio was varied from 2.8 to 3.4. The films were then annealed at various times and temperatures. The times ranged from 15 min to 3 hr, while the annealing temperatures used ranged from 850 C to 900 C. A good correlation was found between transition temperature (T sub c) and the annealing conditions; the films annealed at 900 C on SrTiO3 had the best T sub c's. There was a weaker correlation between composition and T sub c. Barium poor films exhibitied semiconducting normal state resistance behavior while barium rich films were metallic. The films were analyzed by resistance versus temperature measurements and scanning electron microscopy. The analysis of the films and the correlations are reported.

Method of making sulfur-resistant composite metal membranes

DOEpatents

Way, J Douglas [Boulder, CO; Lusk, Mark [Golden, CO; Thoen, Paul [Littleton, CO

2012-01-24

The invention provides thin, hydrogen-permeable, sulfur-resistant membranes formed from palladium or palladium-alloy coatings on porous, ceramic or metal supports. Also disclosed are methods of making these membranes via sequential electroless plating techniques, wherein the method of making the membrane includes decomposing any organic ligands present on the substrate, reducing the palladium crystallites on the substrate to reduced palladium crystallites, depositing a film of palladium metal on the substrate and then depositing a second, gold film on the palladium film. These two metal films are then annealed at a temperature between about 200.degree. C. and about 1200.degree. C. to form a sulfur-resistant, composite PdAu alloy membrane.

Anisotropy of electrical conductivity in dc due to intrinsic defect formation in α-Al2O3 single crystal implanted with Mg ions

NASA Astrophysics Data System (ADS)

Tardío, M.; Egaña, A.; Ramírez, R.; Muñoz-Santiuste, J. E.; Alves, E.

2016-07-01

The electrical conductivity in α-Al2O3 single crystals implanted with Mg ions in two different crystalline orientations, parallel and perpendicular to c axis, was investigated. The samples were implanted at room temperature with energies of 50 and 100 keV and fluences of 1 × 1015, 5 × 1015 and 5 × 1016 ions/cm2. Optical characterization reveals slight differences in the absorption bands at 6.0 and 4.2 eV, attributed to F type centers and Mie scattering from Mg precipitates, respectively. DC electrical measurements using the four and two-point probe methods, between 295 and 490 K, were used to characterize the electrical conductivity of the implanted area (Meshakim and Tanabe, 2001). Measurements in this temperature range indicate that: (1) the electrical conductivity is thermally activated independently of crystallographic orientation, (2) resistance values in the implanted region decrease with fluence levels, and (3) the I-V characteristic of electrical contacts in samples with perpendicular c axis orientation is clearly ohmic, whereas contacts are blocking in samples with parallel c axis. When thin layers are sequentially removed from the implanted region by immersing the sample in a hot solution of nitric and fluorhydric acids the electrical resistance increases until reaching the values of non-implanted crystal (Jheeta et al., 2006). We conclude that the enhancement in conductivity observed in the implanted regions is related to the intrinsic defects created by the implantation rather than to the implanted Mg ions (da Silva et al., 2002; Tardío et al., 2001; Tardío et al., 2008).

CACTI: free, open-source software for the sequential coding of behavioral interactions.

PubMed

Glynn, Lisa H; Hallgren, Kevin A; Houck, Jon M; Moyers, Theresa B

2012-01-01

The sequential analysis of client and clinician speech in psychotherapy sessions can help to identify and characterize potential mechanisms of treatment and behavior change. Previous studies required coding systems that were time-consuming, expensive, and error-prone. Existing software can be expensive and inflexible, and furthermore, no single package allows for pre-parsing, sequential coding, and assignment of global ratings. We developed a free, open-source, and adaptable program to meet these needs: The CASAA Application for Coding Treatment Interactions (CACTI). Without transcripts, CACTI facilitates the real-time sequential coding of behavioral interactions using WAV-format audio files. Most elements of the interface are user-modifiable through a simple XML file, and can be further adapted using Java through the terms of the GNU Public License. Coding with this software yields interrater reliabilities comparable to previous methods, but at greatly reduced time and expense. CACTI is a flexible research tool that can simplify psychotherapy process research, and has the potential to contribute to the improvement of treatment content and delivery.

Sequential Superresolution Imaging of Multiple Targets Using a Single Fluorophore

PubMed Central

Lidke, Diane S.; Lidke, Keith A.

2015-01-01

Fluorescence superresolution (SR) microscopy, or fluorescence nanoscopy, provides nanometer scale detail of cellular structures and allows for imaging of biological processes at the molecular level. Specific SR imaging methods, such as localization-based imaging, rely on stochastic transitions between on (fluorescent) and off (dark) states of fluorophores. Imaging multiple cellular structures using multi-color imaging is complicated and limited by the differing properties of various organic dyes including their fluorescent state duty cycle, photons per switching event, number of fluorescent cycles before irreversible photobleaching, and overall sensitivity to buffer conditions. In addition, multiple color imaging requires consideration of multiple optical paths or chromatic aberration that can lead to differential aberrations that are important at the nanometer scale. Here, we report a method for sequential labeling and imaging that allows for SR imaging of multiple targets using a single fluorophore with negligible cross-talk between images. Using brightfield image correlation to register and overlay multiple image acquisitions with ~10 nm overlay precision in the x-y imaging plane, we have exploited the optimal properties of AlexaFluor647 for dSTORM to image four distinct cellular proteins. We also visualize the changes in co-localization of the epidermal growth factor (EGF) receptor and clathrin upon EGF addition that are consistent with clathrin-mediated endocytosis. These results are the first to demonstrate sequential SR (s-SR) imaging using direct stochastic reconstruction microscopy (dSTORM), and this method for sequential imaging can be applied to any superresolution technique. PMID:25860558

Plasmidic Expression of nemA and yafC* Increased Resistance of Ethanologenic Escherichia coli LY180 to Nonvolatile Side Products from Dilute Acid Treatment of Sugarcane Bagasse and Artificial Hydrolysate

PubMed Central

Shi, Aiqin; Zheng, Huabao; Yomano, Lorraine P.; York, Sean W.; Shanmugam, Keelnatham T.

2016-01-01

Hydrolysate-resistant Escherichia coli SL100 was previously isolated from ethanologenic LY180 after sequential transfers in AM1 medium containing a dilute acid hydrolysate of sugarcane bagasse and was used as a source of resistance genes. Many genes that affect tolerance to furfural, the most abundant inhibitor, have been described previously. To identify genes associated with inhibitors other than furfural, plasmid clones were selected in an artificial hydrolysate that had been treated with a vacuum to remove furfural. Two new resistance genes were discovered from Sau3A1 libraries of SL100 genomic DNA: nemA (N-ethylmaleimide reductase) and a putative regulatory gene containing a mutation in the coding region, yafC*. The presence of these mutations in SL100 was confirmed by sequencing. A single mutation was found in the upstream regulatory region of nemR (nemRA operon) in SL100. This mutation increased nemA activity 20-fold over that of the parent organism (LY180) in AM1 medium without hydrolysate and increased nemA mRNA levels >200-fold. Addition of hydrolysates induced nemA expression (mRNA and activity), in agreement with transcriptional control. NemA activity was stable in cell extracts (9 h, 37°C), eliminating a role for proteinase in regulation. LY180 with a plasmid expressing nemA or yafC* was more resistant to a vacuum-treated sugarcane bagasse hydrolysate and to a vacuum-treated artificial hydrolysate than LY180 with an empty-vector control. Neither gene affected furfural tolerance. The vacuum-treated hydrolysates inhibited the reduction of N-ethylmaleimide by NemA while also serving as substrates. Expression of the nemA or yafC* plasmid in LY180 doubled the rate of ethanol production from the vacuum-treated sugarcane bagasse hydrolysate. PMID:26826228

Plasmidic Expression of nemA and yafC* Increased Resistance of Ethanologenic Escherichia coli LY180 to Nonvolatile Side Products from Dilute Acid Treatment of Sugarcane Bagasse and Artificial Hydrolysate.

PubMed

Shi, Aiqin; Zheng, Huabao; Yomano, Lorraine P; York, Sean W; Shanmugam, Keelnatham T; Ingram, Lonnie O

2016-01-29

Hydrolysate-resistant Escherichia coli SL100 was previously isolated from ethanologenic LY180 after sequential transfers in AM1 medium containing a dilute acid hydrolysate of sugarcane bagasse and was used as a source of resistance genes. Many genes that affect tolerance to furfural, the most abundant inhibitor, have been described previously. To identify genes associated with inhibitors other than furfural, plasmid clones were selected in an artificial hydrolysate that had been treated with a vacuum to remove furfural. Two new resistance genes were discovered from Sau3A1 libraries of SL100 genomic DNA: nemA (N-ethylmaleimide reductase) and a putative regulatory gene containing a mutation in the coding region, yafC*. The presence of these mutations in SL100 was confirmed by sequencing. A single mutation was found in the upstream regulatory region of nemR (nemRA operon) in SL100. This mutation increased nemA activity 20-fold over that of the parent organism (LY180) in AM1 medium without hydrolysate and increased nemA mRNA levels >200-fold. Addition of hydrolysates induced nemA expression (mRNA and activity), in agreement with transcriptional control. NemA activity was stable in cell extracts (9 h, 37°C), eliminating a role for proteinase in regulation. LY180 with a plasmid expressing nemA or yafC* was more resistant to a vacuum-treated sugarcane bagasse hydrolysate and to a vacuum-treated artificial hydrolysate than LY180 with an empty-vector control. Neither gene affected furfural tolerance. The vacuum-treated hydrolysates inhibited the reduction of N-ethylmaleimide by NemA while also serving as substrates. Expression of the nemA or yafC* plasmid in LY180 doubled the rate of ethanol production from the vacuum-treated sugarcane bagasse hydrolysate. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Advanced electric-field scanning probe lithography on molecular resist using active cantilever

NASA Astrophysics Data System (ADS)

Kaestner, Marcus; Aydogan, Cemal; Ivanov, Tzvetan; Ahmad, Ahmad; Angelov, Tihomir; Reum, Alexander; Ishchuk, Valentyn; Krivoshapkina, Yana; Hofer, Manuel; Lenk, Steve; Atanasov, Ivaylo; Holz, Mathias; Rangelow, Ivo W.

2015-07-01

The routine "on demand" fabrication of features smaller than 10 nm opens up new possibilities for the realization of many devices. Driven by the thermally actuated piezoresistive cantilever technology, we have developed a prototype of a scanning probe lithography (SPL) platform which is able to image, inspect, align, and pattern features down to the single digit nanoregime. Here, we present examples of practical applications of the previously published electric-field based current-controlled scanning probe lithography. In particular, individual patterning tests are carried out on calixarene by using our developed table-top SPL system. We have demonstrated the application of a step-and-repeat SPL method including optical as well as atomic force microscopy-based navigation and alignment. The closed-loop lithography scheme was applied to sequentially write positive and negative tone features. Due to the integrated unique combination of read-write cycling, each single feature is aligned separately with the highest precision and inspected after patterning. This routine was applied to create a pattern step by step. Finally, we have demonstrated the patterning over larger areas, over existing topography, and the practical applicability of the SPL processes for lithography down to 13-nm pitch patterns. To enhance the throughput capability variable beam diameter electric field, current-controlled SPL is briefly discussed.

Lactate dehydrogenase predicts combined progression-free survival after sequential therapy with abiraterone and enzalutamide for patients with castration-resistant prostate cancer.

PubMed

Mori, Keiichiro; Kimura, Takahiro; Onuma, Hajime; Kimura, Shoji; Yamamoto, Toshihiro; Sasaki, Hiroshi; Miki, Jun; Miki, Kenta; Egawa, Shin

2017-07-01

An array of clinical issues remains to be resolved for castration-resistant prostate cancer (CRPC), including the sequence of drug use and drug cross-resistance. At present, no clear guidelines are available for the optimal sequence of use of novel agents like androgen-receptor axis-targeted (ARAT) agents, particularly enzalutamide, and abiraterone. This study retrospectively analyzed a total of 69 patients with CRPC treated with sequential therapy using enzalutamide followed by abiraterone or vice versa. The primary outcome measure was the comparative combined progression-free survival (PFS) comprising symptomatic and/or radiographic PFS. Patients were also compared for total prostate-specific antigen (PSA)-PFS, overall survival (OS), and PSA response. The predictors of combined PFS and OS were analyzed with a backward-stepwise multivariate Cox model. Of the 69 patients, 46 received enzalutamide first, followed by abiraterone (E-A group), and 23 received abiraterone, followed by enzalutamide (A-E group). The two groups were not significantly different with regard to basic data, except for hemoglobin values. In a comparison with the E-A group, the A-E group was shown to be associated with better combined PFS in Kaplan-Meier analysis (P = 0.043). Similar results were obtained for total PSA-PFS (P = 0.049), while OS did not differ between groups (P = 0.62). Multivariate analysis demonstrated that pretreatment lactate dehydrogenase (LDH) values and age were significant predictors of longer combined PFS (P < 0.05). Likewise, multivariate analysis demonstrated that pretreatment hemoglobin values and performance status were significant predictors of longer OS (P < 0.05). The results of this study suggested the A-E sequence had longer combined PSA and total PSA-PFS compared to the E-A sequence in patients with CRPC. LDH values in sequential therapy may serve as a predictor of longer combined PFS. © 2017 Wiley Periodicals, Inc.

Memristive and neuromorphic behavior in a LixCoO2 nanobattery

NASA Astrophysics Data System (ADS)

Mai, V. H.; Moradpour, A.; Senzier, P. Auban; Pasquier, C.; Wang, K.; Rozenberg, M. J.; Giapintzakis, J.; Mihailescu, C. N.; Orfanidou, C. M.; Svoukis, E.; Breza, A.; Lioutas, Ch B.; Franger, S.; Revcolevschi, A.; Maroutian, T.; Lecoeur, P.; Aubert, P.; Agnus, G.; Salot, R.; Albouy, P. A.; Weil, R.; Alamarguy, D.; March, K.; Jomard, F.; Chrétien, P.; Schneegans, O.

2015-01-01

The phenomenon of resistive switching (RS), which was initially linked to non-volatile resistive memory applications, has recently also been associated with the concept of memristors, whose adjustable multilevel resistance characteristics open up unforeseen perspectives in cognitive computing. Herein, we demonstrate that the resistance states of LixCoO2 thin film-based metal-insulator-metal (MIM) solid-state cells can be tuned by sequential programming voltage pulses, and that these resistance states are dramatically dependent on the pulses input rate, hence emulating biological synapse plasticity. In addition, we identify the underlying electrochemical processes of RS in our MIM cells, which also reveal a nanobattery-like behavior, leading to the generation of electrical signals that bring an unprecedented new dimension to the connection between memristors and neuromorphic systems. Therefore, these LixCoO2-based MIM devices allow for a combination of possibilities, offering new perspectives of usage in nanoelectronics and bio-inspired neuromorphic circuits.

A versatile semi-permanent sequential bilayer/diblock polymer coating for capillary isoelectric focusing.

PubMed

Bahnasy, Mahmoud F; Lucy, Charles A

2012-12-07

A sequential surfactant bilayer/diblock copolymer coating was previously developed for the separation of proteins. The coating is formed by flushing the capillary with the cationic surfactant dioctadecyldimethylammonium bromide (DODAB) followed by the neutral polymer poly-oxyethylene (POE) stearate. Herein we show the method development and optimization for capillary isoelectric focusing (cIEF) separations based on the developed sequential coating. Electroosmotic flow can be tuned by varying the POE chain length which allows optimization of resolution and analysis time. DODAB/POE 40 stearate can be used to perform single-step cIEF, while both DODAB/POE 40 and DODAB/POE 100 stearate allow performing two-step cIEF methodologies. A set of peptide markers is used to assess the coating performance. The sequential coating has been applied successfully to cIEF separations using different capillary lengths and inner diameters. A linear pH gradient is established only in two-step CIEF methodology using 3-10 pH 2.5% (v/v) carrier ampholyte. Hemoglobin A(0) and S variants are successfully resolved on DODAB/POE 40 stearate sequentially coated capillaries. Copyright © 2012 Elsevier B.V. All rights reserved.

A Novel Ship-Tracking Method for GF-4 Satellite Sequential Images.

PubMed

Yao, Libo; Liu, Yong; He, You

2018-06-22

The geostationary remote sensing satellite has the capability of wide scanning, persistent observation and operational response, and has tremendous potential for maritime target surveillance. The GF-4 satellite is the first geostationary orbit (GEO) optical remote sensing satellite with medium resolution in China. In this paper, a novel ship-tracking method in GF-4 satellite sequential imagery is proposed. The algorithm has three stages. First, a local visual saliency map based on local peak signal-to-noise ratio (PSNR) is used to detect ships in a single frame of GF-4 satellite sequential images. Second, the accuracy positioning of each potential target is realized by a dynamic correction using the rational polynomial coefficients (RPCs) and automatic identification system (AIS) data of ships. Finally, an improved multiple hypotheses tracking (MHT) algorithm with amplitude information is used to track ships by further removing the false targets, and to estimate ships’ motion parameters. The algorithm has been tested using GF-4 sequential images and AIS data. The results of the experiment demonstrate that the algorithm achieves good tracking performance in GF-4 satellite sequential images and estimates the motion information of ships accurately.

Learning Sequential Composition Control.

PubMed

Najafi, Esmaeil; Babuska, Robert; Lopes, Gabriel A D

2016-11-01

Sequential composition is an effective supervisory control method for addressing control problems in nonlinear dynamical systems. It executes a set of controllers sequentially to achieve a control specification that cannot be realized by a single controller. As these controllers are designed offline, sequential composition cannot address unmodeled situations that might occur during runtime. This paper proposes a learning approach to augment the standard sequential composition framework by using online learning to handle unforeseen situations. New controllers are acquired via learning and added to the existing supervisory control structure. In the proposed setting, learning experiments are restricted to take place within the domain of attraction (DOA) of the existing controllers. This guarantees that the learning process is safe (i.e., the closed loop system is always stable). In addition, the DOA of the new learned controller is approximated after each learning trial. This keeps the learning process short as learning is terminated as soon as the DOA of the learned controller is sufficiently large. The proposed approach has been implemented on two nonlinear systems: 1) a nonlinear mass-damper system and 2) an inverted pendulum. The results show that in both cases a new controller can be rapidly learned and added to the supervisory control structure.

Efficacy of Helicobacter pylori eradication therapies in Korea: A systematic review and network meta-analysis.

PubMed

Jung, Yoon Suk; Park, Chan Hyuk; Park, Jung Ho; Nam, Eunwoo; Lee, Hang Lak

2017-08-01

The efficacy of Helicobacter pylori eradication regimens may depend on the country where the studies were performed because of the difference in antibiotic resistance. We aimed to analyze the efficacy of H. pylori eradication regimens in Korea where clarithromycin resistance rate is high. We searched for all relevant randomized controlled trials published until November 2016 that investigated the efficacy of H. pylori eradication therapies in Korea. A network meta-analysis was performed to calculate the direct and indirect estimates of efficacy among the eradication regimens. Forty-three studies were identified through a systematic review, of which 34 studies, published since 2005, were included in the meta-analysis. Among 21 included regimens, quinolone-containing sequential therapy for 14 days (ST-Q-14) showed the highest eradication rate (91.4% [95% confidence interval [CI], 86.9%-94.4%] in the intention-to-treat [ITT] analysis). The eradication rate of the conventional triple therapy for 7 days, standard sequential therapy for 10 days, hybrid therapy for 10-14 days, and concomitant therapy for 10-14 days was 71.1% (95% CI, 68.3%-73.7%), 76.2% (95% CI, 72.8%-79.3%), 79.4% (95% CI, 75.5%-82.8%), and 78.3% (95% CI, 75.3%-80.9%), respectively, in the ITT analysis. In the network meta-analysis, ST-Q-14 showed a better comparative efficacy than the conventional triple therapy, standard sequential therapy, hybrid therapy, and concomitant therapy. In addition, tolerability of ST-Q-14 was comparable to those regimens. In Korea, ST-Q-14 showed the highest efficacy in terms of eradication and a comparable tolerability, compared to the results reported for the conventional triple therapy, standard sequential therapy, hybrid therapy, and concomitant therapy. © 2017 John Wiley & Sons Ltd.

Benefits and Drawbacks of Using Multiple Instructors to Teach Single Courses

ERIC Educational Resources Information Center

Jones, Francis; Harris, Sara

2012-01-01

We set out to identify the benefits and drawbacks of using more than one instructor to teach single section science courses at a large research university. Nine courses were investigated involving widely differing subjects and levels. Teaching models included: sequential teaching with two to six instructors each covering only their own modules,…

A fast and accurate online sequential learning algorithm for feedforward networks.

PubMed

Liang, Nan-Ying; Huang, Guang-Bin; Saratchandran, P; Sundararajan, N

2006-11-01

In this paper, we develop an online sequential learning algorithm for single hidden layer feedforward networks (SLFNs) with additive or radial basis function (RBF) hidden nodes in a unified framework. The algorithm is referred to as online sequential extreme learning machine (OS-ELM) and can learn data one-by-one or chunk-by-chunk (a block of data) with fixed or varying chunk size. The activation functions for additive nodes in OS-ELM can be any bounded nonconstant piecewise continuous functions and the activation functions for RBF nodes can be any integrable piecewise continuous functions. In OS-ELM, the parameters of hidden nodes (the input weights and biases of additive nodes or the centers and impact factors of RBF nodes) are randomly selected and the output weights are analytically determined based on the sequentially arriving data. The algorithm uses the ideas of ELM of Huang et al. developed for batch learning which has been shown to be extremely fast with generalization performance better than other batch training methods. Apart from selecting the number of hidden nodes, no other control parameters have to be manually chosen. Detailed performance comparison of OS-ELM is done with other popular sequential learning algorithms on benchmark problems drawn from the regression, classification and time series prediction areas. The results show that the OS-ELM is faster than the other sequential algorithms and produces better generalization performance.

Hydrodynamic trapping for rapid assembly and in situ electrical characterization of droplet interface bilayer arrays

DOE PAGES

Nguyen, Mary -Anne; Srijanto, Bernadeta; Collier, C. Patrick; ...

2016-08-02

The droplet interface bilayer (DIB) is a modular technique for assembling planar lipid membranes between water droplets in oil. The DIB method thus provides a unique capability for developing digital, droplet-based membrane platforms for rapid membrane characterization, drug screening and ion channel recordings. This paper demonstrates a new, low-volume microfluidic system that automates droplet generation, sorting, and sequential trapping in designated locations to enable the rapid assembly of arrays of DIBs. The channel layout of the device is guided by an equivalent circuit model, which predicts that a serial arrangement of hydrodynamic DIB traps enables sequential droplet placement and minimizesmore » the hydrodynamic pressure developed across filled traps to prevent squeeze-through of trapped droplets. Furthermore, the incorporation of thin-film electrodes fabricated via evaporation metal deposition onto the glass substrate beneath the channels allows for the first time in situ, simultaneous electrical interrogation of multiple DIBs within a sealed device. Combining electrical measurements with imaging enables measurements of membrane capacitance and resistance and bilayer area, and our data show that DIBs formed in different trap locations within the device exhibit similar sizes and transport properties. Simultaneous, single channel recordings of ion channel gating in multiple membranes are obtained when alamethicin peptides are incorporated into the captured droplets, qualifying the thin-film electrodes as a means for measuring stimuli-responsive functions of membrane-bound biomolecules. Furthermore, this novel microfluidic-electrophysiology platform provides a reproducible, high throughput method for performing electrical measurements to study transmembrane proteins and biomembranes in low-volume, droplet-based membranes.« less

Hydrodynamic trapping for rapid assembly and in situ electrical characterization of droplet interface bilayer arrays

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

Nguyen, Mary -Anne; Srijanto, Bernadeta; Collier, C. Patrick

The droplet interface bilayer (DIB) is a modular technique for assembling planar lipid membranes between water droplets in oil. The DIB method thus provides a unique capability for developing digital, droplet-based membrane platforms for rapid membrane characterization, drug screening and ion channel recordings. This paper demonstrates a new, low-volume microfluidic system that automates droplet generation, sorting, and sequential trapping in designated locations to enable the rapid assembly of arrays of DIBs. The channel layout of the device is guided by an equivalent circuit model, which predicts that a serial arrangement of hydrodynamic DIB traps enables sequential droplet placement and minimizesmore » the hydrodynamic pressure developed across filled traps to prevent squeeze-through of trapped droplets. Furthermore, the incorporation of thin-film electrodes fabricated via evaporation metal deposition onto the glass substrate beneath the channels allows for the first time in situ, simultaneous electrical interrogation of multiple DIBs within a sealed device. Combining electrical measurements with imaging enables measurements of membrane capacitance and resistance and bilayer area, and our data show that DIBs formed in different trap locations within the device exhibit similar sizes and transport properties. Simultaneous, single channel recordings of ion channel gating in multiple membranes are obtained when alamethicin peptides are incorporated into the captured droplets, qualifying the thin-film electrodes as a means for measuring stimuli-responsive functions of membrane-bound biomolecules. Furthermore, this novel microfluidic-electrophysiology platform provides a reproducible, high throughput method for performing electrical measurements to study transmembrane proteins and biomembranes in low-volume, droplet-based membranes.« less

Development of a multilayered association polymer system for sequential drug delivery

NASA Astrophysics Data System (ADS)

Chinnakavanam Sundararaj, Sharath kumar

As all the physiological processes in our body are controlled by multiple biomolecules, comprehensive treatment of certain disease conditions may be more effectively achieved by administration of more than one type of drug. Thus, the primary objective of this research was to develop a multilayered, polymer-based system for sequential delivery of multiple drugs. This particular device was designed aimed at the treatment of periodontitis, a highly prevalent oral inflammatory disease that affects 90% of the world population. This condition is caused by bacterial biofilm on the teeth, resulting in a chronic inflammatory response that leads to loss of alveolar bone and, ultimately, the tooth. Current treatment methods for periodontitis address specific parts of the disease, with no individual treatment serving as a complete therapy. The polymers used for the fabrication of this multilayered device consists of cellulose acetate phthalate (CAP) complexed with Pluronic F-127 (P). After evaluating morphology of the resulting CAPP system, in vitro release of small molecule drugs and a model protein was studied from both single and multilayered devices. Drug release from single-layered CAPP films followed zero-order kinetics related to surface erosion property of the association polymer. Release studies from multilayered CAPP devices showed the possibility of achieving intermittent release of one type of drug as well as sequential release of more than one type of drug. Mathematical modeling accurately predicted the release profiles for both single layer and multilayered devices. After the initial characterization of the CAPP system, the device was specifically modified to achieve sequential release of drugs aimed at the treatment of periodontitis. The four types of drugs used were metronidazole, ketoprofen, doxycycline, and simvastatin to eliminate infection, inhibit inflammation, prevent tissue destruction, and aid bone regeneration, respectively. To obtain different erosion times and achieve appropriate release profiles specific to the disease condition, the device was modified by increasing the number of layers or by inclusion of a slower eroding polymer layer. In all the cases, the device was able to release the four different drugs in the designed temporal sequence. Analysis of antibiotic and antiinflammatory bioactivity showed that drugs released from the devices retained 100% bioactivity. Following extensive studies on the in vitro sequential drug release from these devices, the in vivo drug release profiles were investigated. The CAPP devices with different release rates and dosage formulations were implanted in a rat calvarial onlay model, and the in vivo drug release and erosion was compared with in vitro results. In vivo studies showed sequential release of drugs comparable to those measured in vitro, with some difference in drug release rates observed. The present CAPP association polymer-based multilayer devices can be used for localized, sequential delivery of multiple drugs for the possible treatment of complex disease conditions, and perhaps for tissue engineering applications, that require delivery of more than one type of biomolecule. KEYWORDS: Multiple drug delivery, Periodontitis, Cellulose acetate phthalate, Pluronic F-127, Sequential drug release, in vitro drug release, in vivo drug release.

Rapid Construction of Complex 2-Pyrrolines through Lewis Acid-Catalyzed, Sequential Three-Component Reactions via in Situ-Generated 1-Azaallyl Cations.

PubMed

Schlegel, Marcel; Schneider, Christoph

2018-05-09

The first Sc(OTf) 3 -catalyzed dehydration of 2-hydroxy oxime ethers to generate benzylic stabilized 1-azaallyl cations, which are captured by 1,3-carbonyls, is described. A subsequent addition of primary amines in a sequential three-component reaction affords highly substituted and densely functionalized tetrahydroindeno[2,1- b]pyrroles as single diastereomers with up to quantitative yield. Thus, three new σ-bonds and two vicinal quaternary stereogenic centers are generated in a one-pot operation.

Localisation in a Growth Model with Interaction

NASA Astrophysics Data System (ADS)

Costa, M.; Menshikov, M.; Shcherbakov, V.; Vachkovskaia, M.

2018-05-01

This paper concerns the long term behaviour of a growth model describing a random sequential allocation of particles on a finite cycle graph. The model can be regarded as a reinforced urn model with graph-based interaction. It is motivated by cooperative sequential adsorption, where adsorption rates at a site depend on the configuration of existing particles in the neighbourhood of that site. Our main result is that, with probability one, the growth process will eventually localise either at a single site, or at a pair of neighbouring sites.

Localisation in a Growth Model with Interaction

NASA Astrophysics Data System (ADS)

Costa, M.; Menshikov, M.; Shcherbakov, V.; Vachkovskaia, M.

2018-06-01

This paper concerns the long term behaviour of a growth model describing a random sequential allocation of particles on a finite cycle graph. The model can be regarded as a reinforced urn model with graph-based interaction. It is motivated by cooperative sequential adsorption, where adsorption rates at a site depend on the configuration of existing particles in the neighbourhood of that site. Our main result is that, with probability one, the growth process will eventually localise either at a single site, or at a pair of neighbouring sites.

A Particle Smoother with Sequential Importance Resampling for soil hydraulic parameter estimation: A lysimeter experiment

NASA Astrophysics Data System (ADS)

Montzka, Carsten; Hendricks Franssen, Harrie-Jan; Moradkhani, Hamid; Pütz, Thomas; Han, Xujun; Vereecken, Harry

2013-04-01

An adequate description of soil hydraulic properties is essential for a good performance of hydrological forecasts. So far, several studies showed that data assimilation could reduce the parameter uncertainty by considering soil moisture observations. However, these observations and also the model forcings were recorded with a specific measurement error. It seems a logical step to base state updating and parameter estimation on observations made at multiple time steps, in order to reduce the influence of outliers at single time steps given measurement errors and unknown model forcings. Such outliers could result in erroneous state estimation as well as inadequate parameters. This has been one of the reasons to use a smoothing technique as implemented for Bayesian data assimilation methods such as the Ensemble Kalman Filter (i.e. Ensemble Kalman Smoother). Recently, an ensemble-based smoother has been developed for state update with a SIR particle filter. However, this method has not been used for dual state-parameter estimation. In this contribution we present a Particle Smoother with sequentially smoothing of particle weights for state and parameter resampling within a time window as opposed to the single time step data assimilation used in filtering techniques. This can be seen as an intermediate variant between a parameter estimation technique using global optimization with estimation of single parameter sets valid for the whole period, and sequential Monte Carlo techniques with estimation of parameter sets evolving from one time step to another. The aims are i) to improve the forecast of evaporation and groundwater recharge by estimating hydraulic parameters, and ii) to reduce the impact of single erroneous model inputs/observations by a smoothing method. In order to validate the performance of the proposed method in a real world application, the experiment is conducted in a lysimeter environment.

Accelerated drug release and clearance of PEGylated epirubicin liposomes following repeated injections: a new challenge for sequential low-dose chemotherapy

PubMed Central

Yang, Qiang; Ma, Yanling; Zhao, Yongxue; She, Zhennan; Wang, Long; Li, Jie; Wang, Chunling; Deng, Yihui

2013-01-01

Background Sequential low-dose chemotherapy has received great attention for its unique advantages in attenuating multidrug resistance of tumor cells. Nevertheless, it runs the risk of producing new problems associated with the accelerated blood clearance phenomenon, especially with multiple injections of PEGylated liposomes. Methods Liposomes were labeled with fluorescent phospholipids of 1,2-dipalmitoyl-snglycero-3-phosphoethanolamine-N-(7-nitro-2-1,3-benzoxadiazol-4-yl) and epirubicin (EPI). The pharmacokinetics profile and biodistribution of the drug and liposome carrier following multiple injections were determined. Meanwhile, the antitumor effect of sequential low-dose chemotherapy was tested. To clarify this unexpected phenomenon, the production of polyethylene glycol (PEG)-specific immunoglobulin M (IgM), drug release, and residual complement activity experiments were conducted in serum. Results The first or sequential injections of PEGylated liposomes within a certain dose range induced the rapid clearance of subsequently injected PEGylated liposomal EPI. Of note, the clearance of EPI was two- to three-fold faster than the liposome itself, and a large amount of EPI was released from liposomes in the first 30 minutes in a complement-activation, direct-dependent manner. The therapeutic efficacy of liposomal EPI following 10 days of sequential injections in S180 tumor-bearing mice of 0.75 mg EPI/kg body weight was almost completely abolished between the sixth and tenth day of the sequential injections, even although the subsequently injected doses were doubled. The level of PEG-specific IgM in the blood increased rapidly, with a larger amount of complement being activated while the concentration of EPI in blood and tumor tissue was significantly reduced. Conclusion Our investigation implied that the accelerated blood clearance phenomenon and its accompanying rapid leakage and clearance of drug following sequential low-dose injections may reverse the unique pharmacokinetic–toxicity profile of liposomes which deserved our attention. Therefore, a more reasonable treatment regime should be selected to lessen or even eliminate this phenomenon. PMID:23576868

Single center, single operator comparative study of the effectiveness of electrohydraulic and electromagnetic lithotripters in the management of 10- to 20-mm single upper urinary tract calculi.

PubMed

Jamshaid, Anila; Ather, M Hammad; Hussain, Ghazi; Khawaja, Karim B

2008-11-01

This study compared the efficacy and safety profile of electrohydraulic (EH) and electromagnetic (EM) lithotriptors in the treatment of 10- to 20-mm renal and proximal ureteric stones at a single center and by a single operator. Between January 2001 and December 2006, we sequentially treated patients meeting study inclusion criteria with MPL 9000 Dornier EH for the first 3 years, followed by the EM Siemens Modularis shockwave lithotripsy (SWL) unit. A single operator performed all SWL treatments under the supervision of an admitting urologist. We analyzed the demographic features and stone- and treatment-related parameters including complications for both groups. In each group, the stone-free rate and efficiency quotient was determined at 1-3 months. Of 274 patients, we sequentially treated 112 using the EH lithotriptor, and 162 the EM lithotriptor. The pre-SWL patients and stone-related parameters were similar in the two groups, except for diagnostic imaging modalities. The mean number of SWL sessions, need for ancillary procedure, retreatment rate, stone location, stone-free rate, and efficiency quotient were not significantly different between groups. The mean number of shockwaves required for complete fragmentation was 2977 and 6044 (P < .000) for the EH and EM groups, respectively. Single center, single operator experience with two types of lithotriptor indicated that both are equally efficacious, with similar safety profiles. The only significant difference was that the EH lithotriptor required fewer shockwaves for fragmentation.

Stepwise π-extension of meso-alkylidenyl porphyrins through sequential 1,3-dipolar cycloaddition and redox reactions.

PubMed

Park, Dowoo; Jeong, Seung Doo; Ishida, Masatoshi; Lee, Chang-Hee

2014-08-25

Several regioselectively π-extended, pyrrole fused porphyrinoids have been synthesized by the 1,3-dipolar cycloaddition of meso-alkylidene-(benzi)porphyrins. Pd(II) complexes gave oxidation resistant, bis-pyrrole fused adducts. The repeated 1,3-dipolar cycloaddition followed by oxidation-reduction of pentaphyrin analogs afforded π-extended porphyrin analogs.

Simultaneous versus sequential optimal experiment design for the identification of multi-parameter microbial growth kinetics as a function of temperature.

PubMed

Van Derlinden, E; Bernaerts, K; Van Impe, J F

2010-05-21

Optimal experiment design for parameter estimation (OED/PE) has become a popular tool for efficient and accurate estimation of kinetic model parameters. When the kinetic model under study encloses multiple parameters, different optimization strategies can be constructed. The most straightforward approach is to estimate all parameters simultaneously from one optimal experiment (single OED/PE strategy). However, due to the complexity of the optimization problem or the stringent limitations on the system's dynamics, the experimental information can be limited and parameter estimation convergence problems can arise. As an alternative, we propose to reduce the optimization problem to a series of two-parameter estimation problems, i.e., an optimal experiment is designed for a combination of two parameters while presuming the other parameters known. Two different approaches can be followed: (i) all two-parameter optimal experiments are designed based on identical initial parameter estimates and parameters are estimated simultaneously from all resulting experimental data (global OED/PE strategy), and (ii) optimal experiments are calculated and implemented sequentially whereby the parameter values are updated intermediately (sequential OED/PE strategy). This work exploits OED/PE for the identification of the Cardinal Temperature Model with Inflection (CTMI) (Rosso et al., 1993). This kinetic model describes the effect of temperature on the microbial growth rate and encloses four parameters. The three OED/PE strategies are considered and the impact of the OED/PE design strategy on the accuracy of the CTMI parameter estimation is evaluated. Based on a simulation study, it is observed that the parameter values derived from the sequential approach deviate more from the true parameters than the single and global strategy estimates. The single and global OED/PE strategies are further compared based on experimental data obtained from design implementation in a bioreactor. Comparable estimates are obtained, but global OED/PE estimates are, in general, more accurate and reliable. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

One-pot growth of two-dimensional lateral heterostructures via sequential edge-epitaxy

NASA Astrophysics Data System (ADS)

Sahoo, Prasana K.; Memaran, Shahriar; Xin, Yan; Balicas, Luis; Gutiérrez, Humberto R.

2018-01-01

Two-dimensional heterojunctions of transition-metal dichalcogenides have great potential for application in low-power, high-performance and flexible electro-optical devices, such as tunnelling transistors, light-emitting diodes, photodetectors and photovoltaic cells. Although complex heterostructures have been fabricated via the van der Waals stacking of different two-dimensional materials, the in situ fabrication of high-quality lateral heterostructures with multiple junctions remains a challenge. Transition-metal-dichalcogenide lateral heterostructures have been synthesized via single-step, two-step or multi-step growth processes. However, these methods lack the flexibility to control, in situ, the growth of individual domains. In situ synthesis of multi-junction lateral heterostructures does not require multiple exchanges of sources or reactors, a limitation in previous approaches as it exposes the edges to ambient contamination, compromises the homogeneity of domain size in periodic structures, and results in long processing times. Here we report a one-pot synthetic approach, using a single heterogeneous solid source, for the continuous fabrication of lateral multi-junction heterostructures consisting of monolayers of transition-metal dichalcogenides. The sequential formation of heterojunctions is achieved solely by changing the composition of the reactive gas environment in the presence of water vapour. This enables selective control of the water-induced oxidation and volatilization of each transition-metal precursor, as well as its nucleation on the substrate, leading to sequential edge-epitaxy of distinct transition-metal dichalcogenides. Photoluminescence maps confirm the sequential spatial modulation of the bandgap, and atomic-resolution images reveal defect-free lateral connectivity between the different transition-metal-dichalcogenide domains within a single crystal structure. Electrical transport measurements revealed diode-like responses across the junctions. Our new approach offers greater flexibility and control than previous methods for continuous growth of transition-metal-dichalcogenide-based multi-junction lateral heterostructures. These findings could be extended to other families of two-dimensional materials, and establish a foundation for the development of complex and atomically thin in-plane superlattices, devices and integrated circuits.

Method for sequentially processing a multi-level interconnect circuit in a vacuum chamber

NASA Technical Reports Server (NTRS)

Routh, D. E.; Sharma, G. C. (Inventor)

1982-01-01

The processing of wafer devices to form multilevel interconnects for microelectronic circuits is described. The method is directed to performing the sequential steps of etching the via, removing the photo resist pattern, back sputtering the entire wafer surface and depositing the next layer of interconnect material under common vacuum conditions without exposure to atmospheric conditions. Apparatus for performing the method includes a vacuum system having a vacuum chamber in which wafers are processed on rotating turntables. The vacuum chamber is provided with an RF sputtering system and a DC magnetron sputtering system. A gas inlet is provided in the chamber for the introduction of various gases to the vacuum chamber and the creation of various gas plasma during the sputtering steps.

Eradication rate of Helicobacter Pylori infection is directly influenced by adherence to therapy in children.

PubMed

Kotilea, Kallirroi; Mekhael, Joyce; Salame, Assaad; Mahler, Tania; Miendje-Deyi, Veronique Yvette; Cadranel, Samy; Bontems, Patrick

2017-08-01

Current commonly accepted strategies to eradicate Helicobacter pylori in children are a 10-day sequential treatment or a triple therapy for 7-14 days. To avoid further expensive and possibly risky investigations as well as induction of secondary antimicrobial resistance, a success rate of elimination strategies over 90% in a per-protocol analysis is the target goal but rates observed in clinical trials are lower. Antimicrobial resistance is a well-recognized risk factor for treatment failure; therefore, only a treatment tailored to susceptibility testing should be recommended. Adherence to therapy is also a risk factor for treatment failure but that has been poorly studied. The purpose of this study was to evaluate the influence of adherence to therapy on the elimination rates obtained with different treatment regimens. Cohort study analysis of children, aged 2-17 years, treated for Helicobacter pylori infection between October 2011 and December 2013. As a routine clinical practice, children infected with a strain susceptible to clarithromycin and to metronidazole received either a sequential regimen or a 10-day triple therapy while children infected with a strain resistant to clarithromycin or metronidazole received a 10-day triple regimen tailored to antimicrobial susceptibility. The eradication rate was assessed by a negative 13 C-urea breath test performed at least 8 weeks after the end of the treatment and adherence evaluated using a diary. One hundred forty-five children (67 girls/78 boys, median age 9.7 years) fulfilled the inclusion criteria, 118 being infected with a strain susceptible to both clarithromycin and metronidazole, 10 with a clarithromycin resistant, and 17 with a metronidazole resistant strain. A sequential regimen was prescribed in 44, a triple therapy containing clarithromycin in 84 and containing metronidazole in 17. Follow-up data were available for 130/145 and clearance of the infection observed in 105 of them. A concordance of more than 90% between the prescribed and the ingested drugs was observed in 109 children, between 50 and 90% in eight, less than 50% in 11 while these data were unknown for 2/130. A successful eradication was achieved for 89.9% of patients that received at least 90% of the prescribed drugs, whereas the eradication rate for nonadherent patients was 36.6%. Adherence above 90% was significantly higher in the absence of chronic concomitant disease, in the absence of adverse event and results in a significantly higher eradication rate. With the proposed strategy and an adherence higher than 90%, eradication was obtained in 98/109 children, the rate being only significantly superior to 90% with the sequential regimen. Adherence to therapy is a very important factor for the outcome and has to be assessed when evaluating the outcome of an H. pylori eradication regimen in order to understand the reasons of treatment failure. As we treated only after evaluation of the resistance of the H. Pylori strains, we were expecting to reach the given objective of 90% successful treatment. Children with adherence to treatment above 90% had a successful outcome of 89,9%, whereas nonadherent had a successful outcome of 36,8%. This is the first time that adherence has been assessed accurately. © 2017 John Wiley & Sons Ltd.

Fracture resistance of retreated roots using different retreatment systems.

PubMed

Er, Kursat; Tasdemir, Tamer; Siso, Seyda Herguner; Celik, Davut; Cora, Sabri

2011-08-01

This study was designed to evaluate the fracture resistance of retreated roots using different rotary retreatment systems. Forty eight freshly extracted human canine teeth with single straight root canals were instrumented sequentially increasing from size 30 to a size 55 using K-files whit a stepback technique. The teeth were randomly divided into three experimental and one control groups of 12 specimens each. The root canals were filled using cold lateral compaction of gutta-percha and AH Plus (Dentsply Detrey, Konstanz, Germany) sealer in experimental groups. Removal of gutta-percha was performed with the following devices and techniques: ProTaper Universal (Dentsply Maillefer, Ballaigues, Switzerland), R-Endo (Micro-Mega, Besançon, France), and Mtwo (Sweden & Martina, Padova, Italy) rotary retreatment systems. Control group specimens were only instrumented, not filled or retreated. The specimens were then mounted in copper rings, were filled with a self-curing polymethylmethacrylate resin, and the force required to cause vertical root fracture was measured using a universal testing device. The force of fracture of the roots was recorded and the results in the various groups were compared. Statistical analysis was accomplished by one-way ANOVA and a post hoc Tukey tests. There were statistically significant differences between the control and experimental groups (P<.05). However, there were no significant differences among the experimental groups. Based on the results, all rotary retreatment techniques used in this in vitro study produced similar root weakness.

The cost-effectiveness of 10 antenatal syphilis screening and treatment approaches in Peru, Tanzania, and Zambia.

PubMed

Terris-Prestholt, Fern; Vickerman, Peter; Torres-Rueda, Sergio; Santesso, Nancy; Sweeney, Sedona; Mallma, Patricia; Shelley, Katharine D; Garcia, Patricia J; Bronzan, Rachel; Gill, Michelle M; Broutet, Nathalie; Wi, Teodora; Watts, Charlotte; Mabey, David; Peeling, Rosanna W; Newman, Lori

2015-06-01

Rapid plasma reagin (RPR) is frequently used to test women for maternal syphilis. Rapid syphilis immunochromatographic strip tests detecting only Treponema pallidum antibodies (single RSTs) or both treponemal and non-treponemal antibodies (dual RSTs) are now available. This study assessed the cost-effectiveness of algorithms using these tests to screen pregnant women. Observed costs of maternal syphilis screening and treatment using clinic-based RPR and single RSTs in 20 clinics across Peru, Tanzania, and Zambia were used to model the cost-effectiveness of algorithms using combinations of RPR, single, and dual RSTs, and no and mass treatment. Sensitivity analyses determined drivers of key results. Although this analysis found screening using RPR to be relatively cheap, most (>70%) true cases went untreated. Algorithms using single RSTs were the most cost-effective in all observed settings, followed by dual RSTs, which became the most cost-effective if dual RST costs were halved. Single test algorithms dominated most sequential testing algorithms, although sequential algorithms reduced overtreatment. Mass treatment was relatively cheap and effective in the absence of screening supplies, though treated many uninfected women. This analysis highlights the advantages of introducing RSTs in three diverse settings. The results should be applicable to other similar settings. Copyright © 2015 International Federation of Gynecology and Obstetrics. All rights reserved.

The cost-effectiveness of 10 antenatal syphilis screening and treatment approaches in Peru, Tanzania, and Zambia

PubMed Central

Terris-Prestholt, Fern; Vickerman, Peter; Torres-Rueda, Sergio; Santesso, Nancy; Sweeney, Sedona; Mallma, Patricia; Shelley, Katharine D.; Garcia, Patricia J.; Bronzan, Rachel; Gill, Michelle M.; Broutet, Nathalie; Wi, Teodora; Watts, Charlotte; Mabey, David; Peeling, Rosanna W.; Newman, Lori

2015-01-01

Objective Rapid plasma reagin (RPR) is frequently used to test women for maternal syphilis. Rapid syphilis immunochromatographic strip tests detecting only Treponema pallidum antibodies (single RSTs) or both treponemal and non-treponemal antibodies (dual RSTs) are now available. This study assessed the cost-effectiveness of algorithms using these tests to screen pregnant women. Methods Observed costs of maternal syphilis screening and treatment using clinic-based RPR and single RSTs in 20 clinics across Peru, Tanzania, and Zambia were used to model the cost-effectiveness of algorithms using combinations of RPR, single, and dual RSTs, and no and mass treatment. Sensitivity analyses determined drivers of key results. Results Although this analysis found screening using RPR to be relatively cheap, most (> 70%) true cases went untreated. Algorithms using single RSTs were the most cost-effective in all observed settings, followed by dual RSTs, which became the most cost-effective if dual RST costs were halved. Single test algorithms dominated most sequential testing algorithms, although sequential algorithms reduced overtreatment. Mass treatment was relatively cheap and effective in the absence of screening supplies, though treated many uninfected women. Conclusion This analysis highlights the advantages of introducing RSTs in three diverse settings. The results should be applicable to other similar settings. PMID:25963907

14 day sequential therapy versus 10 day bismuth quadruple therapy containing high-dose esomeprazole in the first-line and second-line treatment of Helicobacter pylori: a multicentre, non-inferiority, randomized trial.

PubMed

Liou, Jyh-Ming; Chen, Chieh-Chang; Fang, Yu-Jen; Chen, Po-Yueh; Chang, Chi-Yang; Chou, Chu-Kuang; Chen, Mei-Jyh; Tseng, Cheng-Hao; Lee, Ji-Yuh; Yang, Tsung-Hua; Chiu, Min-Chin; Yu, Jian-Jyun; Kuo, Chia-Chi; Luo, Jiing-Chyuan; Hsu, Wen-Feng; Hu, Wen-Hao; Tsai, Min-Horn; Lin, Jaw-Town; Shun, Chia-Tung; Twu, Gary; Lee, Yi-Chia; Bair, Ming-Jong; Wu, Ming-Shiang

2018-05-29

Whether extending the treatment length and the use of high-dose esomeprazole may optimize the efficacy of Helicobacter pylori eradication remains unknown. To compare the efficacy and tolerability of optimized 14 day sequential therapy and 10 day bismuth quadruple therapy containing high-dose esomeprazole in first-line therapy. We recruited 620 adult patients (≥20 years of age) with H. pylori infection naive to treatment in this multicentre, open-label, randomized trial. Patients were randomly assigned to receive 14 day sequential therapy or 10 day bismuth quadruple therapy, both containing esomeprazole 40 mg twice daily. Those who failed after 14 day sequential therapy received rescue therapy with 10 day bismuth quadruple therapy and vice versa. Our primary outcome was the eradication rate in the first-line therapy. Antibiotic susceptibility was determined. ClinicalTrials.gov: NCT03156855. The eradication rates of 14 day sequential therapy and 10 day bismuth quadruple therapy were 91.3% (283 of 310, 95% CI 87.4%-94.1%) and 91.6% (284 of 310, 95% CI 87.8%-94.3%) in the ITT analysis, respectively (difference -0.3%, 95% CI -4.7% to 4.4%, P = 0.886). However, the frequencies of adverse effects were significantly higher in patients treated with 10 day bismuth quadruple therapy than those treated with 14 day sequential therapy (74.4% versus 36.7% P < 0.0001). The eradication rate of 14 day sequential therapy in strains with and without 23S ribosomal RNA mutation was 80% (24 of 30) and 99% (193 of 195), respectively (P < 0.0001). Optimized 14 day sequential therapy was non-inferior to, but better tolerated than 10 day bismuth quadruple therapy and both may be used in first-line treatment in populations with low to intermediate clarithromycin resistance.

Comparison of bioavailable vanadium in alfalfa rhizosphere soil extracted by an improved BCR procedure and EDTA, HCl, and NaNO₃ single extractions in a pot experiment with V-Cd treatments.

PubMed

Yang, Jie; Teng, Yanguo; Zuo, Rui; Song, Liuting

2015-06-01

The BCR sequential extraction procedure was compared with EDTA, HCl, and NaNO3 single extractions for evaluating vanadium bioavailability in alfalfa rhizosphere soil. The amounts of vanadium extracted by these methods were in the following order: BCR (bioavailable V) > EDTA ≈ HCl > NaNO3. Both correlation analysis and stepwise regression were adopted to illustrate the extractable vanadium between different reagents. The correlation coefficients between extracted vanadium and the vanadium contents in alfalfa roots were R NaNO3 = 0.948, R HCl = 0.902, R EDTA = 0.816, and R bioavailable V = 0.819. The stepwise multiple regression equation of the NaNO3 extraction was the most significant at a 95 % confidence interval. The influence of pH, total organic carbon, and cadmium content of soil to vanadium bioavailability were not definite. In summary, both the BCR sequential extraction and the single extraction methods were valid approaches for predicting vanadium bioavailability in alfalfa rhizosphere soil, especially the single extractions.

Numerical Modeling of Electrode Degradation During Resistance Spot Welding Using CuCrZr Electrodes

NASA Astrophysics Data System (ADS)

Gauthier, Elise; Carron, Denis; Rogeon, Philippe; Pilvin, Philippe; Pouvreau, Cédric; Lety, Thomas; Primaux, François

2014-05-01

Resistance spot welding is a technique widely used by the automotive industry to assemble thin steel sheets. The cyclic thermo-mechanical loading associated with the accumulation of weld spots progressively deteriorates the electrodes. This study addresses the development of a comprehensive multi-physical model that describes the sequential deterioration. Welding tests achieved on uncoated and Zn-coated steel sheets are analyzed. Finite element analysis is performed using an electrical-thermal-metallurgical model. A numerical experimental design is carried out to highlight the main process parameters and boundary conditions which affect electrode degradation.

Multifunctional picoliter droplet manipulation platform and its application in single cell analysis.

PubMed

Gu, Shu-Qing; Zhang, Yun-Xia; Zhu, Ying; Du, Wen-Bin; Yao, Bo; Fang, Qun

2011-10-01

We developed an automated and multifunctional microfluidic platform based on DropLab to perform flexible generation and complex manipulations of picoliter-scale droplets. Multiple manipulations including precise droplet generation, sequential reagent merging, and multistep solid-phase extraction for picoliter-scale droplets could be achieved in the present platform. The system precision in generating picoliter-scale droplets was significantly improved by minimizing the thermo-induced fluctuation of flow rate. A novel droplet fusion technique based on the difference of droplet interfacial tensions was developed without the need of special microchannel networks or external devices. It enabled sequential addition of reagents to droplets on demand for multistep reactions. We also developed an effective picoliter-scale droplet splitting technique with magnetic actuation. The difficulty in phase separation of magnetic beads from picoliter-scale droplets due to the high interfacial tension was overcome using ferromagnetic particles to carry the magnetic beads to pass through the phase interface. With this technique, multistep solid-phase extraction was achieved among picoliter-scale droplets. The present platform had the ability to perform complex multistep manipulations to picoliter-scale droplets, which is particularly required for single cell analysis. Its utility and potentials in single cell analysis were preliminarily demonstrated in achieving high-efficiency single-cell encapsulation, enzyme activity assay at the single cell level, and especially, single cell DNA purification based on solid-phase extraction.

Room-temperature current blockade in atomically defined single-cluster junctions

NASA Astrophysics Data System (ADS)

Lovat, Giacomo; Choi, Bonnie; Paley, Daniel W.; Steigerwald, Michael L.; Venkataraman, Latha; Roy, Xavier

2017-11-01

Fabricating nanoscopic devices capable of manipulating and processing single units of charge is an essential step towards creating functional devices where quantum effects dominate transport characteristics. The archetypal single-electron transistor comprises a small conducting or semiconducting island separated from two metallic reservoirs by insulating barriers. By enabling the transfer of a well-defined number of charge carriers between the island and the reservoirs, such a device may enable discrete single-electron operations. Here, we describe a single-molecule junction comprising a redox-active, atomically precise cobalt chalcogenide cluster wired between two nanoscopic electrodes. We observe current blockade at room temperature in thousands of single-cluster junctions. Below a threshold voltage, charge transfer across the junction is suppressed. The device is turned on when the temporary occupation of the core states by a transiting carrier is energetically enabled, resulting in a sequential tunnelling process and an increase in current by a factor of ∼600. We perform in situ and ex situ cyclic voltammetry as well as density functional theory calculations to unveil a two-step process mediated by an orbital localized on the core of the cluster in which charge carriers reside before tunnelling to the collector reservoir. As the bias window of the junction is opened wide enough to include one of the cluster frontier orbitals, the current blockade is lifted and charge carriers can tunnel sequentially across the junction.

The Domino Way to Heterocycles

PubMed Central

Padwa, Albert; Bur, Scott K.

2007-01-01

Sequential transformations enable the facile synthesis of complex target molecules from simple building blocks in a single preparative step. Their value is amplified if they also create multiple stereogenic centers. In the ongoing search for new domino processes, emphasis is usually placed on sequential reactions which occur cleanly and without forming by-products. As a prerequisite for an ideally proceeding one-pot sequential transformation, the reactivity pattern of all participating components has to be such that each building block gets involved in a reaction only when it is supposed to do so. The development of sequences that combine transformations of fundamentally different mechanisms broadens the scope of such procedures in synthetic chemistry. This mini review contains a representative sampling from the last 15 years on the kinds of reactions that have been sequenced into cascades to produce heterocyclic molecules. PMID:17940591

A comparison of disinfection by-products formation during sequential or simultaneous disinfection of surface waters with chlorine dioxide and chlor(am)ine.

PubMed

Shi, Yanwei; Ling, Wencui; Qiang, Zhimin

2013-01-01

The effect of chlorine dioxide (ClO2) oxidation on the formation of disinfection by-products (DBPs) during sequential (ClO2 pre-oxidation for 30 min) and simultaneous disinfection processes with free chlorine (FC) or monochloramine (MCA) was investigated. The formation of DBPs from synthetic humic acid (HA) water and three natural surface waters containing low bromide levels (11-27 microg/L) was comparatively examined in the FC-based (single FC, sequential ClO2-FC, and simultaneous ClO2/FC) and MCA-based (single MCA, ClO2-MCA, and ClO2/MCA) disinfection processes. The results showed that much more DBPs were formed from the synthetic HA water than from the three natural surface waters with comparative levels of dissolved organic carbon. In the FC-based processes, ClO2 oxidation could reduce trihalomethanes (THMs) by 27-35% and haloacetic acids (HAAs) by 14-22% in the three natural surface waters, but increased THMs by 19% and HAAs by 31% in the synthetic HA water after an FC contact time of 48 h. In the MCA-based processes, similar trends were observed although DBPs were produced at a much lower level. There was an insignificant difference in DBPs formation between the sequential and simultaneous processes. The presence of a high level of bromide (320 microg/L) remarkably promoted the DBPs formation in the FC-based processes. Therefore, the simultaneous disinfection process of ClO2/MCA is recommended particularly for waters with a high bromide level.

Sequential strand displacement beacon for detection of DNA coverage on functionalized gold nanoparticles.

PubMed

Paliwoda, Rebecca E; Li, Feng; Reid, Michael S; Lin, Yanwen; Le, X Chris

2014-06-17

Functionalizing nanomaterials for diverse analytical, biomedical, and therapeutic applications requires determination of surface coverage (or density) of DNA on nanomaterials. We describe a sequential strand displacement beacon assay that is able to quantify specific DNA sequences conjugated or coconjugated onto gold nanoparticles (AuNPs). Unlike the conventional fluorescence assay that requires the target DNA to be fluorescently labeled, the sequential strand displacement beacon method is able to quantify multiple unlabeled DNA oligonucleotides using a single (universal) strand displacement beacon. This unique feature is achieved by introducing two short unlabeled DNA probes for each specific DNA sequence and by performing sequential DNA strand displacement reactions. Varying the relative amounts of the specific DNA sequences and spacing DNA sequences during their coconjugation onto AuNPs results in different densities of the specific DNA on AuNP, ranging from 90 to 230 DNA molecules per AuNP. Results obtained from our sequential strand displacement beacon assay are consistent with those obtained from the conventional fluorescence assays. However, labeling of DNA with some fluorescent dyes, e.g., tetramethylrhodamine, alters DNA density on AuNP. The strand displacement strategy overcomes this problem by obviating direct labeling of the target DNA. This method has broad potential to facilitate more efficient design and characterization of novel multifunctional materials for diverse applications.

Sequential intravenous injection of anionic polymer and cationic lipoplex of siRNA could effectively deliver siRNA to the liver.

PubMed

Hattori, Yoshiyuki; Arai, Shohei; Okamoto, Ryou; Hamada, Megumi; Kawano, Kumi; Yonemochi, Etsuo

2014-12-10

In this study, we developed novel siRNA transfer method to the liver by sequential intravenous injection of anionic polymer and cationic liposome/cholesterol-modified siRNA complex (cationic lipoplex). When cationic lipoplex was intravenously injected into mice, the accumulation of siRNA was mainly observed in the lungs. In contrast, when cationic lipoplex was intravenously injected at 1 min after intravenous injection of poly-L-glutamic acid (PGA) or chondroitin sulfate C (CS), siRNA was accumulated in the liver. In terms of suppression of gene expression in vivo, apolipoprotein B (ApoB) mRNA in the liver and low-density-lipoprotein (LDL) and very low-density-lipoprotein (VLDL) cholesterol level in serum were reduced at 48 h after single sequential injection of PGA or CS plus cationic lipoplex of cholesterol-modified ApoB siRNA. Furthermore, sequential injections of PGA plus cationic lipoplex of cholesterol-modified luciferase siRNA could reduce luciferase activity in tumor xenografts bearing liver metastasis of human breast tumor MCF-7-Luc. From these findings, sequential injection of anionic polymer and cationic lipoplex of siRNA might produce a systemic vector of siRNA to the liver. Copyright © 2014 Elsevier B.V. All rights reserved.

Sequential bilateral cochlear implantation improves working performance, quality of life, and quality of hearing.

PubMed

Härkönen, Kati; Kivekäs, Ilkka; Rautiainen, Markus; Kotti, Voitto; Sivonen, Ville; Vasama, Juha-Pekka

2015-05-01

This prospective study shows that working performance, quality of life (QoL), and quality of hearing (QoH) are better with two compared with a single cochlear implant (CI). The impact of the second CI on the patient's QoL is as significant as the impact of the first CI. To evaluate the benefits of sequential bilateral cochlear implantation in working, QoL, and QoH. We studied working performance, work-related stress, QoL, and QoH with specific questionnaires in 15 patients with unilateral CI scheduled for sequential CI of another ear. Sound localization performance and speech perception in noise were measured with specific tests. All questionnaires and tests were performed before the second CI surgery and 6 and 12 months after its activation. Bilateral CIs increased patients' working performance and their work-related stress and fatigue decreased. Communication with co-workers was easier and patients were more active in their working environment. Sequential bilateral cochlear implantation improved QoL, QoH, sound localization, and speech perception in noise statistically significantly.

Devaluation and sequential decisions: linking goal-directed and model-based behavior

PubMed Central

Friedel, Eva; Koch, Stefan P.; Wendt, Jean; Heinz, Andreas; Deserno, Lorenz; Schlagenhauf, Florian

2014-01-01

In experimental psychology different experiments have been developed to assess goal–directed as compared to habitual control over instrumental decisions. Similar to animal studies selective devaluation procedures have been used. More recently sequential decision-making tasks have been designed to assess the degree of goal-directed vs. habitual choice behavior in terms of an influential computational theory of model-based compared to model-free behavioral control. As recently suggested, different measurements are thought to reflect the same construct. Yet, there has been no attempt to directly assess the construct validity of these different measurements. In the present study, we used a devaluation paradigm and a sequential decision-making task to address this question of construct validity in a sample of 18 healthy male human participants. Correlational analysis revealed a positive association between model-based choices during sequential decisions and goal-directed behavior after devaluation suggesting a single framework underlying both operationalizations and speaking in favor of construct validity of both measurement approaches. Up to now, this has been merely assumed but never been directly tested in humans. PMID:25136310

Forecasting daily streamflow using online sequential extreme learning machines

NASA Astrophysics Data System (ADS)

Lima, Aranildo R.; Cannon, Alex J.; Hsieh, William W.

2016-06-01

While nonlinear machine methods have been widely used in environmental forecasting, in situations where new data arrive continually, the need to make frequent model updates can become cumbersome and computationally costly. To alleviate this problem, an online sequential learning algorithm for single hidden layer feedforward neural networks - the online sequential extreme learning machine (OSELM) - is automatically updated inexpensively as new data arrive (and the new data can then be discarded). OSELM was applied to forecast daily streamflow at two small watersheds in British Columbia, Canada, at lead times of 1-3 days. Predictors used were weather forecast data generated by the NOAA Global Ensemble Forecasting System (GEFS), and local hydro-meteorological observations. OSELM forecasts were tested with daily, monthly or yearly model updates. More frequent updating gave smaller forecast errors, including errors for data above the 90th percentile. Larger datasets used in the initial training of OSELM helped to find better parameters (number of hidden nodes) for the model, yielding better predictions. With the online sequential multiple linear regression (OSMLR) as benchmark, we concluded that OSELM is an attractive approach as it easily outperformed OSMLR in forecast accuracy.

CACTI: Free, Open-Source Software for the Sequential Coding of Behavioral Interactions

PubMed Central

Glynn, Lisa H.; Hallgren, Kevin A.; Houck, Jon M.; Moyers, Theresa B.

2012-01-01

The sequential analysis of client and clinician speech in psychotherapy sessions can help to identify and characterize potential mechanisms of treatment and behavior change. Previous studies required coding systems that were time-consuming, expensive, and error-prone. Existing software can be expensive and inflexible, and furthermore, no single package allows for pre-parsing, sequential coding, and assignment of global ratings. We developed a free, open-source, and adaptable program to meet these needs: The CASAA Application for Coding Treatment Interactions (CACTI). Without transcripts, CACTI facilitates the real-time sequential coding of behavioral interactions using WAV-format audio files. Most elements of the interface are user-modifiable through a simple XML file, and can be further adapted using Java through the terms of the GNU Public License. Coding with this software yields interrater reliabilities comparable to previous methods, but at greatly reduced time and expense. CACTI is a flexible research tool that can simplify psychotherapy process research, and has the potential to contribute to the improvement of treatment content and delivery. PMID:22815713

Spin effects in transport through single-molecule magnets in the sequential and cotunneling regimes

NASA Astrophysics Data System (ADS)

Misiorny, Maciej; Weymann, Ireneusz; Barnaś, Józef

2009-06-01

We analyze the stationary spin-dependent transport through a single-molecule magnet weakly coupled to external ferromagnetic leads. Using the real-time diagrammatic technique, we calculate the sequential and cotunneling contributions to current, tunnel magnetoresistance, and Fano factor in both linear and nonlinear response regimes. We show that the effects of cotunneling are predominantly visible in the blockade regime and lead to enhancement of tunnel magnetoresistance (TMR) above the Julliere value, which is accompanied with super-Poissonian shot noise due to bunching of inelastic cotunneling processes through different virtual spin states of the molecule. The effects of external magnetic field and the role of type and strength of exchange interaction between the LUMO level and the molecule’s spin are also considered. When the exchange coupling is ferromagnetic, we find an enhanced TMR, while in the case of antiferromagnetic coupling we predict a large negative TMR effect.

Operation of a single-channel, sequential Navstar GPS receiver in a helicopter mission environment

NASA Technical Reports Server (NTRS)

Edwards, F. G.; Hamlin, J. R.

1984-01-01

It is pointed out that the future utilization of the Navstar Global Positioning System (GPS) by civil helicopters will provide an enhanced performance not obtainable with current navigations systems. GPS will supply properly equipped users with extremely accurate three-dimensional position and velocity information anywhere in the world. Preliminary studies have been conducted to investigate differential GPS concept mechanizations and cost, and to theoretically predict navigation performance and the impact of degradation of the GPS C/A code for national security considerations. The obtained results are encouraging, but certain improvements are needed. As a second step in the program, a single-channel sequential GPS navigator was installed and operated in the NASA SH-3G helicopter. A series of flight tests were conducted. It is found that performance of the Navstar GPS Z-set is quite acceptable to support area navigation and nonprecision approach operations.

Sequential voluntary cough and aspiration or aspiration risk in Parkinson's disease.

PubMed

Hegland, Karen Wheeler; Okun, Michael S; Troche, Michelle S

2014-08-01

Disordered swallowing, or dysphagia, is almost always present to some degree in people with Parkinson's disease (PD), either causing aspiration or greatly increasing the risk for aspiration during swallowing. This likely contributes to aspiration pneumonia, a leading cause of death in this patient population. Effective airway protection is dependent upon multiple behaviors, including cough and swallowing. Single voluntary cough function is disordered in people with PD and dysphagia. However, the appropriate response to aspirate material is more than one cough, or sequential cough. The goal of this study was to examine voluntary sequential coughing in people with PD, with and without dysphagia. Forty adults diagnosed with idiopathic PD produced two trials of sequential voluntary cough. The cough airflows were obtained using pneumotachograph and facemask and subsequently digitized and recorded. All participants received a modified barium swallow study as part of their clinical care, and the worst penetration-aspiration score observed was used to determine whether the patient had dysphagia. There were significant differences in the compression phase duration, peak expiratory flow rates, and amount of air expired of the sequential cough produced by participants with and without dysphagia. The presence of dysphagia in people with PD is associated with disordered cough function. Sequential cough, which is important in removing aspirate material from large- and smaller-diameter airways, is also impaired in people with PD and dysphagia compared with those without dysphagia. There may be common neuroanatomical substrates for cough and swallowing impairment in PD leading to the co-occurrence of these dysfunctions.

Treating Children with Early-Onset Conduct Problems and Callous-Unemotional Traits: An Empirical Evaluation of KooLKIDS

ERIC Educational Resources Information Center

Houghton, Stephen; Carroll, Annemaree; Zadow, Corinne; O'connor, Emma Sanders; Hattie, John; Lynn, Sasha

2017-01-01

Children with early-onset conduct problems (EOCP) and callous-unemotional (CU) traits are highly resistant to treatment and cost society significantly more than their healthy counterparts. Employing a multiple baseline design, 13 males (9.0-10.2 years of age) with a history of school suspensions were sequentially introduced to KooLKIDS, a…

Flavanoid-rich fraction from Sageretia theezans leaves scavenges reactive oxygen radical species and increases the resistance of low-density lipoprotein to oxidation

USDA-ARS?s Scientific Manuscript database

To explore their bioactive fractions, S. theezans leaves were extracted 2 with 60% acetone and then fractionated sequentially with hexane, ethyl acetate, and water. ROS (HOCl, ONOO-, and O2 deg -) scavenging activity, ORAC value and total phenolic content of each fraction were investigated. The ethy...

Structural profiling of individual glycosphingolipids in a single thin-layer chromatogram by multiple sequential immunodetection matched with Direct IR-MALDI-o-TOF mass spectrometry.

PubMed

Souady, Jamal; Soltwisch, Jens; Dreisewerd, Klaus; Haier, Jörg; Peter-Katalinić, Jasna; Müthing, Johannes

2009-11-15

The thin-layer chromatography (TLC) immunoenzyme overlay assay is a widely used tool for antibody-mediated identification of glycosphingolipids (GSLs) in mixtures. However, because the majority of GSLs is left unexamined in a chromatogram of a single assay, we developed a novel method that permits detection of various GSLs by sequential multiple immunostaining combined with individual coloring of GSLs in the same chromatogram. Specific staining was achieved by means of primary anti-GSL antibodies, directed against lactosylceramide, globotriaosylceramide, and globotetraosylceramide, in conjunction with alkaline phosphatase (AP)- or horseradish peroxidase (HRP)-conjugated secondary antibodies together with the appropriate chromogenic substrates. Triple coloring with 5-bromo-4-chloro-3-indolyl phosphate (BCIP)-AP, Fast Red-AP, and 3,3'-diaminobenzidine (DAB)-HRP resulted in blue, red, and black precipitates, respectively, following three sequential immunostaining rounds. Structures of antibody-detected GSLs were determined by direct coupling of TLC with infrared matrix-assisted laser desorption/ionization orthogonal time-of-flight mass spectrometry. This combinatorial technique was used to demonstrate structural GSL profiling of crude lipid extracts from human hepatocellular cancer. This powerful technology allows efficient structural characterization of GSLs in small tissue samples and marks a further step forward in the emerging field of glycosphingolipidomics.

Using a water-confined carbon nanotube to probe the electricity of sequential charged segments of macromolecules

NASA Astrophysics Data System (ADS)

Wang, Yu; Zhao, Yan-Jiao; Huang, Ji-Ping

2012-07-01

The detection of macromolecular conformation is particularly important in many physical and biological applications. Here we theoretically explore a method for achieving this detection by probing the electricity of sequential charged segments of macromolecules. Our analysis is based on molecular dynamics simulations, and we investigate a single file of water molecules confined in a half-capped single-walled carbon nanotube (SWCNT) with an external electric charge of +e or -e (e is the elementary charge). The charge is located in the vicinity of the cap of the SWCNT and along the centerline of the SWCNT. We reveal the picosecond timescale for the re-orientation (namely, from one unidirectional direction to the other) of the water molecules in response to a switch in the charge signal, -e → +e or +e → -e. Our results are well understood by taking into account the electrical interactions between the water molecules and between the water molecules and the external charge. Because such signals of re-orientation can be magnified and transported according to Tu et al. [2009 Proc. Natl. Acad. Sci. USA 106 18120], it becomes possible to record fingerprints of electric signals arising from sequential charged segments of a macromolecule, which are expected to be useful for recognizing the conformations of some particular macromolecules.

Ambulatory Care Data Base (ACDB) Data Dictionary Sequential Files of Phase 2.

DTIC Science & Technology

1992-04-01

ARTERIES 4340 CEREBRAL THROMBOSIS 43491 STROKE , ISCHEMIC 435 TRANSIENT CEREBRAL ISCHEMIA 4359 TRANSIENT ISCHEMIC ATTACK (TIA) 43591 TRANS ISCHEMIC ATTACK W...CRISIS 4373 ANEURYSM, CEREBRAL , NONRUPTURED 4374 ARTERITIS, CEREBRAL 4378 CEREBROVASCULAR DISEASE, OTHER ILL-DEFINED 43781 STROKE , LACUNAR 438 LATE...FOR LOCALIZATION OF CEREBRAL SEIZURE FOC 95999 OTHER NEUROLOGICAL DIAGNOSTIC PROCEDURES 96500 CHEMO INJ, SINGLE, PRE-MIX, PUSH 96501 CHEMO INJ, SINGLE

Rapid Multistep Synthesis of 1,2,4-Oxadiazoles in a Single Continuous Microreactor Sequence

PubMed Central

Grant, Daniel; Dahl, Russell; Cosford, Nicholas D. P.

2009-01-01

A general method for the synthesis of bis-substituted 1,2,4-oxadiazoles from readily available arylnitriles and activated carbonyls in a single continuous microreactor sequence is described. The synthesis incorporates three sequential microreactors to produce 1,2,4-oxadiazoles in ~30 min in quantities (40–80 mg) sufficient for full characterization and rapid library supply. PMID:18687005

Substitutions at Amino Acid Positions 143, 148, and 155 of HIV-1 Integrase Define Distinct Genetic Barriers to Raltegravir Resistance In Vivo

PubMed Central

Fransen, Signe; Gupta, Soumi; Frantzell, Arne; Petropoulos, Christos J.

2012-01-01

Mutations at amino acids 143, 148, and 155 in HIV-1 integrase (IN) define primary resistance pathways in subjects failing raltegravir (RAL)-containing treatments. Although each pathway appears to be genetically distinct, shifts in the predominant resistant virus population have been reported under continued drug pressure. To better understand this dynamic, we characterized the RAL susceptibility of 200 resistant viruses, and we performed sequential clonal analysis for selected cases. Patient viruses containing Y143R, Q148R, or Q148H mutations consistently exhibited larger reductions in RAL susceptibility than patient viruses containing N155H mutations. Sequential analyses of virus populations from three subjects revealed temporal shifts in subpopulations representing N155H, Y143R, or Q148H escape pathways. Evaluation of molecular clones isolated from different time points demonstrated that Y143R and Q148H variants exhibited larger reductions in RAL susceptibility and higher IN-mediated replication capacity (RC) than N155H variants within the same subject. Furthermore, shifts from the N155H pathway to either the Q148R or H pathway or the Y143R pathway were dependent on the amino acid substitution at position 148 and the secondary mutations in Y143R- or Q148R- or H-containing variants and correlated with reductions in RAL susceptibility and restorations in RC. Our observations in patient viruses were confirmed by analyzing site-directed mutations. In summary, viruses that acquire mutations defining the 143 or 148 escape pathways are less susceptible to RAL and exhibit greater RC than viruses containing 155 pathway mutations. These selective pressures result in the displacement of N155H variants by 143 or 148 variants under continued drug exposure. PMID:22553340

Numerical simulation on behaviour of timber-concrete composite beams in fire

NASA Astrophysics Data System (ADS)

Du, Hao; Hu, Xiamin; Zhang, Bing; Minli, Yao

2017-08-01

This paper established sequentially coupled thermal-mechanical models of timber--concrete composite (TCC) beams by finite element software ANSYS to investigate the fire resistance of TCC beam. Existing experimental results were used to verify the coupled thermal-mechanical model. The influencing parameters consisted of the width of timber beam, the thickness of the concrete slab and the timber board. Based on the numerical results, the effects of these parameters on fire resistance of TCC beams were investigated in detail. The results showed that modeling results agreed well with test results, and verified the reliability of the finite element model. The width of the timber beam had a significant influence on the fire resistance of TCC beams. The fire resistance of TCC beams would be enhanced by increasing the width of timber beam, the thickness of concrete slab and the timber board.

Classic hippocampal sclerosis and hippocampal-onset epilepsy produced by a single “cryptic” episode of focal hippocampal excitation in awake rats

PubMed Central

Norwood, Braxton A.; Bumanglag, Argyle V.; Osculati, Francesco; Sbarbati, Andrea; Marzola, Pasquina; Nicolato, Elena; Fabene, Paolo F.; Sloviter, Robert S.

2010-01-01

In refractory temporal lobe epilepsy, seizures often arise from a shrunken hippocampus exhibiting a pattern of selective neuron loss called “classic hippocampal sclerosis.” No single experimental injury has reproduced this specific pathology, suggesting that hippocampal atrophy might be a progressive “endstage” pathology resulting from years of spontaneous seizures. We posed the alternate hypothesis that classic hippocampal sclerosis results from a single excitatory event that has never been successfully modeled experimentally because convulsive status epilepticus, the insult most commonly used to produce epileptogenic brain injury, is too severe and necessarily terminated before the hippocampus receives the needed duration of excitation. We tested this hypothesis by producing prolonged hippocampal excitation in awake rats without causing convulsive status epilepticus. Two daily 30-minute episodes of perforant pathway stimulation in Sprague-Dawley rats increased granule cell paired-pulse inhibition, decreased epileptiform afterdischarge durations during 8 hours of subsequent stimulation, and prevented convulsive status epilepticus. Similarly, one 8-hour episode of reduced-intensity stimulation in Long-Evans rats, which are relatively resistant to developing status epilepticus, produced hippocampal discharges without causing status epilepticus. Both paradigms immediately produced the extensive neuronal injury that defines classic hippocampal sclerosis, without giving any clinical indication during the insult that an injury was being inflicted. Spontaneous hippocampal-onset seizures began 16–25 days post-injury, before hippocampal atrophy developed, as demonstrated by sequential magnetic resonance imaging. These results indicate that classic hippocampal sclerosis is uniquely produced by a single episode of clinically “cryptic” excitation. Epileptogenic insults may often involve prolonged excitation that goes undetected at the time of injury. PMID:20575073

Mechanism of Tacrine Block at Adult Human Muscle Nicotinic Acetylcholine Receptors

PubMed Central

Prince, Richard J.; Pennington, Richard A.; Sine, Steven M.

2002-01-01

We used single-channel kinetic analysis to study the inhibitory effects of tacrine on human adult nicotinic receptors (nAChRs) transiently expressed in HEK 293 cells. Single channel recording from cell-attached patches revealed concentration- and voltage-dependent decreases in mean channel open probability produced by tacrine (IC50 4.6 μM at −70 mV, 1.6 μM at −150 mV). Two main effects of tacrine were apparent in the open- and closed-time distributions. First, the mean channel open time decreased with increasing tacrine concentration in a voltage-dependent manner, strongly suggesting that tacrine acts as an open-channel blocker. Second, tacrine produced a new class of closings whose duration increased with increasing tacrine concentration. Concentration dependence of closed-times is not predicted by sequential models of channel block, suggesting that tacrine blocks the nAChR by an unusual mechanism. To probe tacrine's mechanism of action we fitted a series of kinetic models to our data using maximum likelihood techniques. Models incorporating two tacrine binding sites in the open receptor channel gave dramatically improved fits to our data compared with the classic sequential model, which contains one site. Improved fits relative to the sequential model were also obtained with schemes incorporating a binding site in the closed channel, but only if it is assumed that the channel cannot gate with tacrine bound. Overall, the best description of our data was obtained with a model that combined two binding sites in the open channel with a single site in the closed state of the receptor. PMID:12198092

Mind the Gap: The Effects of Temporal and Spatial Separation in Localization of Dual Touches on the Hand.

PubMed

Sadibolova, Renata; Tamè, Luigi; Walsh, Eamonn; Longo, Matthew R

2018-01-01

In this study, we aimed to relate the findings from two predominantly separate streams of literature, one reporting on the localization of single touches on the skin, and the other on the distance perception of dual touches. Participants were touched with two points, delivered either simultaneously or separated by a short delay to various locations on their left hand dorsum. They then indicated on a size-matched hand silhouette the perceived locations of tactile stimuli. We quantified the deviations between the actual stimulus grid and the corresponding perceptual map which was constructed from the perceived tactile locations, and we calculated the precision of tactile localization (i.e., the variability across localization attempts). The evidence showed that the dual touches, akin to single touch stimulations, were mislocalized distally and that their variable localization error was reduced near joints, particularly near knuckles. However, contrary to single-touch localization literature, we observed for the dual touches to be mislocalized towards the ulnar side of the hand, particularly when they were presented sequentially. Further, the touches presented in a sequential order were slightly "repelled" from each other and their perceived distance increased, while the simultaneous tactile pairs were localized closer to each other and their distance was compressed. Whereas the sequential touches may have been localized with reference to the body, the compression of tactile perceptual space for simultaneous touches was related in the previous literature to signal summation and inhibition and the low-level factors, including the innervation density and properties of receptive fields (RFs) of somatosensory neurons.

History of antibiotic adaptation influences microbial evolutionary dynamics during subsequent treatment

PubMed Central

Papin, Jason A.

2017-01-01

Antibiotic regimens often include the sequential changing of drugs to limit the development and evolution of resistance of bacterial pathogens. It remains unclear how history of adaptation to one antibiotic can influence the resistance profiles when bacteria subsequently adapt to a different antibiotic. Here, we experimentally evolved Pseudomonas aeruginosa to six 2-drug sequences. We observed drug order–specific effects, whereby adaptation to the first drug can limit the rate of subsequent adaptation to the second drug, adaptation to the second drug can restore susceptibility to the first drug, or final resistance levels depend on the order of the 2-drug sequence. These findings demonstrate how resistance not only depends on the current drug regimen but also the history of past regimens. These order-specific effects may allow for rational forecasting of the evolutionary dynamics of bacteria given knowledge of past adaptations and provide support for the need to consider the history of past drug exposure when designing strategies to mitigate resistance and combat bacterial infections. PMID:28792497

Experimental evaluation of P-Y curves considering liquefaction development.

DOT National Transportation Integrated Search

2010-12-01

This report presents details and findings of a test series conducted on a single pile embedded in homogeneous saturated Nevada sand, which was subjected to sequential dynamic shaking and lateral (inertial-equivalent) loading. This report documents th...

Encoding Sequential Information in Semantic Space Models: Comparing Holographic Reduced Representation and Random Permutation

PubMed Central

Recchia, Gabriel; Sahlgren, Magnus; Kanerva, Pentti; Jones, Michael N.

2015-01-01

Circular convolution and random permutation have each been proposed as neurally plausible binding operators capable of encoding sequential information in semantic memory. We perform several controlled comparisons of circular convolution and random permutation as means of encoding paired associates as well as encoding sequential information. Random permutations outperformed convolution with respect to the number of paired associates that can be reliably stored in a single memory trace. Performance was equal on semantic tasks when using a small corpus, but random permutations were ultimately capable of achieving superior performance due to their higher scalability to large corpora. Finally, “noisy” permutations in which units are mapped to other units arbitrarily (no one-to-one mapping) perform nearly as well as true permutations. These findings increase the neurological plausibility of random permutations and highlight their utility in vector space models of semantics. PMID:25954306

Meta-cognitive online sequential extreme learning machine for imbalanced and concept-drifting data classification.

PubMed

Mirza, Bilal; Lin, Zhiping

2016-08-01

In this paper, a meta-cognitive online sequential extreme learning machine (MOS-ELM) is proposed for class imbalance and concept drift learning. In MOS-ELM, meta-cognition is used to self-regulate the learning by selecting suitable learning strategies for class imbalance and concept drift problems. MOS-ELM is the first sequential learning method to alleviate the imbalance problem for both binary class and multi-class data streams with concept drift. In MOS-ELM, a new adaptive window approach is proposed for concept drift learning. A single output update equation is also proposed which unifies various application specific OS-ELM methods. The performance of MOS-ELM is evaluated under different conditions and compared with methods each specific to some of the conditions. On most of the datasets in comparison, MOS-ELM outperforms the competing methods. Copyright © 2016 Elsevier Ltd. All rights reserved.

Involvement of the Efflux Pumps in Chloramphenicol Selected Strains of Burkholderia thailandensis: Proteomic and Mechanistic Evidence

PubMed Central

Biot, Fabrice V.; Valade, Eric; Garnotel, Eric; Chevalier, Jacqueline; Villard, Claude; Thibault, François M.; Vidal, Dominique R.; Pagès, Jean-Marie

2011-01-01

Burkholderia is a bacterial genus comprising several pathogenic species, including two species highly pathogenic for humans, B. pseudomallei and B. mallei. B. thailandensis is a weakly pathogenic species closely related to both B. pseudomallei and B. mallei. It is used as a study model. These bacteria are able to exhibit multiple resistance mechanisms towards various families of antibiotics. By sequentially plating B. thailandensis wild type strains on chloramphenicol we obtained several resistant variants. This chloramphenicol-induced resistance was associated with resistance against structurally unrelated antibiotics including quinolones and tetracyclines. We functionally and proteomically demonstrate that this multidrug resistance phenotype, identified in chloramphenicol-resistant variants, is associated with the overexpression of two different efflux pumps. These efflux pumps are able to expel antibiotics from several families, including chloramphenicol, quinolones, tetracyclines, trimethoprim and some β-lactams, and present a partial susceptibility to efflux pump inhibitors. It is thus possible that Burkholderia species can develop such adaptive resistance mechanisms in response to antibiotic pressure resulting in emergence of multidrug resistant strains. Antibiotics known to easily induce overexpression of these efflux pumps should be used with discernment in the treatment of Burkholderia infections. PMID:21347382

Antibiotic Resistance and Single-Nucleotide Polymorphism Cluster Grouping Type in a Multinational Sample of Resistant Mycobacterium tuberculosis Isolates▿

PubMed Central

Brimacombe, M.; Hazbon, M.; Motiwala, A. S.; Alland, D.

2007-01-01

A single-nucleotide polymorphism-based cluster grouping (SCG) classification system for Mycobacterium tuberculosis was used to examine antibiotic resistance type and resistance mutations in relationship to specific evolutionary lineages. Drug resistance and resistance mutations were seen across all SCGs. SCG-2 had higher proportions of katG codon 315 mutations and resistance to four drugs. PMID:17846140

The Anti-Methicillin-Resistant Staphylococcus aureus Quinolone WCK 771 Has Potent Activity against Sequentially Selected Mutants, Has a Narrow Mutant Selection Window against Quinolone-Resistant Staphylococcus aureus, and Preferentially Targets DNA Gyrase▿ †

PubMed Central

Bhagwat, Sachin S.; Mundkur, Lakshmi A.; Gupte, Shrikant V.; Patel, Mahesh V.; Khorakiwala, Habil F.

2006-01-01

WCK 771 is a broad-spectrum fluoroquinolone with enhanced activity against quinolone-resistant staphylococci. To understand the impact of the target-level interactions of WCK 771 on its antistaphylococcal pharmacodynamic properties, we determined the MICs for genetically defined mutants and studied the mutant prevention concentrations (MPCs), the frequency of mutation, and the cidality against the wild type and double mutants. There was a twofold increase in the MICs of WCK 771 for single gyrA mutants, indicating that DNA gyrase is its primary target. All first- and second-step mutants selected by WCK 771 revealed gyrA and grlA mutations, respectively. The MICs of WCK 771 and clinafloxacin were found to be superior to those of other quinolones against strains with double and triple mutations. WCK 771 was also cidal for high-density double mutants at low concentrations. WCK 771 and clinafloxacin showed narrow mutant selection windows compared to those of the other quinolones. Against a panel of 50 high-level quinolone-resistant clinical isolates of staphylococci (ciprofloxacin MIC ≥ 16 μg/ml), the WCK 771 MPCs were ≤2 μg/ml for 68% of the strains and ≤4 μg/ml for 28% of the strains. Our results demonstrate that gyrA is the primary target of WCK 771 and that it has pharmacodynamic properties remarkably different from those of quinolones with dual targets (garenoxacin and moxifloxacin) and topoisomerase IV-specific quinolones (trovafloxacin). WCK 771 displayed an activity profile comparable to that of clinafloxacin, a dual-acting quinolone with a high affinity to DNA gyrase. Overall, the findings signify the key role of DNA gyrase in determining the optimal antistaphylococcal features of quinolones. PMID:16940059

Progression-Free and Overall Survival in ALK-Positive NSCLC Patients Treated with Sequential Crizotinib and Ceritinib.

PubMed

Gainor, Justin F; Tan, Daniel S W; De Pas, Tomasso; Solomon, Benjamin J; Ahmad, Aziah; Lazzari, Chiara; de Marinis, Filippo; Spitaleri, Gianluca; Schultz, Katherine; Friboulet, Luc; Yeap, Beow Y; Engelman, Jeffrey A; Shaw, Alice T

2015-06-15

Anaplastic lymphoma kinase (ALK) rearrangements are important therapeutic targets in non-small cell lung cancer (NSCLC) that confer sensitivity to the ALK inhibitors crizotinib and ceritinib. To determine the outcome of sequential treatment with crizotinb and ceritinib, we retrospectively evaluated a cohort of ALK-positive patients treated with both agents. We identified 73 ALK-positive NSCLC patients treated with crizotinib followed by ceritinib at four institutions. Medical records were reviewed to determine overall survival (OS) and progression-free survival (PFS) on crizotinib and ceritinib. Among 73 ALK-positive patients, the median PFS (mPFS) on crizotinib was 8.2 months [95% confidence interval (CI), 7.4-10.6]. The median interval from crizotinib discontinuation to initiation of ceritinib was 25 days (range, 1-694). The mPFS on ceritinib was 7.8 months (6.5-9.1). Among 53 patients with no interval therapies between crizotinib and ceritinib, the mPFS on ceritinib was similar at 7.8 months (5.4-9.8). The median combined PFS for sequential treatment with crizotinib and ceritinib was 17.4 months (15.5-19.4). Among 23 patients who underwent post-crizotinib/pre-ceritinib biopsies, there was no difference in PFS on ceritinib between patients with or without ALK resistance mutations (mPFS 5.8 vs. 6.5 months, respectively; P = 0.510). In the overall study population, median OS was 49.4 months (35.5-63.1). Ceritinib has significant antitumor activity in ALK-positive NSCLC-even when crizotinib immediately precedes treatment with ceritinib (median combined PFS 17.0 months). Additional studies are necessary to further define the impact of specific ALK resistance mutations on duration of response to ceritinib. ©2015 American Association for Cancer Research.

Impact of CTLA-4 blockade in conjunction with metronomic chemotherapy on preclinical breast cancer growth

PubMed Central

Parra, Karla; Valenzuela, Paloma; Lerma, Natzidielly; Gallegos, Alejandra; Reza, Luis C; Rodriguez, Georgialina; Emmenegger, Urban; Di Desidero, Teresa; Bocci, Guido; Felder, Mitchell S; Manciu, Marian; Kirken, Robert A; Francia, Giulio

2017-01-01

Background: Although there are reports that metronomic cyclophosphamide (CTX) can be immune stimulating, the impact of its combination with anti-CTLA-4 immunotherapy for the treatment of cancer remains to be evaluated. Methods: Murine EMT-6/P breast cancer, or its cisplatin or CTX-resistant variants, or CT-26 colon, were implanted into Balb/c mice. Established tumours were monitored for relative growth following treatment with anti-CTLA-4 antibody alone or in combination with; (a) metronomic CTX (ldCTX; 20 mg kg−1 day−1), b) bolus (150 mg kg−1) plus ldCTX, or (c) sequential treatment with gemcitabine (160 mg kg−1 every 3 days). Results: EMT-6/P tumours responded to anti-CTLA-4 therapy, but this response was less effective when combined with bolus plus ldCTX. Anti-CTLA-4 could be effectively combined with either ldCTX (without a bolus), or with regimens of either sequential or concomitant gemcitabine, including in orthotopic EMT-6 tumours, and independently of the schedule of drug administration. Tumour responses were confirmed with CT-26 tumours but were less pronounced in drug-resistant EMT-6/CTX or EMT-6/DDP tumour models than in the parent tumour. A number of tumour bearing mice developed spontaneous metastases under continuous therapy. The majority of cured mice rejected tumour re-challenges. Conclusions: Metronomic CTX can be combined with anti-CTLA-4 therapy, but this therapy is impaired by concomitant bolus CTX. Sequential therapy of anti-CTLA-4 followed by gemcitabine is effective in chemotherapy-naive tumours, although tumour relapses can occur, in some cases accompanied by the development of spontaneous metastases. PMID:28056464

Single-room usage patterns and allocation decision-making in an Australian public hospital: a sequential exploratory study.

PubMed

Bloomer, Melissa J; Lee, Susan F; Lewis, David P; Biro, Mary Anne; Moss, Cheryle

2016-08-01

The aims are to (1) measure occupancy rates of single and shared rooms; (2) compare single room usage patterns and (3) explore the practice, rationale and decision-making processes associated with single rooms; across one Australian public health service. There is a tendency in Australia and internationally to increase the proportion of single patient rooms in hospitals. To date there have been no Australian studies that investigate the use of single rooms in clinical practice. This study used a sequential exploratory design with data collected in 2014. A descriptive survey was used to measure the use of single rooms across a two-week time frame. Semi-structured interviews were undertaken with occupancy decision-makers to explore the practices, rationale decision-making process associated with single-room allocation. Total bed occupancy did not fall below 99·4% during the period of data collection. Infection control was the primary reason for patients to be allocated to a single room, however, the patterns varied according to ward type and single-room availability. For occupancy decision-makers, decisions about patient allocation was a complex and challenging process, influenced and complicated by numerous factors including occupancy rates, the infection status of the patient/s, funding and patient/family preference. Bed moves were common resulting from frequent re-evaluation of need. Apart from infection control mandates, there was little tangible evidence to guide decision-making about single-room allocation. Further work is necessary to assist nurses in their decision-making. There is a trend towards increasing the proportion of single rooms in new hospital builds. Coupled with the competing clinical demands for single room care, this study highlights the complexity of nursing decision-making about patient allocation to single rooms, an issue urgently requiring further attention. © 2016 John Wiley & Sons Ltd.

The repertoire of resistance: Non-compliance with directives in Milgram's 'obedience' experiments.

PubMed

Hollander, Matthew M

2015-09-01

This paper is the first extensive conversation-analytic study of resistance to directives in one of the most controversial series of experiments in social psychology, Stanley Milgram's 1961-1962 study of 'obedience to authority'. As such, it builds bridges between interactionist and experimental areas of social psychology that do not often communicate with one another. Using as data detailed transcripts of 117 of the original sessions representing five experimental conditions, I show how research participants' resistance to experimental progressivity takes shape against a background of directive/response and complaint/remedy conversational sequences--sequence types that project opposing and competing courses of action. In local contexts of competing sequential relevancies, participants mobilize six forms of resistance to the confederate experimenter's directives to continue. These range along a continuum of explicitness, from relatively subtle resistance that momentarily postpones continuation to techniques for explicitly trying to stop the experiment. Although both 'obedient'- and 'defiant'-outcome participants use all six of the forms, evidence is provided suggesting precisely how members of the two groups differ in manner and frequency of resistance. © 2015 The British Psychological Society.

Inactivation of microbiota from urban wastewater by single and sequential electrocoagulation and electro-Fenton treatments.

PubMed

Anfruns-Estrada, Eduard; Bruguera-Casamada, Carmina; Salvadó, Humbert; Brillas, Enric; Sirés, Ignasi; Araujo, Rosa M

2017-12-01

This work aims at comparing the ability of two kinds of electrochemical technologies, namely electrocoagulation (EC) and electro-Fenton (EF), to disinfect primary and secondary effluents from municipal wastewater treatment plants. Heterotrophic bacteria, Escherichia coli, enterococci, Clostridium perfringens spores, somatic coliphages and eukaryotes (amoebae, flagellates, ciliates and metazoa) were tested as indicator microorganisms. EC with an Fe/Fe cell at 200 A m -2 and natural pH allowed >5 log unit removal of E. coli and final concentration below 1 bacteria mL -1 of coliphages and eukaryotes from both effluents in ca. 60 min, whereas heterotrophic bacteria, enterococci and spores were more resistant. A larger removal was obtained for the primary effluent, probably because the flocs remove higher amount of total organic carbon (TOC), entrapping more easily the microbiota. EF with a boron-doped diamond (BDD) anode and an air-diffusion cathode that produces H 2 O 2 on site was first performed at pH 3.0, with large or even total inactivation of microorganisms within 30 min. A more effective microorganism removal was attained as compared to EC thanks to • OH formed from Fenton's reaction. A quicker disinfection was observed for the secondary effluent owing to its lower TOC content, allowing the attack of greater quantities of electrogenerated oxidants on microorganisms. Wastewater disinfection by EF was also feasible at natural pH (∼7), showing similar abatement of active microorganisms as a result of the synergistic action of generated oxidants like active chlorine and coagulation with iron hydroxides. A sequential EC/EF treatment (30 min each) was more effective for a combined decontamination and disinfection of urban wastewater. Copyright © 2017 Elsevier Ltd. All rights reserved.

Memory strength and lineup presentation moderate effects of administrator influence on mistaken identifications.

PubMed

Zimmerman, David M; Chorn, Jacqueline Austin; Rhead, Lindsey M; Evelo, Andrew J; Kovera, Margaret Bull

2017-12-01

Administrator/witness pairs (N = 313) were randomly assigned to target-absent lineups in a 2 (Suspect/Perpetrator Similarity: High Suspect Similarity vs. Low Suspect Similarity) × 2 (Retention Interval: 30 min vs. 1 week) × 2 (Lineup Presentation: Simultaneous vs. Sequential) × 2 (Administrator Knowledge: Single-Blind vs. Double-Blind) factorial design to test whether suspect similarity and memory strength constrain interpersonal expectancy effects on eyewitness identification accuracy. Administrators who knew which lineup member was the suspect (single-blind) or who administered simultaneous lineups were more likely to emit verbal and nonverbal behaviors that suggested to the witness who the suspect was. Additionally, single-blind administrators exerted more pressure on witnesses to choose the suspect as opposed to fillers. Administrator knowledge interacted with retention interval and lineup presentation to influence mistaken identifications of innocent suspects; witnesses were more likely to mistakenly identify an innocent suspect from single-blind than double-blind lineups when witness retention intervals were long and photographs were presented simultaneously. Contrary to our predictions, suspect/perpetrator similarity did not interact with other manipulated variables to influence identification decisions. Both sequential and double-blind procedures should be used to reduce the use of suggestive behavior during lineup administration. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Pharmacokinetics and Safety of Intravenous Murepavadin Infusion in Healthy Adult Subjects Administered Single and Multiple Ascending Doses.

PubMed

Wach, Achim; Dembowsky, Klaus; Dale, Glenn E

2018-04-01

Murepavadin is the first in class of the outer membrane protein-targeting antibiotics (OMPTA) and a pathogen-specific peptidomimetic antibacterial with a novel, nonlytic mechanism of action targeting Pseudomonas aeruginosa Murepavadin is being developed for the treatment of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). The pharmacokinetics (PK) and safety of single and multiple doses of murepavadin were investigated in healthy male subjects. Part A of the study was a double-blind, randomized, placebo-controlled, single-ascending-dose investigation in 10 sequential cohorts where each cohort comprised 6 healthy male subjects; 4 subjects were randomized to murepavadin, and 2 subjects were randomized to placebo. Part B was a double-blind, randomized, placebo-controlled, multiple-ascending-dose investigation in 3 sequential cohorts. After a single dose of murepavadin, the geometric mean half-life (2.52 to 5.30 h), the total clearance (80.1 to 114 ml/h/kg), and the volume of distribution (415 to 724 ml/kg) were consistent across dose levels. The pharmacokinetics of the dosing regimens evaluated were dose proportional and linear. Murepavadin was well tolerated, adverse events were transient and generally mild, and no dose-limiting toxicity was identified. Copyright © 2018 American Society for Microbiology.

Quantum Otto engine using a single ion and a single thermal bath

NASA Astrophysics Data System (ADS)

Biswas, Asoka; Chand, Suman

2016-05-01

Quantum heat engines employ a quantum system as the working fluid, that gives rise to large work efficiency, beyond the limit for classical heat engines. Existing proposals for implementing quantum heat engines require that the system interacts with the hot bath and the cold bath (both modelled as a classical system) in an alternative fashion and therefore assumes ability to switch off the interaction with the bath during a certain stage of the heat-cycle. However, it is not possible to decouple a quantum system from its always-on interaction with the bath without use of complex pulse sequences. It is also hard to identify two different baths at two different temperatures in quantum domain, that sequentially interact with the system. Here, we show how to implement a quantum Otto engine without requiring to decouple the bath in a sequential manner. This is done by considering a single thermal bath, coupled to a single trapped ion. The electronic degree of freedom of the ion is chosen as a two-level working fluid while the vibrational degree of freedom plays the role of the cold bath. Measuring the electronic state mimics the release of heat into the cold bath. Thus, our model is fully quantum and exhibits very large work efficiency, asymptotically close to unity.

Moving Synergistically Acting Drug Combinations to the Clinic by Comparing Sequential versus Simultaneous Drug Administrations.

PubMed

Dinavahi, Saketh S; Noory, Mohammad A; Gowda, Raghavendra; Drabick, Joseph J; Berg, Arthur; Neves, Rogerio I; Robertson, Gavin P

2018-03-01

Drug combinations acting synergistically to kill cancer cells have become increasingly important in melanoma as an approach to manage the recurrent resistant disease. Protein kinase B (AKT) is a major target in this disease but its inhibitors are not effective clinically, which is a major concern. Targeting AKT in combination with WEE1 (mitotic inhibitor kinase) seems to have potential to make AKT-based therapeutics effective clinically. Since agents targeting AKT and WEE1 have been tested individually in the clinic, the quickest way to move the drug combination to patients would be to combine these agents sequentially, enabling the use of existing phase I clinical trial toxicity data. Therefore, a rapid preclinical approach is needed to evaluate whether simultaneous or sequential drug treatment has maximal therapeutic efficacy, which is based on a mechanistic rationale. To develop this approach, melanoma cell lines were treated with AKT inhibitor AZD5363 [4-amino- N -[(1 S )-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7 H -pyrrolo[2,3- d ]pyrimidin-4-yl)piperidine-4-carboxamide] and WEE1 inhibitor AZD1775 [2-allyl-1-(6-(2-hydroxypropan-2-yl)pyridin-2-yl)-6-((4-(4-methylpiperazin-1-yl)phenyl)amino)-1 H -pyrazolo[3,4- d ]pyrimidin-3(2 H )-one] using simultaneous and sequential dosing schedules. Simultaneous treatment synergistically reduced melanoma cell survival and tumor growth. In contrast, sequential treatment was antagonistic and had a minimal tumor inhibitory effect compared with individual agents. Mechanistically, simultaneous targeting of AKT and WEE1 enhanced deregulation of the cell cycle and DNA damage repair pathways by modulating transcription factors p53 and forkhead box M1, which was not observed with sequential treatment. Thus, this study identifies a rapid approach to assess the drug combinations with a mechanistic basis for selection, which suggests that combining AKT and WEE1 inhibitors is needed for maximal efficacy. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Comparison of Sequential Drug Release in Vitro and in Vivo

PubMed Central

Sundararaj, Sharath C.; Al-Sabbagh, Mohanad; Rabek, Cheryl L.; Dziubla, Thomas D.; Thomas, Mark V.; Puleo, David A.

2015-01-01

Development of drug delivery devices typically involves characterizing in vitro release performance with the inherent assumption that this will closely approximate in vivo performance. Yet, as delivery devices become more complex, for instance with a sequential drug release pattern, it is important to confirm that in vivo properties correlate with the expected “programming” achieved in vitro. In this work, a systematic comparison between in vitro and in vivo biomaterial erosion and sequential release was performed for a multilayered association polymer system comprising cellulose acetate phthalate and Pluronic F-127. After assessing the materials during incubation in phosphate-buffered saline, devices were implanted supracalvarially in rats. Devices with two different doses and with different erosion rates were harvested at increasing times post-implantation, and the in vivo thickness loss, mass loss, and the drug release profiles were compared with their in vitro counterparts. The sequential release of four different drugs observed in vitro was successfully translated to in vivo conditions. Results suggest, however, that the total erosion time of the devices was longer and release rates of the four drugs were different, with drugs initially released more quickly and then more slowly in vivo. Whereas many comparative studies of in vitro and in vivo drug release from biodegradable polymers involved a single drug, the present research demonstrated that sequential release of four drugs can be maintained following implantation. PMID:26111338

Comparison of human embryomorphokinetic parameters in sequential or global culture media.

PubMed

Kazdar, Nadia; Brugnon, Florence; Bouche, Cyril; Jouve, Guilhem; Veau, Ségolène; Drapier, Hortense; Rousseau, Chloé; Pimentel, Céline; Viard, Patricia; Belaud-Rotureau, Marc-Antoine; Ravel, Célia

2017-08-01

A prospective study on randomized patients was conducted to determine how morphokinetic parameters are altered in embryos grown in sequential versus global culture media. Eleven morphokinetic parameters of 160 single embryos transferred were analyzed by time lapse imaging involving two University-affiliated in vitro fertilization (IVF) centers. We found that the fading of the two pronuclei occurred earlier in global (22.56±2.15 hpi) versus sequential media (23.63±2.71 hpi; p=0.0297). Likewise, the first cleavage started earlier at 24.52±2.33 hpi vs 25.76±2.95 hpi (p=0.0158). Also, the first cytokinesis was shorter in global medium, lasting 18±10.2 minutes in global versus 36±37.8 minutes in sequential culture medium (p <0.0001). We also observed a significant shortening in the duration of the 2-cell stage in sequential medium: 10.64 h±2.75 versus 11.66 h±1.11 in global medium (p=0.0225) which suggested a faster progression of the embryos through their first mitotic cell cycle. In conclusion, morphokinetic analysis of human embryos by Time lapse imaging reveals significant differences in five kinetic variables according to culture medium. Our study highlights the need to adapt morphokinetic analysis accordingly to the type of media used to best support human early embryo development.

Sequential Voluntary Cough and Aspiration or Aspiration Risk in Parkinson’s Disease

PubMed Central

Hegland, Karen Wheeler; Okun, Michael S.; Troche, Michelle S.

2015-01-01

Background Disordered swallowing, or dysphagia, is almost always present to some degree in people with Parkinson’s disease (PD), either causing aspiration or greatly increasing the risk for aspiration during swallowing. This likely contributes to aspiration pneumonia, a leading cause of death in this patient population. Effective airway protection is dependent upon multiple behaviors, including cough and swallowing. Single voluntary cough function is disordered in people with PD and dysphagia. However, the appropriate response to aspirate material is more than one cough, or sequential cough. The goal of this study was to examine voluntary sequential coughing in people with PD, with and without dysphagia. Methods Forty adults diagnosed with idiopathic PD produced two trials of sequential voluntary cough. The cough airflows were obtained using pneumotachograph and facemask and subsequently digitized and recorded. All participants received a modified barium swallow study as part of their clinical care, and the worst penetration–aspiration score observed was used to determine whether the patient had dysphagia. Results There were significant differences in the compression phase duration, peak expiratory flow rates, and amount of air expired of the sequential cough produced by participants with and without dysphagia. Conclusions The presence of dysphagia in people with PD is associated with disordered cough function. Sequential cough, which is important in removing aspirate material from large- and smaller-diameter airways, is also impaired in people with PD and dysphagia compared with those without dysphagia. There may be common neuroanatomical substrates for cough and swallowing impairment in PD leading to the co-occurrence of these dysfunctions. PMID:24792231

Multi-Toxin Resistance Enables Pink Bollworm Survival on Pyramided Bt Cotton

PubMed Central

Fabrick, Jeffrey A.; Unnithan, Gopalan C.; Yelich, Alex J.; DeGain, Ben; Masson, Luke; Zhang, Jie; Carrière, Yves; Tabashnik, Bruce E.

2015-01-01

Transgenic crops producing Bacillus thuringiensis (Bt) proteins kill key insect pests, providing economic and environmental benefits. However, the evolution of pest resistance threatens the continued success of such Bt crops. To delay or counter resistance, transgenic plant “pyramids” producing two or more Bt proteins that kill the same pest have been adopted extensively. Field populations of the pink bollworm (Pectinophora gossypiella) in the United States have remained susceptible to Bt toxins Cry1Ac and Cry2Ab, but field-evolved practical resistance to Bt cotton producing Cry1Ac has occurred widely in India. Here we used two rounds of laboratory selection to achieve 18,000- to 150,000-fold resistance to Cry2Ab in pink bollworm. Inheritance of resistance to Cry2Ab was recessive, autosomal, conferred primarily by one locus, and independent of Cry1Ac resistance. We created a strain with high resistance to both toxins by crossing the Cry2Ab-resistant strain with a Cry1Ac-resistant strain, followed by one selection with Cry2Ab. This multi-toxin resistant strain survived on field-collected Bt cotton bolls producing both toxins. The results here demonstrate the risk of evolution of resistance to pyramided Bt plants, particularly when toxins are deployed sequentially and refuges are scarce, as seen with Bt cotton and pink bollworm in India. PMID:26559899

First-line treatment of Helicobacter pylori in Lebanon: Comparison of bismuth-containing quadruple therapy versus 14-days sequential therapy.

PubMed

Tarhini, Mahdi; Fayyad-Kazan, Mohammad; Fayyad-Kazan, Hussein; Mokbel, Mahmoud; Nasreddine, Mohammad; Badran, Bassam; Kchour, Ghada

2018-04-01

Helicobacter Pylori (H. Pylori) is the most common cause of peptic ulcer disease (PUD) and represents a strong risk factor for gastric cancer. Treatment of H. Pylori is, therefore, a persistent need to avoid serious medical complications. Resistance to antibiotics remains to be the major challenge for H. Pylori eradication. In this study, we determined the prevalence of H. pylori infection and evaluated H. pylori eradication efficacy of bismuth-containing quadruple therapy (Pylera) versus 14-days sequential therapy in treatment naïve-Lebanese patients. 1030 patients, showing symptoms of peptic ulcer (PU) and gastritis, underwent 14 C-Urea Breath Test and esophagogastroduodenoscopy to examine H. Pylori infection and gastrointestinal disorders. Among the H. Pylori-positive patients 60 individuals were randomly selected, separated into two groups (each consisting of 30 patients) and treated with either bismuth-containing quadruple therapy or 14-days sequential therapy. We show that of the 1050 patients tested: 46.2% were H. pylori-positive, 55% had gastritis, 46.2% had both gastritis and H. pylori infection, 8.8% had gastritis but no H. pylori infection, 44.9% had neither gastritis nor H. pylori infection. Following the 14-days sequential therapy, the eradication rate was significantly higher than that obtained upon using bismuth-containing quadruple therapy [80% (24/30) versus 50% (15/30), χ 2  = 5.93, P = 0.015]. In conclusion, we determined H. pylori and gastritis prevalence among Lebanese PU-patients and showed that 14-days sequential therapy is more efficient than bismuth-containing quadruple therapy in terms of H. Pylori-eradication. Published by Elsevier Ltd.

Development of Potent Antiviral Drugs Inspired by Viral Hexameric DNA-Packaging Motors with Revolving Mechanism

PubMed Central

Pi, Fengmei; Zhao, Zhengyi; Chelikani, Venkata; Yoder, Kristine; Kvaratskhelia, Mamuka

2016-01-01

The intracellular parasitic nature of viruses and the emergence of antiviral drug resistance necessitate the development of new potent antiviral drugs. Recently, a method for developing potent inhibitory drugs by targeting biological machines with high stoichiometry and a sequential-action mechanism was described. Inspired by this finding, we reviewed the development of antiviral drugs targeting viral DNA-packaging motors. Inhibiting multisubunit targets with sequential actions resembles breaking one bulb in a series of Christmas lights, which turns off the entire string. Indeed, studies on viral DNA packaging might lead to the development of new antiviral drugs. Recent elucidation of the mechanism of the viral double-stranded DNA (dsDNA)-packaging motor with sequential one-way revolving motion will promote the development of potent antiviral drugs with high specificity and efficiency. Traditionally, biomotors have been classified into two categories: linear and rotation motors. Recently discovered was a third type of biomotor, including the viral DNA-packaging motor, beside the bacterial DNA translocases, that uses a revolving mechanism without rotation. By analogy, rotation resembles the Earth's rotation on its own axis, while revolving resembles the Earth's revolving around the Sun (see animations at http://rnanano.osu.edu/movie.html). Herein, we review the structures of viral dsDNA-packaging motors, the stoichiometries of motor components, and the motion mechanisms of the motors. All viral dsDNA-packaging motors, including those of dsDNA/dsRNA bacteriophages, adenoviruses, poxviruses, herpesviruses, mimiviruses, megaviruses, pandoraviruses, and pithoviruses, contain a high-stoichiometry machine composed of multiple components that work cooperatively and sequentially. Thus, it is an ideal target for potent drug development based on the power function of the stoichiometries of target complexes that work sequentially. PMID:27356896

Depth treatment of coal-chemical engineering wastewater by a cost-effective sequential heterogeneous Fenton and biodegradation process.

PubMed

Fang, Yili; Yin, Weizhao; Jiang, Yanbin; Ge, Hengjun; Li, Ping; Wu, Jinhua

2018-05-01

In this study, a sequential Fe 0 /H 2 O 2 reaction and biological process was employed as a low-cost depth treatment method to remove recalcitrant compounds from coal-chemical engineering wastewater after regular biological treatment. First of all, a chemical oxygen demand (COD) and color removal efficiency of 66 and 63% was achieved at initial pH of 6.8, 25 mmol L -1 of H 2 O 2 , and 2 g L -1 of Fe 0 in the Fe 0 /H 2 O 2 reaction. According to the gas chromatography-mass spectrometer (GC-MS) and gas chromatography-flame ionization detector (GC-FID) analysis, the recalcitrant compounds were effectively decomposed into short-chain organic acids such as acetic, propionic, and butyric acids. Although these acids were resistant to the Fe 0 /H 2 O 2 reaction, they were effectively eliminated in the sequential air lift reactor (ALR) at a hydraulic retention time (HRT) of 2 h, resulting in a further decrease of COD and color from 120 to 51 mg L -1 and from 70 to 38 times, respectively. A low operational cost of 0.35 $ m -3 was achieved because pH adjustment and iron-containing sludge disposal could be avoided since a total COD and color removal efficiency of 85 and 79% could be achieved at an original pH of 6.8 by the above sequential process with a ferric ion concentration below 0.8 mg L -1 after the Fe 0 /H 2 O 2 reaction. It indicated that the above sequential process is a promising and cost-effective method for the depth treatment of coal-chemical engineering wastewaters to satisfy discharge requirements.

Randomized Controlled Trial for Helicobacter pylori Eradication in a Naive Portuguese Population: Is Sequential Treatment Superior to Triple Therapy in Real World Clinical Setting?

PubMed

Boal Carvalho, Pedro; Magalhães, Joana; Dias de Castro, Francisca; Rosa, Bruno; Cotter, José

2017-03-31

Helicobacter pylori eradication has become increasingly difficult as resistances to several antibiotics develop. We aimed to compare Helicobacter pylori eradication rates between triple therapy and sequential therapy in a naive Portuguese population. Prospective randomized trial including consecutive patients referred for first-line Helicobacter pylori eradication treatment. previous gastric surgery/neoplasia, pregnancy/lactancy, allergy to any of the drugs. The compared eradication regimens were triple therapy (pantoprazol, amoxicillin and clarithromycin 12/12 hours, 14 days) and sequential therapy (pantoprazol 12/12 hours for 10 days, amoxicillin 12/12 hours for days 1 - 5 and clarithromycin plus metronidazol 12/12 hours during days 6 - 10). Eradication success was confirmed with urea breath test. Statistical analysis was performed with SPSS v21.0 and a p-value < 0.05 was considered statistically significant. Included 60 patients, 39 (65%) female with mean age 52 years (SD ± 14.3). Treatment groups were homogeneous for gender, age, indication for treatment and smoking status. No statistical differences were encountered between sequential and triple therapy eradication rates (86.2% vs 77.4%, p = 0.379), global eradication rate was 82%. Tobacco consumption was associated with a significantly lower eradication success (54.5 vs 87.8%, p = 0.022). In this randomized controlled trial in a naive Portuguese population, we found a satisfactory global Helicobacter pylori eradication rate of 82%, with no statistical differences observed in the efficacy of the treatment between triple and sequential regimens. These results support the use of either therapy for the first-line eradication of Helicobacter pylori.

Total hepatocellular disposition profiling of rosuvastatin and pitavastatin in sandwich-cultured human hepatocytes.

PubMed

Kanda, Katsuhiro; Takahashi, Ryosuke; Yoshikado, Takashi; Sugiyama, Yuichi

2018-04-09

This study describes the total disposition profiling of rosuvastatin (RSV) and pitavastatin (PTV) using a single systematic procedure called D-PREX (Disposition Profile Exploration) in sandwich-cultured human hepatocytes (SCHH). The biliary excretion fractions of both statins were clearly observed, which were significantly decreased dependent on the concentration of Ko143, an inhibitor for breast cancer resistance protein (BCRP). Ko143 also decreased the basolateral efflux fraction of RSV, whereas that of PTV was not significantly affected. To understand these phenomena, effects of Ko143 on biliary excretion (BCRP and multidrug resistance-associated protein (MRP) 2) and basolateral efflux (MRP3 and MRP4) transporters were examined using transporter-expressing membrane vesicles. BCRP, MRP3 and MRP4-mediated transport of RSV was observed, and Ko143 inhibited these transporters except MRP3. BCRP and MRP4 also mediated the transport of PTV, but the Ko143-mediated inhibition was only clear for BCRP. These results might explain the Ko143-mediated complete and partial inhibition of the biliary excretion and the basolateral efflux of RSV, respectively, in SCHH. In conclusion, D-PREX with sequential sampling of supernatants prior to cell lysis enables the evaluation of total drug disposition profiles resulting from complex interplays of intracellular pathways, which would provide high-throughput evaluation of drug disposition during drug discovery. Copyright © 2018 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Fracture Resistance of Retreated Roots Using Different Retreatment Systems

PubMed Central

Er, Kursat; Tasdemir, Tamer; Siso, Seyda Herguner; Celik, Davut; Cora, Sabri

2011-01-01

Objectives: This study was designed to evaluate the fracture resistance of retreated roots using different rotary retreatment systems. Methods: Forty eight freshly extracted human canine teeth with single straight root canals were instrumented sequentially increasing from size 30 to a size 55 using K-files whit a stepback technique. The teeth were randomly divided into three experimental and one control groups of 12 specimens each. The root canals were filled using cold lateral compaction of gutta-percha and AH Plus (Dentsply Detrey, Konstanz, Germany) sealer in experimental groups. Removal of gutta-percha was performed with the following devices and techniques: ProTaper Universal (Dentsply Maillefer, Ballaigues, Switzerland), R-Endo (Micro-Mega, Besançon, France), and Mtwo (Sweden & Martina, Padova, Italy) rotary retreatment systems. Control group specimens were only instrumented, not filled or retreated. The specimens were then mounted in copper rings, were filled with a self-curing polymethylmethacrylate resin, and the force required to cause vertical root fracture was measured using a universal testing device. The force of fracture of the roots was recorded and the results in the various groups were compared. Statistical analysis was accomplished by one-way ANOVA and a post hoc Tukey tests. Results: There were statistically significant differences between the control and experimental groups (P<.05). However, there were no significant differences among the experimental groups. Conclusions: Based on the results, all rotary retreatment techniques used in this in vitro study produced similar root weakness. PMID:21912497

The genetic basis of new treatment modalities in melanoma.

PubMed

Kunz, Manfred

2015-01-01

In recent years, intracellular signal transduction via RAS-RAF-MEK-ERK has been successfully targeted in new treatment approaches for melanoma using small molecule inhibitors against activated BRAF (V600E mutation) and activated MEK1/2. Also mutated c-KIT has been identified as a promising target. Meanwhile, evidence has been provided that combinations between BRAF inhibitors and MEK1/2 inhibitors are more promising than single-agent treatments. Moreover, new treatment algorithms favor sequential treatment using BRAF inhibitors and newly developed immunotherapies targeting common T lymphocyte antigen 4 (CTLA-4) or programmed cell death 1 (PD-1). In depth molecular analyses have uncovered new mechanisms of treatment resistance and recurrence, which may impact on future treatment decisions. Moreover, next-generation sequencing data have shown that recurrent lesions harbor specific genetic aberrations. At the same time, high throughput sequencing studies of melanoma unraveled a series of new treatment candidates for future treatment approaches such as ERBB4, GRIN2A, GRM3, and RAC1. More recent bioinformatic technologies provided genetic evidence for extensive tumor heterogeneity and tumor clonality of solid tumors, which might also be of relevance for melanoma. However, these technologies have not yet been applied to this tumor. In this review, an overview on the genetic basis of current treatment of melanoma, treatment resistance and recurrences including new treatment perspectives based on recent high-throughput sequencing data is provided. Moreover, future aspects of individualized treatment based on each patient's individual mutational landscape are discussed.

Endogenous Sequential Cortical Activity Evoked by Visual Stimuli

PubMed Central

Miller, Jae-eun Kang; Hamm, Jordan P.; Jackson, Jesse; Yuste, Rafael

2015-01-01

Although the functional properties of individual neurons in primary visual cortex have been studied intensely, little is known about how neuronal groups could encode changing visual stimuli using temporal activity patterns. To explore this, we used in vivo two-photon calcium imaging to record the activity of neuronal populations in primary visual cortex of awake mice in the presence and absence of visual stimulation. Multidimensional analysis of the network activity allowed us to identify neuronal ensembles defined as groups of cells firing in synchrony. These synchronous groups of neurons were themselves activated in sequential temporal patterns, which repeated at much higher proportions than chance and were triggered by specific visual stimuli such as natural visual scenes. Interestingly, sequential patterns were also present in recordings of spontaneous activity without any sensory stimulation and were accompanied by precise firing sequences at the single-cell level. Moreover, intrinsic dynamics could be used to predict the occurrence of future neuronal ensembles. Our data demonstrate that visual stimuli recruit similar sequential patterns to the ones observed spontaneously, consistent with the hypothesis that already existing Hebbian cell assemblies firing in predefined temporal sequences could be the microcircuit substrate that encodes visual percepts changing in time. PMID:26063915

40 CFR 53.35 - Test procedure for Class II and Class III methods for PM2.5 and PM-2.5

Code of Federal Regulations, 2010 CFR

2010-07-01

... reference method samplers shall be of single-filter design (not multi-filter, sequential sample design... and multiplicative bias (comparative slope and intercept). (1) For each test site, calculate the mean...

40 CFR 53.35 - Test procedure for Class II and Class III methods for PM2.5 and PM-2.5

Code of Federal Regulations, 2011 CFR

2011-07-01

... reference method samplers shall be of single-filter design (not multi-filter, sequential sample design... and multiplicative bias (comparative slope and intercept). (1) For each test site, calculate the mean...

40 CFR 53.35 - Test procedure for Class II and Class III methods for PM2.5 and PM−2.5.

Code of Federal Regulations, 2012 CFR

2012-07-01

... reference method samplers shall be of single-filter design (not multi-filter, sequential sample design... and multiplicative bias (comparative slope and intercept). (1) For each test site, calculate the mean...

Sequential episodes of ethylene glycol poisoning in the same person.

PubMed

Sugunaraj, Jaya Prakash; Thakur, Lokendra Kumar; Jha, Kunal Kishor; Bucaloiu, Ion Dan

2017-05-27

Ethylene glycol is a common alcohol found in many household products such as household hard surface cleaner, paints, varnish, auto glass cleaner and antifreeze. While extremely toxic and often fatal on ingestion, few cases with early presentation by the patient have resulted in death; thus, rapid diagnosis is paramount to effectively treating ethylene glycol poisoning. In this study, we compare two sequential cases of ethylene glycol poisoning in a single individual, which resulted in strikingly different outcomes. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

A fluidic diode, valves, and a sequential-loading circuit fabricated on layered paper.

PubMed

Chen, Hong; Cogswell, Jeremy; Anagnostopoulos, Constantine; Faghri, Mohammad

2012-08-21

Current microfluidic paper-based devices lack crucial components for fluid manipulation. We created a fluidic diode fabricated entirely on a single layer of paper to control the wicking of fluids. The fluidic diode is a two-terminal component that promotes or stops wicking along a paper channel. We further constructed a trigger and a delay valve based on the fluidic diode. Furthermore, we demonstrated a high-level functional circuit, consisting of a diode and a delay valve, to manipulate two fluids in a sequential manner. Our study provides new, transformative tools to manipulate fluid in microfluidic paper-based devices.

Binding intensity and metal partitioning in soils affected by mining and smelting activities in Minas Gerais, Brazil.

PubMed

Lopes, G; Costa, E T S; Penido, E S; Sparks, D L; Guilherme, L R G

2015-09-01

Mining and smelting activities are potential sources of heavy metal contamination, which pose a threat to human health and ecological systems. This study investigated single and sequential extractions of Zn, Pb, and Cd in Brazilian soils affected by mining and smelting activities. Soils from a Zn mining area (soils A, B, C, D, E, and the control soil) and a tailing from a smelting area were collected in Minas Gerais state, Brazil. The samples were subjected to single (using Mehlich I solution) and sequential extractions. The risk assessment code (RAC), the redistribution index (U ts ), and the reduced partition index (I R ) have been applied to the sequential extraction data. Zinc and Cd, in soil samples from the mining area, were found mainly associated with carbonate forms. This same pattern did not occur for Pb. Moreover, the Fe-Mn oxides and residual fractions had important contributions for Zn and Pb in those soils. For the tailing, more than 70 % of Zn and Cd were released in the exchangeable fraction, showing a much higher mobility and availability of these metals at this site, which was also supported by results of RAC and I R . These differences in terms of mobility might be due to different chemical forms of the metals in the two sites, which are attributable to natural occurrence as well as ore processing.

General Methods for Analysis of Sequential “n-step” Kinetic Mechanisms: Application to Single Turnover Kinetics of Helicase-Catalyzed DNA Unwinding

PubMed Central

Lucius, Aaron L.; Maluf, Nasib K.; Fischer, Christopher J.; Lohman, Timothy M.

2003-01-01

Helicase-catalyzed DNA unwinding is often studied using “all or none” assays that detect only the final product of fully unwound DNA. Even using these assays, quantitative analysis of DNA unwinding time courses for DNA duplexes of different lengths, L, using “n-step” sequential mechanisms, can reveal information about the number of intermediates in the unwinding reaction and the “kinetic step size”, m, defined as the average number of basepairs unwound between two successive rate limiting steps in the unwinding cycle. Simultaneous nonlinear least-squares analysis using “n-step” sequential mechanisms has previously been limited by an inability to float the number of “unwinding steps”, n, and m, in the fitting algorithm. Here we discuss the behavior of single turnover DNA unwinding time courses and describe novel methods for nonlinear least-squares analysis that overcome these problems. Analytic expressions for the time courses, fss(t), when obtainable, can be written using gamma and incomplete gamma functions. When analytic expressions are not obtainable, the numerical solution of the inverse Laplace transform can be used to obtain fss(t). Both methods allow n and m to be continuous fitting parameters. These approaches are generally applicable to enzymes that translocate along a lattice or require repetition of a series of steps before product formation. PMID:14507688

General methods for analysis of sequential "n-step" kinetic mechanisms: application to single turnover kinetics of helicase-catalyzed DNA unwinding.

PubMed

Lucius, Aaron L; Maluf, Nasib K; Fischer, Christopher J; Lohman, Timothy M

2003-10-01

Helicase-catalyzed DNA unwinding is often studied using "all or none" assays that detect only the final product of fully unwound DNA. Even using these assays, quantitative analysis of DNA unwinding time courses for DNA duplexes of different lengths, L, using "n-step" sequential mechanisms, can reveal information about the number of intermediates in the unwinding reaction and the "kinetic step size", m, defined as the average number of basepairs unwound between two successive rate limiting steps in the unwinding cycle. Simultaneous nonlinear least-squares analysis using "n-step" sequential mechanisms has previously been limited by an inability to float the number of "unwinding steps", n, and m, in the fitting algorithm. Here we discuss the behavior of single turnover DNA unwinding time courses and describe novel methods for nonlinear least-squares analysis that overcome these problems. Analytic expressions for the time courses, f(ss)(t), when obtainable, can be written using gamma and incomplete gamma functions. When analytic expressions are not obtainable, the numerical solution of the inverse Laplace transform can be used to obtain f(ss)(t). Both methods allow n and m to be continuous fitting parameters. These approaches are generally applicable to enzymes that translocate along a lattice or require repetition of a series of steps before product formation.

Semiautomatic sequential extraction of polycyclic aromatic hydrocarbons and elemental bio-accessible fraction by accelerated solvent extraction on a single particulate matter sample.

PubMed

Astolfi, Maria Luisa; Di Filippo, Patrizia; Gentili, Alessandra; Canepari, Silvia

2017-11-01

We describe the optimization and validation of a sequential extractive method for the determination of the polycyclic aromatic hydrocarbons (PAHs) and elements (Al, As, Cd, Cr, Cu, Fe, Mn, Ni, Pb, Se, V and Zn) that are chemically fractionated into bio-accessible and mineralized residual fractions on a single particulate matter filter. The extraction is performed by automatic accelerated solvent extraction (ASE); samples are sequentially treated with dichloromethane/acetone (4:1) for PAHs extraction and acetate buffer (0.01M; pH 4.5) for elements extraction (bio-accessible fraction). The remaining solid sample is then collected and subjected to acid digestion with HNO 3 :H 2 O 2 (2:1) to determine the mineralized residual element fraction. We also describe a homemade ASE cell that reduces the blank values for most elements; in this cell, the steel frit was replaced by a Teflon pierced disk and a Teflon cylinder was used as the filler. The performance of the proposed method was evaluated in terms of recovery from standard reference material (SRM 1648 and SRM 1649a) and repeatability. The equivalence between the new ASE method and conventional methods was verified for PAHs and for bio-accessible and mineralized residual fractions of elements on PM 10 twin filters. Copyright © 2017 Elsevier B.V. All rights reserved.

Single dose of bisphosphonate preserves gains in bone mass following cessation of sclerostin antibody in Brtl/+ osteogenesis imperfecta model.

PubMed

Perosky, Joseph E; Khoury, Basma M; Jenks, Terese N; Ward, Ferrous S; Cortright, Kai; Meyer, Bethany; Barton, David K; Sinder, Benjamin P; Marini, Joan C; Caird, Michelle S; Kozloff, Kenneth M

2016-12-01

Sclerostin antibody has demonstrated a bone-forming effect in pre-clinical models of osteogenesis imperfecta, where mutations in collagen or collagen-associated proteins often result in high bone fragility in pediatric patients. Cessation studies in osteoporotic patients have demonstrated that sclerostin antibody, like intermittent PTH treatment, requires sequential anti-resorptive therapy to preserve the anabolic effects in adult populations. However, the persistence of anabolic gains from either drug has not been explored clinically in OI, or in any animal model. To determine whether cessation of sclerostin antibody therapy in a growing OI skeleton requires sequential anti-resorptive treatment to preserve anabolic gains in bone mass, we treated 3week old Brtl/+ and wild type mice for 5weeks with SclAb, and then withdrew treatment for an additional 6weeks. Trabecular bone loss was evident following cessation, but was preserved in a dose-dependent manner with single administration of pamidronate at the time of cessation. In vivo longitudinal near-infrared optical imaging of cathepsin K activation in the proximal tibia suggests an anti-resorptive effect of both SclAb and pamidronate which is reversed after three weeks of cessation. Cortical bone was considerably less susceptible to cessation effects, and showed no structural or functional deficits in the absence of pamidronate during this cessation period. In conclusion, while SclAb induces a considerable anabolic gain in the rapidly growing Brtl/+ murine model of OI, a single sequential dose of antiresorptive drug is required to maintain bone mass at trabecular sites for 6weeks following cessation. Copyright © 2016 Elsevier Inc. All rights reserved.

Sequential evaporation of water molecules from protonated water clusters: measurement of the velocity distributions of the evaporated molecules and statistical analysis.

PubMed

Berthias, F; Feketeová, L; Abdoul-Carime, H; Calvo, F; Farizon, B; Farizon, M; Märk, T D

2018-06-22

Velocity distributions of neutral water molecules evaporated after collision induced dissociation of protonated water clusters H+(H2O)n≤10 were measured using the combined correlated ion and neutral fragment time-of-flight (COINTOF) and velocity map imaging (VMI) techniques. As observed previously, all measured velocity distributions exhibit two contributions, with a low velocity part identified by statistical molecular dynamics (SMD) simulations as events obeying the Maxwell-Boltzmann statistics and a high velocity contribution corresponding to non-ergodic events in which energy redistribution is incomplete. In contrast to earlier studies, where the evaporation of a single molecule was probed, the present study is concerned with events involving the evaporation of up to five water molecules. In particular, we discuss here in detail the cases of two and three evaporated molecules. Evaporation of several water molecules after CID can be interpreted in general as a sequential evaporation process. In addition to the SMD calculations, a Monte Carlo (MC) based simulation was developed allowing the reconstruction of the velocity distribution produced by the evaporation of m molecules from H+(H2O)n≤10 cluster ions using the measured velocity distributions for singly evaporated molecules as the input. The observed broadening of the low-velocity part of the distributions for the evaporation of two and three molecules as compared to the width for the evaporation of a single molecule results from the cumulative recoil velocity of the successive ion residues as well as the intrinsically broader distributions for decreasingly smaller parent clusters. Further MC simulations were carried out assuming that a certain proportion of non-ergodic events is responsible for the first evaporation in such a sequential evaporation series, thereby allowing to model the entire velocity distribution.

Patterns and Practices for Future Architectures

DTIC Science & Technology

2014-08-01

14. SUBJECT TERMS computing architecture, graph algorithms, high-performance computing, big data , GPU 15. NUMBER OF PAGES 44 16. PRICE CODE 17...at Vertex 1 6 Figure 4: Data Structures Created by Kernel 1 of Single CPU, List Implementation Using the Graph in the Example from Section 1.2 9...Figure 5: Kernel 2 of Graph500 BFS Reference Implementation: Single CPU, List 10 Figure 6: Data Structures for Sequential CSR Algorithm 12 Figure 7

Study of Sequential Dexter Energy Transfer in High Efficient Phosphorescent White Organic Light-Emitting Diodes with Single Emissive Layer

NASA Astrophysics Data System (ADS)

Kim, Jin Wook; You, Seung Il; Kim, Nam Ho; Yoon, Ju-An; Cheah, Kok Wai; Zhu, Fu Rong; Kim, Woo Young

2014-11-01

In this study, we report our effort to realize high performance single emissive layer three color white phosphorescent organic light emitting diodes (PHOLEDs) through sequential Dexter energy transfer of blue, green and red dopants. The PHOLEDs had a structure of; ITO(1500 Å)/NPB(700 Å)/mCP:Firpic-x%:Ir(ppy)3-0.5%:Ir(piq)3-y%(300 Å)/TPBi(300 Å)/Liq(20 Å)/Al(1200 Å). The dopant concentrations of FIrpic, Ir(ppy)3 and Ir(piq)3 were adjusted and optimized to facilitate the preferred energy transfer processes attaining both the best luminous efficiency and CIE color coordinates. The presence of a deep trapping center for charge carriers in the emissive layer was confirmed by the observed red shift in electroluminescent spectra. White PHOLEDs, with phosphorescent dopant concentrations of FIrpic-8.0%:Ir(ppy)3-0.5%:Ir(piq)3-0.5% in the mCP host of the single emissive layer, had a maximum luminescence of 37,810 cd/m2 at 11 V and a luminous efficiency of 48.10 cd/A at 5 V with CIE color coordinates of (0.35, 0.41).

Characteristics of vertigo and the affected vestibular nerve systems in idiopathic bilateral vestibulopathy.

PubMed

Fujimoto, Chisato; Kinoshita, Makoto; Kamogashira, Teru; Egami, Naoya; Sugasawa, Keiko; Yamasoba, Tatsuya; Iwasaki, Shinichi

2016-01-01

Vertigo attacks in IBV patients involving both the superior and inferior vestibular nerve systems were significantly more severe than vertigo attacks in patients with selective involvement of the inferior vestibular nerve system alone. To investigate the relationship between the frequency and duration of vertigo and the affected vestibular nerve system in idiopathic bilateral vestibulopathy (IBV). This study categorized 44 IBV patients into the following three sub-groups according to the affected vestibular nerve system: superior, inferior, and mixed type. These patients were also categorized into the following three sub-groups according to their clinical time course: progressive type showing no episodes of vertigo, sequential type showing recurrent vertigo attacks and single-attack type showing a single episode of vertigo. Ten, 11 and 23 patients were classified as the superior, the inferior, and the mixed type, respectively. Seventeen, 23, and four patients were classified as the progressive, the sequential, and the single-attack type, respectively. For the patients having one or more vertigo attacks, the duration of the vertigo attack was longer than 24 h in 69% of the mixed type, and the duration of vertigo in the mixed type was significantly longer than that in the inferior type (p < 0.05).

Partner-Drug Resistance and Population Substructuring of Artemisinin-Resistant Plasmodium falciparum in Cambodia

PubMed Central

Parobek, Christian M.; Parr, Jonathan B.; Brazeau, Nicholas F.; Lon, Chanthap; Chaorattanakawee, Suwanna; Gosi, Panita; Barnett, Eric J.; Norris, Lauren D.; Meshnick, Steven R.; Spring, Michele D.; Lanteri, Charlotte A.; Bailey, Jeffrey A.; Saunders, David L.; Lin, Jessica T.

2017-01-01

Abstract Plasmodium falciparum in western Cambodia has developed resistance to artemisinin and its partner drugs, causing frequent treatment failure. Understanding this evolution can inform the deployment of new therapies. We investigated the genetic architecture of 78 falciparum isolates using whole-genome sequencing, correlating results to in vivo and ex vivo drug resistance and exploring the relationship between population structure, demographic history, and partner drug resistance. Principle component analysis, network analysis and demographic inference identified a diverse central population with three clusters of clonally expanding parasite populations, each associated with specific K13 artemisinin resistance alleles and partner drug resistance profiles which were consistent with the sequential deployment of artemisinin combination therapies in the region. One cluster displayed ex vivo piperaquine resistance and mefloquine sensitivity with a high rate of in vivo failure of dihydroartemisinin-piperaquine. Another cluster displayed ex vivo mefloquine resistance and piperaquine sensitivity with high in vivo efficacy of dihydroartemisinin-piperaquine. The final cluster was clonal and displayed intermediate sensitivity to both drugs. Variations in recently described piperaquine resistance markers did not explain the difference in mean IC90 or clinical failures between the high and intermediate piperaquine resistance groups, suggesting additional loci may be involved in resistance. The results highlight an important role for partner drug resistance in shaping the P. falciparum genetic landscape in Southeast Asia and suggest that further work is needed to evaluate for other mutations that drive piperaquine resistance. PMID:28854635

Electrical power system WP-04

NASA Astrophysics Data System (ADS)

Nored, Donald L.

Viewgraphs on Space Station Freedom Electrical Power System (EPS) WP-40 are presented. Topics covered include: key EPS technical requirements; photovoltaic power module systems; solar array assembly; blanket containment box and box positioning subassemblies; solar cell; bypass diode assembly; Kapton with atomic oxygen resistant coating; sequential shunt unit; gimbal assembly; energy storage subsystem; thermal control subsystem; direct current switching unit; integrated equipment assembly; PV cargo element; PMAD system; and PMC and AC architecture.

Electrical power system WP-04

NASA Technical Reports Server (NTRS)

Nored, Donald L.

1990-01-01

Viewgraphs on Space Station Freedom Electrical Power System (EPS) WP-40 are presented. Topics covered include: key EPS technical requirements; photovoltaic power module systems; solar array assembly; blanket containment box and box positioning subassemblies; solar cell; bypass diode assembly; Kapton with atomic oxygen resistant coating; sequential shunt unit; gimbal assembly; energy storage subsystem; thermal control subsystem; direct current switching unit; integrated equipment assembly; PV cargo element; PMAD system; and PMC and AC architecture.

Escalating risk and the moderating effect of resistance to peer influence on the P200 and feedback-related negativity.

PubMed

Kiat, John; Straley, Elizabeth; Cheadle, Jacob E

2016-03-01

Young people frequently socialize together in contexts that encourage risky decision making, pointing to a need for research into how susceptibility to peer influence is related to individual differences in the neural processing of decisions during sequentially escalating risk. We applied a novel analytic approach to analyze EEG activity from college-going students while they completed the Balloon Analogue Risk Task (BART), a well-established risk-taking propensity assessment. By modeling outcome-processing-related changes in the P200 and feedback-related negativity (FRN) sequentially within each BART trial as a function of pump order as an index of increasing risk, our results suggest that analyzing the BART in a progressive fashion may provide valuable new insights into the temporal neurophysiological dynamics of risk taking. Our results showed that a P200, localized to the left caudate nucleus, and an FRN, localized to the left dACC, were positively correlated with the level of risk taking and reward. Furthermore, consistent with our hypotheses, the rate of change in the FRN was higher among college students with greater self-reported resistance to peer influence. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Physico-chemical, microbiological and ecotoxicological evaluation of a septic tank/Fenton reaction combination for the treatment of hospital wastewaters.

PubMed

Berto, Josiani; Rochenbach, Gisele Canan; Barreiros, Marco Antonio B; Corrêa, Albertina X R; Peluso-Silva, Sandra; Radetski, Claudemir Marcos

2009-05-01

Hospital wastewater is considered a complex mixture populated with pathogenic microorganisms. The genetic constitution of these microorganisms can be changed through the direct and indirect effects of hospital wastewater constituents, leading to the appearance of antibiotic multi-resistant bacteria. To avoid environmental contamination hospital wastewaters must be treated. The objective of this study was to evaluate the efficiency of hospital wastewater treated by a combined process of biological degradation (septic tank) and the Fenton reaction. Thus, after septic tank biodegradation, batch Fenton reaction experiments were performed in a laboratory-scale reactor and the effectiveness of this sequential treatment was evaluated by a physico-chemical/microbiological time-course analysis of COD, BOD(5), and thermotolerant and total coliforms. The results showed that after 120min of Fenton treatment BOD(5) and COD values decreased by 90.6% and 91.0%, respectively. The BOD(5)/COD ratio changed from 0.46 to 0.48 after 120min of treatment. Bacterial removal efficiency reached 100%, while biotests carried out with Scenedesmus subspicatus and Daphnia magna showed a significant decrease in the ecotoxicity of hospital wastewater after the sequential treatment. The use of this combined system would ensure that neither multi-resistant bacteria nor ecotoxic substances are released to the environment through hospital wastewater discharge.

Long-term changes in community assembly, resistance, and resilience following experimental floods.

PubMed

Robinson, Christopher T

2012-10-01

This study examined the long-term changes in community assembly, resistance, and resilience of macroinvertebrates following 10 years of experimental floods in a flow regulated river. Physico-chemistry, macroinvertebrates, and periphyton biomass were monitored before and sequentially after each of 22 floods, and drift/seston was collected during six separate floods over the study period. The floods reduced the density and taxon richness of macroinvertebrates, and a nonmetric dimensional scaling (NMDS) analysis distinguished temporal shifts in community assembly. Resistance (measured as the relative lack of loss in density) tofloods varied among taxa, and the abundance of resistant taxa was related to the temporal changes in community assembly. Community resistance was inversely related to flood magnitude with all larger floods (> 25 m3/s, > 16-fold over baseflow) reducing densities by > 75% regardless of flood year, whereas smaller floods (< 20 m3/s) reduced taxon richness approximately twofold less than larger floods. No relationship was found between flood magnitude and the relative loss in periphyton biomass. Resilience was defined as the recovery slope (positive slope of a parameter with time following each flood) and was unrelated to shifts in community assembly or resistance. Macroinvertebrate drift and seston demonstrated hysteresis (i.e., a temporal response in parameter quantity with change in discharge) during each flood, although larger floods typically had two peaks in both parameters. The first peak was a response to the initial increases in flow, whereas the second peak was associated with streambed disturbance (substrate mobility) and side-slope failure causing increased scour. Drift density was 3-9 times greater and that of seston 3-30 times greater during larger floods than smaller floods. These results demonstrate temporal shifts in macroinvertebrate community assembly toward a pre-dam assemblage following sequential floods in this flow regulated river, thus confirming the ecological role of habitat filtering in organism distribution and abundance. Community resistance and resilience were unrelated to shifts in community assembly, suggesting that they are mostly evolutionary properties of ecosystems as populations adapt to changing environmental (disturbance regimes) and biotic (novel colonists) conditions. As these systems show behaviors similar to dispersal-limited ecosystems, a long-term perspective is required for management actions targeted toward regulated and fragmented rivers.

Resistance Mechanisms and the Future of Bacterial Enoyl-Acyl Carrier Protein Reductase (FabI) Antibiotics

PubMed Central

Yao, Jiangwei; Rock, Charles O.

2016-01-01

Missense mutations leading to clinical antibiotic resistance are a liability of single-target inhibitors. The enoyl-acyl carrier protein reductase (FabI) inhibitors have one intracellular protein target and drug resistance is increased by the acquisition of single-base-pair mutations that alter drug binding. The spectrum of resistance mechanisms to FabI inhibitors suggests criteria that should be considered during the development of single-target antibiotics that would minimize the impact of missense mutations on their clinical usefulness. These criteria include high-affinity, fast on/off kinetics, few drug contacts with residue side chains, and no toxicity. These stringent criteria are achievable by structure-guided design, but this approach will only yield pathogen-specific drugs. Single-step acquisition of resistance may limit the clinical application of broad-spectrum, single-target antibiotics, but appropriately designed pathogen-specific antibiotics have the potential to overcome this liability. PMID:26931811

Ceruletide intravenous dose-response study by a simplified scintigraphic technique

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

Krishnamurthy, G.T.; Turner, F.E.; Mangham, D.

1985-04-01

The intravenous dose response of a ceruletide diethylamine (ceruletide) was established by a simplified scintigraphic technique where multiple graded doses were given sequentially on a single occasion. The gallbladder volume was presented nongeometrically by /sup 99m/Tc-IDA counts. The mean latent period, ejection period, and ejection rate were similar for all four groups of subjects given 1-20 ng/kg of ceruletide. The ejection fractions were similar to the values when the identical dose of ceruletide was administered sequentially either before or after another dose. A dose of 5 ng/kg produced the most physiologic type of emptying. Intravenous doses of 10 ng/kg andmore » larger caused adverse reactions in 42% of the total doses in the form of abdominal pain, nausea, systolic and diastolic hypotension, or bradycardia. It is concluded that the dose response of a cholecystokininlike agent (ceruletide) can be established reliably by a scintigraphic technique where multiple graded doses are given on a single occasion.« less

Verification of hypergraph states

NASA Astrophysics Data System (ADS)

Morimae, Tomoyuki; Takeuchi, Yuki; Hayashi, Masahito

2017-12-01

Hypergraph states are generalizations of graph states where controlled-Z gates on edges are replaced with generalized controlled-Z gates on hyperedges. Hypergraph states have several advantages over graph states. For example, certain hypergraph states, such as the Union Jack states, are universal resource states for measurement-based quantum computing with only Pauli measurements, while graph state measurement-based quantum computing needs non-Clifford basis measurements. Furthermore, it is impossible to classically efficiently sample measurement results on hypergraph states unless the polynomial hierarchy collapses to the third level. Although several protocols have been proposed to verify graph states with only sequential single-qubit Pauli measurements, there was no verification method for hypergraph states. In this paper, we propose a method for verifying a certain class of hypergraph states with only sequential single-qubit Pauli measurements. Importantly, no i.i.d. property of samples is assumed in our protocol: any artificial entanglement among samples cannot fool the verifier. As applications of our protocol, we consider verified blind quantum computing with hypergraph states, and quantum computational supremacy demonstrations with hypergraph states.

Sequential use of hemoperfusion and single-pass albumin dialysis can safely reverse methotrexate nephrotoxicity.

PubMed

Chan, Winnie Kwai Yu; Hui, Wun Fung

2016-10-01

High-dose methotrexate therapy (HDMTX) is a common form of chemotherapy used in children with high-grade malignancy such as osteosarcoma. Treatment with HDMTX requires careful monitoring of drug levels with folinic acid (leucovorin) rescue therapy. Toxicity from methotrexate is not uncommon and sometimes causes significant morbidity and mortality. We report an 11-year-old child whose 24-h post-HDMTX serum level was 651.8 μmol/L (recommended level <20 μmol/L), which was complicated by septic shock and progressive renal and liver failure. As carboxypeptidase (glucarpidase) was not available locally, she was treated with the sequential use of charcoal hemoperfusion (CHP) and single-pass albumin dialysis (SPAD). The patient recovered without complications. Both liver and renal function recovered with no significant late sequelae. CHP and SPAD are effective extracorporeal methods of removing methotrexate. They provide alternative treatment options for critical care nephrologists in the management of methotrexate toxicity.

AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance

PubMed Central

O’Hare, Thomas; Shakespeare, William C.; Zhu, Xiaotian; Eide, Christopher A.; Rivera, Victor M.; Wang, Frank; Adrian, Lauren T.; Zhou, Tianjun; Huang, Wei-Sheng; Xu, Qihong; Metcalf, Chester A.; Tyner, Jeffrey W.; Loriaux, Marc M.; Corbin, Amie S.; Wardwell, Scott; Ning, Yaoyu; Keats, Jeffrey A.; Wang, Yihan; Sundaramoorthi, Raji; Thomas, Mathew; Zhou, Dong; Snodgrass, Joseph; Commodore, Lois; Sawyer, Tomi K.; Dalgarno, David C.; Deininger, Michael W.N.; Druker, Brian J.; Clackson, Tim

2009-01-01

SUMMARY Inhibition of BCR-ABL by imatinib induces durable responses in many patients with chronic myeloid leukemia (CML), but resistance attributable to kinase domain mutations can lead to relapse and a switch to second-line therapy with nilotinib or dasatinib. Despite three approved therapeutic options, the cross-resistant BCR-ABLT315I mutation and compound mutants selected on sequential inhibitor therapy remain major clinical challenges. We report design and pre-clinical evaluation of AP24534, a potent, orally available multi-targeted kinase inhibitor active against T315I and other BCR-ABL mutants. AP24534 inhibited all tested BCR-ABL mutants in cellular and biochemical assays, suppressed BCR-ABLT315I-driven tumor growth in mice, and completely abrogated resistance in cell-based mutagenesis screens. Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML. PMID:19878872

AP24534, a Pan-BCR-ABL Inhibitor for Chronic Myeloid Leukemia, Potently Inhibits the T315I Mutant and Overcomes Mutation-Based Resistance

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

O’Hare, Thomas; Shakespeare, William C.; Zhu, Xiaotian

2010-09-07

Inhibition of BCR-ABL by imatinib induces durable responses in many patients with chronic myeloid leukemia (CML), but resistance attributable to kinase domain mutations can lead to relapse and a switch to second-line therapy with nilotinib or dasatinib. Despite three approved therapeutic options, the cross-resistant BCR-ABL{sup T315I} mutation and compound mutants selected on sequential inhibitor therapy remain major clinical challenges. We report design and preclinical evaluation of AP24534, a potent, orally available multitargeted kinase inhibitor active against T315I and other BCR-ABL mutants. AP24534 inhibited all tested BCR-ABL mutants in cellular and biochemical assays, suppressed BCR-ABL{sup T315I}-driven tumor growth in mice, andmore » completely abrogated resistance in cell-based mutagenesis screens. Our work supports clinical evaluation of AP24534 as a pan-BCR-ABL inhibitor for treatment of CML.« less

Durable graft-versus-leukaemia effects without donor lymphocyte infusions - results of a phase II study of sequential T-replete allogeneic transplantation for high-risk acute myeloid leukaemia and myelodysplasia.

PubMed

Davies, Jeff K; Hassan, Sandra; Sarker, Shah-Jalal; Besley, Caroline; Oakervee, Heather; Smith, Matthew; Taussig, David; Gribben, John G; Cavenagh, Jamie D

2018-02-01

Allogeneic haematopoietic stem-cell transplantation remains the only curative treatment for relapsed/refractory acute myeloid leukaemia (AML) and high-risk myelodysplasia but has previously been limited to patients who achieve remission before transplant. New sequential approaches employing T-cell depleted transplantation directly after chemotherapy show promise but are burdened by viral infection and require donor lymphocyte infusions (DLI) to augment donor chimerism and graft-versus-leukaemia effects. T-replete transplantation in sequential approaches could reduce both viral infection and DLI usage. We therefore performed a single-arm prospective Phase II clinical trial of sequential chemotherapy and T-replete transplantation using reduced-intensity conditioning without planned DLI. The primary endpoint was overall survival. Forty-seven patients with relapsed/refractory AML or high-risk myelodysplasia were enrolled; 43 proceeded to transplantation. High levels of donor chimerism were achieved spontaneously with no DLI. Overall survival of transplanted patients was 45% and 33% at 1 and 3 years. Only one patient developed cytomegalovirus disease. Cumulative incidences of treatment-related mortality and relapse were 35% and 20% at 1 year. Patients with relapsed AML and myelodysplasia had the most favourable outcomes. Late-onset graft-versus-host disease protected against relapse. In conclusion, a T-replete sequential transplantation using reduced-intensity conditioning is feasible for relapsed/refractory AML and myelodysplasia and can deliver graft-versus-leukaemia effects without DLI. © 2017 John Wiley & Sons Ltd.

Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines.

PubMed

Arguedas, A; Soley, C; Loaiza, C; Rincon, G; Guevara, S; Perez, A; Porras, W; Alvarado, O; Aguilar, L; Abdelnour, A; Grunwald, U; Bedell, L; Anemona, A; Dull, P M

2010-04-19

This Phase III study evaluates an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM (Novartis Vaccines), when administered concomitantly or sequentially with two other recommended adolescent vaccines; combined tetanus, reduced diphtheria and acellular pertussis (Tdap), and human papillomavirus (HPV) vaccine. In this single-centre study, 1620 subjects 11-18 years of age, were randomized to three groups (1:1:1) to receive MenACWY-CRM concomitantly or sequentially with Tdap and HPV. Meningococcal serogroup-specific serum bactericidal assay using human complement (hSBA), and antibodies to Tdap antigens and HPV virus-like particles were determined before and 1 month after study vaccinations. Proportions of subjects with hSBA titres > or =1:8 for all four meningococcal serogroups (A, C, W-135, Y) were non-inferior for both concomitant and sequential administration. Immune responses to Tdap and HPV antigens were comparable when these vaccines were given alone or concomitantly with MenACWY-CRM. All vaccines were well tolerated; concomitant or sequential administration did not increase reactogenicity. MenACWY-CRM was well tolerated and immunogenic in subjects 11-18 years of age, with comparable immune responses to the four serogroups when given alone or concomitantly with Tdap or HPV antigens. This is the first demonstration that these currently recommended adolescent vaccines could be administered concomitantly without causing increased reactogenicity. Copyright 2010 Elsevier Ltd. All rights reserved.

Efficient sequential and parallel algorithms for record linkage.

PubMed

Mamun, Abdullah-Al; Mi, Tian; Aseltine, Robert; Rajasekaran, Sanguthevar

2014-01-01

Integrating data from multiple sources is a crucial and challenging problem. Even though there exist numerous algorithms for record linkage or deduplication, they suffer from either large time needs or restrictions on the number of datasets that they can integrate. In this paper we report efficient sequential and parallel algorithms for record linkage which handle any number of datasets and outperform previous algorithms. Our algorithms employ hierarchical clustering algorithms as the basis. A key idea that we use is radix sorting on certain attributes to eliminate identical records before any further processing. Another novel idea is to form a graph that links similar records and find the connected components. Our sequential and parallel algorithms have been tested on a real dataset of 1,083,878 records and synthetic datasets ranging in size from 50,000 to 9,000,000 records. Our sequential algorithm runs at least two times faster, for any dataset, than the previous best-known algorithm, the two-phase algorithm using faster computation of the edit distance (TPA (FCED)). The speedups obtained by our parallel algorithm are almost linear. For example, we get a speedup of 7.5 with 8 cores (residing in a single node), 14.1 with 16 cores (residing in two nodes), and 26.4 with 32 cores (residing in four nodes). We have compared the performance of our sequential algorithm with TPA (FCED) and found that our algorithm outperforms the previous one. The accuracy is the same as that of this previous best-known algorithm.

Comparison between variable and fixed dwell-time PN acquisition algorithms. [for synchronization in pseudonoise spread spectrum systems

NASA Technical Reports Server (NTRS)

Braun, W. R.

1981-01-01

Pseudo noise (PN) spread spectrum systems require a very accurate alignment between the PN code epochs at the transmitter and receiver. This synchronism is typically established through a two-step algorithm, including a coarse synchronization procedure and a fine synchronization procedure. A standard approach for the coarse synchronization is a sequential search over all code phases. The measurement of the power in the filtered signal is used to either accept or reject the code phase under test as the phase of the received PN code. This acquisition strategy, called a single dwell-time system, has been analyzed by Holmes and Chen (1977). A synopsis of the field of sequential analysis as it applies to the PN acquisition problem is provided. From this, the implementation of the variable dwell time algorithm as a sequential probability ratio test is developed. The performance of this algorithm is compared to the optimum detection algorithm and to the fixed dwell-time system.

Sequential bearings-only-tracking initiation with particle filtering method.

PubMed

Liu, Bin; Hao, Chengpeng

2013-01-01

The tracking initiation problem is examined in the context of autonomous bearings-only-tracking (BOT) of a single appearing/disappearing target in the presence of clutter measurements. In general, this problem suffers from a combinatorial explosion in the number of potential tracks resulted from the uncertainty in the linkage between the target and the measurement (a.k.a the data association problem). In addition, the nonlinear measurements lead to a non-Gaussian posterior probability density function (pdf) in the optimal Bayesian sequential estimation framework. The consequence of this nonlinear/non-Gaussian context is the absence of a closed-form solution. This paper models the linkage uncertainty and the nonlinear/non-Gaussian estimation problem jointly with solid Bayesian formalism. A particle filtering (PF) algorithm is derived for estimating the model's parameters in a sequential manner. Numerical results show that the proposed solution provides a significant benefit over the most commonly used methods, IPDA and IMMPDA. The posterior Cramér-Rao bounds are also involved for performance evaluation.

Sequential ChIP Protocol for Profiling Bivalent Epigenetic Modifications (ReChIP).

PubMed

Desvoyes, Bénédicte; Sequeira-Mendes, Joana; Vergara, Zaida; Madeira, Sofia; Gutierrez, Crisanto

2018-01-01

Identification of chromatin modifications, e.g., histone acetylation and methylation, among others, is widely carried out by using a chromatin immunoprecipitation (ChIP) strategy. The information obtained with these procedures is useful to gain an overall picture of modifications present in all cells of the population under study. It also serves as a basis to figure out the mechanisms of chromatin organization and gene regulation at the population level. However, the ultimate goal is to understand gene regulation at the level of single chromatin fibers. This requires the identification of chromatin modifications that occur at a given genomic location and within the same chromatin fiber. This is achieved by following a sequential ChIP strategy using two antibodies to distinguish different chromatin modifications. Here, we describe a sequential ChIP protocol (Re-ChIP), paying special attention to the controls needed and the required steps to obtain meaningful and reproducible results. The protocol is developed for young Arabidopsis seedlings but could be adapted to other plant materials.

Combined techniques for characterising pasta structure reveals how the gluten network slows enzymic digestion rate.

PubMed

Zou, Wei; Sissons, Mike; Gidley, Michael J; Gilbert, Robert G; Warren, Frederick J

2015-12-01

The aim of the present study is to characterise the influence of gluten structure on the kinetics of starch hydrolysis in pasta. Spaghetti and powdered pasta were prepared from three different cultivars of durum semolina, and starch was also purified from each cultivar. Digestion kinetic parameters were obtained through logarithm-of-slope analysis, allowing identification of sequential digestion steps. Purified starch and semolina were digested following a single first-order rate constant, while pasta and powdered pasta followed two sequential first-order rate constants. Rate coefficients were altered by pepsin hydrolysis. Confocal microscopy revealed that, following cooking, starch granules were completely swollen for starch, semolina and pasta powder samples. In pasta, they were completely swollen in the external regions, partially swollen in the intermediate region and almost intact in the pasta strand centre. Gluten entrapment accounts for sequential kinetic steps in starch digestion of pasta; the compact microstructure of pasta also reduces digestion rates. Copyright © 2015 Elsevier Ltd. All rights reserved.

CO-OCCURRENCE OF OZONE AND ACIDIC CLOUD WATER IN HIGH-ELEVATION FORESTS

EPA Science Inventory

A chemical climatology for high-elevation forests was estimated from ozone and cloudwater acidity data collected in the eastern United States. esides frequent ozone-only and pH-only single-pollutant episodes, both simultaneous and sequential co-occurrence of ozone and acidic clou...

Management of mendelian traits in breeding programs by gene editing

USDA-ARS?s Scientific Manuscript database

High-density single nucleotide polymorphism genotypes have recently been used to identify a number of novel recessive mutations that adversely affect fertility in dairy cattle, as well as to track conditions such as polled. Recent findings suggest that the use of sequential mate allocation strategie...

Learning and Parallelization Boost Constraint Search

ERIC Educational Resources Information Center

Yun, Xi

2013-01-01

Constraint satisfaction problems are a powerful way to abstract and represent academic and real-world problems from both artificial intelligence and operations research. A constraint satisfaction problem is typically addressed by a sequential constraint solver running on a single processor. Rather than construct a new, parallel solver, this work…

Static Evaluation of a NAVSTAR GPS (Magnavox Z-Set) Receiver - May-September 1979

DOT National Transportation Integrated Search

1980-05-01

The report documents the results of the static testing of a NAVSTAR Global Positioning System (GPS) single channel sequential receiver (Magnavox Z-Set). These tests were performed at the Coast Guard District 11 office in Long Beach, CA from May to Se...

Sequential Super-Resolution Imaging of Bacterial Regulatory Proteins: The Nucleoid and the Cell Membrane in Single, Fixed E. coli Cells.

PubMed

Spahn, Christoph; Glaesmann, Mathilda; Gao, Yunfeng; Foo, Yong Hwee; Lampe, Marko; Kenney, Linda J; Heilemann, Mike

2017-01-01

Despite their small size and the lack of compartmentalization, bacteria exhibit a striking degree of cellular organization, both in time and space. During the last decade, a group of new microscopy techniques emerged, termed super-resolution microscopy or nanoscopy, which facilitate visualizing the organization of proteins in bacteria at the nanoscale. Single-molecule localization microscopy (SMLM) is especially well suited to reveal a wide range of new information regarding protein organization, interaction, and dynamics in single bacterial cells. Recent developments in click chemistry facilitate the visualization of bacterial chromatin with a resolution of ~20 nm, providing valuable information about the ultrastructure of bacterial nucleoids, especially at short generation times. In this chapter, we describe a simple-to-realize protocol that allows determining precise structural information of bacterial nucleoids in fixed cells, using direct stochastic optical reconstruction microscopy (dSTORM). In combination with quantitative photoactivated localization microscopy (PALM), the spatial relationship of proteins with the bacterial chromosome can be studied. The position of a protein of interest with respect to the nucleoids and the cell cylinder can be visualized by super-resolving the membrane using point accumulation for imaging in nanoscale topography (PAINT). The combination of the different SMLM techniques in a sequential workflow maximizes the information that can be extracted from single cells, while maintaining optimal imaging conditions for each technique.

Electron Scattering at Surfaces of Epitaxial Metal Layers

NASA Astrophysics Data System (ADS)

Chawla, Jasmeet Singh

In the field of electron transport in metal films and wires, the 'size effect' refers to the increase in the resistivity of the films and wires as their critical dimensions (thickness of film, width and height of wires) approach or become less than the electron mean free path lambda, which is, for example, 39 nm for bulk copper at room temperature. This size-effect is currently of great concern to the semiconductor industry because the continued downscaling of feature sizes has already lead to Cu interconnect wires in this size effect regime, with a reported 2.5 times higher resistivity for 40 nm wide Cu wires than for bulk Cu. Silver is a possible alternate material for interconnect wires and titanium nitride is proposed as a gate metal in novel field-effect-transistors. Therefore, it is important to develop an understanding of how the growth, the surface morphology, and the microstructure of ultrathin (few nanometers) Cu, Ag and TiN layers affect their electrical properties. This dissertation aims to advance the scientific knowledge of electron scattering at surfaces (external surfaces and grain boundaries), that are, the primary reasons for the size-effect in metal conductors. The effect of surface and grain boundary scattering on the resistivity of Cu thin films and nanowires is separately quantified using (i) in situ transport measurements on single-crystal, atomically smooth Cu(001) layers, (ii) textured polycrystalline Cu(111) layers and patterned wires with independently varying grain size, thickness and line width, and (iii) in situ grown interfaces including Cu-Ta, Cu-MgO, Cu-vacuum and Cu-oxygen. In addition, the electron surface scattering is also measured in situ for single-crystal Ag(001), (111) twinned epitaxial Ag(001), and single-crystal TiN(001) layers. Cu(001), Ag(001), and TiN(001) layers with a minimum continuous thickness of 4, 3.5 and 1.8 nm, respectively, are grown by ultra-high vacuum magnetron sputter deposition on MgO(001) substrates with and without thin epitaxial TiN(001) wetting layers and are studied for structure, crystalline quality, surface morphology, density and composition by a combination of x-ray diffraction theta-2theta scans, o-rocking curves, pole figures, reciprocal space mapping, Rutherford backscattering, x-ray reflectometry and transmission electron microscopy. The TiN(001) surface suppresses Cu and Ag dewetting, yielding lower defect density, no twinning, and smaller surface roughness than if grown on MgO(001). Textured polycrystalline Cu(111) layers 25-50-nm-thick are deposited on a stack of 7.5-nm-Ta on SiO2/Si(001), and subsequent in situ annealing at 350°C followed by sputter etching in Ar plasma yields Cu layers with independently variable thickness and grain size. Cu nanowires, 75 to 350 nm wide, are fabricated from Cu layers with different average grain size using a subtractive patterning process. In situ electron transport measurements at room temperature in vacuum and at 77 K in liquid nitrogen for single-crystal Cu and Ag layers is consistent with the Fuchs-Sondheimer (FS) model and indicates specular scattering at the metal-vacuum boundary with an average specularity parameter p = 0.8 and 0.6, respectively. In contrast, layers measured ex situ show diffuse surface scattering due to sub-monolayer oxidation. Also, addition of Ta atoms on Cu(001) surface perturbs the smooth interface potential and results in completely diffuse scattering at the Cu-Ta interface, and in turn, a higher resistivity of single-crystal Cu layers. In situ exposure of Cu(001) layers to O2 between 10 -3 and 105 Pa-s results in a sequential increase, decrease and increase of the electrical resistance which is attributed to specular surface scattering for clean Cu(001) and for surfaces with a complete adsorbed monolayer, but diffuse scattering at partial coverage and after chemical oxidation. Electron transport measurements for polycrystalline Cu layers and wires show a 10-15% and 7-9% decrease in resistivity, respectively, when increasing the average lateral grain size by a factor of 1.8. The maximum resistivity decrease that can be achieved by increasing the grain size of polycrystalline Cu layers with an average grain size approximately ˜2.5x the layer thickness is 20-26%.

Electrical resistivity measurements on fragile organic single crystals in the diamond anvil cell

NASA Astrophysics Data System (ADS)

Adachi, T.; Tanaka, H.; Kobayashi, H.; Miyazaki, T.

2001-05-01

A method of sample assembly for four-probe resistivity measurements on fragile organic single crystals using a diamond anvil cell is presented. A procedure to keep insulation between the metal gasket and four leads of thin gold wires bonded to the sample crystal by gold paint is described in detail. The resistivity measurements performed on a single crystal of an organic semiconductor and that of neutral molecules up to 15 GPa and down to 4.2 K showed that this new procedure of four-probe diamond anvil resistivity measurements enables us to obtain sufficiently accurate resistivity data of organic crystals.

Re-animation of muscle flaps for improved function in dynamic myoplasty.

PubMed

Stremel, R W; Zonnevijlle, E D

2001-01-01

The authors report on a series of experiments designed to produce a skeletal muscle contraction functional for dynamic myoplasties. Conventional stimulation techniques recruit all or most of the muscle fibers simultaneously and with maximal strength. This approach has limitations in free dynamic muscle flap transfers that require the muscle to contract immediately after transfer and before re-innervation. Sequential stimulation of segments of the transferred muscle provides a means of producing non-fatiguing contractions of the muscle in the presence or absence of innervation. The muscles studied were the canine gracilis, and all experiments were acute studies in anesthetized animals. Comparison of conventional and sequential segmental neuromuscular stimulation revealed an increase in muscle fatigue resistance and muscle blood flow with the new approach. This approach offers the opportunity for development of physiologically animated tissue and broadening the abilities of reconstructive surgeons in the repair of functional defects. Copyright 2001 Wiley-Liss, Inc.

The structure and evolution of galacto-detonation waves - Some analytic results in sequential star formation models of spiral galaxies

NASA Technical Reports Server (NTRS)

Cowie, L. L.; Rybicki, G. B.

1982-01-01

Waves of star formation in a uniform, differentially rotating disk galaxy are treated analytically as a propagating detonation wave front. It is shown, that if single solitary waves could be excited, they would evolve asymptotically to one of two stable spiral forms, each of which rotates with a fixed pattern speed. Simple numerical solutions confirm these results. However, the pattern of waves that develop naturally from an initially localized disturbance is more complex and dies out within a few rotation periods. These results suggest a conclusive observational test for deciding whether sequential star formation is an important determinant of spiral structure in some class of galaxies.

Can sequential parallel comparison design and two-way enriched design be useful in medical device clinical trials?

PubMed

Ivanova, Anastasia; Zhang, Zhiwei; Thompson, Laura; Yang, Ying; Kotz, Richard M; Fang, Xin

2016-01-01

Sequential parallel comparison design (SPCD) was proposed for trials with high placebo response. In the first stage of SPCD subjects are randomized between placebo and active treatment. In the second stage placebo nonresponders are re-randomized between placebo and active treatment. Data from the population of "all comers" and the subpopulations of placebo nonresponders then combined to yield a single p-value for treatment comparison. Two-way enriched design (TED) is an extension of SPCD where active treatment responders are also re-randomized between placebo and active treatment in Stage 2. This article investigates the potential uses of SPCD and TED in medical device trials.

Sequential establishment of stripe patterns in an expanding cell population.

PubMed

Liu, Chenli; Fu, Xiongfei; Liu, Lizhong; Ren, Xiaojing; Chau, Carlos K L; Li, Sihong; Xiang, Lu; Zeng, Hualing; Chen, Guanhua; Tang, Lei-Han; Lenz, Peter; Cui, Xiaodong; Huang, Wei; Hwa, Terence; Huang, Jian-Dong

2011-10-14

Periodic stripe patterns are ubiquitous in living organisms, yet the underlying developmental processes are complex and difficult to disentangle. We describe a synthetic genetic circuit that couples cell density and motility. This system enabled programmed Escherichia coli cells to form periodic stripes of high and low cell densities sequentially and autonomously. Theoretical and experimental analyses reveal that the spatial structure arises from a recurrent aggregation process at the front of the continuously expanding cell population. The number of stripes formed could be tuned by modulating the basal expression of a single gene. The results establish motility control as a simple route to establishing recurrent structures without requiring an extrinsic pacemaker.

Simultaneous regulation of apoptotic gene silencing and angiogenic gene expression for myocardial infarction therapy: Single-carrier delivery of SHP-1 siRNA and VEGF-expressing pDNA.

PubMed

Kim, Dongkyu; Ku, Sook Hee; Kim, Hyosuk; Jeong, Ji Hoon; Lee, Minhyung; Kwon, Ick Chan; Choi, Donghoon; Kim, Sun Hwa

2016-12-10

Gene therapy is aimed at selectively knocking up or knocking down the target genes involved in the development of diseases. In many human diseases, dysregulation of disease-associated genes is occurred concurrently: some genes are abnormally turned up and some are turned down. In the field of non-viral gene therapy, plasmid DNA (pDNA) and small interfering RNA (siRNA) are suggested as representative regulation tools for activating and silencing the expression of genes of interest, representatively. Herein, we simultaneously loaded both siRNA (Src homology region 2 domain-containing tyrosine phosphatase-1 siRNA, siSHP-1) for anti-apoptosis and pDNA (hypoxia-inducible vascular endothelial growth factor expression vector, pHI-VEGF) for angiogenesis in a single polymeric nanocarrier and used to synergistically attenuate ischemia-reperfusion (IR)-induced myocardial infarction, which is mainly caused by dysregulating of cardiac apoptosis and angiogenesis. For dual-modality cardiac gene delivery, siSHP-1 and pHI-VEGF were sequentially incorporated into a stable nanocomplex by using deoxycholic acid-modified polyethylenimine (DA-PEI). The resulting DA-PEI/siSHP-1/pHI-VEGF complexes exhibited the high structural stability against polyanion competition and the improved resistance to digestion by nucleases. The cardiac administration of DA-PEI/siSHP-1/pHI-VEGF reduced cardiomyocyte apoptosis and enhanced cardiac microvessel formation, thereby reducing infarct size in rat ischemia-reperfusion model. The simultaneous anti-apoptotic and angiogenic gene therapies synergized the cardioprotective effects of each strategy; thus our dual-modal single-carrier gene delivery system can be considered as a promising candidate for treating ischemic heart diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Static evaluation of a NAVSTAR Global Positioning System (GPS) (Magnavox Z-Set) receiver, May-September, 1979

DOT National Transportation Integrated Search

1980-05-01

The report documents the results of the static testing of a NAVSTAR Global Positioning System (GPS) single channel sequential receiver (Magnavox Z-Set). These tests were performed at the Coast Guard District 11 office in Long Beach, CA from May to Se...

Scaling a Single Attribute: A Methodological Study of Conservation

ERIC Educational Resources Information Center

Hofmann, Richard J.; Trepanier, Mary

1975-01-01

This study was designed to assess the acquisition of conservation of number on equal addition tasks through scalogram analysis to determine if this analysis defines a scale or continuum. Ten block tasks administered to 85 kindergarten children validated Piaget's theory that cognitive development is sequential and continuous. (Author/ED)

Commander Brand shaves in front of forward middeck lockers

NASA Technical Reports Server (NTRS)

1982-01-01

Commander Brand, wearing shorts, shaves in front of forward middeck lockers using personal hygiene mirror assembly (assy). Open modular locker single tray assy, Field Sequential (FS) crew cabin camera, communications kit assy mini headset (HDST) and HDST interface unit (HIU), personal hygiene kit, and meal tray assemblies appear in view.

Hinge specification for a square-faceted tetrahedral truss

NASA Technical Reports Server (NTRS)

Adams, L. R.

1984-01-01

A square-faceted tetrahedral truss is geometrically analyzed. Expressions are developed for single degree of freedom hinges which allow packaging of the structure into a configuration in which all members are parallel and closely packed in a square pattern. Deployment is sequential, thus providing control over the structure during deployment.

Narrated Animated Solution Videos in a Mastery Setting

ERIC Educational Resources Information Center

Schroeder, Noah; Gladding, Gary; Gutmann, Brianne; Stelzer, Timothy

2015-01-01

Narrated animated solution videos were implemented in a clinical study that compared a mastery setting that employed repeated cycles of testing with instructional support to a group that had a single opportunity to experience the materials. The mastery setting students attempted sequential questions sets on a topic, with animated solutions between…

Say again? How complexity and format of air traffic control instructions affect pilot recall

DOT National Transportation Integrated Search

1999-01-01

This study compared the recall of ATC information presented in cither grouped or sequential format : in a part-task simulation. It also tested the effect of complexity of ATC clearances on recall, that is, : how many pieces of information a single tr...

An Adaptable Investigative Graduate Laboratory Course for Teaching Protein Purification

ERIC Educational Resources Information Center

Carroll, Christopher W.; Keller, Lani C.

2014-01-01

This adaptable graduate laboratory course on protein purification offers students the opportunity to explore a wide range of techniques while allowing the instructor the freedom to incorporate their own personal research interests. The course design involves two sequential purification schemes performed in a single semester. The first part…

The Influence of Stimulus Properties on Category Construction

ERIC Educational Resources Information Center

Milton, Fraser; Wills, A. J.

2004-01-01

It has been demonstrated that when people free classify stimuli presented simultaneously in an array, they have a preference to categorize by a single dimension. However, when people are encouraged to categorize items sequentially, they sort by "family resemblance," grouping by overall similarity. The present studies extended this research,…

Understanding Single-Stranded Telomere End Binding by an Essential Protein

DTIC Science & Technology

2000-08-01

BioPharma Inc., 1885 33rd Street, Boulder, CO 80301 Traditional sequential medicinal chemistry methods have been augmented by combinatorial synthesis...on the same wells that were being analyzed in parallel by RP-HPLC/UV for purity. The sampling protocol for purity determination at Array BioPharma is

High Temperature Superconductor/Semiconductor Hybrid Microwave Devices and Circuits

NASA Technical Reports Server (NTRS)

Romanofsky, Robert R.; Miranda, Felix A.

1999-01-01

Contents include following: film deposition technique; laser ablation; magnetron sputtering; sequential evaporation; microwave substrates; film characterization at microwave frequencies; complex conductivity; magnetic penetration depth; surface impedance; planar single-mode filters; small antennas; antenna arrays phase noise; tunable oscillations; hybrid superconductor/semiconductor receiver front ends; and noise modeling.

Speeded Recognition of Ungrammaticality: Double Violations.

ERIC Educational Resources Information Center

Moore, Timothy E.; Biederman, Irving

1979-01-01

The speed at which sentences with various kinds of violations could be rejected was studied. Compatible with the sequential model was the finding that noun-verb and adjective-noun double violations did not result in shorter reaction times than noun-verb single violations, although double violations were judged less acceptable. (Author/RD)

Attentional effects on orientation judgements are dependent on memory consolidation processes.

PubMed

Haskell, Christie; Anderson, Britt

2016-11-01

Are the effects of memory and attention on perception synergistic, antagonistic, or independent? Tested separately, memory and attention have been shown to affect the accuracy of orientation judgements. When multiple stimuli are presented sequentially versus simultaneously, error variance is reduced. When a target is validly cued, precision is increased. What if they are manipulated together? We combined memory and attention manipulations in an orientation judgement task to answer this question. Two circular gratings were presented sequentially or simultaneously. On some trials a brief luminance cue preceded the stimuli. Participants were cued to report the orientation of one of the two gratings by rotating a response grating. We replicated the finding that error variance is reduced on sequential trials. Critically, we found interacting effects of memory and attention. Valid cueing reduced the median, absolute error only when two stimuli appeared together and improved it to the level of performance on uncued sequential trials, whereas invalid cueing always increased error. This effect was not mediated by cue predictiveness; however, predictive cues reduced the standard deviation of the error distribution, whereas nonpredictive cues reduced "guessing". Our results suggest that, when the demand on memory is greater than a single stimulus, attention is a bottom-up process that prioritizes stimuli for consolidation. Thus attention and memory are synergistic.

Organometallic exposure dependence on organic–inorganic hybrid material formation in polyethylene terephthalate and polyamide 6 polymer fibers

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

Akyildiz, Halil I.; Jur, Jesse S., E-mail: jsjur@ncsu.edu

2015-03-15

The effect of exposure conditions and surface area on hybrid material formation during sequential vapor infiltrations of trimethylaluminum (TMA) into polyamide 6 (PA6) and polyethylene terephthalate (PET) fibers is investigated. Mass gain of the fabric samples after infiltration was examined to elucidate the reaction extent with increasing number of sequential TMA single exposures, defined as the times for a TMA dose and a hold period. An interdependent relationship between dosing time and holding time on the hybrid material formation is observed for TMA exposure PET, exhibited as a linear trend between the mass gain and total exposure (dose time ×more » hold time × number of sequential exposures). Deviation from this linear relationship is only observed under very long dose or hold times. In comparison, amount of hybrid material formed during sequential exposures to PA6 fibers is found to be highly dependent on amount of TMA dosed. Increasing the surface area of the fiber by altering its cross-sectional dimension is shown to have little on the reaction behavior but does allow for improved diffusion of the TMA into the fiber. This work allows for the projection of exposure parameters necessary for future high-throughput hybrid modifications to polymer materials.« less

Comparative study of lesions created by high-intensity focused ultrasound using sequential discrete and continuous scanning strategies.

PubMed

Fan, Tingbo; Liu, Zhenbo; Zhang, Dong; Tang, Mengxing

2013-03-01

Lesion formation and temperature distribution induced by high-intensity focused ultrasound (HIFU) were investigated both numerically and experimentally via two energy-delivering strategies, i.e., sequential discrete and continuous scanning modes. Simulations were presented based on the combination of Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation and bioheat equation. Measurements were performed on tissue-mimicking phantoms sonicated by a 1.12-MHz single-element focused transducer working at an acoustic power of 75 W. Both the simulated and experimental results show that, in the sequential discrete mode, obvious saw-tooth-like contours could be observed for the peak temperature distribution and the lesion boundaries, with the increasing interval space between two adjacent exposure points. In the continuous scanning mode, more uniform peak temperature distributions and lesion boundaries would be produced, and the peak temperature values would decrease significantly with the increasing scanning speed. In addition, compared to the sequential discrete mode, the continuous scanning mode could achieve higher treatment efficiency (lesion area generated per second) with a lower peak temperature. The present studies suggest that the peak temperature and tissue lesion resulting from the HIFU exposure could be controlled by adjusting the transducer scanning speed, which is important for improving the HIFU treatment efficiency.

Sequential Probability Ratio Testing with Power Projective Base Method Improves Decision-Making for BCI

PubMed Central

Liu, Rong

2017-01-01

Obtaining a fast and reliable decision is an important issue in brain-computer interfaces (BCI), particularly in practical real-time applications such as wheelchair or neuroprosthetic control. In this study, the EEG signals were firstly analyzed with a power projective base method. Then we were applied a decision-making model, the sequential probability ratio testing (SPRT), for single-trial classification of motor imagery movement events. The unique strength of this proposed classification method lies in its accumulative process, which increases the discriminative power as more and more evidence is observed over time. The properties of the method were illustrated on thirteen subjects' recordings from three datasets. Results showed that our proposed power projective method outperformed two benchmark methods for every subject. Moreover, with sequential classifier, the accuracies across subjects were significantly higher than that with nonsequential ones. The average maximum accuracy of the SPRT method was 84.1%, as compared with 82.3% accuracy for the sequential Bayesian (SB) method. The proposed SPRT method provides an explicit relationship between stopping time, thresholds, and error, which is important for balancing the time-accuracy trade-off. These results suggest SPRT would be useful in speeding up decision-making while trading off errors in BCI. PMID:29348781

Dabigatran for the prevention of stroke and systemic embolism in atrial fibrillation: A NICE single technology appraisal.

PubMed

Faria, Rita; Spackman, Eldon; Burch, Jane; Corbacho, Belen; Todd, Derick; Pepper, Chris; Woolacott, Nerys; Palmer, Stephen

2013-07-01

The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of dabigatran etexilate (Boehringer Ingelheim Ltd, UK) to submit evidence for the clinical and cost-effectiveness of this drug for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) as part of the NICE single technology appraisal process. The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the evidence review group (ERG). This article presents a summary of the manufacturer's submission, the ERG report and the subsequent development of NICE guidance for the use of dabigatran within the UK National Health Service. Dabigatran was granted marketing authorisation by the European Medicines Agency for a sequential dosing regimen (DBG sequential), in which patients under 80 years are treated with dabigatran 150 mg twice daily (DBG150) and patients 80 years and over are given dabigatran 110 mg twice daily (DBG110). NICE decisions are bound by the marketing authorisation; therefore, the decision problem faced by the committee was whether the DBG sequential regimen was effective and cost-effective compared with warfarin or aspirin for patients with non-valvular AF and one or more risk factors. The RE-LY trial, a large multi-centre non-inferiority randomised clinical trial, was the primary source of clinical evidence. DBG150 was shown to be non-inferior, and subsequently superior to warfarin, for the primary outcome of all stroke/systemic embolism. DBG110 was found to be non-inferior to warfarin. Results were presented for a post hoc subgroup analysis for patients under and over 80 years of age, where DBG110 showed a statistically significant reduction of haemorrhagic stroke and intracranial haemorrhage in comparison to warfarin in patients over 80 years of age. This post hoc subgroup analysis by age was the basis for the licensed DBG sequential regimen. The economic evaluation compared the costs and outcomes of DBG110, DBG150 and DBG sequential against warfarin, aspirin, and aspirin plus clopidogrel. Across the three dosing regimens, dabigatran was associated with greater costs and better health outcomes than warfarin; however, DBG150 offered the most benefits and dominated DBG110 and DBG sequential (i.e. less costly and more effective). The cost-effectiveness of DBG150 was less favourable for patients well controlled on warfarin. In the first appraisal meeting, the committee issued a 'minded no' decision until additional analyses on the licensed DBG sequential regimen were presented by the manufacturer. These additional analyses indicated that the incremental cost-effectiveness ratio (ICER) of the DBG sequential regimen compared with warfarin ranged from £8,388 to £18,987 per quality-adjusted life year (QALY) gained depending on the level of monitoring costs assumed for warfarin. Patients on warfarin would need to be within therapeutic range 83-85 % of the time for the ICER to exceed £30,000 per additional QALY. Following consideration of the additional evidence and the responses from a large number of consultees and commentators, the committee recommended dabigatran as DBG sequential as an option for the prevention of stroke and systemic embolism in people with non-valvular AF with one or more risk factors for ischaemic stroke.

Identification of Pseudomonas syringae pathogens of Arabidopsis and a bacterial locus determining avirulence on both Arabidopsis and soybean.

PubMed

Whalen, M C; Innes, R W; Bent, A F; Staskawicz, B J

1991-01-01

To develop a model system for molecular genetic analysis of plant-pathogen interactions, we studied the interaction between Arabidopsis thaliana and the bacterial pathogen Pseudomonas syringae pv tomato (Pst). Pst strains were found to be virulent or avirulent on specific Arabidopsis ecotypes, and single ecotypes were resistant to some Pst strains and susceptible to others. In many plant-pathogen interactions, disease resistance is controlled by the simultaneous presence of single plant resistance genes and single pathogen avirulence genes. Therefore, we tested whether avirulence genes in Pst controlled induction of resistance in Arabidopsis. Cosmids that determine avirulence were isolated from Pst genomic libraries, and the Pst avirulence locus avrRpt2 was defined. This allowed us to construct pathogens that differed only by the presence or absence of a single putative avirulence gene. We found that Arabidopsis ecotype Col-0 was susceptible to Pst strain DC3000 but resistant to the same strain carrying avrRpt2, suggesting that a single locus in Col-0 determines resistance. As a first step toward genetically mapping the postulated resistance locus, an ecotype susceptible to infection by DC3000 carrying avrRpt2 was identified. The avrRpt2 locus from Pst was also moved into virulent strains of the soybean pathogen P. syringae pv glycinea to test whether this locus could determine avirulence on soybean. The resulting strains induced a resistant response in a cultivar-specific manner, suggesting that similar resistance mechanisms may function in Arabidopsis and soybean.

Nevirapine Resistance by Timing of HIV Type 1 Infection in Infants Treated with Single-Dose Nevirapine

PubMed Central

Micek, Mark A.; Blanco, Ana Judith; Beck, Ingrid A.; Dross, Sandra; Matunha, Laurinda; Montoya, Pablo; Seidel, Kristy; Gantt, Soren; Matediane, Eduardo; Jamisse, Lilia; Gloyd, Stephen; Frenkel, Lisa M.

2011-01-01

Background In women, single-dose nevirapine for prophylaxis against mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) selects for nevirapine-resistant HIV-1, which subsequently decays rapidly. We hypothesized that the selection, acquisition, and decay of nevirapine-resistant HIV-1 differs in infants, varying by the timing of HIV-1 infection. Methods We conducted a prospective, observational study of 740 Mozambican infants receiving single-dose nevirapine prophylaxis and determined the timing of infection and concentrations of nevirapine-resistant HIV-1 over time. Results Infants with established in utero infection had a high rate (87.0%) of selection of nevirapine-resistant HIV-1 mutants, which rapidly decayed to undetectable levels. The few without nevirapine resistance received zidovudine with single-dose nevirapine and/or their mothers took alternative antiretroviral drugs. Infants with acute in utero infection had a lower rate of nevirapine-resistant HIV-1 (33.3%; P =.006, compared with established in utero infection), but mutants persisted over time. Infants with peripartum infection also had a lower rate of nevirapine-resistant HIV-1 (38.1%; P =.001, compared with established in utero infection) but often acquired 100% mutant virus that persisted over time (P =.017, compared with established in utero infection). Conclusions The detection and persistence of nevirapine-resistant HIV-1 in infants after single-dose nevirapine therapy vary by the timing of infection and the antiretroviral regimen. In infants with persistent high-level nevirapine-resistant HIV-1, nevirapine-based antiretroviral therapy is unlikely to ever be efficacious because of concentrations in long-lived viral reservoirs. However, the absence or decay of nevirapine-resistant HIV-1 in many infants suggests that nevirapine antiretroviral therapy may be effective if testing can identify these individuals. PMID:20384494

CAR-T cells are serial killers

PubMed Central

Davenport, Alexander J; Jenkins, Misty R; Ritchie, David S; Prince, H Miles; Trapani, Joseph A; Kershaw, Michael H; Darcy, Phillip K; Neeson, Paul J

2015-01-01

Chimeric antigen receptor (CAR) T cells have enjoyed unprecedented clinical success against haematological malignancies in recent years. However, several aspects of CAR T cell biology remain unknown. We recently compared CAR and T cell receptor (TCR)-based killing in the same effector cell and showed that CAR T cells can not only efficiently kill single tumor targets, they can also kill multiple tumor targets in a sequential manner. Single and serial killing events were not sustained long term due to CAR down-regulation after 20 hours. PMID:26587330

CAR-T cells are serial killers.

PubMed

Davenport, Alexander J; Jenkins, Misty R; Ritchie, David S; Prince, H Miles; Trapani, Joseph A; Kershaw, Michael H; Darcy, Phillip K; Neeson, Paul J

2015-12-01

Chimeric antigen receptor (CAR) T cells have enjoyed unprecedented clinical success against haematological malignancies in recent years. However, several aspects of CAR T cell biology remain unknown. We recently compared CAR and T cell receptor (TCR)-based killing in the same effector cell and showed that CAR T cells can not only efficiently kill single tumor targets, they can also kill multiple tumor targets in a sequential manner. Single and serial killing events were not sustained long term due to CAR down-regulation after 20 hours.

Deferred discrimination algorithm (nibbling) for target filter management

NASA Astrophysics Data System (ADS)

Caulfield, H. John; Johnson, John L.

1999-07-01

A new method of classifying objects is presented. Rather than trying to form the classifier in one step or in one training algorithm, it is done in a series of small steps, or nibbles. This leads to an efficient and versatile system that is trained in series with single one-shot examples but applied in parallel, is implemented with single layer perceptrons, yet maintains its fully sequential hierarchical structure. Based on the nibbling algorithm, a basic new method of target reference filter management is described.

Method for rapid base sequencing in DNA and RNA with two base labeling

DOEpatents

Jett, J.H.; Keller, R.A.; Martin, J.C.; Posner, R.G.; Marrone, B.L.; Hammond, M.L.; Simpson, D.J.

1995-04-11

A method is described for rapid-base sequencing in DNA and RNA with two-base labeling and employing fluorescent detection of single molecules at two wavelengths. Bases modified to accept fluorescent labels are used to replicate a single DNA or RNA strand to be sequenced. The bases are then sequentially cleaved from the replicated strand, excited with a chosen spectrum of electromagnetic radiation, and the fluorescence from individual, tagged bases detected in the order of cleavage from the strand. 4 figures.

An empirical relationship for homogenization in single-phase binary alloy systems

NASA Technical Reports Server (NTRS)

Unnam, J.; Tenney, D. R.; Stein, B. A.

1979-01-01

A semiempirical formula is developed for describing the extent of interaction between constituents in single-phase binary alloy systems with planar, cylindrical, or spherical interfaces. The formula contains two parameters that are functions of mean concentration and interface geometry of the couple. The empirical solution is simple, easy to use, and does not involve sequential calculations, thereby allowing quick estimation of the extent of interactions without lengthy calculations. Results obtained with this formula are in good agreement with those from a finite-difference analysis.

Single-Band and Dual-Band Infrared Detectors

NASA Technical Reports Server (NTRS)

Ting, David Z. (Inventor); Gunapala, Sarath D. (Inventor); Soibel, Alexander (Inventor); Nguyen, Jean (Inventor); Khoshakhlagh, Arezou (Inventor)

2015-01-01

Bias-switchable dual-band infrared detectors and methods of manufacturing such detectors are provided. The infrared detectors are based on a back-to-back heterojunction diode design, where the detector structure consists of, sequentially, a top contact layer, a unipolar hole barrier layer, an absorber layer, a unipolar electron barrier, a second absorber, a second unipolar hole barrier, and a bottom contact layer. In addition, by substantially reducing the width of one of the absorber layers, a single-band infrared detector can also be formed.

Single-Band and Dual-Band Infrared Detectors

NASA Technical Reports Server (NTRS)

Ting, David Z. (Inventor); Gunapala, Sarath D. (Inventor); Soibel, Alexander (Inventor); Nguyen, Jean (Inventor); Khoshakhlagh, Arezou (Inventor)

2017-01-01

Bias-switchable dual-band infrared detectors and methods of manufacturing such detectors are provided. The infrared detectors are based on a back-to-back heterojunction diode design, where the detector structure consists of, sequentially, a top contact layer, a unipolar hole barrier layer, an absorber layer, a unipolar electron barrier, a second absorber, a second unipolar hole barrier, and a bottom contact layer. In addition, by substantially reducing the width of one of the absorber layers, a single-band infrared detector can also be formed.

Method for rapid base sequencing in DNA and RNA with two base labeling

DOEpatents

Jett, James H.; Keller, Richard A.; Martin, John C.; Posner, Richard G.; Marrone, Babetta L.; Hammond, Mark L.; Simpson, Daniel J.

1995-01-01

Method for rapid-base sequencing in DNA and RNA with two-base labeling and employing fluorescent detection of single molecules at two wavelengths. Bases modified to accept fluorescent labels are used to replicate a single DNA or RNA strand to be sequenced. The bases are then sequentially cleaved from the replicated strand, excited with a chosen spectrum of electromagnetic radiation, and the fluorescence from individual, tagged bases detected in the order of cleavage from the strand.

Length-dependent thermal transport in one-dimensional self-assembly of planar π-conjugated molecules

NASA Astrophysics Data System (ADS)

Tang, Hao; Xiong, Yucheng; Zu, Fengshuo; Zhao, Yang; Wang, Xiaomeng; Fu, Qiang; Jie, Jiansheng; Yang, Juekuan; Xu, Dongyan

2016-06-01

This work reports a thermal transport study in quasi-one-dimensional organic nanostructures self-assembled from conjugated planar molecules via π-π interactions. Thermal resistances of single crystalline copper phthalocyanine (CuPc) and perylenetetracarboxylic diimide (PTCDI) nanoribbons are measured via a suspended thermal bridge method. We experimentally observed the deviation from the linear length dependence for the thermal resistance of single crystalline β-phase CuPc nanoribbons, indicating possible subdiffusion thermal transport. Interestingly, a gradual transition to the linear length dependence is observed with the increase of the lateral dimensions of CuPc nanoribbons. The measured thermal resistance of single crystalline CuPc nanoribbons shows an increasing trend with temperature. However, the trend of temperature dependence of thermal resistance is reversed after electron irradiation, i.e., decreasing with temperature, indicating that the single crystalline CuPc nanoribbons become `amorphous'. Similar behavior is also observed for PTCDI nanoribbons after electron irradiation, proving that the electron beam can induce amorphization of single crystalline self-assembled nanostructures of planar π-conjugated molecules. The measured thermal resistance of the `amorphous' CuPc nanoribbon demonstrates a roughly linear dependence on the nanoribbon length, suggesting that normal diffusion dominates thermal transport.This work reports a thermal transport study in quasi-one-dimensional organic nanostructures self-assembled from conjugated planar molecules via π-π interactions. Thermal resistances of single crystalline copper phthalocyanine (CuPc) and perylenetetracarboxylic diimide (PTCDI) nanoribbons are measured via a suspended thermal bridge method. We experimentally observed the deviation from the linear length dependence for the thermal resistance of single crystalline β-phase CuPc nanoribbons, indicating possible subdiffusion thermal transport. Interestingly, a gradual transition to the linear length dependence is observed with the increase of the lateral dimensions of CuPc nanoribbons. The measured thermal resistance of single crystalline CuPc nanoribbons shows an increasing trend with temperature. However, the trend of temperature dependence of thermal resistance is reversed after electron irradiation, i.e., decreasing with temperature, indicating that the single crystalline CuPc nanoribbons become `amorphous'. Similar behavior is also observed for PTCDI nanoribbons after electron irradiation, proving that the electron beam can induce amorphization of single crystalline self-assembled nanostructures of planar π-conjugated molecules. The measured thermal resistance of the `amorphous' CuPc nanoribbon demonstrates a roughly linear dependence on the nanoribbon length, suggesting that normal diffusion dominates thermal transport. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr09043a

Nebo: An efficient, parallel, and portable domain-specific language for numerically solving partial differential equations

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

Earl, Christopher; Might, Matthew; Bagusetty, Abhishek

This study presents Nebo, a declarative domain-specific language embedded in C++ for discretizing partial differential equations for transport phenomena on multiple architectures. Application programmers use Nebo to write code that appears sequential but can be run in parallel, without editing the code. Currently Nebo supports single-thread execution, multi-thread execution, and many-core (GPU-based) execution. With single-thread execution, Nebo performs on par with code written by domain experts. With multi-thread execution, Nebo can linearly scale (with roughly 90% efficiency) up to 12 cores, compared to its single-thread execution. Moreover, Nebo’s many-core execution can be over 140x faster than its single-thread execution.

Nebo: An efficient, parallel, and portable domain-specific language for numerically solving partial differential equations

DOE PAGES

Earl, Christopher; Might, Matthew; Bagusetty, Abhishek; ...

2016-01-26

This study presents Nebo, a declarative domain-specific language embedded in C++ for discretizing partial differential equations for transport phenomena on multiple architectures. Application programmers use Nebo to write code that appears sequential but can be run in parallel, without editing the code. Currently Nebo supports single-thread execution, multi-thread execution, and many-core (GPU-based) execution. With single-thread execution, Nebo performs on par with code written by domain experts. With multi-thread execution, Nebo can linearly scale (with roughly 90% efficiency) up to 12 cores, compared to its single-thread execution. Moreover, Nebo’s many-core execution can be over 140x faster than its single-thread execution.

A new scintillator detector system for the quality assurance of 60Co and high-energy therapy machines.

PubMed

Beddar, A S

1994-02-01

A new single-channel detector system has been developed to perform routine quality assurance of 60Co and high-energy therapy machines. This detector is composed of an orange plastic scintillator, optically coupled to a radiation-resistant polycarbonate light pipe and a shielded silicon photodiode imbedded in a hollow solid water phantom block. No temperature and pressure corrections are required. Stability results were consistent with standard deviations fluctuating from 0.03% up to 0.09% for 60Co and from 0.05% up to 0.18% for other high energies. This device provides a quick, easy and reliable beam output check remotely, using an automatic reset based on a radiation triggering system device, storing multiple sequential readings. The reproducibility of this detector was checked on a daily and weekly basis at different energies (60Co, 6 MV and 18 MV x-rays and 6, 9, 12, 16 and 20 MeV electron beams). These results were found to be consistent with those obtained using an ion chamber. Other characteristics of this detector, including the consequences of the radiation-induced light in the light pipe (stem effect) and the radiation damage on this system are briefly discussed.

Disease resistance in Atlantic salmon (Salmo salar): coinfection of the intracellular bacterial pathogen Piscirickettsia salmonis and the sea louse Caligus rogercresseyi.

PubMed

Lhorente, Jean Paul; Gallardo, José A; Villanueva, Beatriz; Carabaño, María J; Neira, Roberto

2014-01-01

Naturally occurring coinfections of pathogens have been reported in salmonids, but their consequences on disease resistance are unclear. We hypothesized that 1) coinfection of Caligus rogercresseyi reduces the resistance of Atlantic salmon to Piscirickettsia salmonis; and 2) coinfection resistance is a heritable trait that does not correlate with resistance to a single infection. In total, 1,634 pedigreed Atlantic salmon were exposed to a single infection (SI) of P. salmonis (primary pathogen) or coinfection with C. rogercresseyi (secondary pathogen). Low and high level of coinfection were evaluated (LC = 44 copepodites per fish; HC = 88 copepodites per fish). Survival and quantitative genetic analyses were performed to determine the resistance to the single infection and coinfections. C. rogercresseyi significantly increased the mortality in fish infected with P. salmonis (SI mortality = 251/545; LC mortality = 544/544 and HC mortality = 545/545). Heritability estimates for resistance to P. salmonis were similar and of medium magnitude in all treatments (h2SI = 0.23 ± 0.07; h2LC = 0.17 ± 0.08; h2HC = 0.24 ± 0.07). A large and significant genetic correlation with regard to resistance was observed between coinfection treatments (rg LC-HC = 0.99 ± 0.01) but not between the single and coinfection treatments (rg SI-LC = -0.14 ± 0.33; rg SI-HC = 0.32 ± 0.34). C. rogercresseyi, as a secondary pathogen, reduces the resistance of Atlantic salmon to the pathogen P. salmonis. Resistance to coinfection of Piscirickettsia salmonis and Caligus rogercresseyi in Atlantic salmon is a heritable trait. The absence of a genetic correlation between resistance to a single infection and resistance to coinfection indicates that different genes control these processes. Coinfection of different pathogens and resistance to coinfection needs to be considered in future research on salmon farming, selective breeding and conservation.

Thermal evaluation by infrared measurement of implant site preparation between single and gradual drilling in artificial bone blocks of different densities.

PubMed

Möhlhenrich, S C; Abouridouane, M; Heussen, N; Hölzle, F; Klocke, F; Modabber, A

2016-11-01

The aim of this study was to investigate the influence of bone density and drilling protocol on heat generation during implant bed preparation. Ten single and 10 gradual implant sites with diameters of 2.8, 3.5, and 4.2mm were prepared in four artificial bone blocks (density types I-IV; D1-D4). Drilling was done at constant speed (1500rpm) and with external irrigation (50ml/min); vertical speed was set at 2mm/s. An infrared camera was used for temperature measurements. Significantly higher temperatures for single drilling were found between 2.8-mm drills in D1 (P=0.0014) and D4 (P<0.0001) and between 3.5-mm drills in D3 (P=0.0087) and D4 (P<0.0001), as well as between 4.2-mm drills in D1 (P<0.0001) and D4 (P=0.0014). Low bone density led to a thermal decrease after single drilling and a thermal increase after gradual drilling. Burs with a large diameter always showed a higher temperature generation. In comparisons between 2.8- and 4.2-mm diameters for both single and gradual drills, significant differences (P<0.001) were noted for bone types II, III, and IV. Single drilling could generate more heat than traditional sequential drilling, and bone density, as well as drill diameter, influenced thermal increases. Particularly in lower-density bone, conventional sequential drilling seems to raise the temperature less. Copyright © 2016 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

System level analysis of cacao seed ripening reveals a sequential interplay of primary and secondary metabolism leading to polyphenol accumulation and preparation of stress resistance.

PubMed

Wang, Lei; Nägele, Thomas; Doerfler, Hannes; Fragner, Lena; Chaturvedi, Palak; Nukarinen, Ella; Bellaire, Anke; Huber, Werner; Weiszmann, Jakob; Engelmeier, Doris; Ramsak, Ziva; Gruden, Kristina; Weckwerth, Wolfram

2016-08-01

Theobroma cacao and its popular product, chocolate, are attracting attention due to potential health benefits including antioxidative effects by polyphenols, anti-depressant effects by high serotonin levels, inhibition of platelet aggregation and prevention of obesity-dependent insulin resistance. The development of cacao seeds during fruit ripening is the most crucial process for the accumulation of these compounds. In this study, we analyzed the primary and the secondary metabolome as well as the proteome during Theobroma cacao cv. Forastero seed development by applying an integrative extraction protocol. The combination of multivariate statistics and mathematical modelling revealed a complex consecutive coordination of primary and secondary metabolism and corresponding pathways. Tricarboxylic acid (TCA) cycle and aromatic amino acid metabolism dominated during the early developmental stages (stages 1 and 2; cell division and expansion phase). This was accompanied with a significant shift of proteins from phenylpropanoid metabolism to flavonoid biosynthesis. At stage 3 (reserve accumulation phase), metabolism of sucrose switched from hydrolysis into raffinose synthesis. Lipids as well as proteins involved in lipid metabolism increased whereas amino acids and N-phenylpropenoyl amino acids decreased. Purine alkaloids, polyphenols, and raffinose as well as proteins involved in abiotic and biotic stress accumulated at stage 4 (maturation phase) endowing cacao seeds the characteristic astringent taste and resistance to stress. In summary, metabolic key points of cacao seed development comprise the sequential coordination of primary metabolites, phenylpropanoid, N-phenylpropenoyl amino acid, serotonin, lipid and polyphenol metabolism thereby covering the major compound classes involved in cacao aroma and health benefits. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Sequential photo-bleaching to delineate single Schwann cells at the neuromuscular junction.

PubMed

Brill, Monika S; Marinković, Petar; Misgeld, Thomas

2013-01-11

Sequential photo-bleaching provides a non-invasive way to label individual SCs at the NMJ. The NMJ is the largest synapse of the mammalian nervous system and has served as guiding model to study synaptic structure and function. In mouse NMJs motor axon terminals form pretzel-like contact sites with muscle fibers. The motor axon and its terminal are sheathed by SCs. Over the past decades, several transgenic mice have been generated to visualize motor neurons and SCs, for example Thy1-XFP and Plp-GFP mice, respectively. Along motor axons, myelinating axonal SCs are arranged in non-overlapping internodes, separated by nodes of Ranvier, to enable saltatory action potential propagation. In contrast, terminal SCs at the synapse are specialized glial cells, which monitor and promote neurotransmission, digest debris and guide regenerating axons. NMJs are tightly covered by up to half a dozen non-myelinating terminal SCs - these, however, cannot be individually resolved by light microscopy, as they are in direct membrane contact. Several approaches exist to individually visualize terminal SCs. None of these are flawless, though. For instance, dye filling, where single cells are impaled with a dye-filled microelectrode, requires destroying a labelled cell before filling a second one. This is not compatible with subsequent time-lapse recordings. Multi-spectral "Brainbow" labeling of SCs has been achieved by using combinatorial expression of fluorescent proteins. However, this technique requires combining several transgenes and is limited by the expression pattern of the promoters used. In the future, expression of "photo-switchable" proteins in SCs might be yet another alternative. Here we present sequential photo-bleaching, where single cells are bleached, and their image obtained by subtraction. We believe that this approach - due to its ease and versatility - represents a lasting addition to the neuroscientist's technology palette, especially as it can be used in vivo and transferred to others cell types, anatomical sites or species. In the following protocol, we detail the application of sequential bleaching and subsequent confocal time-lapse microscopy to terminal SCs in triangularis sterni muscle explants. This thin, superficial and easily dissected nerve-muscle preparation has proven useful for studies of NMJ development, physiology and pathology. Finally, we explain how the triangularis sterni muscle is prepared after fixation to perform correlated high-resolution confocal imaging, immunohistochemistry or ultrastructural examinations.

Evaluation of 19,460 Wheat Accessions Conserved in the Indian National Genebank to Identify New Sources of Resistance to Rust and Spot Blotch Diseases.

PubMed

Kumar, Sundeep; Archak, Sunil; Tyagi, R K; Kumar, Jagdish; Vk, Vikas; Jacob, Sherry R; Srinivasan, Kalyani; Radhamani, J; Parimalan, R; Sivaswamy, M; Tyagi, Sandhya; Yadav, Mamata; Kumari, Jyotisna; Deepali; Sharma, Sandeep; Bhagat, Indoo; Meeta, Madhu; Bains, N S; Chowdhury, A K; Saha, B C; Bhattacharya, P M; Kumari, Jyoti; Singh, M C; Gangwar, O P; Prasad, P; Bharadwaj, S C; Gogoi, Robin; Sharma, J B; Gm, Sandeep Kumar; Saharan, M S; Bag, Manas; Roy, Anirban; Prasad, T V; Sharma, R K; Dutta, M; Sharma, Indu; Bansal, K C

2016-01-01

A comprehensive germplasm evaluation study of wheat accessions conserved in the Indian National Genebank was conducted to identify sources of rust and spot blotch resistance. Genebank accessions comprising three species of wheat-Triticum aestivum, T. durum and T. dicoccum were screened sequentially at multiple disease hotspots, during the 2011-14 crop seasons, carrying only resistant accessions to the next step of evaluation. Wheat accessions which were found to be resistant in the field were then assayed for seedling resistance and profiled using molecular markers. In the primary evaluation, 19,460 accessions were screened at Wellington (Tamil Nadu), a hotspot for wheat rusts. We identified 4925 accessions to be resistant and these were further evaluated at Gurdaspur (Punjab), a hotspot for stripe rust and at Cooch Behar (West Bengal), a hotspot for spot blotch. The second round evaluation identified 498 accessions potentially resistant to multiple rusts and 868 accessions potentially resistant to spot blotch. Evaluation of rust resistant accessions for seedling resistance against seven virulent pathotypes of three rusts under artificial epiphytotic conditions identified 137 accessions potentially resistant to multiple rusts. Molecular analysis to identify different combinations of genetic loci imparting resistance to leaf rust, stem rust, stripe rust and spot blotch using linked molecular markers, identified 45 wheat accessions containing known resistance genes against all three rusts as well as a QTL for spot blotch resistance. The resistant germplasm accessions, particularly against stripe rust, identified in this study can be excellent potential candidates to be employed for breeding resistance into the background of high yielding wheat cultivars through conventional or molecular breeding approaches, and are expected to contribute toward food security at national and global levels.

Evaluation of 19,460 Wheat Accessions Conserved in the Indian National Genebank to Identify New Sources of Resistance to Rust and Spot Blotch Diseases

PubMed Central

Jacob, Sherry R.; Srinivasan, Kalyani; Radhamani, J.; Parimalan, R.; Sivaswamy, M.; Tyagi, Sandhya; Yadav, Mamata; Kumari, Jyotisna; Deepali; Sharma, Sandeep; Bhagat, Indoo; Meeta, Madhu; Bains, N. S.; Chowdhury, A. K.; Saha, B. C.; Bhattacharya, P. M.; Kumari, Jyoti; Singh, M. C.; Gangwar, O. P.; Prasad, P.; Bharadwaj, S. C.; Gogoi, Robin; Sharma, J. B.; GM, Sandeep Kumar; Saharan, M. S.; Bag, Manas; Roy, Anirban; Prasad, T. V.; Sharma, R. K.; Dutta, M.; Sharma, Indu; Bansal, K. C.

2016-01-01

A comprehensive germplasm evaluation study of wheat accessions conserved in the Indian National Genebank was conducted to identify sources of rust and spot blotch resistance. Genebank accessions comprising three species of wheat–Triticum aestivum, T. durum and T. dicoccum were screened sequentially at multiple disease hotspots, during the 2011–14 crop seasons, carrying only resistant accessions to the next step of evaluation. Wheat accessions which were found to be resistant in the field were then assayed for seedling resistance and profiled using molecular markers. In the primary evaluation, 19,460 accessions were screened at Wellington (Tamil Nadu), a hotspot for wheat rusts. We identified 4925 accessions to be resistant and these were further evaluated at Gurdaspur (Punjab), a hotspot for stripe rust and at Cooch Behar (West Bengal), a hotspot for spot blotch. The second round evaluation identified 498 accessions potentially resistant to multiple rusts and 868 accessions potentially resistant to spot blotch. Evaluation of rust resistant accessions for seedling resistance against seven virulent pathotypes of three rusts under artificial epiphytotic conditions identified 137 accessions potentially resistant to multiple rusts. Molecular analysis to identify different combinations of genetic loci imparting resistance to leaf rust, stem rust, stripe rust and spot blotch using linked molecular markers, identified 45 wheat accessions containing known resistance genes against all three rusts as well as a QTL for spot blotch resistance. The resistant germplasm accessions, particularly against stripe rust, identified in this study can be excellent potential candidates to be employed for breeding resistance into the background of high yielding wheat cultivars through conventional or molecular breeding approaches, and are expected to contribute toward food security at national and global levels. PMID:27942031

Radiation Effects of Commercial Resistive Random Access Memories

NASA Technical Reports Server (NTRS)

Chen, Dakai; LaBel, Kenneth A.; Berg, Melanie; Wilcox, Edward; Kim, Hak; Phan, Anthony; Figueiredo, Marco; Buchner, Stephen; Khachatrian, Ani; Roche, Nicolas

2014-01-01

We present results for the single-event effect response of commercial production-level resistive random access memories. We found that the resistive memory arrays are immune to heavy ion-induced upsets. However, the devices were susceptible to single-event functional interrupts, due to upsets from the control circuits. The intrinsic radiation tolerant nature of resistive memory makes the technology an attractive consideration for future space applications.

Gas Separation Using Organic-Vapor-Resistent Membranes In Conjunctin With Organic-Vapor-Selective Membranes

DOEpatents

Baker, Richard W.; Pinnau, Ingo; He, Zhenjie; Da Costa, Andre R.; Daniels, Ramin; Amo, Karl D.; Wijmans, Johannes G.

2003-06-03

A process for treating a gas mixture containing at least an organic compound gas or vapor and a second gas, such as natural gas, refinery off-gas or air. The process uses two sequential membrane separation steps, one using membrane selective for the organic compound over the second gas, the other selective for the second gas over the organic vapor. The second-gas-selective membranes use a selective layer made from a polymer having repeating units of a fluorinated polymer, and demonstrate good resistance to plasticization by the organic components in the gas mixture under treatment, and good recovery after exposure to liquid aromatic hydrocarbons. The membrane steps can be combined in either order.

Operating characteristics of HTS power supply for and improving temporal stability of coated conductor magnet in liquid helium

NASA Astrophysics Data System (ADS)

Park, D. K.; Kim, Y. J.; Yang, S. E.; Kwon, N. Y.; Lee, H. G.; Ko, T. K.

2009-10-01

High temperature superconducting (HTS) magnets have been studied for insert coils of high field nuclear magnetic resonance (NMR) magnets but the temporal stability required for NMR is hard to achieve due to low index value and high joint resistance. In this research, the HTS power supply with magnets using coated conductor (CC) was investigated and tested in helium cryogenic system. All joints were conducted by soldering after etching stabilizer of the CC to minimize joint resistance. The pumping rate was determined by current amplitude and timing sequential control of heaters and the electromagnet. Operating characteristics were analyzed to enhance charging efficiency and the feasibility of temporally stable CC magnet during persistent mode was studied.

Sequential and Simultaneous Applications of UV and Chlorine for Adenovirus Inactivation.

PubMed

Rattanakul, Surapong; Oguma, Kumiko; Takizawa, Satoshi

2015-09-01

Adenoviruses are water-borne human pathogens with high resistance to UV disinfection. Combination of UV treatment and chlorination could be an effective approach to deal with adenoviruses. In this study, human adenovirus 5 (HAdV-5) was challenged in a bench-scale experiment by separate applications of UV or chlorine and by combined applications of UV and chlorine in either a sequential or simultaneous manner. The treated samples were then propagated in human lung carcinoma epithelial cells to quantify the log inactivation of HAdV-5. When the processes were separate, a fluence of 100 mJ/cm(2) and a CT value of 0.02 mg min/L were required to achieve 2 log inactivation of HAdV-5 by UV disinfection and chlorination, respectively. Interestingly, synergistic effects on the HAdV-5 inactivation rates were found in the sequential process of chlorine followed by UV (Cl2-UV) (p < 0.05, ANCOVA) in comparison to the separate processes or the simultaneous application of UV/Cl2. This implies that a pretreatment with chlorine may increase the sensitivity of the virus to the subsequent UV disinfection. In conclusion, this study suggests that the combined application of UV and chlorine could be an effective measure against adenoviruses as a multi-barrier approach in water disinfection.

Empirical first-line treatment with tigecycline for febrile episodes following abdominal surgery in cancer patients.

PubMed

Secondo, Giovanni; Vassallo, Francesca; Solari, Nicola; Moresco, Luciano; Percivale, Pierluigi; Zappi, Lucia; Cafiero, Ferdinando; De Maria, Andrea

2010-11-01

Cancer patients with complicated infections following abdominal surgery represent one of the worst clinical scenarios that is useful for testing the efficacy of empirical antimicrobial therapy. No study so far has evaluated the performance of tigecycline (TIG) when administered as empirical first-line treatment in a homogeneous population of surgical cancer patients with a febrile episode. An observational review of the data records of 24 sequential patients receiving TIG for a febrile episode following a major abdominal procedure in a single cancer institute was performed. Large bowel surgery represented 68% of all procedures, followed by gastric surgery (16%) and urinary-gynaecologic-biliary surgery (16%). Complications following surgery were observed in 68% of febrile episodes, with peritonitis and sepsis accounting for 59% and 24% of complications, respectively. Eight patients needed repeat surgery for source control. The mean duration of TIG treatment was 8 days. Causative pathogens were detected in 16 episodes (64%), and a total of 44 microorganisms were recovered (29% Escherichia coli, 9% Enterococcus faecalis and 9% coagulase-negative staphylococci). TIG was effective in 12 episodes (48%). The success rate was 67% when infectious episodes sustained by intrinsically resistant bacteria and fungi were excluded. Treatment failure was associated with the presence of complications and with microbiologically documented infection. TIG may be useful as a first-line treatment option in cancer patients requiring antibiotic treatment following surgery when complications are not present or suspected on clinical grounds and when local microbial epidemiology shows a low incidence of primary resistant bacteria. Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Destruction of Bacillus cereus spores in a thick soy bean paste (doenjang) by continuous ohmic heating with five sequential electrodes.

PubMed

Ryang, J H; Kim, N H; Lee, B S; Kim, C T; Rhee, M S

2016-07-01

This study selected spores from Bacillus cereus FSP-2 strain (the isolate from a commercial doenjang processing line) as the test strain which showed significantly higher thermal resistance (P < 0·05) than B. cereus reference strain (ATCC 27348). The spores in doenjang were subjected to ohmic heating (OH) at 95, 105, 115 and 125°C for 30, 60 or 90 s using a five sequential electrode system (electrical field: 26·7 V cm(-1) ; alternating current frequency: 25 kHz). OH at 105°C for 30-90 s reduced the B. cereus spore count in doenjang samples to <4 log CFU g(-1) . Since OH treatment at 115 and 125°C caused a perceivable colour change in the product (>1·5 National Bureau of Standards units), treatment at 105°C for 60 s was selected and applied on a large scale (500 kg of product). Reliable and reproducible destruction of B. cereus spores occurred; the reductions achieved (to < 4 log CFU g(-1) ) met the Korean national standards. Scanning electron microscopy revealed microstructural alterations in the spores (shrinkage and a distorted outer spore coat). OH is an effective method for destroying B. cereus spores to ensure the microbiological quality and safety of a thick, highly viscous sauce. This study shows that an ohmic heating (OH) using a five sequential electrode system can effectively destroy highly heat-resistant Bacillus cereus spores which have been frequently found in a commercial doenjang processing line without perceivable quality change in the product. In addition, it may demonstrate high potential of the unique OH system used in this study that will further contribute to ensure microbiological quality and safety of crude sauces containing high levels of electrolyte other than doenjang as well. © 2016 The Society for Applied Microbiology.

BHC80 is Critical in Suppression of Snail-LSD1 Interaction and Breast Cancer Metastasis

DTIC Science & Technology

2013-01-01

characteristics such as invasion and metastasis. The most common chemotherapeutic drugs function by introducing DNA damage to impair cell division...expression confers drug resistancy on cancer cells indicates that Snail can function as a survival factor. Recently we performed a sequential protein...one of alanine, isoleucine , leucine and valine (Figure 3A). While the sequence surrounding Arg151, Lys152 and Ala153 does not exactly follow the rule

LaRC-RP41: A Tough, High-Performance Composite Matrix

NASA Technical Reports Server (NTRS)

Pater, Ruth H.; Johnston, Norman J.; Smith, Ricky E.; Snoha, John J.; Gautreaux, Carol R.; Reddy, Rakasi M.

1991-01-01

New polymer exhibits increased toughness and resistance to microcracking. Cross-linking PMR-15 and linear LaRC-TPI combined to provide sequential semi-2-IPN designated as LaRC-RP41. Synthesized from PMR-15 imide prepolymer undergoing cross-linking in immediate presence of LaRC-TPI polyamic acid, also undergoing simultaneous imidization and linear chain extension. Potentially high-temperature matrix resin, adhesive, and molding resin. Applications include automobiles, electronics, aircraft, and aerospace structures.

Heat accumulation during sequential cortical bone drilling.

PubMed

Palmisano, Andrew C; Tai, Bruce L; Belmont, Barry; Irwin, Todd A; Shih, Albert; Holmes, James R

2016-03-01

Significant research exists regarding heat production during single-hole bone drilling. No published data exist regarding repetitive sequential drilling. This study elucidates the phenomenon of heat accumulation for sequential drilling with both Kirschner wires (K wires) and standard two-flute twist drills. It was hypothesized that cumulative heat would result in a higher temperature with each subsequent drill pass. Nine holes in a 3 × 3 array were drilled sequentially on moistened cadaveric tibia bone kept at body temperature (about 37 °C). Four thermocouples were placed at the center of four adjacent holes and 2 mm below the surface. A battery-driven hand drill guided by a servo-controlled motion system was used. Six samples were drilled with each tool (2.0 mm K wire and 2.0 and 2.5 mm standard drills). K wire drilling increased temperature from 5 °C at the first hole to 20 °C at holes 6 through 9. A similar trend was found in standard drills with less significant increments. The maximum temperatures of both tools increased from <0.5 °C to nearly 13 °C. The difference between drill sizes was found to be insignificant (P > 0.05). In conclusion, heat accumulated during sequential drilling, with size difference being insignificant. K wire produced more heat than its twist-drill counterparts. This study has demonstrated the heat accumulation phenomenon and its significant effect on temperature. Maximizing the drilling field and reducing the number of drill passes may decrease bone injury. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Cost-effectiveness of allopurinol and febuxostat for the management of gout.

PubMed

Jutkowitz, Eric; Choi, Hyon K; Pizzi, Laura T; Kuntz, Karen M

2014-11-04

Gout is the most common inflammatory arthritis in the United States. To evaluate the cost-effectiveness of urate-lowering treatment strategies for the management of gout. Markov model. Published literature and expert opinion. Patients for whom allopurinol or febuxostat is a suitable initial urate-lowering treatment. Lifetime. Health care payer. 5 urate-lowering treatment strategies were evaluated: no treatment; allopurinol- or febuxostat-only therapy; allopurinol-febuxostat sequential therapy; and febuxostat-allopurinol sequential therapy. Two dosing scenarios were investigated: fixed dose (80 mg of febuxostat daily, 0.80 success rate; 300 mg of allopurinol daily, 0.39 success rate) and dose escalation (≤120 mg of febuxostat daily, 0.82 success rate; ≤800 mg of allopurinol daily, 0.78 success rate). Discounted costs, discounted quality-adjusted life-years, and incremental cost-effectiveness ratios. In both dosing scenarios, allopurinol-only therapy was cost-saving. Dose-escalation allopurinol-febuxostat sequential therapy was more costly but more effective than dose-escalation allopurinol therapy, with an incremental cost-effectiveness ratio of $39 400 per quality-adjusted life-year. The relative rankings of treatments did not change. Our results were relatively sensitive to several potential variations of model assumptions; however, the cost-effectiveness ratios of dose escalation with allopurinol-febuxostat sequential therapy remained lower than the willingness-to-pay threshold of $109 000 per quality-adjusted life-year. Long-term outcome data for patients with gout, including medication adherence, are limited. Allopurinol single therapy is cost-saving compared with no treatment. Dose-escalation allopurinol-febuxostat sequential therapy is cost-effective compared with accepted willingness-to-pay thresholds. Agency for Healthcare Research and Quality.

Efficient sequential and parallel algorithms for record linkage

PubMed Central

Mamun, Abdullah-Al; Mi, Tian; Aseltine, Robert; Rajasekaran, Sanguthevar

2014-01-01

Background and objective Integrating data from multiple sources is a crucial and challenging problem. Even though there exist numerous algorithms for record linkage or deduplication, they suffer from either large time needs or restrictions on the number of datasets that they can integrate. In this paper we report efficient sequential and parallel algorithms for record linkage which handle any number of datasets and outperform previous algorithms. Methods Our algorithms employ hierarchical clustering algorithms as the basis. A key idea that we use is radix sorting on certain attributes to eliminate identical records before any further processing. Another novel idea is to form a graph that links similar records and find the connected components. Results Our sequential and parallel algorithms have been tested on a real dataset of 1 083 878 records and synthetic datasets ranging in size from 50 000 to 9 000 000 records. Our sequential algorithm runs at least two times faster, for any dataset, than the previous best-known algorithm, the two-phase algorithm using faster computation of the edit distance (TPA (FCED)). The speedups obtained by our parallel algorithm are almost linear. For example, we get a speedup of 7.5 with 8 cores (residing in a single node), 14.1 with 16 cores (residing in two nodes), and 26.4 with 32 cores (residing in four nodes). Conclusions We have compared the performance of our sequential algorithm with TPA (FCED) and found that our algorithm outperforms the previous one. The accuracy is the same as that of this previous best-known algorithm. PMID:24154837

Randomised clinical trial: the efficacy of a 10-day sequential therapy vs. a 14-day standard proton pump inhibitor-based triple therapy for Helicobacter pylori in Korea.

PubMed

Kim, Y S; Kim, S J; Yoon, J H; Suk, K T; Kim, J B; Kim, D J; Kim, D Y; Min, H J; Park, S H; Shin, W G; Kim, K H; Kim, H Y; Baik, G H

2011-11-01

The eradication rates of Helicobacter pylori (H. pylori) using a proton pump inhibitor (PPI)-based triple therapy have declined due to antibiotic resistance worldwide. To compare the eradication rate of the 10-day sequential therapy for H. pylori infection with that of the 14-day standard PPI-based triple therapy. This was a prospective, randomised, controlled study. A total of 409 patients with H. pylori infection were randomly assigned to receive either the 10-day sequential therapy regimen, which consisted of pantoprazole (40 mg) plus amoxicillin (1000 mg) twice a day for 5 days, then pantoprazole (40 mg) with clarithromycin (500 mg) and metronidazole (500 mg) twice a day for another five consecutive days or the 14-day PPI-based triple therapy regimen, which consisted of pantoprazole (40 mg) with amoxicillin (1000 mg) and clarithromycin (500 mg) twice a day for 14 days. The pre- and post-treatment H. pylori status were assessed by rapid urease test, urea breath test, or histology. Successful eradication was confirmed at least 4 weeks after finishing the treatment. In the intention-to-treat analysis, the eradication rates of the 10-day sequential therapy and of the 14-day PPI-based triple therapy were 85.9% (176/205) and 75.0% (153/205), respectively (P = 0.006). In the per-protocol analysis, the eradication rates were 92.6% (175/205) and 85% (153/204), respectively (P = 0.019). There was no statistically significant difference between the two investigated groups regarding the occurrence of adverse event rates (18.9% vs. 13.3%, P = 0.143). The 10-day sequential therapy achieved significantly higher eradication rates than the 14-day standard PPI-based triple therapy in Korea. © 2011 Blackwell Publishing Ltd.

Daptomycin Resistance in Clinical MRSA Strains Is Associated with a High Biological Fitness Cost

PubMed Central

Roch, Melanie; Gagetti, Paula; Davis, James; Ceriana, Paola; Errecalde, Laura; Corso, Alejandra; Rosato, Adriana E.

2017-01-01

Daptomycin remains as one of the main treatment options for Methicillin-Resistant Staphylococcus aureus (MRSA). Sporadic resistance cases reported in patients treated with either daptomycin or glycopeptides are a growing concern. In a previous study, we described a clinical case of a patient with a community-acquired MRSA infection resistant to daptomycin and with intermediate resistance to vancomycin who developed a recurrent infection with a susceptible isogenic strain. In the present work, we further investigated the sequential events to determine whether the switch from a daptomycin resistance to a susceptible phenotype was due to a phenomenon of resistance reversion or recurrent infection with a susceptible strain. Pairwise competition experiments showed that the susceptible clinical recurrent SA6850 strain had increased fitness when compared to the resistant counterpart SA6820 strain. In fact, although we have demonstrated that reversion of daptomycin resistance to daptomycin susceptible can occur in vitro after serial passages in drug-free media, phylogenetic analysis suggested that the in vivo process was the result of a recurrent infection with a previous susceptible isolate carried by the patient rather than a resistance reversion of the strain. Whole genome sequence of evolved strains showed that daptomycin resistance in MRSA is associated with a high fitness cost mediated by mutations in mprF gene, revealed as a key element of the biological cost. Moreover, we determined that daptomycin resistance-associated fitness cost was independent of vancomycin intermediate resistance phenotype, as demonstrated in additional clinical MRSA vancomycin susceptible strains. This study highlights important observations as, despite daptomycin offers a useful treatment option for the patients with persistent infections, it has to be carefully monitored. The high fitness cost associated to daptomycin resistance may explain the reduced dissemination of daptomycin resistance and the absence of daptomycin reported outbreaks. PMID:29259579

Daptomycin Resistance in Clinical MRSA Strains Is Associated with a High Biological Fitness Cost.

PubMed

Roch, Melanie; Gagetti, Paula; Davis, James; Ceriana, Paola; Errecalde, Laura; Corso, Alejandra; Rosato, Adriana E

2017-01-01

Daptomycin remains as one of the main treatment options for Methicillin-Resistant Staphylococcus aureus (MRSA). Sporadic resistance cases reported in patients treated with either daptomycin or glycopeptides are a growing concern. In a previous study, we described a clinical case of a patient with a community-acquired MRSA infection resistant to daptomycin and with intermediate resistance to vancomycin who developed a recurrent infection with a susceptible isogenic strain. In the present work, we further investigated the sequential events to determine whether the switch from a daptomycin resistance to a susceptible phenotype was due to a phenomenon of resistance reversion or recurrent infection with a susceptible strain. Pairwise competition experiments showed that the susceptible clinical recurrent SA6850 strain had increased fitness when compared to the resistant counterpart SA6820 strain. In fact, although we have demonstrated that reversion of daptomycin resistance to daptomycin susceptible can occur in vitro after serial passages in drug-free media, phylogenetic analysis suggested that the in vivo process was the result of a recurrent infection with a previous susceptible isolate carried by the patient rather than a resistance reversion of the strain. Whole genome sequence of evolved strains showed that daptomycin resistance in MRSA is associated with a high fitness cost mediated by mutations in mprF gene, revealed as a key element of the biological cost. Moreover, we determined that daptomycin resistance-associated fitness cost was independent of vancomycin intermediate resistance phenotype, as demonstrated in additional clinical MRSA vancomycin susceptible strains. This study highlights important observations as, despite daptomycin offers a useful treatment option for the patients with persistent infections, it has to be carefully monitored. The high fitness cost associated to daptomycin resistance may explain the reduced dissemination of daptomycin resistance and the absence of daptomycin reported outbreaks.

The Role of Self-Injury in the Organisation of Behaviour

ERIC Educational Resources Information Center

Sandman, C. A.; Kemp, A. S.; Mabini, C.; Pincus, D.; Magnusson, M.

2012-01-01

Background: Self-injuring acts are among the most dramatic behaviours exhibited by human beings. There is no known single cause and there is no universally agreed upon treatment. Sophisticated sequential and temporal analysis of behaviour has provided alternative descriptions of self-injury that provide new insights into its initiation and…

Two New Real-Time PCR-based Surveillance Systems for “Candidatus Liberibacter” Species Detection

USDA-ARS?s Scientific Manuscript database

We developed two novel surveillance systems for “Candidatus Liberibacter” (CL) species detection and identification. The first system is called “single tube dual primer Taq-Man PCR” (STDP). The procedure involves two sequential rounds of PCR using the CL asiaticus species-specific outer and inner pr...

Political and Economic Behavior of Man: A Course of Study.

ERIC Educational Resources Information Center

Cooperative Curriculum Service Center, Centerville, MD.

This curriculum guide is designed to assist teachers in using such innovative techniques in the new social studies as concept teaching and inquiry with below average students. It is divided into two non-sequential semesters. Each of eleven units emphasize a single concept, in economics: 1) consumption, consumer purchasing, credit, deception,…

Neural Correlates of Sequence Learning with Stochastic Feedback

ERIC Educational Resources Information Center

Averbeck, Bruno B.; Kilner, James; Frith, Christopher D.

2011-01-01

Although much is known about decision making under uncertainty when only a single step is required in the decision process, less is known about sequential decision making. We carried out a stochastic sequence learning task in which subjects had to use noisy feedback to learn sequences of button presses. We compared flat and hierarchical behavioral…

The Effect of Guided Imagery and Internal Visualization on Learning

DTIC Science & Technology

1987-01-01

existance) of - . memory traces, and how retrival cues operate, to name a few. The lack of a single theory or a coherent approach has not deterred movement...and function (Subtask 3) to a 31% gain over the control group for information emphasizing the rote memory of sequential data (Subtask 1). Overall, the

A Writing Intervention to Teach Simple Sentences and Descriptive Paragraphs to Adolescents with Writing Difficulties

ERIC Educational Resources Information Center

Datchuk, Shawn M.; Kubina, Richard M., Jr.

2017-01-01

The present study used a multiple-baseline, single-case experimental design to investigate the effects of a multicomponent intervention on construction of simple sentences and word sequences. The intervention entailed sequential delivery of sentence instruction and frequency building to a performance criterion and paragraph instruction.…

Speech Sequence Skill Learning in Adults Who Stutter

ERIC Educational Resources Information Center

Bauerly, Kim R.; De Nil, Luc F.

2011-01-01

The present study compared the ability of 12 people who stutter (PWS) and 12 people who do not stutter (PNS) to consolidate a novel sequential speech task. Participants practiced 100 repetitions of a single, monosyllabic, nonsense word sequence during an initial practice session and returned 24-h later to perform an additional 50 repetitions.…

Automated microbial metabolism laboratory. [design of advanced labeled release experiment based on single addition of soil and multiple sequential additions of media into test chambers

NASA Technical Reports Server (NTRS)

1974-01-01

The design and rationale of an advanced labeled release experiment based on single addition of soil and multiple sequential additions of media into each of four test chambers are outlined. The feasibility for multiple addition tests was established and various details of the methodology were studied. The four chamber battery of tests include: (1) determination of the effect of various atmospheric gases and selection of that gas which produces an optimum response; (2) determination of the effect of incubation temperature and selection of the optimum temperature for performing Martian biochemical tests; (3) sterile soil is dosed with a battery of C-14 labeled substrates and subjected to experimental temperature range; and (4) determination of the possible inhibitory effects of water on Martian organisms is performed initially by dosing with 0.01 ml and 0.5 ml of medium, respectively. A series of specifically labeled substrates are then added to obtain patterns in metabolic 14CO2 (C-14)O2 evolution.

Hybrid fluorescence and electron cryo-microscopy for simultaneous electron and photon imaging.

PubMed

Iijima, Hirofumi; Fukuda, Yoshiyuki; Arai, Yoshihiro; Terakawa, Susumu; Yamamoto, Naoki; Nagayama, Kuniaki

2014-01-01

Integration of fluorescence light and transmission electron microscopy into the same device would represent an important advance in correlative microscopy, which traditionally involves two separate microscopes for imaging. To achieve such integration, the primary technical challenge that must be solved regards how to arrange two objective lenses used for light and electron microscopy in such a manner that they can properly focus on a single specimen. To address this issue, both lateral displacement of the specimen between two lenses and specimen rotation have been proposed. Such movement of the specimen allows sequential collection of two kinds of microscopic images of a single target, but prevents simultaneous imaging. This shortcoming has been made up by using a simple optical device, a reflection mirror. Here, we present an approach toward the versatile integration of fluorescence and electron microscopy for simultaneous imaging. The potential of simultaneous hybrid microscopy was demonstrated by fluorescence and electron sequential imaging of a fluorescent protein expressed in cells and cathodoluminescence imaging of fluorescent beads. Copyright © 2013 Elsevier Inc. All rights reserved.

BioChar Amendments for Improved Plant Microbiome and Crop Health Project

NASA Technical Reports Server (NTRS)

Zeitlin, Nancy; Smith, David; Catechis, John; Khodadad, Christina; Koss, Lawrence; Mejia, Oscar Monje; Spencer, Lashelle

2015-01-01

Plant-based Environmental Control and Life Support Systems (ECLSS) enable human existence beyond Low Earth Orbit (LEO) by providing oxygen, water and food. The root modules are key to success of sustainable plant-based ECLSS. In microgravity, hydroponics is not viable as gases separate from fluids, thus plants are grown in soil substrates, which are bulky and must be maintained for optimal plant growth. Soil substrate selection also impacts ECLSS self-sufficiency. Savings in resupply mass and volume are possible if soil is developed in-situ from regolith found on moons or planets. Biochar, a soil amendment used by ancient civilizations to improve soil fertility that promotes plant health and root zone microbes, can be produced by pyrolysis of plant biomass. The goal is to study the effect of biochar on sequential crop plantings in a single root module. The objectives are: 1) follow changes in root-microbe interactions using metagenomic techniques, 2) measure changes in microbial populations during sequential cropping in a single root module, and 3) examine effect of biochar amendments.

Sequential Total Variation Denoising for the Extraction of Fetal ECG from Single-Channel Maternal Abdominal ECG

PubMed Central

Lee, Kwang Jin; Lee, Boreom

2016-01-01

Fetal heart rate (FHR) is an important determinant of fetal health. Cardiotocography (CTG) is widely used for measuring the FHR in the clinical field. However, fetal movement and blood flow through the maternal blood vessels can critically influence Doppler ultrasound signals. Moreover, CTG is not suitable for long-term monitoring. Therefore, researchers have been developing algorithms to estimate the FHR using electrocardiograms (ECGs) from the abdomen of pregnant women. However, separating the weak fetal ECG signal from the abdominal ECG signal is a challenging problem. In this paper, we propose a method for estimating the FHR using sequential total variation denoising and compare its performance with that of other single-channel fetal ECG extraction methods via simulation using the Fetal ECG Synthetic Database (FECGSYNDB). Moreover, we used real data from PhysioNet fetal ECG databases for the evaluation of the algorithm performance. The R-peak detection rate is calculated to evaluate the performance of our algorithm. Our approach could not only separate the fetal ECG signals from the abdominal ECG signals but also accurately estimate the FHR. PMID:27376296

Sequential Total Variation Denoising for the Extraction of Fetal ECG from Single-Channel Maternal Abdominal ECG.

PubMed

Lee, Kwang Jin; Lee, Boreom

2016-07-01

Fetal heart rate (FHR) is an important determinant of fetal health. Cardiotocography (CTG) is widely used for measuring the FHR in the clinical field. However, fetal movement and blood flow through the maternal blood vessels can critically influence Doppler ultrasound signals. Moreover, CTG is not suitable for long-term monitoring. Therefore, researchers have been developing algorithms to estimate the FHR using electrocardiograms (ECGs) from the abdomen of pregnant women. However, separating the weak fetal ECG signal from the abdominal ECG signal is a challenging problem. In this paper, we propose a method for estimating the FHR using sequential total variation denoising and compare its performance with that of other single-channel fetal ECG extraction methods via simulation using the Fetal ECG Synthetic Database (FECGSYNDB). Moreover, we used real data from PhysioNet fetal ECG databases for the evaluation of the algorithm performance. The R-peak detection rate is calculated to evaluate the performance of our algorithm. Our approach could not only separate the fetal ECG signals from the abdominal ECG signals but also accurately estimate the FHR.

Sequential cooling insert for turbine stator vane

DOEpatents

Jones, Russel B

2017-04-04

A sequential flow cooling insert for a turbine stator vane of a small gas turbine engine, where the impingement cooling insert is formed as a single piece from a metal additive manufacturing process such as 3D metal printing, and where the insert includes a plurality of rows of radial extending impingement cooling air holes alternating with rows of radial extending return air holes on a pressure side wall, and where the insert includes a plurality of rows of chordwise extending second impingement cooling air holes on a suction side wall. The insert includes alternating rows of radial extending cooling air supply channels and return air channels that form a series of impingement cooling on the pressure side followed by the suction side of the insert.

[Not Available].

PubMed

Paturzo, Marco; Colaceci, Sofia; Clari, Marco; Mottola, Antonella; Alvaro, Rosaria; Vellone, Ercole

2016-01-01

. Mixed methods designs: an innovative methodological approach for nursing research. The mixed method research designs (MM) combine qualitative and quantitative approaches in the research process, in a single study or series of studies. Their use can provide a wider understanding of multifaceted phenomena. This article presents a general overview of the structure and design of MM to spread this approach in the Italian nursing research community. The MM designs most commonly used in the nursing field are the convergent parallel design, the sequential explanatory design, the exploratory sequential design and the embedded design. For each method a research example is presented. The use of MM can be an added value to improve clinical practices as, through the integration of qualitative and quantitative methods, researchers can better assess complex phenomena typical of nursing.

Comparison of simultaneous and sequential administration of fentanyl-propofol for surgical abortion: a randomized single-blinded controlled trial.

PubMed

Gao, Wei; Sha, Baoyong; Zhao, Yuan; Fan, Zhe; Liu, Lin; Shen, Xin

2017-08-01

Propofol lipid emulsion (PLE) is a nanosized sedative, and it is used with a combination of salted antalgic prodrug, fentanyl citrate (FC). To illustrate the synergistic effect of mixing, we compared the sedation/analgesia resulting from simultaneous and sequential administration in surgically induced abortion (No. ChiCTR-IPC-15006153). Simultaneous group showed lower bispectral index, blood pressure, and heart rate, when cannula was inserted into the uterus. It also showed less frequency of hypertension, sinus tachycardia, movement, pain at the injection site, and additional FC. Therefore, premixing of PLE and FC enhanced the sedation and analgesia; stabilized the hemodynamics; lessened the incidence of movement and injection pain; and reduced the requirement of drugs.

Granular activated carbon promoted ozonation of a food-processing secondary effluent.

PubMed

Alvarez, Pedro M; Pocostales, J Pablo; Beltrán, Fernando J

2011-01-30

This paper reports on the application of a simultaneous combination of ozone and a granular activated carbon (O(3)/GAC) as a tertiary treatment of a wastewater generated from the activity of various food-processing industries. Prior to the O(3)/GAC treatment, the wastewater was subjected to conventional primary and secondary treatments in a full-scale wastewater treatment plant (WWTP). The effluent from the WWTP presented high organic load (COD>500 mg/l and TOC>150 mg/l), which could be much reduced by the O(3)/GAC treatment. Results from the O(3)/GAC experiments were compared with those obtained in single ozonation, single adsorption onto GAC and sequential O(3)-GAC adsorption experiments. While single processes and the sequential one showed limited capacity to remove organic matter for the food-processing effluent (COD removal <40%), the simultaneous O(3)/GAC process led to decreases of COD up to 82% at the conditions here applied. The combined process also improved the ozone consumption, which decreased from about 19 g O(3)/g TOC (single ozonation process) to 8.2-10.7 g O(3)/g TOC (O(3)/GAC process). The reusability of the GAC throughout a series of consecutive O(3)/GAC experiments was studied with no apparent loss of activity for a neutral GAC (PZC = 6.7) but for a basic GAC (PZC = 9.1). Copyright © 2010 Elsevier B.V. All rights reserved.

Comparison of four methods of differential typing of isolates of Shigella sonnei.

PubMed Central

Helgason, S.; Old, D. C.

1981-01-01

An epidemiological study of Sonne dysentery in Dundee during the years 1971-6 was made by examining, in respect of 1420 isolates of Shigella sonnei, the discriminating power of colicine typing, antibiogram testing, biotyping and resistotyping and the stabilty of the markers they provided. Colicine typing identified nine colicine types, including four not previously described. However, because types 4 and 4 var., determined by col Ib, and type U, producing no colicines, accounted for 96% of the isolates, discrimination with colicine typing was poor. In antibiotic sensitivity test, 13 different antibiogram patterns were noted. Less than 1% of the isolates were sensitive to all of the eight antibiotics tested; most were multiply drug-resistant. Resistance to kanamycin, neomycin and paromomycin (KNP) was apparently due to a single resistance determinant, widely distributed in a majority (53%) of the isolates. When definitive times were chosen for reading each biotyping test, only maltose and rhamnose of the 13 "sugars' tested differentiated isolates into prompt- and late-fermenting types. Though the ability to ferment rhamnose was a stable property, it discriminated only 1.5% of the minority, late-fermenting type. Resistotyping with six chemicals discriminated eight epidemiologically valid resistotypes, including three new types. However, 93 of the isolates belonged to only three resistotypes. Analysis of the data for isolated from 286 epidemiologically distinct episodes showed that the variability of colicine and antibiogram characters, found among isolates within, respectively, 40 and 28% of the episodes, was generally associated with loss or gain of a plasmid ("col Ib-KNP') which determined production of colicine Ib and KNP resistance. These characters varied both in vivo and in vitro. Variability of resistotype characters, on the other hand, was observed in only 28 (9%) episodes, 14 of which possibly represented examples of mixed or sequential infections. For accurate epidemiological tracing of strains of Sh. sonnei in a community, resistotyping, the technique showing the greatest discrimination and least variability of the four tested, should be included as the principal typing method. Images Plate 1 PMID:7031123

Variation in sperm displacement and its association with accessory gland protein loci in Drosophila melanogaster.

PubMed

Clark, A G; Aguadé, M; Prout, T; Harshman, L G; Langley, C H

1995-01-01

Genes that influence mating and/or fertilization success may be targets for strong natural selection. If females remate frequently relative to the duration of sperm storage and rate of sperm use, sperm displacement may be an important component of male reproductive success. Although it has long been known that mutant laboratory stocks of Drosophila differ in sperm displacement, the magnitude of the naturally occurring genetic variation in this character has not been systematically quantified. Here we report the results of a screen for variation in sperm displacement among 152 lines of Drosophilia melanogaster that were made homozygous for second and/or third chromosomes recovered from natural populations. Sperm displacement was assayed by scoring the progeny of cn;bw females that had been mated sequentially to cn;bw and tested males in either order. Highly significant differences were seen in both the ability to displace sperm that is resident in the female's reproductive tract and in the ability to resist displacement by subsequent sperm. Most lines exhibited nearly complete displacement, having nearly all progeny sired by the second male, but several lines had as few as half the progeny fathered by the second male. Lines that were identified in the screen for naturally occurring variation in sperm displacement were also characterized for single-strand conformation polymorphisms (SSCP) at seven accessory gland protein (Acp) genes, Glucose dehydrogenase (Gld), and Esterase-6 (Est-6). Acp genes encode proteins that are in some cases known to be transmitted to the female in the seminal fluid and are likely candidates for genes that might mediate the phenomenon of sperm displacement. Significant associations were found between particular Acp alleles at four different loci (Acp26Aa/Ab, Acp29B, Acp36DE and Acp53E) and the ability of males to resist displacement by subsequent sperm. There was no correlation between the ability to displace resident sperm and the ability to resist being displaced by subsequent sperm. This lack of correlation, and the association of Acp alleles with resisting subsequent sperm only, suggests that different mechanisms mediate the two components of sperm displacement.

Antitumour Activity and Safety of Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer Previously Treated with Abiraterone Acetate Plus Prednisone for ≥24 weeks in Europe.

PubMed

de Bono, Johann S; Chowdhury, Simon; Feyerabend, Susan; Elliott, Tony; Grande, Enrique; Melhem-Bertrandt, Amal; Baron, Benoit; Hirmand, Mohammad; Werbrouck, Patrick; Fizazi, Karim

2018-07-01

Enzalutamide and abiraterone acetate plus prednisone, which target the androgen receptor axis, have expanded the treatment of advanced prostate cancer. Retrospective analyses suggest some cross-resistance between these two drugs when used sequentially, but robust, prospective studies have not yet been reported. To fulfil a regulatory postregistration commitment by evaluating the efficacy and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed following abiraterone acetate plus prednisone treatment. Multicentre, single-arm, open-label study, enrolled patients with progressing mCRPC after ≥24 wk of abiraterone acetate plus prednisone treatment. All patients maintained castration therapy during the trial. Prior chemotherapy was allowed but not required. Patients received enzalutamide 160mg/d orally. The primary endpoint was radiographic progression-free survival. Secondary endpoints were overall survival, prostate-specific antigen (PSA) response, and time-to-PSA progression. Safety data were also assessed. Kaplan-Meier methods were used to descriptively analyse time-to-event endpoints. Overall, 214 patients received enzalutamide treatment, 145 of whom were chemotherapy-naïve. Median radiographic progression-free survival was 8.1 mo (95% confidence interval: 6.1-8.3); median overall survival had not been reached. Unconfirmed PSA response rate was 27% (48 of 181). Median time-to-PSA progression was 5.7 mo (95% confidence interval: 5.6-5.8). The most common treatment-emergent adverse events were fatigue (32%), decreased appetite (25%), asthenia (18%), back pain (17%), and arthralgia (16%). No seizures were reported. Enzalutamide showed antitumour activity in some patients with mCRPC who had previously progressed following ≥24 wk of abiraterone acetate plus prednisone treatment. Patients with mCRPC who progressed on previous abiraterone acetate plus prednisone treatment, with or without prior chemotherapy, received enzalutamide. Although cross-resistance between the two agents was observed in a majority of patients, some still benefited from enzalutamide treatment. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

In-plane dissipation maxima and vortex-line distortions in the resistive transitions of oxygen-doped Bi2Sr2CaCu2O(8+delta) single crystals

NASA Astrophysics Data System (ADS)

Hsu, J. W. P.; Mitzi, D. B.; Kapitulnik, A.; Lee, Mark

1991-10-01

Measurements of the in-plane resistive transition of Bi2Sr2CaCu2O(8+delta) single crystals in perpendicular magnetic fields reveal that in oxygen-reduced samples a giant resistance maximum evolves with field. This is not seen in oxygenated samples with similar metallic normal resistivities. As the peak resistivity may exceed the normal resistivity, it cannot arise from ordinary vortex-motion dissipation. A model is proposed where the excess resistance results from nonrigid vortex motion coupling the out-of-plane dissipation to the in-plane resistance at temperatures where pinning effects are negligible.

Anti-cancer effect of oncolytic adenovirus-armed shRNA targeting MYCN gene on doxorubicin-resistant neuroblastoma cells.

PubMed

Li, Yuan; Zhuo, Baobiao; Yin, Yiyu; Han, Tao; Li, Shixian; Li, Zhengwei; Wang, Jian

2017-09-09

Chemotherapy is one of the few effective choices for patients with neuroblastoma. However, the development of muti-drug resistance (MDR) to chemotherapy is a major obstacle to the effective treatment of advanced or recurrent neuroblastoma. The muti-drug resistance-associated protein (MRP), which encodes a transmembrane glycoprotein, is a key regulator of MDR. The expression of MRP is a close correlation with MYCN oncogene in neuroblastoma. We have recently shown ZD55-shMYCN (oncolytic virus armed with shRNA against MYCN) can down-regulate MYCN to inhibit tumor cells proliferation and induce apoptosis in neuroblastoma. Here we further report ZD55-shMYCN re-sensitized doxorubicin-resistant cells to doxorubicin (as shown by reduced proliferation, increased apoptosis, and inhibited cell migration), and reduced the in vivo growth rate of neuroblastoma xenografts by down-regulation of MRP expression. Sequential therapy with doxorubicin did not affect the replication of ZD55-shMYCN in doxorubicin-resistant neuroblastoma cells, but decreased the expression of Bcl-2, Bcl-X L , MMP-1. Thus, this synergistic effect of ZD55-shMYCN in combination with doxorubicin provides a novel therapy strategy for doxorubicin-resistant neuroblastoma, and is a promising approach for further clinical development. Copyright © 2017 Elsevier Inc. All rights reserved.

A thorough investigation of the progressive reset dynamics in HfO{sub 2}-based resistive switching structures

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

Lorenzi, P., E-mail: lorenzi@die.uniroma1.it; Rao, R.; Irrera, F.

2015-09-14

According to previous reports, filamentary electron transport in resistive switching HfO{sub 2}-based metal-insulator-metal structures can be modeled using a diode-like conduction mechanism with a series resistance. Taking the appropriate limits, the model allows simulating the high (HRS) and low (LRS) resistance states of the devices in terms of exponential and linear current-voltage relationships, respectively. In this letter, we show that this simple equivalent circuit approach can be extended to represent the progressive reset transition between the LRS and HRS if a generalized logistic growth model for the pre-exponential diode current factor is considered. In this regard, it is demonstrated heremore » that a Verhulst logistic model does not provide accurate results. The reset dynamics is interpreted as the sequential deactivation of multiple conduction channels spanning the dielectric film. Fitting results for the current-voltage characteristics indicate that the voltage sweep rate only affects the deactivation rate of the filaments without altering the main features of the switching dynamics.« less

Validation of a single biopsy approach and bolus protein feeding to determine myofibrillar protein synthesis in stable isotope tracer studies in humans

PubMed Central

2011-01-01

Background Minimizing the number of muscle biopsies has important methodological implications and minimizes subject discomfort during a stable isotope amino acid infusion. We aimed to determine the reliability of obtaining a single muscle biopsy for the calculation of muscle protein fractional synthetic rate (FSR) as well as the amount of incorporation time necessary to obtain that biopsy after initiating a stable isotope infusion (Study 1). The calculation of muscle protein FSR requires tracer steady-state during the stable isotope infusion. Therefore, a second aim was to examine if steady-state conditions are compromised in the precursor pools (plasma free or muscle intracellular [IC]) after ingestion of a tracer enriched protein drink and after resistance exercise (Study 2). Methods Sixteen men (23 ± 3 years; BMI = 23.8 ± 2.2 kg/m2, means ± SD) were randomized to perform Study 1 or Study 2 (n = 8, per study). Subjects received a primed, constant infusion of L-[ring-13C6]phenylalanine coupled with muscle biopsies of the vastus lateralis to measure rates of myofibrillar protein synthesis (MPS). Subjects in Study 2 were fed 25 g of whey protein immediately after an acute bout of unilateral resistance exercise. Results There was no difference (P = 0.3) in rates of MPS determined using the steady-state precursor-product equation and determination of tracer incorporation between sequential biopsies 150 min apart or using plasma protein as the baseline enrichment, provided the infusion length was sufficient (230 ± 0.3 min). We also found that adding a modest amount of tracer (4% enriched), calculated based on the measured phenylalanine content of the protein (3.5%) in the drink, did not compromise steady-state conditions (slope of the enrichment curve not different from zero) in the plasma free or, more importantly, the IC pool (both P > 0.05). Conclusions These data demonstrate that the single biopsy approach yields comparable rates of muscle protein synthesis, provided a longer incorporation time is utilized, to that seen with a traditional two biopsy approach. In addition, we demonstrate that enriching protein-containing drinks with tracer does not disturb isotopic steady-state and thus both are reliable techniques to determine rates of MPS in humans. PMID:21388545

Single, simultaneous and sequential applications of ultrasonic frequencies for the elimination of ibuprofen in water.

PubMed

Ziylan-Yavas, Asu; Ince, Nilsun H

2018-01-01

The study is about the assessment of single and multi-frequency operations for the overall degradation of a widely consumed analgesic pharmaceutical-ibuprofen (IBP). The selected frequencies were in the range of 20-1130kHz emissions coming from probes, baths and piezo-electric transducers attached to plate-type devices. Multi-frequency operations were applied either simultaneously as "duals", or sequentially at fixed time intervals; and the total reaction time in all operations was 30-min. The work also covers evaluation of the effect of zero-valent iron (ZVI) on the efficiency of the degradation process and the performance of the reaction systems. It was found that low-frequency probe type devices especially at 20kHz were ineffective when applied singly and without ZVI, and relatively more effective in combined-frequency operations in the presence of ZVI. The power efficiencies of the reactors and/or reaction systems showed that 20-kHz probe was considerably more energy intensive than all others, and was therefore not used in multi-frequency operations. The most efficient reactor in terms of power consumption was the bath (200kHz), which however provided insufficient mineralization of the test chemical. The highest percentage of TOC decay (37%) was obtained in a dual-frequency operation (40/572kHz) with ZVI, in which the energy consumption was neither low nor exceptionally too high. A sequential operation (40+200kHz) in that respect was more efficient, because it required much less energy for a similar TOC decay performance (30%). In general, the degradation of IBP increased with increased power consumption, which in turn reduced the sonochemical yield. The study also showed that advanced Fenton reactions with ZVI were faster in the presence of ultrasound, and the metal was very effective in improving the performance of low-frequency operations. Copyright © 2017 Elsevier B.V. All rights reserved.

Sequential Modular Position and Momentum Measurements of a Trapped Ion Mechanical Oscillator

NASA Astrophysics Data System (ADS)

Flühmann, C.; Negnevitsky, V.; Marinelli, M.; Home, J. P.

2018-04-01

The noncommutativity of position and momentum observables is a hallmark feature of quantum physics. However, this incompatibility does not extend to observables that are periodic in these base variables. Such modular-variable observables have been suggested as tools for fault-tolerant quantum computing and enhanced quantum sensing. Here, we implement sequential measurements of modular variables in the oscillatory motion of a single trapped ion, using state-dependent displacements and a heralded nondestructive readout. We investigate the commutative nature of modular variable observables by demonstrating no-signaling in time between successive measurements, using a variety of input states. Employing a different periodicity, we observe signaling in time. This also requires wave-packet overlap, resulting in quantum interference that we enhance using squeezed input states. The sequential measurements allow us to extract two-time correlators for modular variables, which we use to violate a Leggett-Garg inequality. Signaling in time and Leggett-Garg inequalities serve as efficient quantum witnesses, which we probe here with a mechanical oscillator, a system that has a natural crossover from the quantum to the classical regime.

Meta-analyses and adaptive group sequential designs in the clinical development process.

PubMed

Jennison, Christopher; Turnbull, Bruce W

2005-01-01

The clinical development process can be viewed as a succession of trials, possibly overlapping in calendar time. The design of each trial may be influenced by results from previous studies and other currently proceeding trials, as well as by external information. Results from all of these trials must be considered together in order to assess the efficacy and safety of the proposed new treatment. Meta-analysis techniques provide a formal way of combining the information. We examine how such methods can be used in combining results from: (1) a collection of separate studies, (2) a sequence of studies in an organized development program, and (3) stages within a single study using a (possibly adaptive) group sequential design. We present two examples. The first example concerns the combining of results from a Phase IIb trial using several dose levels or treatment arms with those of the Phase III trial comparing the treatment selected in Phase IIb against a control This enables a "seamless transition" from Phase IIb to Phase III. The second example examines the use of combination tests to analyze data from an adaptive group sequential trial.

Uncertainty assessment of PM2.5 contamination mapping using spatiotemporal sequential indicator simulations and multi-temporal monitoring data.

PubMed

Yang, Yong; Christakos, George; Huang, Wei; Lin, Chengda; Fu, Peihong; Mei, Yang

2016-04-12

Because of the rapid economic growth in China, many regions are subjected to severe particulate matter pollution. Thus, improving the methods of determining the spatiotemporal distribution and uncertainty of air pollution can provide considerable benefits when developing risk assessments and environmental policies. The uncertainty assessment methods currently in use include the sequential indicator simulation (SIS) and indicator kriging techniques. However, these methods cannot be employed to assess multi-temporal data. In this work, a spatiotemporal sequential indicator simulation (STSIS) based on a non-separable spatiotemporal semivariogram model was used to assimilate multi-temporal data in the mapping and uncertainty assessment of PM2.5 distributions in a contaminated atmosphere. PM2.5 concentrations recorded throughout 2014 in Shandong Province, China were used as the experimental dataset. Based on the number of STSIS procedures, we assessed various types of mapping uncertainties, including single-location uncertainties over one day and multiple days and multi-location uncertainties over one day and multiple days. A comparison of the STSIS technique with the SIS technique indicate that a better performance was obtained with the STSIS method.

Uncertainty assessment of PM2.5 contamination mapping using spatiotemporal sequential indicator simulations and multi-temporal monitoring data

NASA Astrophysics Data System (ADS)

Yang, Yong; Christakos, George; Huang, Wei; Lin, Chengda; Fu, Peihong; Mei, Yang

2016-04-01

Because of the rapid economic growth in China, many regions are subjected to severe particulate matter pollution. Thus, improving the methods of determining the spatiotemporal distribution and uncertainty of air pollution can provide considerable benefits when developing risk assessments and environmental policies. The uncertainty assessment methods currently in use include the sequential indicator simulation (SIS) and indicator kriging techniques. However, these methods cannot be employed to assess multi-temporal data. In this work, a spatiotemporal sequential indicator simulation (STSIS) based on a non-separable spatiotemporal semivariogram model was used to assimilate multi-temporal data in the mapping and uncertainty assessment of PM2.5 distributions in a contaminated atmosphere. PM2.5 concentrations recorded throughout 2014 in Shandong Province, China were used as the experimental dataset. Based on the number of STSIS procedures, we assessed various types of mapping uncertainties, including single-location uncertainties over one day and multiple days and multi-location uncertainties over one day and multiple days. A comparison of the STSIS technique with the SIS technique indicate that a better performance was obtained with the STSIS method.

[Revascularization of left anterior descending artery area using a skeletonized left internal mammary artery: a comparison between sequential and separate grafting].

PubMed

Shen, J Q; Ji, Q; Ding, W J; Xia, L M; Wei, L; Wang, C S

2018-03-13

Objective: To evaluate in-hospital and mid-term outcomes of sequential versus separate grafting of in situ skeletonized left internal mammary artery (LIMA) to the left coronary system in a single-center, propensity-matched study. Methods: After propensity score matching, 120 pairs of patients undergoing first, scheduled, isolated coronary artery bypass grafting (CABG) with in situ skeletonized LIMA grafting to the left anterior descending artery (LAD) territory were entered into a sequential group (sequential grafting of LIMA to the diagonal artery and then to the LAD) or a control group (separate grafting of LIMA to the LAD). The in-hospital and follow-up clinical outcomes and follow-up LIMA graft patency were compared. Results: The two propensity score-matched groups had similar in-hospital and follow-up clinical outcomes. The number of bypass conduits ranged from 3 to 6 (with a mean of 3.5), and 91.3%(219/240)of the included patients received off-pump CABG surgery. No significant differences were found between the two propensity score-matched groups in the in-hospital outcomes, including in-hospital death and the incidence of complications associated with CABG (prolonged ventilation, peroperative stroke, re-operation before discharge, and deep sternal wound infection). During follow-up, 9 patients (4 patients from the sequential group and 5 patients from the control group) died, and the all-cause mortality rate was 3.9%. No significant difference was found in the all-cause mortality rate between the 2 groups[3.4% (4/116) vs 4.3% (5/115), P =0.748]. During follow-up period, 99.1% (115/116) patency for the diagonal site and 98.3% (114/116) for the LAD site were determined by coronary computed tomographic angiography after sequential LIMA grafting, both of which were similar with graft patency of separate grafting of in situ skeletonized LIMA to the LAD. Conclusions: Revascularization of the left coronary system using a skeletonized LIMA resulted in excellent in-hospital and mid-term clinical outcomes and graft patency using sequential grafting.

A behavioural and neural evaluation of prospective decision-making under risk

PubMed Central

Symmonds, Mkael; Bossaerts, Peter; Dolan, Raymond J.

2010-01-01

Making the best choice when faced with a chain of decisions requires a person to judge both anticipated outcomes and future actions. Although economic decision-making models account for both risk and reward in single choice contexts there is a dearth of similar knowledge about sequential choice. Classical utility-based models assume that decision-makers select and follow an optimal pre-determined strategy, irrespective of the particular order in which options are presented. An alternative model involves continuously re-evaluating decision utilities, without prescribing a specific future set of choices. Here, using behavioral and functional magnetic resonance imaging (fMRI) data, we studied human subjects in a sequential choice task and use these data to compare alternative decision models of valuation and strategy selection. We provide evidence that subjects adopt a model of re-evaluating decision utilities, where available strategies are continuously updated and combined in assessing action values. We validate this model by using simultaneously-acquired fMRI data to show that sequential choice evokes a pattern of neural response consistent with a tracking of anticipated distribution of future reward, as expected in such a model. Thus, brain activity evoked at each decision point reflects the expected mean, variance and skewness of possible payoffs, consistent with the idea that sequential choice evokes a prospective evaluation of both available strategies and possible outcomes. PMID:20980595

A behavioral and neural evaluation of prospective decision-making under risk.

PubMed

Symmonds, Mkael; Bossaerts, Peter; Dolan, Raymond J

2010-10-27

Making the best choice when faced with a chain of decisions requires a person to judge both anticipated outcomes and future actions. Although economic decision-making models account for both risk and reward in single-choice contexts, there is a dearth of similar knowledge about sequential choice. Classical utility-based models assume that decision-makers select and follow an optimal predetermined strategy, regardless of the particular order in which options are presented. An alternative model involves continuously reevaluating decision utilities, without prescribing a specific future set of choices. Here, using behavioral and functional magnetic resonance imaging (fMRI) data, we studied human subjects in a sequential choice task and use these data to compare alternative decision models of valuation and strategy selection. We provide evidence that subjects adopt a model of reevaluating decision utilities, in which available strategies are continuously updated and combined in assessing action values. We validate this model by using simultaneously acquired fMRI data to show that sequential choice evokes a pattern of neural response consistent with a tracking of anticipated distribution of future reward, as expected in such a model. Thus, brain activity evoked at each decision point reflects the expected mean, variance, and skewness of possible payoffs, consistent with the idea that sequential choice evokes a prospective evaluation of both available strategies and possible outcomes.

Process research of non-CZ silicon material

NASA Technical Reports Server (NTRS)

Campbell, R. B.

1984-01-01

Advanced processing techniques for non-CZ silicon sheet material that might improve the cost effectiveness of photovoltaic module production were investigated. Specifically, the simultaneous diffusion of liquid boron and liquid phosphorus organometallic precursors into n-type dendritic silicon web was examined. The simultaneous junction formation method for solar cells was compared with the sequential junction formation method. The electrical resistivity of the n-n and p-n junctions was discussed. Further research activities for this program along with a program documentation schedule are given.

A posteriori model validation for the temporal order of directed functional connectivity maps.

PubMed

Beltz, Adriene M; Molenaar, Peter C M

2015-01-01

A posteriori model validation for the temporal order of neural directed functional connectivity maps is rare. This is striking because models that require sequential independence among residuals are regularly implemented. The aim of the current study was (a) to apply to directed functional connectivity maps of functional magnetic resonance imaging data an a posteriori model validation procedure (i.e., white noise tests of one-step-ahead prediction errors combined with decision criteria for revising the maps based upon Lagrange Multiplier tests), and (b) to demonstrate how the procedure applies to single-subject simulated, single-subject task-related, and multi-subject resting state data. Directed functional connectivity was determined by the unified structural equation model family of approaches in order to map contemporaneous and first order lagged connections among brain regions at the group- and individual-levels while incorporating external input, then white noise tests were run. Findings revealed that the validation procedure successfully detected unmodeled sequential dependencies among residuals and recovered higher order (greater than one) simulated connections, and that the procedure can accommodate task-related input. Findings also revealed that lags greater than one were present in resting state data: With a group-level network that contained only contemporaneous and first order connections, 44% of subjects required second order, individual-level connections in order to obtain maps with white noise residuals. Results have broad methodological relevance (e.g., temporal validation is necessary after directed functional connectivity analyses because the presence of unmodeled higher order sequential dependencies may bias parameter estimates) and substantive implications (e.g., higher order lags may be common in resting state data).

"Looking-at-nothing" during sequential sensorimotor actions: Long-term memory-based eye scanning of remembered target locations.

PubMed

Foerster, Rebecca M

2018-03-01

Before acting humans saccade to a target object to extract relevant visual information. Even when acting on remembered objects, locations previously occupied by relevant objects are fixated during imagery and memory tasks - a phenomenon called "looking-at-nothing". While looking-at-nothing was robustly found in tasks encouraging declarative memory built-up, results are mixed in the case of procedural sensorimotor tasks. Eye-guidance to manual targets in complete darkness was observed in a task practiced for days beforehand, while investigations using only a single session did not find fixations to remembered action targets. Here, it is asked whether looking-at-nothing can be found in a single sensorimotor session and thus independent from sleep consolidation, and how it progresses when visual information is repeatedly unavailable. Eye movements were investigated in a computerized version of the trail making test. Participants clicked on numbered circles in ascending sequence. Fifty trials were performed with the same spatial arrangement of 9 visual targets to enable long-term memory consolidation. During 50 consecutive trials, participants had to click the remembered target sequence on an empty screen. Participants scanned the visual targets and also the empty target locations sequentially with their eyes, however, the latter less precise than the former. Over the course of the memory trials, manual and oculomotor sequential target scanning became more similar to the visual trials. Results argue for robust looking-at-nothing during procedural sensorimotor tasks provided that long-term memory information is sufficient. Copyright © 2018 Elsevier Ltd. All rights reserved.

Disease Resistance in Atlantic Salmon (Salmo salar): Coinfection of the Intracellular Bacterial Pathogen Piscirickettsia salmonis and the Sea Louse Caligus rogercresseyi

PubMed Central

Lhorente, Jean Paul; Gallardo, José A.; Villanueva, Beatriz; Carabaño, María J.; Neira, Roberto

2014-01-01

Background Naturally occurring coinfections of pathogens have been reported in salmonids, but their consequences on disease resistance are unclear. We hypothesized that 1) coinfection of Caligus rogercresseyi reduces the resistance of Atlantic salmon to Piscirickettsia salmonis; and 2) coinfection resistance is a heritable trait that does not correlate with resistance to a single infection. Methodology In total, 1,634 pedigreed Atlantic salmon were exposed to a single infection (SI) of P. salmonis (primary pathogen) or coinfection with C. rogercresseyi (secondary pathogen). Low and high level of coinfection were evaluated (LC = 44 copepodites per fish; HC = 88 copepodites per fish). Survival and quantitative genetic analyses were performed to determine the resistance to the single infection and coinfections. Main Findings C. rogercresseyi significantly increased the mortality in fish infected with P. salmonis (SI mortality = 251/545; LC mortality = 544/544 and HC mortality = 545/545). Heritability estimates for resistance to P. salmonis were similar and of medium magnitude in all treatments (h 2 SI = 0.23±0.07; h 2 LC = 0.17±0.08; h 2 HC = 0.24±0.07). A large and significant genetic correlation with regard to resistance was observed between coinfection treatments (rg LC-HC = 0.99±0.01) but not between the single and coinfection treatments (rg SI-LC = −0.14±0.33; rg SI-HC = 0.32±0.34). Conclusions/Significance C. rogercresseyi, as a secondary pathogen, reduces the resistance of Atlantic salmon to the pathogen P. salmonis. Resistance to coinfection of Piscirickettsia salmonis and Caligus rogercresseyi in Atlantic salmon is a heritable trait. The absence of a genetic correlation between resistance to a single infection and resistance to coinfection indicates that different genes control these processes. Coinfection of different pathogens and resistance to coinfection needs to be considered in future research on salmon farming, selective breeding and conservation. PMID:24736323

Genetic mapping of the rice resistance-breaking gene of the brown planthopper Nilaparvata lugens

PubMed Central

Kobayashi, Tetsuya; Yamamoto, Kimiko; Suetsugu, Yoshitaka; Kuwazaki, Seigo; Hattori, Makoto; Jairin, Jirapong; Sanada-Morimura, Sachiyo; Matsumura, Masaya

2014-01-01

Host plant resistance has been widely used for controlling the major rice pest brown planthopper (BPH, Nilaparvata lugens). However, adaptation of the wild BPH population to resistance limits the effective use of resistant rice varieties. Quantitative trait locus (QTL) analysis was conducted to identify resistance-breaking genes against the anti-feeding mechanism mediated by the rice resistance gene Bph1. QTL analysis in iso-female BPH lines with single-nucleotide polymorphism (SNP) markers detected a single region on the 10th linkage group responsible for the virulence. The QTL explained from 57 to 84% of the total phenotypic variation. Bulked segregant analysis with next-generation sequencing in F2 progenies identified five SNPs genetically linked to the virulence. These analyses showed that virulence to Bph1 was controlled by a single recessive gene. In contrast to previous studies, the gene-for-gene relationship between the major resistance gene Bph1 and virulence gene of BPH was confirmed. Identified markers are available for map-based cloning of the major gene controlling BPH virulence to rice resistance. PMID:24870048

Robust Population Inversion by Polarization Selective Pulsed Excitation

PubMed Central

Mantei, D.; Förstner, J.; Gordon, S.; Leier, Y. A.; Rai, A. K.; Reuter, D.; Wieck, A. D.; Zrenner, A.

2015-01-01

The coherent state preparation and control of single quantum systems is an important prerequisite for the implementation of functional quantum devices. Prominent examples for such systems are semiconductor quantum dots, which exhibit a fine structure split single exciton state and a V-type three level structure, given by a common ground state and two distinguishable and separately excitable transitions. In this work we introduce a novel concept for the preparation of a robust inversion by the sequential excitation in a V-type system via distinguishable paths. PMID:26000910

Dual-wavelength quantum cascade laser for trace gas spectroscopy

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

Jágerská, J.; Tuzson, B.; Mangold, M.

2014-10-20

We demonstrate a sequentially operating dual-wavelength quantum cascade laser with electrically separated laser sections, emitting single-mode at 5.25 and 6.25 μm. Based on a single waveguide ridge, this laser represents a considerable asset to optical sensing and trace gas spectroscopy, as it allows probing multiple gas species with spectrally distant absorption features using conventional optical setups without any beam combining optics. The laser capability was demonstrated in simultaneous NO and NO{sub 2} detection, reaching sub-ppb detection limits and selectivity comparable to conventional high-end spectroscopic systems.

Optically phase-locked electronic speckle pattern interferometer system performance for vibration measurement in random displacement fields

NASA Astrophysics Data System (ADS)

Moran, Steve E.; Lugannani, Robert; Craig, Peter N.; Law, Robert L.

1989-02-01

An analysis is made of the performance of an optically phase-locked electronic speckle pattern interferometer in the presence of random noise displacements. Expressions for the phase-locked speckle contrast for single-frame imagery and the composite rms exposure for two sequentially subtracted frames are obtained in terms of the phase-locked composite and single-frame fringe functions. The noise fringe functions are evaluated for stationary, coherence-separable noise displacements obeying Gauss-Markov temporal statistics. The theoretical findings presented here are qualitatively supported by experimental results.

Resin/graphite fiber composites

NASA Technical Reports Server (NTRS)

Cavano, P. J.; Jones, R. J.; Vaughan, R. W.

1972-01-01

High temperature resin matrices suitable for use in advanced graphite fiber composites for jet engine applications were evaluated. A series of planned, sequential screening experiments with resin systems in composite form were performed to reduce the number of candidates to a single A-type polyimide resin that repetitively produced void-free, high strength and modulus composites acceptable for use in the 550 F range for 1000 hours. An optimized processing procedure was established for this system. Extensive mechanical property studies characterized this single system, at room temperature, 500 F, 550 F and 600 F, for various exposure times.

Modified SSCP method using sequential electrophoresis of multiple nucleic acid segments

DOEpatents

Gatti, Richard A.

2002-10-01

The present invention is directed to a method of screening large, complex, polyexonic eukaryotic genes such as the ATM gene for mutations and polymorphisms by an improved version of single strand conformation polymorphism (SSCP) electrophoresis that allows electrophoresis of two or three amplified segments in a single lane. The present invention also is directed to new mutations and polymorphisms in the ATM gene that are useful in performing more accurate screening of human DNA samples for mutations and in distinguishing mutations from polymorphisms, thereby improving the efficiency of automated screening methods.

Ultrasound-assisted debridement of neuroischaemic diabetic foot ulcers, clinical and microbiological effects: a case series.

PubMed

Lázaro-Martínez, José Luis; Álvaro-Afonso, Francisco Javier; García-Álvarez, Yolanda; Molines-Barroso, Raúl Juan; García-Morales, Esther; Sevillano-Fernández, David

2018-05-02

To evaluate the clinical and microbiological effects of sequential wound debridement in a case series of neuroischaemic diabetic foot ulcers (DFUs) using an ultrasound-assisted wound debridement (UAW) device. A prospective, single-centre study, involving a case series of 24 neuroischaemic DFUs, was conducted to evaluate sequential wound debridement with UAW during a six-week treatment period. Soft tissue punch biopsies were taken every second week of treatment, both before and after wound debridement sessions. Qualitative and quantitative microbiological analysis was performed and wounds were assessed at patient admission, and before and after each debridement procedure. Wound tissue quality scores improved significantly from a mean score of 2.1±1.3 points at patient inclusion, to 5.3±1.7 points (p=0.001). Mean wound sizes were 4.45cm 2 (range: 2-12.25cm 2 ) at week zero, and 2.75cm 2 (range: 1.67-10.70cm 2 ) at week six (p=0.04). The mean number of bacterial species per culture determined at week zero and at week six was 2.53±1.55 and 1.90±1.16, respectively (p=0.023). Wound debridement resulted in significant decreases in bacterial counts (1.17, 1.31 and 0.77 log units in colony forming units (CFU) for week zero, three and six, respectively). The average bacterial load in tissue samples before and after wound debridement after the six-week treatment was Log 5.55±0.91CFU/g and Log 4.59±0.89CFU/g, respectively (p<0.001). The study results showed a significant bacterial load reduction in DFU tissue samples as a result of UAW debridement, independent of bacterial species, some of which exhibited antibiotic-resistance. Significant bacterial load reduction was correlated with improved wound conditions and significant reductions of wound size.

Muscular and functional effects of partitioning exercising muscle mass in patients with chronic obstructive pulmonary disease - a study protocol for a randomized controlled trial.

PubMed

Nyberg, Andrè; Saey, Didier; Martin, Mickaël; Maltais, François

2015-04-27

Low-load, high-repetitive single-limb resistance training may increase limb muscle function and functional exercise capacity in patients with chronic obstructive pulmonary disease (COPD) while minimizing the occurrence of limiting exertional symptoms. Whether high-repetitive single-limb resistance training would perform better than high-repetitive two-limb resistance training is unknown. In addition, the mechanisms underlying possible benefits of high-repetitive resistance training has not been investigated. The aims of this study are to compare single versus two-limb high-repetitive resistance training in patients with COPD and to investigate mechanisms of action of these training modalities. This trial is a prospective, assessor-blind, randomized controlled trial. The participants are patients with stable severe to very severe COPD who are older than 40 years of age and healthy controls. The intervention is single-limb, high-repetitive, resistance training with elastic bands, three times/week for 8 weeks. The control is two-limb high-repetitive resistance training with elastic bands, three times/week for 8 weeks. The primary outcomes is change in the 6-min walking distance after 8 weeks of single-limb or two-limb high-repetitive resistance training. The secondary outcomes are changes in limb muscle strength and endurance capacity, key protein involved in quadriceps anabolic/catabolic signalization, fiber-type distribution and capillarization, subjective dyspnea and muscle fatigue, muscle oxygenation, cardiorespiratory demand and health-related quality-of-life after 8 weeks of single-limb or two-limb high-repetitive resistance training. The acute effects of single-limb versus two-limb high-repetitive resistance training on contractile fatigue, exercise stimulus (the product of number of repetition and load), subjective dyspnea and muscle fatigue, muscle oxygenation, and cardiorespiratory demand during upper and lower limb exercises will also be investigated in patients with COPD and healthy controls. Randomization will be performed using a random number generator by a person independent of the recruitment process, using 1:1 allocation to the intervention and the control group using random block sizes. All outcome assessors will be blinded to group assignment. The results of this project will provide important information to help developing and implementing customized exercise training programs for patients with COPD. ClinicalTrials.gov Identifier NCT02283580 Registration date: 4 November 2014. First participant randomized: 10 November 2014.

Single- and multistep resistance selection studies on the activity of retapamulin compared to other agents against Staphylococcus aureus and Streptococcus pyogenes.

PubMed

Kosowska-Shick, Klaudia; Clark, Catherine; Credito, Kim; McGhee, Pamela; Dewasse, Bonifacio; Bogdanovich, Tatiana; Appelbaum, Peter C

2006-02-01

Retapamulin had the lowest rate of spontaneous mutations by single-step passaging and the lowest parent and selected mutant MICs by multistep passaging among all drugs tested for all Staphylococcus aureus strains and three Streptococcus pyogenes strains which yielded resistant clones. Retapamulin has a low potential for resistance selection in S. pyogenes, with a slow and gradual propensity for resistance development in S. aureus.

Single- and Multistep Resistance Selection Studies on the Activity of Retapamulin Compared to Other Agents against Staphylococcus aureus and Streptococcus pyogenes

PubMed Central

Kosowska-Shick, Klaudia; Clark, Catherine; Credito, Kim; McGhee, Pamela; Dewasse, Bonifacio; Bogdanovich, Tatiana; Appelbaum, Peter C.

2006-01-01

Retapamulin had the lowest rate of spontaneous mutations by single-step passaging and the lowest parent and selected mutant MICs by multistep passaging among all drugs tested for all Staphylococcus aureus strains and three Streptococcus pyogenes strains which yielded resistant clones. Retapamulin has a low potential for resistance selection in S. pyogenes, with a slow and gradual propensity for resistance development in S. aureus. PMID:16436741

Six Basic Plan Concepts Used for California School Housing. A Sequential Development from 1900 to Today.

ERIC Educational Resources Information Center

California State Dept. of Education, Sacramento. Bureau of School Planning.

A floor plan accompanies each of six chronologically arranged schemes for housing educational programs. Scheme A represents the in-line corridor plan whose main characteristics are--(1) double loaded corridors with fixed bearing walls, (2) single window walls providing minimal light and ventilation, and (3) small classrooms with fixed desks and…

Purification and characterization of a papaya (Carica papaya L.) pectin methylesterase isolated from a commercial papain preparation

USDA-ARS?s Scientific Manuscript database

We purified a single stable pectin methylesterase (CpL-PME; EC 3.1.1.11) from a commercial papain preparation, which is isolated from Carica papaya (L.) fruit latex. This CpL-PME was separated from the abundant cysteine endopeptidases activities using sequential hydrophobic interaction and cation-ex...

Sequential Bimodal Bilingual Acquisition: Mediation Using a Cochlear Implant as a Tool

ERIC Educational Resources Information Center

Cramér-Wolrath, Emelie

2013-01-01

Most deaf children are born to hearing families. During the last twenty years deaf children, in increasing numbers and at an early age, receive a cochlear implant, a highly technological hearing device. The aim of this qualitative, longitudinal, single-case study was to explore and describe critical changes in naturalistic, video-observed…

Quantifying the abundance of co-occurring conifers along Inland Northwest (USA) climate gradients

Treesearch

Gerald E. Rehfeldt; Dennis E. Ferguson; Nicholas L. Crookston

2008-01-01

The occurrence and abundance of conifers along climate gradients in the Inland Northwest (USA) was assessed using data from 5082 field plots, 81% of which were forested. Analyses using the Random Forests classification tree revealed that the sequential distribution of species along an altitudinal gradient could be predicted with reasonable accuracy from a single...

ViSA: A Neurodynamic Model for Visuo-Spatial Working Memory, Attentional Blink, and Conscious Access

ERIC Educational Resources Information Center

Simione, Luca; Raffone, Antonino; Wolters, Gezinus; Salmas, Paola; Nakatani, Chie; Belardinelli, Marta Olivetti; van Leeuwen, Cees

2012-01-01

Two separate lines of study have clarified the role of selectivity in conscious access to visual information. Both involve presenting multiple targets and distracters: one "simultaneously" in a spatially distributed fashion, the other "sequentially" at a single location. To understand their findings in a unified framework, we propose a…

40 CFR 761.302 - Proportion of the total surface area to sample.

Code of Federal Regulations, 2011 CFR

2011-07-01

... surface into approximately 1 meter square portions and mark the portions so that they are clearly... surfaces contaminated by a single source of PCBs with a uniform concentration, assign each 1 meter square surface a unique sequential number. (i) For three or fewer 1 meter square areas, sample all of the areas...

40 CFR 761.302 - Proportion of the total surface area to sample.

Code of Federal Regulations, 2014 CFR

2014-07-01

... surface into approximately 1 meter square portions and mark the portions so that they are clearly... surfaces contaminated by a single source of PCBs with a uniform concentration, assign each 1 meter square surface a unique sequential number. (i) For three or fewer 1 meter square areas, sample all of the areas...

40 CFR 761.302 - Proportion of the total surface area to sample.

Code of Federal Regulations, 2010 CFR

2010-07-01

... surface into approximately 1 meter square portions and mark the portions so that they are clearly... surfaces contaminated by a single source of PCBs with a uniform concentration, assign each 1 meter square surface a unique sequential number. (i) For three or fewer 1 meter square areas, sample all of the areas...

40 CFR 761.302 - Proportion of the total surface area to sample.

Code of Federal Regulations, 2012 CFR

2012-07-01

... surface into approximately 1 meter square portions and mark the portions so that they are clearly... surfaces contaminated by a single source of PCBs with a uniform concentration, assign each 1 meter square surface a unique sequential number. (i) For three or fewer 1 meter square areas, sample all of the areas...

40 CFR 761.302 - Proportion of the total surface area to sample.

Code of Federal Regulations, 2013 CFR

2013-07-01

... surface into approximately 1 meter square portions and mark the portions so that they are clearly... surfaces contaminated by a single source of PCBs with a uniform concentration, assign each 1 meter square surface a unique sequential number. (i) For three or fewer 1 meter square areas, sample all of the areas...

The Development of Anaphora Resolution at the Syntax-Discourse Interface: Pronominal Subjects in Greek Learners of Spanish

ERIC Educational Resources Information Center

Lozano, Cristóbal

2018-01-01

This study explores the development of anaphora resolution (AR) in late sequential bilinguals, namely, adult Greek learners of Spanish at three proficiency levels (intermediate, lower advanced, upper advanced). The use of an overt/null pronominal subject anaphor is investigated in three discourse contexts: topic-continuity (a single antecedent…

Predictive Validity of Sepsis-3 Definitions and Sepsis Outcomes in Critically Ill Patients: A Cohort Study in 49 ICUs in Argentina.

PubMed

Estenssoro, Elisa; Kanoore Edul, Vanina S; Loudet, Cecilia I; Osatnik, Javier; Ríos, Fernando G; Vázquez, Daniela N; Pozo, Mario O; Lattanzio, Bernardo; Pálizas, Fernando; Klein, Francisco; Piezny, Damián; Rubatto Birri, Paolo N; Tuhay, Graciela; Díaz, Anatilde; Santamaría, Analía; Zakalik, Graciela; Dubin, Arnaldo

2018-05-08

The new Sepsis-3 definitions have been scarcely assessed in low- and middle-income countries; besides, regional information of sepsis outcomes is sparse. Our objective was to evaluate Sepsis-3 definition performance in Argentina. Cohort study of 3-month duration beginning on July 1, 2016. Forty-nine ICUs. Consecutive patients admitted to the ICU with suspected infection that triggered blood cultures and antibiotic administration. None. Patients were classified as having infection, sepsis (infection + change in Sequential Organ Failure Assessment ≥ 2 points), and septic shock (vasopressors + lactate > 2 mmol/L). Patients on vasopressors and lactate less than or equal to 2 mmol/L (cardiovascular dysfunction) were analyzed separately, as those on vasopressors without serum lactate measurement. Systemic inflammatory response syndrome was also recorded. Main outcome was hospital mortality. Of 809 patients, 6% had infection, 29% sepsis, 20% cardiovascular dysfunction, 40% septic shock, and 3% received vasopressors with lactate unmeasured. Hospital mortality was 13%, 20%, 39%, 51%, and 41%, respectively (p = 0.000). Independent predictors of outcome were lactate, Sequential Organ Failure Assessment score, comorbidities, prior duration of symptoms (hr), mechanical ventilation requirement, and infection by highly resistant microorganisms. Area under the receiver operating characteristic curves for mortality for systemic inflammatory response syndrome and Sequential Organ Failure Assessment were 0.53 (0.48-0.55) and 0.74 (0.69-0.77), respectively (p = 0.000). Increasing severity of Sepsis-3 categories adequately tracks mortality; cardiovascular dysfunction subgroup, not included in Sepsis-3, has distinct characteristics. Sequential Organ Failure Assessment score shows adequate prognosis accuracy-contrary to systemic inflammatory response syndrome. This study supports the predictive validity of Sepsis-3 definitions.

Efficacy of premixed versus sequential administration of clonidine as an adjuvant to hyperbaric bupivacaine intrathecally in cesarean section

PubMed Central

Sachan, Prachee; Kumar, Nidhi; Sharma, Jagdish Prasad

2014-01-01

Background: Density of the drugs injected intrathecally is an important factor that influences spread in the cerebrospinal fluid. Mixing adjuvants with local anesthetics (LA) alters their density and hence their spread compared to when given sequentially in seperate syringes. Aims: To evaluate the efficacy of intrathecal administration of hyperbaric bupivacaine (HB) and clonidine as a mixture and sequentially in terms of block characteristics, hemodynamics, neonatal outcome, and postoperative pain. Setting and Design: Prospective randomized single blind study at a tertiary center from 2010 to 2012. Materials and Methods: Ninety full-term parturient scheduled for elective cesarean sections were divided into three groups on the basis of technique of intrathecal drug administration. Group M received mixture of 75 μg clonidine and 10 mg HB 0.5%. Group A received 75 μg clonidine after administration of 10 mg HB 0.5% through separate syringe. Group B received 75 μg clonidine before HB 0.5% (10 mg) through separate syringe. Statistical analysis used: Observational descriptive statistics, analysis of variance with Bonferroni multiple comparison post hoc test, and Chi-square test. Results: Time to achieve complete sensory and motor block was less in group A and B in which drugs were given sequentially. Duration of analgesia lasted longer in group B (474.3 ± 20.79 min) and group A (472.50 ± 22.11 min) than in group M (337 ± 18.22 min) with clinically insignificant influence on hemodynamic parameters and sedation. Conclusion: Sequential technique reduces time to achieve complete sensory and motor block, delays block regression, and significantly prolongs the duration of analgesia. However, it did not matter much whether clonidine was administered before or after HB. PMID:25886098

Simultaneous biodegradation of three mononitrophenol isomers by a tailor-made microbial consortium immobilized in sequential batch reactors.

PubMed

Fu, H; Zhang, J-J; Xu, Y; Chao, H-J; Zhou, N-Y

2017-03-01

The ortho-nitrophenol (ONP)-utilizing Alcaligenes sp. strain NyZ215, meta-nitrophenol (MNP)-utilizing Cupriavidus necator JMP134 and para-nitrophenol (PNP)-utilizing Pseudomonas sp. strain WBC-3 were assembled as a consortium to degrade three nitrophenol isomers in sequential batch reactors. Pilot test was conducted in flasks to demonstrate that a mixture of three mononitrophenols at 0·5 mol l -1 each could be mineralized by this microbial consortium within 84 h. Interestingly, neither ONP nor MNP was degraded until PNP was almost consumed by strain WBC-3. By immobilizing this consortium into polyurethane cubes, all three mononitrophenols were continuously degraded in lab-scale sequential reactors for six batch cycles over 18 days. Total concentrations of ONP, MMP and PNP that were degraded were 2·8, 1·5 and 2·3 mol l -1 during this time course respectively. Quantitative real-time PCR analysis showed that each member in the microbial consortium was relatively stable during the entire degradation process. This study provides a novel approach to treat polluted water, particularly with a mixture of co-existing isomers. Nitroaromatic compounds are readily spread in the environment and pose great potential toxicity concerns. Here, we report the simultaneous degradation of three isomers of mononitrophenol in a single system by employing a consortium of three bacteria, both in flasks and lab-scale sequential batch reactors. The results demonstrate that simultaneous biodegradation of three mononitrophenol isomers can be achieved by a tailor-made microbial consortium immobilized in sequential batch reactors, providing a pilot study for a novel approach for the bioremediation of mixed pollutants, especially isomers present in wastewater. © 2016 The Society for Applied Microbiology.

Sequentially reweighted TV minimization for CT metal artifact reduction.

PubMed

Zhang, Xiaomeng; Xing, Lei

2013-07-01

Metal artifact reduction has long been an important topic in x-ray CT image reconstruction. In this work, the authors propose an iterative method that sequentially minimizes a reweighted total variation (TV) of the image and produces substantially artifact-reduced reconstructions. A sequentially reweighted TV minimization algorithm is proposed to fully exploit the sparseness of image gradients (IG). The authors first formulate a constrained optimization model that minimizes a weighted TV of the image, subject to the constraint that the estimated projection data are within a specified tolerance of the available projection measurements, with image non-negativity enforced. The authors then solve a sequence of weighted TV minimization problems where weights used for the next iteration are computed from the current solution. Using the complete projection data, the algorithm first reconstructs an image from which a binary metal image can be extracted. Forward projection of the binary image identifies metal traces in the projection space. The metal-free background image is then reconstructed from the metal-trace-excluded projection data by employing a different set of weights. Each minimization problem is solved using a gradient method that alternates projection-onto-convex-sets and steepest descent. A series of simulation and experimental studies are performed to evaluate the proposed approach. Our study shows that the sequentially reweighted scheme, by altering a single parameter in the weighting function, flexibly controls the sparsity of the IG and reconstructs artifacts-free images in a two-stage process. It successfully produces images with significantly reduced streak artifacts, suppressed noise and well-preserved contrast and edge properties. The sequentially reweighed TV minimization provides a systematic approach for suppressing CT metal artifacts. The technique can also be generalized to other "missing data" problems in CT image reconstruction.

Multidrug Resistant Pseudomonas aeruginosa Causing Prosthetic Valve Endocarditis: A Genetic-Based Chronicle of Evolving Antibiotic Resistance.

PubMed

Domitrovic, T Nicholas; Hujer, Andrea M; Perez, Federico; Marshall, Steven H; Hujer, Kristine M; Woc-Colburn, Laila E; Parta, Mark; Bonomo, Robert A

2016-10-01

Background.  Successful treatment of infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa is thwarted by the emergence of antibiotic resistance and biofilm formation on prosthetic devices. Our aims were to decipher the molecular basis of resistance in a unique case of prosthetic valve endocarditis (PVE) caused by MDR P. aeruginosa . Methods.  Five sequential MDR P. aeruginosa blood isolates collected during a 7-month period were recovered from a patient suffering from PVE previously exposed to β-lactam antibiotics. Minimum inhibitory concentrations (MICs) of several classes of antibiotics were used to indicate clinical resistance characteristics; relatedness of the isolates was determined using multilocus sequence typing and repetitive sequence-based polymerase chain reaction. Amplification and sequencing of regulatory and resistance genes was performed. Results.  All isolates belonged to ST 298, possessed bla PDC-16 , and were resistant to fluoroquinolones and carbapenems. In the course of therapy, we observed a >2-fold increase in cephalosporin resistance (4 µg/mL to >16 µg/mL). Sequencing of the AmpC regulator, amp R, revealed a D135N point mutation in cephalosporin-resistant isolates. Common carbapenemase genes were not identified. All isolates demonstrated a premature stop codon at amino acid 79 of the outer membrane protein OprD and mutations in the quinolone resistance-determining regions of gyr A and par C. Point mutations in nal C, an efflux pump regulator, were also observed. Conclusions.  In this analysis, we chart the molecular evolution of β-lactam resistance in a case of PVE. We show that mutations in regulatory genes controlling efflux and cephalosporinase production contributed to the MDR phenotype.

Prospectivity Modeling of Karstic Groundwater Using a Sequential Exploration Approach in Tepal Area, Iran

NASA Astrophysics Data System (ADS)

Sharifi, Fereydoun; Arab-Amiri, Ali Reza; Kamkar-Rouhani, Abolghasem; Yousefi, Mahyar; Davoodabadi-Farahani, Meysam

2017-09-01

The purpose of this study is water prospectivity modeling (WPM) for recognizing karstic water-bearing zones by using analyses of geo-exploration data in Kal-Qorno valley, located in Tepal area, north of Iran. For this, a sequential exploration method applied on geo-evidential data to delineate target areas for further exploration. In this regard, two major exploration phases including regional and local scales were performed. In the first phase, indicator geological features, structures and lithological units, were used to model groundwater prospectivity as a regional scale. In this phase, for karstic WPM, fuzzy lithological and structural evidence layers were generated and combined using fuzzy operators. After generating target areas using WPM, in the second phase geophysical surveys including gravimetry and geoelectrical resistivity were carried out on the recognized high potential zones as a local scale exploration. Finally the results of geophysical analyses in the second phase were used to select suitable drilling locations to access and extract karstic groundwater in the study area.

A role for FOXO1 in BCR–ABL1-independent tyrosine kinase inhibitor resistance in chronic myeloid leukemia

PubMed Central

Wagle, M; Eiring, A M; Wongchenko, M; Lu, S; Guan, Y; Wang, Y; Lackner, M; Amler, L; Hampton, G; Deininger, M W; O'Hare, T; Yan, Y

2016-01-01

Chronic myeloid leukemia (CML) patients who relapse on imatinib due to acquired ABL1 kinase domain mutations are successfully treated with second-generation ABL1-tyrosine kinase inhibitors (ABL-TKIs) such as dasatinib, nilotinib or ponatinib. However, ~40% of relapsed patients have uncharacterized BCR–ABL1 kinase-independent mechanisms of resistance. To identify these mechanisms of resistance and potential treatment options, we generated ABL-TKI-resistant K562 cells through prolonged sequential exposure to imatinib and dasatinib. Dual-resistant K562 cells lacked BCR–ABL1 kinase domain mutations, but acquired other genomic aberrations that were characterized by next-generation sequencing and copy number analyses. Proteomics showed that dual-resistant cells had elevated levels of FOXO1, phospho-ERK and BCL-2, and that dasatinib no longer inhibited substrates of the PI3K/AKT pathway. In contrast to parental cells, resistant cells were sensitive to growth inhibition and apoptosis induced by the class I PI3K inhibitor, GDC-0941 (pictilisib), which also induced FOXO1 nuclear translocation. FOXO1 was elevated in a subset of primary specimens from relapsed CML patients lacking BCR–ABL1 kinase domain mutations, and these samples were responsive to GDC-0941 treatment ex vivo. We conclude that elevated FOXO1 contributes to BCR–ABL1 kinase-independent resistance experienced by these CML patients and that PI3K inhibition coupled with BCR–ABL1 inhibition may represent a novel therapeutic approach. PMID:27044711

A role for FOXO1 in BCR-ABL1-independent tyrosine kinase inhibitor resistance in chronic myeloid leukemia.

PubMed

Wagle, M; Eiring, A M; Wongchenko, M; Lu, S; Guan, Y; Wang, Y; Lackner, M; Amler, L; Hampton, G; Deininger, M W; O'Hare, T; Yan, Y

2016-07-01

Chronic myeloid leukemia (CML) patients who relapse on imatinib due to acquired ABL1 kinase domain mutations are successfully treated with second-generation ABL1-tyrosine kinase inhibitors (ABL-TKIs) such as dasatinib, nilotinib or ponatinib. However, ~40% of relapsed patients have uncharacterized BCR-ABL1 kinase-independent mechanisms of resistance. To identify these mechanisms of resistance and potential treatment options, we generated ABL-TKI-resistant K562 cells through prolonged sequential exposure to imatinib and dasatinib. Dual-resistant K562 cells lacked BCR-ABL1 kinase domain mutations, but acquired other genomic aberrations that were characterized by next-generation sequencing and copy number analyses. Proteomics showed that dual-resistant cells had elevated levels of FOXO1, phospho-ERK and BCL-2, and that dasatinib no longer inhibited substrates of the PI3K/AKT pathway. In contrast to parental cells, resistant cells were sensitive to growth inhibition and apoptosis induced by the class I PI3K inhibitor, GDC-0941 (pictilisib), which also induced FOXO1 nuclear translocation. FOXO1 was elevated in a subset of primary specimens from relapsed CML patients lacking BCR-ABL1 kinase domain mutations, and these samples were responsive to GDC-0941 treatment ex vivo. We conclude that elevated FOXO1 contributes to BCR-ABL1 kinase-independent resistance experienced by these CML patients and that PI3K inhibition coupled with BCR-ABL1 inhibition may represent a novel therapeutic approach.

Removal of Heterologous Sequences from Plasmodium falciparum Mutants Using FLPe-Recombinase

PubMed Central

van Schaijk, Ben C. L.; Vos, Martijn W.; Janse, Chris J.; Sauerwein, Robert W.; Khan, Shahid M.

2010-01-01

Genetically-modified mutants are now indispensable Plasmodium gene-function reagents, which are also being pursued as genetically attenuated parasite vaccines. Currently, the generation of transgenic malaria-parasites requires the use of drug-resistance markers. Here we present the development of an FRT/FLP-recombinase system that enables the generation of transgenic parasites free of resistance genes. We demonstrate in the human malaria parasite, P. falciparum, the complete and efficient removal of the introduced resistance gene. We targeted two neighbouring genes, p52 and p36, using a construct that has a selectable marker cassette flanked by FRT-sequences. This permitted the subsequent removal of the selectable marker cassette by transient transfection of a plasmid that expressed a 37°C thermostable and enhanced FLP-recombinase. This method of removing heterologous DNA sequences from the genome opens up new possibilities in Plasmodium research to sequentially target multiple genes and for using genetically-modified parasites as live, attenuated malaria vaccines. PMID:21152048

Phase transition in a spatial Lotka-Volterra model

NASA Astrophysics Data System (ADS)

Szabó, György; Czárán, Tamás

2001-06-01

Spatial evolution is investigated in a simulated system of nine competing and mutating bacterium strains, which mimics the biochemical war among bacteria capable of producing two different bacteriocins (toxins) at most. Random sequential dynamics on a square lattice is governed by very symmetrical transition rules for neighborhood invasions of sensitive strains by killers, killers by resistants, and resistants by sensitives. The community of the nine possible toxicity/resistance types undergoes a critical phase transition as the uniform transmutation rates between the types decreases below a critical value Pc above that all the nine types of strains coexist with equal frequencies. Passing the critical mutation rate from above, the system collapses into one of three topologically identical (degenerated) states, each consisting of three strain types. Of the three possible final states each accrues with equal probability and all three maintain themselves in a self-organizing polydomain structure via cyclic invasions. Our Monte Carlo simulations support that this symmetry-breaking transition belongs to the universality class of the three-state Potts model.

Aphid Resistance in Medicago truncatula Involves Antixenosis and Phloem-Specific, Inducible Antibiosis, and Maps to a Single Locus Flanked by NBS-LRR Resistance Gene Analogs1

PubMed Central

Klingler, John; Creasy, Robert; Gao, Lingling; Nair, Ramakrishnan M.; Calix, Alonso Suazo; Jacob, Helen Spafford; Edwards, Owain R.; Singh, Karam B.

2005-01-01

Aphids and related insects feed from a single cell type in plants: the phloem sieve element. Genetic resistance to Acyrthosiphon kondoi Shinji (bluegreen aphid or blue alfalfa aphid) has been identified in Medicago truncatula Gaert. (barrel medic) and backcrossed into susceptible cultivars. The status of M. truncatula as a model legume allows an in-depth study of defense against this aphid at physiological, biochemical, and molecular levels. In this study, two closely related resistant and susceptible genotypes were used to characterize the aphid-resistance phenotype. Resistance conditions antixenosis since migratory aphids were deterred from settling on resistant plants within 6 h of release, preferring to settle on susceptible plants. Analysis of feeding behavior revealed the trait affects A. kondoi at the level of the phloem sieve element. Aphid reproduction on excised shoots demonstrated that resistance requires an intact plant. Antibiosis against A. kondoi is enhanced by prior infestation, indicating induction of this phloem-specific defense. Resistance segregates as a single dominant gene, AKR (Acyrthosiphon kondoi resistance), in two mapping populations, which have been used to map the locus to a region flanked by resistance gene analogs predicted to encode the CC-NBS-LRR subfamily of resistance proteins. This work provides the basis for future molecular analysis of defense against phloem parasitism in a plant model system. PMID:15778464

Sequential Modelling of Building Rooftops by Integrating Airborne LIDAR Data and Optical Imagery: Preliminary Results

NASA Astrophysics Data System (ADS)

Sohn, G.; Jung, J.; Jwa, Y.; Armenakis, C.

2013-05-01

This paper presents a sequential rooftop modelling method to refine initial rooftop models derived from airborne LiDAR data by integrating it with linear cues retrieved from single imagery. A cue integration between two datasets is facilitated by creating new topological features connecting between the initial model and image lines, with which new model hypotheses (variances to the initial model) are produced. We adopt Minimum Description Length (MDL) principle for competing the model candidates and selecting the optimal model by considering the balanced trade-off between the model closeness and the model complexity. Our preliminary results, combined with the Vaihingen data provided by ISPRS WGIII/4 demonstrate the image-driven modelling cues can compensate the limitations posed by LiDAR data in rooftop modelling.

CRISPR/Cas9-mediated gene targeting in Arabidopsis using sequential transformation.

PubMed

Miki, Daisuke; Zhang, Wenxin; Zeng, Wenjie; Feng, Zhengyan; Zhu, Jian-Kang

2018-05-17

Homologous recombination-based gene targeting is a powerful tool for precise genome modification and has been widely used in organisms ranging from yeast to higher organisms such as Drosophila and mouse. However, gene targeting in higher plants, including the most widely used model plant Arabidopsis thaliana, remains challenging. Here we report a sequential transformation method for gene targeting in Arabidopsis. We find that parental lines expressing the bacterial endonuclease Cas9 from the egg cell- and early embryo-specific DD45 gene promoter can improve the frequency of single-guide RNA-targeted gene knock-ins and sequence replacements via homologous recombination at several endogenous sites in the Arabidopsis genome. These heritable gene targeting can be identified by regular PCR. Our approach enables routine and fine manipulation of the Arabidopsis genome.

Sequential and direct ionic excitation in the strong-field ionization of 1-butene molecules.

PubMed

Schell, Felix; Boguslavskiy, Andrey E; Schulz, Claus Peter; Patchkovskii, Serguei; Vrakking, Marc J J; Stolow, Albert; Mikosch, Jochen

2018-05-18

We study the Strong-Field Ionization (SFI) of the hydrocarbon 1-butene as a function of wavelength using photoion-photoelectron covariance and coincidence spectroscopy. We observe a striking transition in the fragment-associated photoelectron spectra: from a single Above Threshold Ionization (ATI) progression for photon energies less than the cation D0-D1 gap to two ATI progressions for a photon energy greater than this gap. For the first case, electronically excited cations are created by SFI populating the ground cationic state D0, followed by sequential post-ionization excitation. For the second case, direct sub-cycle SFI to the D1 excited cation state contributes significantly. Our experiments access ionization dynamics in a regime where strong-field and resonance-enhanced processes can interplay.

Production of single heavy charged leptons at a linear collider

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

De Pree, Erin; Sher, Marc; Turan, Ismail

2008-05-01

A sequential fourth generation of quarks and leptons is allowed by precision electroweak constraints if the mass splitting between the heavy quarks is between 50 and 80 GeV. Although heavy quarks can be easily detected at the LHC, it is very difficult to detect a sequential heavy charged lepton, L, due to large backgrounds. Should the L mass be above 250 GeV, it cannot be pair-produced at a 500 GeV ILC. We calculate the cross section for the one-loop process e{sup +}e{sup -}{yields}L{tau}. Although the cross section is small, it may be detectable. We also consider contributions from the two-Higgsmore » doublet model and the Randall-Sundrum model, in which case the cross section can be substantially higher.« less

Sequential power-up circuit

DOEpatents

Kronberg, James W.

1992-01-01

A sequential power-up circuit for starting several electrical load elements in series to avoid excessive current surge, comprising a voltage ramp generator and a set of voltage comparators, each comparator having a different reference voltage and interfacing with a switch that is capable of turning on one of the load elements. As the voltage rises, it passes the reference voltages one at a time and causes the switch corresponding to that voltage to turn on its load element. The ramp is turned on and off by a single switch or by a logic-level electrical signal. The ramp rate for turning on the load element is relatively slow and the rate for turning the elements off is relatively fast. Optionally, the duration of each interval of time between the turning on of the load elements is programmable.

Ultrasensitive surveillance of sensors and processes

DOEpatents

Wegerich, Stephan W.; Jarman, Kristin K.; Gross, Kenneth C.

2001-01-01

A method and apparatus for monitoring a source of data for determining an operating state of a working system. The method includes determining a sensor (or source of data) arrangement associated with monitoring the source of data for a system, activating a method for performing a sequential probability ratio test if the data source includes a single data (sensor) source, activating a second method for performing a regression sequential possibility ratio testing procedure if the arrangement includes a pair of sensors (data sources) with signals which are linearly or non-linearly related; activating a third method for performing a bounded angle ratio test procedure if the sensor arrangement includes multiple sensors and utilizing at least one of the first, second and third methods to accumulate sensor signals and determining the operating state of the system.

Ultrasensitive surveillance of sensors and processes

DOEpatents

Wegerich, Stephan W.; Jarman, Kristin K.; Gross, Kenneth C.

1999-01-01

A method and apparatus for monitoring a source of data for determining an operating state of a working system. The method includes determining a sensor (or source of data) arrangement associated with monitoring the source of data for a system, activating a method for performing a sequential probability ratio test if the data source includes a single data (sensor) source, activating a second method for performing a regression sequential possibility ratio testing procedure if the arrangement includes a pair of sensors (data sources) with signals which are linearly or non-linearly related; activating a third method for performing a bounded angle ratio test procedure if the sensor arrangement includes multiple sensors and utilizing at least one of the first, second and third methods to accumulate sensor signals and determining the operating state of the system.

Epidemic Typhoid in Vietnam: Molecular Typing of Multiple-Antibiotic-Resistant Salmonella enterica Serotype Typhi from Four Outbreaks

PubMed Central

Connerton, Phillippa; Wain, John; Hien, Tran T.; Ali, Tahir; Parry, Christopher; Chinh, Nguyen T.; Vinh, Ha; Ho, Vo A.; Diep, To S.; Day, Nicholas P. J.; White, Nicholas J.; Dougan, Gordon; Farrar, Jeremy J.

2000-01-01

Multidrug-resistant Salmonella enterica serotype Typhi isolates from four outbreaks of typhoid fever in southern Vietnam between 1993 and 1997 were compared. Pulsed-field gel electrophoresis, bacteriophage and plasmid typing, and antibiotic susceptibilities showed that independent outbreaks of multidrug-resistant typhoid fever in southern Vietnam are caused by single bacterial strains. However, different outbreaks do not derive from the clonal expansion of a single multidrug-resistant serotype Typhi strain. PMID:10655411

Sequential structural damage diagnosis algorithm using a change point detection method

NASA Astrophysics Data System (ADS)

Noh, H.; Rajagopal, R.; Kiremidjian, A. S.

2013-11-01

This paper introduces a damage diagnosis algorithm for civil structures that uses a sequential change point detection method. The general change point detection method uses the known pre- and post-damage feature distributions to perform a sequential hypothesis test. In practice, however, the post-damage distribution is unlikely to be known a priori, unless we are looking for a known specific type of damage. Therefore, we introduce an additional algorithm that estimates and updates this distribution as data are collected using the maximum likelihood and the Bayesian methods. We also applied an approximate method to reduce the computation load and memory requirement associated with the estimation. The algorithm is validated using a set of experimental data collected from a four-story steel special moment-resisting frame and multiple sets of simulated data. Various features of different dimensions have been explored, and the algorithm was able to identify damage, particularly when it uses multidimensional damage sensitive features and lower false alarm rates, with a known post-damage feature distribution. For unknown feature distribution cases, the post-damage distribution was consistently estimated and the detection delays were only a few time steps longer than the delays from the general method that assumes we know the post-damage feature distribution. We confirmed that the Bayesian method is particularly efficient in declaring damage with minimal memory requirement, but the maximum likelihood method provides an insightful heuristic approach.

Damage diagnosis algorithm using a sequential change point detection method with an unknown distribution for damage

NASA Astrophysics Data System (ADS)

Noh, Hae Young; Rajagopal, Ram; Kiremidjian, Anne S.

2012-04-01

This paper introduces a damage diagnosis algorithm for civil structures that uses a sequential change point detection method for the cases where the post-damage feature distribution is unknown a priori. This algorithm extracts features from structural vibration data using time-series analysis and then declares damage using the change point detection method. The change point detection method asymptotically minimizes detection delay for a given false alarm rate. The conventional method uses the known pre- and post-damage feature distributions to perform a sequential hypothesis test. In practice, however, the post-damage distribution is unlikely to be known a priori. Therefore, our algorithm estimates and updates this distribution as data are collected using the maximum likelihood and the Bayesian methods. We also applied an approximate method to reduce the computation load and memory requirement associated with the estimation. The algorithm is validated using multiple sets of simulated data and a set of experimental data collected from a four-story steel special moment-resisting frame. Our algorithm was able to estimate the post-damage distribution consistently and resulted in detection delays only a few seconds longer than the delays from the conventional method that assumes we know the post-damage feature distribution. We confirmed that the Bayesian method is particularly efficient in declaring damage with minimal memory requirement, but the maximum likelihood method provides an insightful heuristic approach.

Application of Sequential Extractions and X-ray Absorption Spectroscopy to Determine the Speciation of Chromium in Northern New Jersey Marsh Soils Developed in Chromite ore Processing Residue (COPR)

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

Elzinga, E.; Cirmo, A

2010-01-01

The Cr speciation in marsh soils developed in weathering chromite ore processing residue (COPR) was characterized using sequential extractions and synchrotron microbeam and bulk X-ray absorption spectroscopic (XAS) analyses. The sequential extractions suggested substantial Cr associated with reducible and oxidizable soil components, and significant non-extractable residual Cr. Notable differences in Cr speciation estimates from three extraction schemes underscore the operationally defined nature of Cr speciation provided by these methods. Micro X-ray fluorescence maps and {mu}-XAS data indicated the presence of {micro}m-sized chromite particles scattered throughout the weathered COPR matrix. These particles derive from the original COPR material, and have relativelymore » high resistance towards weathering, and therefore persist even after prolonged leaching. Bulk XAS data further indicated Cr(III) incorporated in Fe(OH){sub 3}, and Cr(III) associated with organic matter. The low Cr contents of the weathered material (200-850 ppm) compared to unweathered COPR (20,000-60,000 ppm) point to substantial Cr leaching during COPR weathering, with partial repartitioning of released Cr into secondary Fe(OH){sub 3} phases and organics. The effects of anoxia on Cr speciation, and the potential of active COPR weathering releasing Cr(VI) deeper in the profile require further study.« less

Implementation of digital equality comparator circuit on memristive memory crossbar array using material implication logic

NASA Astrophysics Data System (ADS)

Haron, Adib; Mahdzair, Fazren; Luqman, Anas; Osman, Nazmie; Junid, Syed Abdul Mutalib Al

2018-03-01

One of the most significant constraints of Von Neumann architecture is the limited bandwidth between memory and processor. The cost to move data back and forth between memory and processor is considerably higher than the computation in the processor itself. This architecture significantly impacts the Big Data and data-intensive application such as DNA analysis comparison which spend most of the processing time to move data. Recently, the in-memory processing concept was proposed, which is based on the capability to perform the logic operation on the physical memory structure using a crossbar topology and non-volatile resistive-switching memristor technology. This paper proposes a scheme to map digital equality comparator circuit on memristive memory crossbar array. The 2-bit, 4-bit, 8-bit, 16-bit, 32-bit, and 64-bit of equality comparator circuit are mapped on memristive memory crossbar array by using material implication logic in a sequential and parallel method. The simulation results show that, for the 64-bit word size, the parallel mapping exhibits 2.8× better performance in total execution time than sequential mapping but has a trade-off in terms of energy consumption and area utilization. Meanwhile, the total crossbar area can be reduced by 1.2× for sequential mapping and 1.5× for parallel mapping both by using the overlapping technique.

Chromosome characterization using single fluorescent dye

DOEpatents

Crissman, Harry A.; Hirons, Gregory T.

1995-01-01

Chromosomes are characterized by fluorescent emissions from a single fluorescent dye that is excited over two different wavelengths. A mixture containing chromosomes is stained with a single dye selected from the group consisting of TOTO and YOYO and the stained chromosomes are placed in a flow cytometer. The fluorescent dye is excited sequentially by a first light having a wavelength in the ultraviolet range to excite the TOTO or YOYO to fluoresce at a first intensity and by a second light having a wavelength effective to excite the TOTO or YOYO dye to fluoresce at a second intensity. Specific chromosomes may be identified and sorted by intensity relationships between the first and second fluorescence emissions.

Optimal Therapy Scheduling Based on a Pair of Collaterally Sensitive Drugs.

PubMed

Yoon, Nara; Vander Velde, Robert; Marusyk, Andriy; Scott, Jacob G

2018-05-07

Despite major strides in the treatment of cancer, the development of drug resistance remains a major hurdle. One strategy which has been proposed to address this is the sequential application of drug therapies where resistance to one drug induces sensitivity to another drug, a concept called collateral sensitivity. The optimal timing of drug switching in these situations, however, remains unknown. To study this, we developed a dynamical model of sequential therapy on heterogeneous tumors comprised of resistant and sensitive cells. A pair of drugs (DrugA, DrugB) are utilized and are periodically switched during therapy. Assuming resistant cells to one drug are collaterally sensitive to the opposing drug, we classified cancer cells into two groups, [Formula: see text] and [Formula: see text], each of which is a subpopulation of cells resistant to the indicated drug and concurrently sensitive to the other, and we subsequently explored the resulting population dynamics. Specifically, based on a system of ordinary differential equations for [Formula: see text] and [Formula: see text], we determined that the optimal treatment strategy consists of two stages: an initial stage in which a chosen effective drug is utilized until a specific time point, T, and a second stage in which drugs are switched repeatedly, during which each drug is used for a relative duration (i.e., [Formula: see text]-long for DrugA and [Formula: see text]-long for DrugB with [Formula: see text] and [Formula: see text]). We prove that the optimal duration of the initial stage, in which the first drug is administered, T, is shorter than the period in which it remains effective in decreasing the total population, contrary to current clinical intuition. We further analyzed the relationship between population makeup, [Formula: see text], and the effect of each drug. We determine a critical ratio, which we term [Formula: see text], at which the two drugs are equally effective. As the first stage of the optimal strategy is applied, [Formula: see text] changes monotonically to [Formula: see text] and then, during the second stage, remains at [Formula: see text] thereafter. Beyond our analytic results, we explored an individual-based stochastic model and presented the distribution of extinction times for the classes of solutions found. Taken together, our results suggest opportunities to improve therapy scheduling in clinical oncology.

Decreasing the time to defibrillation: a comparative study of defibrillator electrode designs.

PubMed

Adams, Bruce D; Easty, David M; Stuffel, Elaine; Hartman, Irma

2005-08-01

Time to defibrillation (T(defib)) is the most important modifiable factor affecting survival from cardiac arrest. Mortality increases by approximately 7--10% for each minute of defibrillation delay. The purpose of this study was to determine whether defibrillator electrode design complexity affects T(defib). This was a randomized sequential design study utilizing a standardized ventricular fibrillation cardiac arrest model for CPR mannequins. We evaluated two common types of defibrillator electrode models: a single connector design and a double connector design that requires an adaptor. We compared the time required by cardiac arrest team leaders to apply the two types of defibrillator electrodes to a manikin, connect them to a defibrillator, and then deliver a first defibrillatory shock. The primary outcome was time to defibrillation. The secondary outcome was difficulty of application as perceived by the physician participants on a 10 cm visual analog scale. Thirty-two residents performed a sequential assessment of both electrodes. The average T(defib) for the double connector model was 42.9s longer than that of the single connector model (87.5s versus 44.6s, p<0.001). As evaluated by the study participants, the single connector model was significantly easier to apply then the double connector model (1.3 cm versus 4.4 cm, p<0.001). The single connector defibrillator electrode design was associated with a significantly shorter T(defib) than the double connector design. It also was judged to be easier to apply in this model. Ergonomic design of defibrillator electrodes can significantly impact time to defibrillation.

Single-molecule detection of proteins with antigen-antibody interaction using resistive-pulse sensing of submicron latex particles

NASA Astrophysics Data System (ADS)

Takakura, T.; Yanagi, I.; Goto, Y.; Ishige, Y.; Kohara, Y.

2016-03-01

We developed a resistive-pulse sensor with a solid-state pore and measured the latex agglutination of submicron particles induced by antigen-antibody interaction for single-molecule detection of proteins. We fabricated the pore based on numerical simulation to clearly distinguish between monomer and dimer latex particles. By measuring single dimers agglutinated in the single-molecule regime, we detected single human alpha-fetoprotein molecules. Adjusting the initial particle concentration improves the limit of detection (LOD) to 95 fmol/l. We established a theoretical model of the LOD by combining the reaction kinetics and the counting statistics to explain the effect of initial particle concentration on the LOD. The theoretical model shows how to improve the LOD quantitatively. The single-molecule detection studied here indicates the feasibility of implementing a highly sensitive immunoassay by a simple measurement method using resistive-pulse sensing.

Geophysical monitoring of solute transport in dual-domain environments through laboratory experiments, field-scale solute tracer tests, and numerical simulation

NASA Astrophysics Data System (ADS)

Swanson, Ryan David

The advection-dispersion equation (ADE) fails to describe non-Fickian solute transport breakthrough curves (BTCs) in saturated porous media in both laboratory and field experiments, necessitating the use of other models. The dual-domain mass transfer (DDMT) model partitions the total porosity into mobile and less-mobile domains with an exchange of mass between the two domains, and this model can reproduce better fits to BTCs in many systems than ADE-based models. However, direct experimental estimation of DDMT model parameters remains elusive and model parameters are often calculated a posteriori by an optimization procedure. Here, we investigate the use of geophysical tools (direct-current resistivity, nuclear magnetic resonance, and complex conductivity) to estimate these model parameters directly. We use two different samples of the zeolite clinoptilolite, a material shown to demonstrate solute mass transfer due to a significant internal porosity, and provide the first evidence that direct-current electrical methods can track solute movement into and out of a less-mobile pore space in controlled laboratory experiments. We quantify the effects of assuming single-rate DDMT for multirate mass transfer systems. We analyze pore structures using material characterization methods (mercury porosimetry, scanning electron microscopy, and X-ray computer tomography), and compare these observations to geophysical measurements. Nuclear magnetic resonance in conjunction with direct-current resistivity measurements can constrain mobile and less-mobile porosities, but complex conductivity may have little value in relation to mass transfer despite the hypothesis that mass transfer and complex conductivity lengths scales are related. Finally, we conduct a geoelectrical monitored tracer test at the Macrodispersion Experiment (MADE) site in Columbus, MS. We relate hydraulic and electrical conductivity measurements to generate a 3D hydraulic conductivity field, and compare to hydraulic conductivity fields estimated through ordinary kriging and sequential Gaussian simulation. Time-lapse electrical measurements are used to verify or dismiss aspects of breakthrough curves for different hydraulic conductivity fields. Our results quantify the potential for geophysical measurements to infer on single-rate DDMT parameters, show site-specific relations between hydraulic and electrical conductivity, and track solute exchange into and out of less-mobile domains.

Efficient transmission of cassava brown streak disease viral pathogens by chip bud grafting.

PubMed

Wagaba, Henry; Beyene, Getu; Trembley, Cynthia; Alicai, Titus; Fauquet, Claude M; Taylor, Nigel J

2013-12-06

Techniques to study plant viral diseases under controlled growth conditions are required to fully understand their biology and investigate host resistance. Cassava brown streak disease (CBSD) presents a major threat to cassava production in East Africa. No infectious clones of the causal viruses, Cassava brown streak virus (CBSV) or Ugandan cassava brown streak virus (UCBSV) are available, and mechanical transmission to cassava is not effective. An improved method for transmission of the viruses, both singly and as co-infections has been developed using bud grafts. Axillary buds from CBSD symptomatic plants infected with virulent isolates of CBSV and UCBSV were excised and grafted onto 6-8 week old greenhouse-grown, disease-free cassava plants of cultivars Ebwanateraka, TME204 and 60444. Plants were assessed visually for development of CBSD symptoms and by RT-PCR for presence of the viruses in leaf and storage root tissues. Across replicated experiments, 70-100% of plants inoculated with CBSV developed CBSD leaf and stem symptoms 2-6 weeks after bud grafting. Infected plants showed typical, severe necrotic lesions in storage roots at harvest 12-14 weeks after graft inoculation. Sequential grafting of buds from plants infected with UCBSV followed 10-14 days later by buds carrying CBSV, onto the same test plant, resulted in 100% of the rootstocks becoming co-infected with both pathogens. This dual transmission rate was greater than that achieved by simultaneous grafting with UCBSV and CBSV (67%), or when grafting first with CBSV followed by UCBSV (17%). The bud grafting method described presents an improved tool for screening cassava germplasm for resistance to CBSD causal viruses, and for studying pathogenicity of this important disease. Bud grafting provides new opportunities compared to previously reported top and side grafting systems. Test plants can be inoculated as young, uniform plants of a size easily handled in a small greenhouse or large growth chamber and can be inoculated in a controlled manner with CBSV and UCBSV, either singly or together. Disease symptoms develop rapidly, allowing better studies of interactions between these viral pathogens, their movement within shoot and root systems, and how they induce their destructive disease symptoms.

Clinical Impact of Fluoroquinolone-Resistant Escherichia coli in the Fecal Flora of Hematological Patients with Neutropenia and Levofloxacin Prophylaxis

PubMed Central

Chong, Yong; Shimoda, Shinji; Yakushiji, Hiroko; Ito, Yoshikiyo; Aoki, Takatoshi; Miyamoto, Toshihiro; Kamimura, Tomohiko; Shimono, Nobuyuki; Akashi, Koichi

2014-01-01

Background Fluoroquinolone prophylaxis in patients with neutropenia and hematological malignancies is said to be effective on febrile netropenia (FN)-related infection and mortality; however, the emergence of antibiotic resistance has become a concern. Ciprofloxacin and levofloxacin prophylaxis are most commonly recommended. A significant increase in the rate of quinolone-resistant Escherichia coli in fecal flora has been reported following ciprofloxacin prophylaxis. The acquisition of quinolone-resistant E. coli after levofloxacin use has not been evaluated. Methods We prospectively examined the incidence of quinolone-resistant E. coli isolates recovered from stool cultures before and after levofloxacin prophylaxis in patients with neutropenia from August 2011 to May 2013. Some patients received chemotherapy multiple times. Results In this trial, 68 patients were registered. Levofloxacin-resistant E. coli isolates were detected from 11 and 13 of all patients before and after the prophylaxis, respectively. However, this was not statistically significant (P = 0.65). Multiple prophylaxis for sequential chemotherapy did not induce additional quinolone resistance among E. coli isolates. Interestingly, quinolone-resistant E. coli, most of which were extended-spectrum β-lactamase (ESBL) producers, were already detected in approximately 20% of all patients before the initiation of prophylaxis. FN-related bacteremia developed in 2 patients, accompanied by a good prognosis. Conclusions Levofloxacin prophylaxis for neutropenia did not result in a significant acquisition of quinolone-resistant E. coli. However, we detected previous colonization of quinolone-resistant E. coli before prophylaxis, which possibly reflects the spread of ESBL. The epidemic spread of resistant E. coli as a local factor may influence strategies toward the use of quinolone prophylaxis. PMID:24465506

Two novel ALK mutations mediate acquired resistance to the next generation ALK inhibitor alectinib

PubMed Central

Katayama, Ryohei; Friboulet, Luc; Koike, Sumie; Lockerman, Elizabeth L.; Khan, Tahsin M.; Gainor, Justin F.; Iafrate, A. John; Takeuchi, Kengo; Taiji, Makoto; Okuno, Yasushi; Fujita, Naoya; Engelman, Jeffrey A.; Shaw, Alice T.

2014-01-01

Purpose The first-generation ALK tyrosine kinase inhibitor (TKI) crizotinib is a standard therapy for patients with ALK-rearranged NSCLC. Several next-generation ALK-TKIs have entered the clinic and have shown promising activity in crizotinib-resistant patients. As patients still relapse even on these next-generation ALK-TKIs, we examined mechanisms of resistance to the next-generation ALK-TKI alectinib and potential strategies to overcome this resistance. Experimental Design We established a cell line model of alectinib resistance, and analyzed a resistant tumor specimen from a patient who had relapsed on alectinib. We developed Ba/F3 models harboring alectinib-resistant ALK mutations and evaluated the potency of other next-generation ALK-TKIs in these models. We tested the antitumor activity of the next-generation ALK-TKI ceritinib in the patient with acquired resistance to alectinib. To elucidate structure-activity-relationships of ALK mutations, we performed computational thermodynamic simulation with MP-CAFEE. Results We identified a novel V1180L gatekeeper mutation from the cell line model and a second novel I1171T mutation from the patient who developed resistance to alectinib. Both ALK mutations conferred resistance to alectinib as well as to crizotinib, but were sensitive to ceritinib and other next-generation ALK-TKIs. Treatment of the patient with ceritinib led to a marked response. Thermodynamics simulation suggests that both mutations lead to distinct structural alterations that decrease the binding affinity with alectinib. Conclusions We have identified two novel ALK mutations arising after alectinib exposure which are sensitive to other next generation ALK-TKIs. The ability of ceritinib to overcome alectinib-resistance mutations suggests a potential role for sequential therapy with multiple next-generation ALK-TKIs. PMID:25228534

Two novel ALK mutations mediate acquired resistance to the next-generation ALK inhibitor alectinib.

PubMed

Katayama, Ryohei; Friboulet, Luc; Koike, Sumie; Lockerman, Elizabeth L; Khan, Tahsin M; Gainor, Justin F; Iafrate, A John; Takeuchi, Kengo; Taiji, Makoto; Okuno, Yasushi; Fujita, Naoya; Engelman, Jeffrey A; Shaw, Alice T

2014-11-15

The first-generation ALK tyrosine kinase inhibitor (TKI) crizotinib is a standard therapy for patients with ALK-rearranged non-small cell lung cancer (NSCLC). Several next-generation ALK-TKIs have entered the clinic and have shown promising activity in crizotinib-resistant patients. As patients still relapse even on these next-generation ALK-TKIs, we examined mechanisms of resistance to the next-generation ALK-TKI alectinib and potential strategies to overcome this resistance. We established a cell line model of alectinib resistance, and analyzed a resistant tumor specimen from a patient who had relapsed on alectinib. We developed Ba/F3 models harboring alectinib-resistant ALK mutations and evaluated the potency of other next-generation ALK-TKIs in these models. We tested the antitumor activity of the next-generation ALK-TKI ceritinib in the patient with acquired resistance to alectinib. To elucidate structure-activity relationships of ALK mutations, we performed computational thermodynamic simulation with MP-CAFEE. We identified a novel V1180L gatekeeper mutation from the cell line model and a second novel I1171T mutation from the patient who developed resistance to alectinib. Both ALK mutations conferred resistance to alectinib as well as to crizotinib, but were sensitive to ceritinib and other next-generation ALK-TKIs. Treatment of the patient with ceritinib led to a marked response. Thermodynamics simulation suggests that both mutations lead to distinct structural alterations that decrease the binding affinity with alectinib. We have identified two novel ALK mutations arising after alectinib exposure that are sensitive to other next-generation ALK-TKIs. The ability of ceritinib to overcome alectinib-resistance mutations suggests a potential role for sequential therapy with multiple next-generation ALK-TKIs. ©2014 American Association for Cancer Research.

The Versatile Mutational Resistome of Pseudomonas aeruginosa

PubMed Central

López-Causapé, Carla; Cabot, Gabriel; del Barrio-Tofiño, Ester; Oliver, Antonio

2018-01-01

One of the most striking features of Pseudomonas aeruginosa is its outstanding capacity for developing antimicrobial resistance to nearly all available antipseudomonal agents through the selection of chromosomal mutations, leading to the failure of the treatment of severe hospital-acquired or chronic infections. Recent whole-genome sequencing (WGS) data obtained from in vitro assays on the evolution of antibiotic resistance, in vivo monitoring of antimicrobial resistance development, analysis of sequential cystic fibrosis isolates, and characterization of widespread epidemic high-risk clones have provided new insights into the evolutionary dynamics and mechanisms of P. aeruginosa antibiotic resistance, thus motivating this review. Indeed, the analysis of the WGS mutational resistome has proven to be useful for understanding the evolutionary dynamics of classical resistance pathways and to describe new mechanisms for the majority of antipseudomonal classes, including β-lactams, aminoglycosides, fluoroquinolones, or polymixins. Beyond addressing a relevant scientific question, the analysis of the P. aeruginosa mutational resistome is expected to be useful, together with the analysis of the horizontally-acquired resistance determinants, for establishing the antibiotic resistance genotype, which should correlate with the antibiotic resistance phenotype and as such, it should be useful for the design of therapeutic strategies and for monitoring the efficacy of administered antibiotic treatments. However, further experimental research and new bioinformatics tools are still needed to overcome the interpretation limitations imposed by the complex interactions (including those leading to collateral resistance or susceptibility) between the 100s of genes involved in the mutational resistome, as well as the frequent difficulties for differentiating relevant mutations from simple natural polymorphisms. PMID:29681898

The Versatile Mutational Resistome of Pseudomonas aeruginosa.

PubMed

López-Causapé, Carla; Cabot, Gabriel; Del Barrio-Tofiño, Ester; Oliver, Antonio

2018-01-01

One of the most striking features of Pseudomonas aeruginosa is its outstanding capacity for developing antimicrobial resistance to nearly all available antipseudomonal agents through the selection of chromosomal mutations, leading to the failure of the treatment of severe hospital-acquired or chronic infections. Recent whole-genome sequencing (WGS) data obtained from in vitro assays on the evolution of antibiotic resistance, in vivo monitoring of antimicrobial resistance development, analysis of sequential cystic fibrosis isolates, and characterization of widespread epidemic high-risk clones have provided new insights into the evolutionary dynamics and mechanisms of P. aeruginosa antibiotic resistance, thus motivating this review. Indeed, the analysis of the WGS mutational resistome has proven to be useful for understanding the evolutionary dynamics of classical resistance pathways and to describe new mechanisms for the majority of antipseudomonal classes, including β-lactams, aminoglycosides, fluoroquinolones, or polymixins. Beyond addressing a relevant scientific question, the analysis of the P. aeruginosa mutational resistome is expected to be useful, together with the analysis of the horizontally-acquired resistance determinants, for establishing the antibiotic resistance genotype, which should correlate with the antibiotic resistance phenotype and as such, it should be useful for the design of therapeutic strategies and for monitoring the efficacy of administered antibiotic treatments. However, further experimental research and new bioinformatics tools are still needed to overcome the interpretation limitations imposed by the complex interactions (including those leading to collateral resistance or susceptibility) between the 100s of genes involved in the mutational resistome, as well as the frequent difficulties for differentiating relevant mutations from simple natural polymorphisms.

A nonlinear HP-type complementary resistive switch

NASA Astrophysics Data System (ADS)

Radtke, Paul K.; Schimansky-Geier, Lutz

2016-05-01

Resistive Switching (RS) is the change in resistance of a dielectric under the influence of an external current or electric field. This change is non-volatile, and the basis of both the memristor and resistive random access memory. In the latter, high integration densities favor the anti-serial combination of two RS-elements to a single cell, termed the complementary resistive switch (CRS). Motivated by the irregular shape of the filament protruding into the device, we suggest a nonlinearity in the resistance-interpolation function, characterized by a single parameter p. Thereby the original HP-memristor is expanded upon. We numerically simulate and analytically solve this model. Further, the nonlinearity allows for its application to the CRS.

Genetic mapping of the rice resistance-breaking gene of the brown planthopper Nilaparvata lugens.

PubMed

Kobayashi, Tetsuya; Yamamoto, Kimiko; Suetsugu, Yoshitaka; Kuwazaki, Seigo; Hattori, Makoto; Jairin, Jirapong; Sanada-Morimura, Sachiyo; Matsumura, Masaya

2014-07-22

Host plant resistance has been widely used for controlling the major rice pest brown planthopper (BPH, Nilaparvata lugens). However, adaptation of the wild BPH population to resistance limits the effective use of resistant rice varieties. Quantitative trait locus (QTL) analysis was conducted to identify resistance-breaking genes against the anti-feeding mechanism mediated by the rice resistance gene Bph1. QTL analysis in iso-female BPH lines with single-nucleotide polymorphism (SNP) markers detected a single region on the 10th linkage group responsible for the virulence. The QTL explained from 57 to 84% of the total phenotypic variation. Bulked segregant analysis with next-generation sequencing in F2 progenies identified five SNPs genetically linked to the virulence. These analyses showed that virulence to Bph1 was controlled by a single recessive gene. In contrast to previous studies, the gene-for-gene relationship between the major resistance gene Bph1 and virulence gene of BPH was confirmed. Identified markers are available for map-based cloning of the major gene controlling BPH virulence to rice resistance. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

First-principles study of the variation of electron transport in a single molecular junction with the length of the molecular wire

NASA Astrophysics Data System (ADS)

Pal, Partha Pratim; Pati, Ranjit

2010-07-01

We report a first-principles study of quantum transport in a prototype two-terminal device consisting of a molecular nanowire acting as an inter-connect between two gold electrodes. The wire is composed of a series of bicyclo[1.1.1]pentane (BCP) cage-units. The length of the wire (L) is increased by sequentially increasing the number of BCP cage units in the wire from 1 to 3. A two terminal model device is made out of each of the three wires. A parameter free, nonequilibrium Green’s function approach, in which the bias effect is explicitly included within a many body framework, is used to calculate the current-voltage characteristics of each of the devices. In the low bias regime that is considered in our study, the molecular devices are found to exhibit Ohmic behavior with resistances of 0.12, 1.4, and 6.5μΩ for the wires containing one, two, and three cages respectively. Thus the conductance value, Gc , which is the reciprocal of resistance, decreases as e-βL with a decay constant (β) of 0.59Å-1 . This observed variation of conductance with the length of the wire is in excellent agreement with the earlier reported exponential decay feature of the electron transfer rate predicted from the electron transfer coupling matrix values obtained using the two-state Marcus-Hush model and the Koopman’s theorem approximation. The downright suppression of the computed electrical current for a bias up to 0.4 V in the longest wire can be exploited in designing a three terminal molecular transistor; this molecular wire could potentially be used as a throttle to avoid leakage gate current.

A Mutation in the PP2C Phosphatase Gene in a Staphylococcus aureus USA300 Clinical Isolate with Reduced Susceptibility to Vancomycin and Daptomycin

PubMed Central

Passalacqua, Karla D.; Satola, Sarah W.; Crispell, Emily K.

2012-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) strains with reduced susceptibility to vancomycin (MIC of 4 to 8 μg/ml) are referred to as vancomycin-intermediate S. aureus (VISA). In this study, we characterized two isogenic USA300 S. aureus isolates collected sequentially from a single patient with endocarditis where the S. aureus isolate changed from being susceptible to vancomycin (VSSA) (1 μg/ml) to VISA (8 μg/ml). In addition, the VISA isolate lost beta-lactamase activity and showed increased resistance to daptomycin and linezolid. The two strains did not differ in growth rate, but the VISA isolate had a thickened cell wall and was less autolytic. Transcriptome sequencing (RNA-seq) analysis comparing the two isolates grown to late exponential phase showed significant differences in transcription of cell surface protein genes (spa, SBI [second immunoglobulin-binding protein of S. aureus], and fibrinogen-binding proteins), regulatory genes (agrBCA, RNAIII, sarT, and saeRS), and others. Using whole-genome shotgun resequencing, we identified 6 insertion/deletion mutations between the VSSA and VISA isolates. A protein phosphatase 2C (PP2C) family phosphatase had a 6-bp (nonframeshift) insertion mutation in a highly conserved metal binding domain. Complementation of the clinical VISA isolate with a wild-type copy of the PP2C gene reduced the vancomycin and daptomycin MICs and increased autolytic activity, suggesting that this gene contributed to the reduced vancomycin susceptibility phenotype acquired in vivo. Creation of de novo mutants from the VSSA strain resulted in different mutations, demonstrating that reduced susceptibility to vancomycin in USA300 strains can occur via multiple routes, highlighting the complex nature of the VISA phenotype. PMID:22850507

Three-dimensional microarchitecture of the plates (primary, secondary, and carinar process) in the developing tooth of Lytechinus variegatus revealed by synchrotron X-ray absorption microtomography (microCT).

PubMed

Stock, S R; Ignatiev, K I; Dahl, T; Veis, A; De Carlo, F

2003-12-01

This paper reports the first noninvasive, volumetric study of entire cross-sections of a sea urchin tooth in which the individual calcite structural elements could be resolved. Two cross-sectionally intact fragments of a Lytechinus variegatus tooth were studied with synchrotron microCT (microcomputed tomography) with 1.66 microm voxels (volume elements). These fragments were from the plumula, that is the tooth zone with rapidly increasing levels of mineral; one fragment was from a position aboral of where the keel developed and the second was from the zone where the keel was developing. The primary plates, secondary plates, carinar process plates, prisms, and elements of the lamellar-needle complex were resolved. Comparison of the microCT data with optical micrographs of stained thin sections confirmed the identifications and measured dimensions of the characteristic microarchitectural features. The interplay of reinforcing structures (plates and prisms) was more clearly revealed in the volumetric numerical data sets than in single or sequential slices. While it is well known that the primary plates and prisms in camarodont teeth are situated to improve resistance to bending (which can be termed primary bending), the data presented provide a new understanding of the mechanical role of the carinar process plates, that is, a geometry consistent with that required in the keel to resist lateral or transverse bending of the tooth about a second axis. The increase in robustness of teeth incorporating lateral keel reinforcement suggests that the relative development of carinar processes (toward a geometry similar to that of L. variegatus) is a character which can be used to infer which sea urchins among the stirodonts are most primitive and among the camarodonts which are more primitive.

Structural insights into the mechanisms of drug resistance in HIV-1 protease NL4-3.

PubMed

Heaslet, Holly; Kutilek, Victoria; Morris, Garrett M; Lin, Ying-Chuan; Elder, John H; Torbett, Bruce E; Stout, C David

2006-03-03

The development of resistance to anti-retroviral drugs targeted against HIV is an increasing clinical problem in the treatment of HIV-1-infected individuals. Many patients develop drug-resistant strains of the virus after treatment with inhibitor cocktails (HAART therapy), which include multiple protease inhibitors. Therefore, it is imperative that we understand the mechanisms by which the viral proteins, in particular HIV-1 protease, develop resistance. We have determined the three-dimensional structure of HIV-1 protease NL4-3 in complex with the potent protease inhibitor TL-3 at 2.0 A resolution. We have also obtained the crystal structures of three mutant forms of NL4-3 protease containing one (V82A), three (V82A, M46I, F53L) and six (V82A, M46I, F53L, V77I, L24I, L63P) point mutations in complex with TL-3. The three protease mutants arose sequentially under ex vivo selective pressure in the presence of TL-3, and exhibit fourfold, 11-fold, and 30-fold resistance to TL-3, respectively. This series of protease crystal structures offers insights into the biochemical and structural mechanisms by which the enzyme can overcome inhibition by TL-3 while recovering some of its native catalytic activity.

Random Plant Viral Variants Attain Temporal Advantages During Systemic Infections and in Turn Resist other Variants of the Same Virus.

PubMed

Zhang, Xiao-Feng; Guo, Jiangbo; Zhang, Xiuchun; Meulia, Tea; Paul, Pierce; Madden, Laurence V; Li, Dawei; Qu, Feng

2015-10-20

Infection of plants with viruses containing multiple variants frequently leads to dominance by a few random variants in the systemically infected leaves (SLs), for which a plausible explanation is lacking. We show here that SL dominance by a given viral variant is adequately explained by its fortuitous lead in systemic spread, coupled with its resistance to superinfection by other variants. We analyzed the fate of a multi-variant turnip crinkle virus (TCV) population in Arabidopsis and N. benthamiana plants. Both wild-type and RNA silencing-defective plants displayed a similar pattern of random dominance by a few variant genotypes, thus discounting a prominent role for RNA silencing. When introduced to plants sequentially as two subpopulations, a twelve-hour head-start was sufficient for the first set to dominate. Finally, SLs of TCV-infected plants became highly resistant to secondary invasions of another TCV variant. We propose that random distribution of variant foci on inoculated leaves allows different variants to lead systemic movement in different plants. The leading variants then colonize large areas of SLs, and resist the superinfection of lagging variants in the same areas. In conclusion, superinfection resistance is the primary driver of random enrichment of viral variants in systemically infected plants.

Effect of antibiotic diversity on ventilator-associated pneumonia caused by ESKAPE Organisms.

PubMed

Sandiumenge, Alberto; Lisboa, Thiago; Gomez, Frederic; Hernandez, Pilar; Canadell, Laura; Rello, Jordi

2011-09-01

The aim of this study was to test in the clinic whether antimicrobial diversity affects resistance of Enterococcus faecium, Staphylococcus aureus, Klebsiella species, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) pathogens in ventilator-associated pneumonia (VAP). Three different strategies of empirical antimicrobial prescription for VAP were consecutively implemented in an ICU: patient specific (10 months); scheduling, including sequential quarterly prioritization (12 months) and restriction (12 months) of antimicrobials; and mixing (10 months). Periods were compared, measuring the antimicrobial heterogeneity index (AHI). Incidence and resistance patterns of VAP caused by ESKAPE were compared. Overall, 127 microbiologic VAP episodes were documented. ESKAPE VAP increased significantly during scheduling (AHI, 0.65) compared with patient-specific (AHI, 0.88) and mixing (AHI, 0.87) periods (relative risk, 2.67 and 3.84, respectively). This finding was associated with a significant (P < .05) increase of carbapenem-resistant A baumannii during the scheduling period (15.0%) compared with the patient-specific (2.4%) and mixing (0%) periods. ICU mortality of resistant patients with ESKAPE VAP was doubled that of patients without ESKAPE VAP (relative risk, 2.25; 95% CI, 1.67-9.48). Thirty-day mechanical ventilation-free days was significantly increased (5 days) in patients with resistant ESKAPE VAP. Antibiotic strategies promoting diversity may prevent the emergence of resistance of ESKAPE organisms, improving use of health-care resources.

Intrahost Evolution of Methicillin-Resistant Staphylococcus aureus USA300 Among Individuals With Reoccurring Skin and Soft-Tissue Infections

PubMed Central

Azarian, Taj; Daum, Robert S.; Petty, Lindsay A.; Steinbeck, Jenny L.; Yin, Zachary; Nolan, David; Boyle-Vavra, Susan; Hanage, W. P.; Salemi, Marco; David, Michael Z.

2016-01-01

Background. Methicillin-resistant Staphylococcus aureus (MRSA) USA300 is the leading cause of MRSA infections in the United States and has caused an epidemic of skin and soft-tissue infections. Recurrent infections with USA300 MRSA are common, yet intrahost evolution during persistence on an individual has not been studied. This gap hinders the ability to clinically manage recurrent infections and reconstruct transmission networks. Methods. To characterize bacterial intrahost evolution, we examined the clinical courses of 4 subjects with 3–6 recurrent USA300 MRSA infections, using patient clinical data, including antibiotic exposure history, and whole-genome sequencing and phylogenetic analysis of all available MRSA isolates (n = 29). Results. Among sequential isolates, we found variability in diversity, accumulation of mutations, and mobile genetic elements. Selection for antimicrobial-resistant populations was observed through both an increase in the number of plasmids conferring multidrug resistance and strain replacement by a resistant population. Two of 4 subjects had strain replacement with a genetically distinct USA300 MRSA population. Discussions. During a 5-year period in 4 subjects, we identified development of antimicrobial resistance, intrahost evolution, and strain replacement among isolates from patients with recurrent MRSA infections. This calls into question the efficacy of decolonization to prevent recurrent infections and highlights the adaptive potential of USA300 and the need for effective sampling. PMID:27288537

40 CFR 53.35 - Test procedure for Class II and Class III methods for PM 2.5 and PM −2.5.

Code of Federal Regulations, 2014 CFR

2014-07-01

... section. All reference method samplers shall be of single-filter design (not multi-filter, sequential sample design). Each candidate method shall be setup and operated in accordance with its associated... precision specified in table C-4 of this subpart. (g) Test for additive and multiplicative bias (comparative...

40 CFR 53.35 - Test procedure for Class II and Class III methods for PM 2.5 and PM −2.5.

Code of Federal Regulations, 2013 CFR

2013-07-01

... section. All reference method samplers shall be of single-filter design (not multi-filter, sequential sample design). Each candidate method shall be setup and operated in accordance with its associated... precision specified in table C-4 of this subpart. (g) Test for additive and multiplicative bias (comparative...

Ambulatory Care Data Base (ACDB) Data Dictionary Sequential Files of Phase 2.

DTIC Science & Technology

1992-04-01

CEREBRAL ARTERIES 4340 CEREBRAL THROMBOSIS 43491 STROKE , ISCHEMIC 435 TRANSIENT CEREBRAL ISCHEMIA 4359 TRANSIENT ISCHEMIC ATTACK (TIA) 43591 TRANS...HYPERTENSIVE CRISIS 4373 ANEURYSM, CEREBRAL , NONRUPTURED 4374 ARTERITIS, CEREBRAL 4378 CEREBROVASCULAR DISEASE, OTHER ILL-DEFINED 43781 STROKE , LACUNAR...95950 MONITORING FOR LOCALIZATION OF CEREBRAL SEIZURE FOC 95999 OTHER NEUROLOGICAL DIAGNOSTIC PROCEDURES 96500 CHEMO INJ, SINGLE, PRE-MIX, PUSH 96501

A Comparison of the Connotative Meaning of Visuals Presented Singly and in Simultaneous and Sequential Juxtapositions.

ERIC Educational Resources Information Center

Noland, Mildred Jean

A study was conducted investigating whether a sequence of visuals presented in a serial manner differs in connotative meaning from the same set of visuals presented simultaneously. How the meanings of pairs of shots relate to their constituent visuals was also explored. Sixteen pairs of visuals were presented to both male and female subjects in…

Autonomous Legged Hill and Stairwell Ascent

DTIC Science & Technology

2011-11-01

environments with little burden to a human operator. Keywords: autonomous robot , hill climbing , stair climbing , sequential composition, hexapod, self...X-RHex robot on a set of stairs with laser scanner, IMU, wireless repeater, and handle payloads. making them useful for both climbing hills and...reconciliation into that more powerful (but restrictive) framework. 1) The Stair Climbing Behavior: RHex robots have been climbing single-flight stairs

Parameter regimes for a single sequential quantum repeater

NASA Astrophysics Data System (ADS)

Rozpędek, F.; Goodenough, K.; Ribeiro, J.; Kalb, N.; Caprara Vivoli, V.; Reiserer, A.; Hanson, R.; Wehner, S.; Elkouss, D.

2018-07-01

Quantum key distribution allows for the generation of a secret key between distant parties connected by a quantum channel such as optical fibre or free space. Unfortunately, the rate of generation of a secret key by direct transmission is fundamentally limited by the distance. This limit can be overcome by the implementation of so-called quantum repeaters. Here, we assess the performance of a specific but very natural setup called a single sequential repeater for quantum key distribution. We offer a fine-grained assessment of the repeater by introducing a series of benchmarks. The benchmarks, which should be surpassed to claim a working repeater, are based on finite-energy considerations, thermal noise and the losses in the setup. In order to boost the performance of the studied repeaters we introduce two methods. The first one corresponds to the concept of a cut-off, which reduces the effect of decoherence during the storage of a quantum state by introducing a maximum storage time. Secondly, we supplement the standard classical post-processing with an advantage distillation procedure. Using these methods, we find realistic parameters for which it is possible to achieve rates greater than each of the benchmarks, guiding the way towards implementing quantum repeaters.

Multi-GPU maximum entropy image synthesis for radio astronomy

NASA Astrophysics Data System (ADS)

Cárcamo, M.; Román, P. E.; Casassus, S.; Moral, V.; Rannou, F. R.

2018-01-01

The maximum entropy method (MEM) is a well known deconvolution technique in radio-interferometry. This method solves a non-linear optimization problem with an entropy regularization term. Other heuristics such as CLEAN are faster but highly user dependent. Nevertheless, MEM has the following advantages: it is unsupervised, it has a statistical basis, it has a better resolution and better image quality under certain conditions. This work presents a high performance GPU version of non-gridding MEM, which is tested using real and simulated data. We propose a single-GPU and a multi-GPU implementation for single and multi-spectral data, respectively. We also make use of the Peer-to-Peer and Unified Virtual Addressing features of newer GPUs which allows to exploit transparently and efficiently multiple GPUs. Several ALMA data sets are used to demonstrate the effectiveness in imaging and to evaluate GPU performance. The results show that a speedup from 1000 to 5000 times faster than a sequential version can be achieved, depending on data and image size. This allows to reconstruct the HD142527 CO(6-5) short baseline data set in 2.1 min, instead of 2.5 days that takes a sequential version on CPU.

Sequential patterns of essential trace elements composition in Gracilaria verrucosa and its generated products

NASA Astrophysics Data System (ADS)

Izzati, Munifatul; Haryanti, Sri; Parman, Sarjana

2018-05-01

Gracilaria widely known as a source of essential trace elements. However this red seaweeds also has great potential for being developed into commercial products. This study examined the sequential pattern of essential trace elements composition in fresh Gracilaria verrucosa and a selection of its generated products, nemely extracted agar, Gracilaria salt and Gracilaria residue. The sample was collected from a brackish water pond, located in north part Semarang, Central Java. The collected sample was then dried under the sun, and subsequently processed into aformentioned generated products. The Gracilaria salt was obtain by soaking the sun dried Gracilaria overnight in fresh water overnight. The resulted salt solution was then boiled leaving crystal salt. Extracted agar was obtained with alkali agar extraction method. The rest of remaining material was considered as Gracilaria residue. The entire process was repeated 3 times. The compositin of trace elements was examined using ICP-MS Spectrometry. Collected data was then analyzed by ANOVA single factor. Resulting sequential pattern of its essential trace elements composition was compared. A regular table salt was used as controls. Resuts from this study revealed that Gracilaria verrucosa and its all generated products all have similarly patterned the composition of essential trace elements, where Mn>Zn>Cu>Mo. Additionally this pattern is similar to different subspecies of Gracilaria from different location and and different season. However, Gracilaria salt has distinctly different pattern of sequential essential trace elements composition compared to table salt.

The Effect of Hydrogen Annealing on the Oxidation Resistance of Four EPM Single Crystal Superalloys

NASA Technical Reports Server (NTRS)

Smialek, James L.; Barrett, Charles A.; Garlick, Ralph G.

2001-01-01

Four single crystal EPM (enabling propulsion materials) developmental airfoil superalloys were hydrogen annealed at 1300 C for up to 100 hours to remove sulfur and improve oxidation resistance. Although the 1100 and 1150 C cyclic oxidation resistance was remarkably improved by annealing for 24 or 100 hours, the behavior was still considerably inferior to that of commercially available single crystal superalloys, especially those that are either Y-doped or hydrogen annealed. Excessive degradation in the developmental alloys appeared to be correlated with low Cr contents and, to a lesser extent, high Co and Re contents.

Is evaluative conditioning really resistant to extinction? Evidence for changes in evaluative judgements without changes in evaluative representations.

PubMed

Gawronski, Bertram; Gast, Anne; De Houwer, Jan

2015-01-01

Evaluative conditioning (EC) is defined as the change in the evaluation of a conditioned stimulus (CS) due to its pairing with a positive or negative unconditioned stimulus (US). Although several individual studies suggest that EC is unaffected by unreinforced presentations of the CS without the US, a recent meta-analysis indicates that EC effects are less pronounced for post-extinction measurements than post-acquisition measurements. The disparity in research findings suggests that extinction of EC may depend on yet unidentified conditions. In an attempt to uncover these conditions, three experiments (N = 784) investigated the influence of unreinforced post-acquisition CS presentations on EC effects resulting from simultaneous versus sequential pairings and pairings with single versus multiple USs. For all four types of CS-US pairings, EC effects on self-reported evaluations were reduced by unreinforced CS presentations, but only when the CSs had been rated after the initial presentation of CS-US pairings. EC effects on an evaluative priming measure remained unaffected by unreinforced CS presentations regardless of whether the CSs had been rated after acquisition. The results suggest that reduced EC effects resulting from unreinforced CS presentations are due to judgement-related processes during the verbal expression of CS evaluations rather than genuine changes in the underlying evaluative representations.

Shape-Dependent Activity of Ceria for Hydrogen Electro-Oxidation in Reduced-Temperature Solid Oxide Fuel Cells.

PubMed

Tong, Xiaofeng; Luo, Ting; Meng, Xie; Wu, Hao; Li, Junliang; Liu, Xuejiao; Ji, Xiaona; Wang, Jianqiang; Chen, Chusheng; Zhan, Zhongliang

2015-11-04

Single crystalline ceria nanooctahedra, nanocubes, and nanorods are hydrothermally synthesized, colloidally impregnated into the porous La0.9Sr0.1Ga0.8Mg0.2O3-δ (LSGM) scaffolds, and electrochemically evaluated as the anode catalysts for reduced temperature solid oxide fuel cells (SOFCs). Well-defined surface terminations are confirmed by the high-resolution transmission electron microscopy--(111) for nanooctahedra, (100) for nanocubes, and both (110) and (100) for nanorods. Temperature-programmed reduction in H2 shows the highest reducibility for nanorods, followed sequentially by nanocubes and nanooctahedra. Measurements of the anode polarization resistances and the fuel cell power densities reveal different orders of activity of ceria nanocrystals at high and low temperatures for hydrogen electro-oxidation, i.e., nanorods > nanocubes > nanooctahedra at T ≤ 450 °C and nanooctahedra > nanorods > nanocubes at T ≥ 500 °C. Such shape-dependent activities of these ceria nanocrystals have been correlated to their difference in the local structure distortions and thus in the reducibility. These findings will open up a new strategy for design of advanced catalysts for reduced-temperature SOFCs by elaborately engineering the shape of nanocrystals and thus selectively exposing the crystal facets. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A novel method to study single-particle dynamics by the resistive pulse technique

NASA Astrophysics Data System (ADS)

Berge, L. I.; Feder, J.; Jøssang, T.

1989-08-01

We have developed a new method, a pressure-reversal technique, which extends the uses of the resistive pulse (Coulter counter) technique to single-particle dynamics. The resistive pulse technique measures the increase in resistance when particles suspended in an electrolyte are transported through a current-carrying aperture. By the new method, the pressure is reversed when a particle exits the pore. A trigger signal, derived from the particle pulses, is used to activate two miniature solenoid valves which serve as pressure switches. In this way, the particle reenters the pore. A single particle flowing back and forth may be studied over a long period of time. The time the particle spends outside the pore between reversals is variable from a few milliseconds to several seconds. We have so far used pore diameters in the range of 3-30 μm. The new technique enables us to study single-particle dissolution and single-particle flow dynamics. The experimental arrangement and the details of the new method are described together with some illustrative measurements.

A posteriori model validation for the temporal order of directed functional connectivity maps

PubMed Central

Beltz, Adriene M.; Molenaar, Peter C. M.

2015-01-01

A posteriori model validation for the temporal order of neural directed functional connectivity maps is rare. This is striking because models that require sequential independence among residuals are regularly implemented. The aim of the current study was (a) to apply to directed functional connectivity maps of functional magnetic resonance imaging data an a posteriori model validation procedure (i.e., white noise tests of one-step-ahead prediction errors combined with decision criteria for revising the maps based upon Lagrange Multiplier tests), and (b) to demonstrate how the procedure applies to single-subject simulated, single-subject task-related, and multi-subject resting state data. Directed functional connectivity was determined by the unified structural equation model family of approaches in order to map contemporaneous and first order lagged connections among brain regions at the group- and individual-levels while incorporating external input, then white noise tests were run. Findings revealed that the validation procedure successfully detected unmodeled sequential dependencies among residuals and recovered higher order (greater than one) simulated connections, and that the procedure can accommodate task-related input. Findings also revealed that lags greater than one were present in resting state data: With a group-level network that contained only contemporaneous and first order connections, 44% of subjects required second order, individual-level connections in order to obtain maps with white noise residuals. Results have broad methodological relevance (e.g., temporal validation is necessary after directed functional connectivity analyses because the presence of unmodeled higher order sequential dependencies may bias parameter estimates) and substantive implications (e.g., higher order lags may be common in resting state data). PMID:26379489

One-stage sequential bilateral thoracic expansion for asphyxiating thoracic dystrophy (Jeune syndrome).

PubMed

Muthialu, Nagarajan; Mussa, Shafi; Owens, Catherine M; Bulstrode, Neil; Elliott, Martin J

2014-10-01

Jeune syndrome (asphyxiating thoracic dystrophy) is a rare disorder characterized by skeletal dysplasia, reduced diameter of the thoracic cage and extrathoracic organ involvement. Fatal, early respiratory insufficiency may occur. Two-stage lateral thoracic expansion has been reported, addressing each side sequentially over 3-12 months. While staged repair theoretically provides less invasive surgery in a small child with respiratory distress, we utilized a single stage, bilateral procedure aiming to rapidly maximize lung development. Combined bilateral surgery also offered the chance of rapid recovery, and reduced hospital stay. We present our early experience of this modification of existing surgical treatment for an extremely rare condition, thought to be generally fatal in early childhood. Nine children (6 males, 3 females; median age 30 months [3.5-75]) underwent thoracic expansion for Jeune syndrome in our centre. All patients required preoperative respiratory support (5 with tracheostomy, 8 requiring positive pressure ventilation regularly within each day/night cycle). Two children underwent sequential unilateral (2-month interval between stages) and 7 children bilateral thoracic expansion by means of staggered osteotomies of third to eighth ribs and plate fixation of fourth to fifth rib and sixth to seventh rib, leaving the remaining ribs floating. There was no operative mortality. There were 2 deaths within 3 months of surgery, due to pulmonary hypertension (1 following two-stage and 1 following single-stage thoracic expansion). At the median follow-up of 11 months (1-15), 3 children have been discharged home from their referring unit and 2 have significantly reduced respiratory support. One child remains on non-invasive ventilation and another is still ventilated with a high oxygen requirement. Jeune syndrome is a difficult condition to manage, but bilateral thoracic expansion offers an effective reduction in ventilator requirements in these children. While two-stage repair has been described previously, this is the first report of single-stage bilateral thoracic expansion. Single-stage repair is feasible and may offer better resource management and significant cost savings by potentially reducing theatre usage and overall length of stay (intensive care and hospital) without compromising clinical outcomes. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Coordination of two sequential ester-transfer reactions: exogenous guanosine binding promotes the subsequent ωG binding to a group I intron

PubMed Central

Bao, Penghui; Wu, Qi-Jia; Yin, Ping; Jiang, Yanfei; Wang, Xu; Xie, Mao-Hua; Sun, Tao; Huang, Lin; Mo, Ding-Ding; Zhang, Yi

2008-01-01

Self-splicing of group I introns is accomplished by two sequential ester-transfer reactions mediated by sequential binding of two different guanosine ligands, but it is yet unclear how the binding is coordinated at a single G-binding site. Using a three-piece trans-splicing system derived from the Candida intron, we studied the effect of the prior GTP binding on the later ωG binding by assaying the ribozyme activity in the second reaction. We showed that adding GTP simultaneously with and prior to the esterified ωG in a substrate strongly accelerated the second reaction, suggesting that the early binding of GTP facilitates the subsequent binding of ωG. GTP-mediated facilitation requires C2 amino and C6 carbonyl groups on the Watson–Crick edge of the base but not the phosphate or sugar groups, suggesting that the base triple interactions between GTP and the binding site are important for the subsequent ωG binding. Strikingly, GTP binding loosens a few local structures of the ribozyme including that adjacent to the base triple, providing structural basis for a rapid exchange of ωG for bound GTP. PMID:18978026

Sequential Auctions with Partially Substitutable Goods

NASA Astrophysics Data System (ADS)

Vetsikas, Ioannis A.; Jennings, Nicholas R.

In this paper, we examine a setting in which a number of partially substitutable goods are sold in sequential single unit auctions. Each bidder needs to buy exactly one of these goods. In previous work, this setting has been simplified by assuming that bidders do not know their valuations for all items a priori, but rather are informed of their true valuation for each item right before the corresponding auction takes place. This assumption simplifies the strategies of bidders, as the expected revenue from future auctions is the same for all bidders due to the complete lack of private information. In our analysis we don't make this assumption. This complicates the computation of the equilibrium strategies significantly. We examine this setting both for first and second-price auction variants, initially when the closing prices are not announced, for which we prove that sequential first and second-price auctions are revenue equivalent. Then we assume that the prices are announced; because of the asymmetry in the announced prices between the two auction variants, revenue equivalence does not hold in this case. We finish the paper, by giving some initial results about the case when free disposal is allowed, and therefore a bidder can purchase more than one item.