Buchacz, Kate; Wiegand, Ryan; Armon, Carl; Chmiel, Joan S.; Wood, Kathleen; Brooks, John T.; Palella, Frank J.
2015-01-01
Objectives Raltegravir (RAL)-containing antiretroviral therapy (ART) produced better immunologic and virologic responses than optimized background ART in clinical trials of heavily ART-experienced patients, but few data exist on long-term outcomes in routine HIV care. Methods We studied ART-experienced HIV outpatient study (HOPS) participants seen at 10 US HIV-specialty clinics during 2007–2011. We identified patients who started (baseline date) either continuous ≥30 days of RAL-containing or RAL-sparing ART, and used propensity score (PS) matching methods to account for baseline clinical and demographic differences. We used Kaplan–Meier methods and log-rank tests for the matched subsets to evaluate probability of death, achieving HIV RNA <50 copies/ml, and CD4 cell count (CD4) increase of ≥50 cells mm−3 during follow-up. Results Among 784 RAL-exposed and 1062 RAL-unexposed patients, 472 from each group were matched by PS. At baseline, the 472 RAL-exposed patients (mean nadir CD4, 205 cells mm−3; mean baseline CD4, 460 cells mm−3; HIV RNA <50 copies ml−1 in 61%; mean years on prescribed ART, 7.5) were similar to RAL unexposed. During a mean follow-up of over 3 years, mortality rates and immunologic and virologic trajectories did not differ between the two groups. Among patients with detectable baseline HIV RNA levels, 76% of RAL-exposed and 63% of RAL-unexposed achieved HIV RNA <50 copies ml−1 (P=0.51); 69 and 58%, respectively, achieved a CD4 increase ≥50 cells mm−3 (P=0.70). Discussion In our large cohort of US ART-experienced patients with a wide spectrum of clinical history, similar outcomes were observed when prescribed RAL containing versus other contemporary ART. PMID:26126549
Arumugam, Sridhar; Wei, Junfei; Liu, Zhuyun; Abraham, David; Bell, Aaron; Bottazzi, Maria Elena; Hotez, Peter J; Zhan, Bin; Lustigman, Sara; Klei, Thomas R
2016-04-01
The Brugia malayi Bm-103 and Bm-RAL-2 proteins are orthologous to Onchocerca volvulus Ov-103 and Ov-RAL-2, and which were selected as the best candidates for the development of an O. volvulus vaccine. The B. malayi gerbil model was used to confirm the efficacy of these Ov vaccine candidates on adult worms and to determine whether their combination is more efficacious. Vaccine efficacy of recombinant Bm-103 and Bm-RAL-2 administered individually, concurrently or as a fusion protein were tested in gerbils using alum as adjuvant. Vaccination with Bm-103 resulted in worm reductions of 39%, 34% and 22% on 42, 120 and 150 days post infection (dpi), respectively, and vaccination with Bm-RAL-2 resulted in worm reductions of 42%, 22% and 46% on 42, 120 and 150 dpi, respectively. Vaccination with a fusion protein comprised of Bm-103 and Bm-RAL-2 resulted in improved efficacy with significant reduction of worm burden of 51% and 49% at 90 dpi, as did the concurrent vaccination with Bm-103 and Bm-RAL-2, with worm reduction of 61% and 56% at 90 dpi. Vaccination with Bm-103 and Bm-RAL-2 as a fusion protein or concurrently not only induced a significant worm reduction of 61% and 42%, respectively, at 150 dpi, but also significantly reduced the fecundity of female worms as determined by embryograms. Elevated levels of antigen-specific IgG were observed in all vaccinated gerbils. Serum from gerbils vaccinated with Bm-103 and Bm-RAL-2 individually, concurrently or as a fusion protein killed third stage larvae in vitro when combined with peritoneal exudate cells. Although vaccination with Bm-103 and Bm-RAL-2 individually conferred protection against B. malayi infection in gerbils, a more consistent and enhanced protection was induced by vaccination with Bm-103 and Bm-RAL-2 fusion protein and when they were used concurrently. Further characterization and optimization of these filarial vaccines are warranted.
Arumugam, Sridhar; Wei, Junfei; Liu, Zhuyun; Abraham, David; Bell, Aaron; Bottazzi, Maria Elena; Hotez, Peter J.; Zhan, Bin; Lustigman, Sara; Klei, Thomas R.
2016-01-01
Background The Brugia malayi Bm-103 and Bm-RAL-2 proteins are orthologous to Onchocerca volvulus Ov-103 and Ov-RAL-2, and which were selected as the best candidates for the development of an O. volvulus vaccine. The B. malayi gerbil model was used to confirm the efficacy of these Ov vaccine candidates on adult worms and to determine whether their combination is more efficacious. Methodology and Principle Findings Vaccine efficacy of recombinant Bm-103 and Bm-RAL-2 administered individually, concurrently or as a fusion protein were tested in gerbils using alum as adjuvant. Vaccination with Bm-103 resulted in worm reductions of 39%, 34% and 22% on 42, 120 and 150 days post infection (dpi), respectively, and vaccination with Bm-RAL-2 resulted in worm reductions of 42%, 22% and 46% on 42, 120 and 150 dpi, respectively. Vaccination with a fusion protein comprised of Bm-103 and Bm-RAL-2 resulted in improved efficacy with significant reduction of worm burden of 51% and 49% at 90 dpi, as did the concurrent vaccination with Bm-103 and Bm-RAL-2, with worm reduction of 61% and 56% at 90 dpi. Vaccination with Bm-103 and Bm-RAL-2 as a fusion protein or concurrently not only induced a significant worm reduction of 61% and 42%, respectively, at 150 dpi, but also significantly reduced the fecundity of female worms as determined by embryograms. Elevated levels of antigen-specific IgG were observed in all vaccinated gerbils. Serum from gerbils vaccinated with Bm-103 and Bm-RAL-2 individually, concurrently or as a fusion protein killed third stage larvae in vitro when combined with peritoneal exudate cells. Conclusion Although vaccination with Bm-103 and Bm-RAL-2 individually conferred protection against B. malayi infection in gerbils, a more consistent and enhanced protection was induced by vaccination with Bm-103 and Bm-RAL-2 fusion protein and when they were used concurrently. Further characterization and optimization of these filarial vaccines are warranted. PMID:27045170
Study of aerodynamic technology for VSTOL fighter/attack aircraft: Horizontal attitude concept
NASA Technical Reports Server (NTRS)
Brown, S. H.
1978-01-01
A horizontal attitude VSTOL (HAVSTOL) supersonic fighter attack aircraft powered by RALS turbofan propulsion system is analyzed. Reaction control for subaerodynamic flight is obtained in pitch and yaw from the RALS and roll from wingtip jets powered by bleed air from the RALS duct. Emphasis is placed on the development of aerodynamic characteristics and the identification of aerodynamic uncertainties. A wind tunnel program is shown to resolve some of the uncertainties. Aerodynamic data developed are static characteristics about all axes, control effectiveness, drag, propulsion induced effects and reaction control characteristics.
Capetti, Amedeo; Landonio, Simona; Meraviglia, Paola; Di Biagio, Antonio; Lo Caputo, Sergio; Sterrantino, Gaetana; Ammassari, Adriana; Menzaghi, Barbara; Franzetti, Marco; De Socio, Giuseppe Vittorio; Pellicanò, Giovanni; Mazzotta, Elena; Soria, Alessandro; Meschiari, Marianna; Trezzi, Michele; Sasset, Lolita; Celesia, Benedetto Maurizio; Zucchi, Patrizia; Melzi, Sara; Ricci, Elena; Rizzardini, Giuliano
2012-01-01
Background Long term efficacy of raltegravir (RAL)-including regimens in highly pre-treated HIV-1-infected patients has been demonstrated in registration trials. However, few studies have assessed durability in routine clinical settings. Methods Antiretroviral treatment-experienced patients initiating a RAL-containing salvage regimen were enrolled. Routine clinical and laboratory follow-up was performed at baseline, week 4, 12, and every 12 weeks thereafter. Data were censored at week 96. Results Out of 320 patients enrolled, 292 (91.25%) subjects maintained their initial regimen for 96 weeks; 28 discontinued prematurely for various reasons: death (11), viral failure (8), adverse events (5), loss to follow-up (3), consent withdrawal (1). Eight among these 28 subjects maintained RAL but changed the accompanying drugs. The mean CD4+ T-cell increase at week 96 was 227/mm3; 273 out of 300 patients (91%), who were still receiving RAL at week 96, achieved viral suppression (HIV-1 RNA <50 copies/mL). When analyzing the immuno-virologic outcome according to the number of drugs used in the regimen, 2 (n = 45), 3 (n = 111), 4 (n = 124), or >4 (n = 40), CD4+ T-cell gain was similar across strata: +270, +214, +216, and +240 cells/mm3, respectively, as was the proportion of subjects with undetectable viral load. Laboratory abnormalities (elevation of liver enzymes, total cholesterol and triglycerides) were rare, ranging from 0.9 to 3.1%. The mean 96-week total cholesterol increase was 23.6 mg/dL. Conclusions In a routine clinical setting, a RAL-based regimen allowed most patients in salvage therapy to achieve optimal viral suppression for at least 96 weeks, with relevant immunologic gain and very few adverse events. PMID:22808029
Central Radar System, Over-the-Horizon Backscatter
1990-03-09
1,2-Dibromo-3- chloropropane (DBCP) 0.3 TABLE 41-6 (Continued). MINNESOTA RECOMMENDED ALLOWABLE LIMITS (RAL) FOR DRINKING WATER WELLS Compound RAL (ug/ 1 ...TABLE OF CONTENTS ENVIRONMENTAL IMPACT ANALYSIS PROCESS OVERVIEW ............ TECHNICAL STUDY 1 FACILITIES...TECHNICAL STUDY 10 0 TECHNICAL STUDY 1 CENTRAL RADAR SYSTEM OVER-THE-HORIZON BACKSCATTER RADAR PROGRAM 0 ENVIRONMENTAL IMPACT
Ras-Related Small GTPases RalA and RalB Regulate Cellular Survival After Ionizing Radiation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kidd, Ambrose R.; Snider, Jared L.; Martin, Timothy D.
2010-09-01
Purpose: Oncogenic activation of Ras renders cancer cells resistant to ionizing radiation (IR), but the mechanisms have not been fully characterized. The Ras-like small GTPases RalA and RalB are downstream effectors of Ras function and are critical for both tumor growth and survival. The Ral effector RalBP1/RLIP76 mediates survival of mice after whole-body irradiation, but the role of the Ral GTPases themselves in response to IR is unknown. We have investigated the role of RalA and RalB in cellular responses to IR. Methods and Materials: RalA, RalB, and their major effectors RalBP1 and Sec5 were knocked down by stable expressionmore » of short hairpin RNAs in the K-Ras-dependent pancreatic cancer-derived cell line MIA PaCa-2. Radiation responses were measured by standard clonogenic survival assays for reproductive survival, {gamma}H2AX expression for double-strand DNA breaks (DSBs), and poly(ADP-ribose)polymerase (PARP) cleavage for apoptosis. Results: Knockdown of K-Ras, RalA, or RalB reduced colony-forming ability post-IR, and knockdown of either Ral isoform decreased the rate of DSB repair post-IR. However, knockdown of RalB, but not RalA, increased cell death. Surprisingly, neither RalBP1 nor Sec5 suppression affected colony formation post-IR. Conclusions: Both RalA and RalB contribute to K-Ras-dependent IR resistance of MIA PaCa-2 cells. Sensitization due to suppressed Ral expression is likely due in part to decreased efficiency of DNA repair (RalA and RalB) and increased susceptibility to apoptosis (RalB). Ral-mediated radioresistance does not depend on either the RalBP1 or the exocyst complex, the two best-characterized Ral effectors, and instead may utilize an atypical or novel effector.« less
Eron, Joseph J; Clotet, Bonaventura; Durant, Jacques; Katlama, Christine; Kumar, Princy; Lazzarin, Adriano; Poizot-Martin, Isabelle; Richmond, Gary; Soriano, Vincent; Ait-Khaled, Mounir; Fujiwara, Tamio; Huang, Jenny; Min, Sherene; Vavro, Cindy; Yeo, Jane
2013-03-01
Dolutegravir (DTG; S/GSK1349572), a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, has limited cross-resistance to raltegravir (RAL) and elvitegravir in vitro. This phase IIb study assessed the activity of DTG in HIV-1-infected subjects with genotypic evidence of RAL resistance. Subjects received DTG 50 mg once daily (cohort I) or 50 mg twice daily (cohort II) while continuing a failing regimen (without RAL) through day 10, after which the background regimen was optimized, when feasible, for cohort I, and at least 1 fully active drug was mandated for cohort II. The primary efficacy end point was the proportion of subjects on day 11 in whom the plasma HIV-1 RNA load decreased by ≥0.7 log(10) copies/mL from baseline or was <400 copies/mL. A rapid antiviral response was observed. More subjects achieved the primary end point in cohort II (23 of 24 [96%]), compared with cohort I (21 of 27 [78%]) at day 11. At week 24, 41% and 75% of subjects had an HIV-1 RNA load of <50 copies/mL in cohorts I and II, respectively. Further integrase genotypic evolution was uncommon. Dolutegravir had a good, similar safety profile with each dosing regimen. Dolutegravir 50 mg twice daily with an optimized background provided greater and more durable benefit than the once-daily regimen. These data are the first clinical demonstration of the activity of any integrase inhibitor in subjects with HIV-1 resistant to RAL.
NASA Technical Reports Server (NTRS)
Willis, W. S.; Konarski, M.; Sutherland, M. V.
1982-01-01
Ejector concepts for use with a remote augmented lift system (RALS) exhaust nozzle were studied. A number of concepts were considered and three were selected as having the greatest promise of providing the desired aircraft and exhaust gas cooling and lift enhancement. A scale model test program is recommended to explore the effects of the more important parameters on ejector performance.
Eron, Joseph J.; Clotet, Bonaventura; Durant, Jacques; Katlama, Christine; Kumar, Princy; Lazzarin, Adriano; Poizot-Martin, Isabelle; Richmond, Gary; Soriano, Vincent; Ait-Khaled, Mounir; Fujiwara, Tamio; Huang, Jenny; Min, Sherene; Vavro, Cindy; Yeo, Jane; Walmsley, Sharon L.; Cox, Joseph; Reynes, Jacques; Morlat, Philippe; Vittecoq, Daniel; Livrozet, Jean-Michel; Fernández, Pompeyo Viciana; Gatell, Jose M.; DeJesus, Edwin; DeVente, Jerome; Lalezari, Jacob P.; McCurdy, Lewis H.; Sloan, Louis A.; Young, Benjamin; LaMarca, Anthony; Hawkins, Trevor
2013-01-01
Background. Dolutegravir (DTG; S/GSK1349572), a human immunodeficiency virus type 1 (HIV-1) integrase inhibitor, has limited cross-resistance to raltegravir (RAL) and elvitegravir in vitro. This phase IIb study assessed the activity of DTG in HIV-1–infected subjects with genotypic evidence of RAL resistance. Methods. Subjects received DTG 50 mg once daily (cohort I) or 50 mg twice daily (cohort II) while continuing a failing regimen (without RAL) through day 10, after which the background regimen was optimized, when feasible, for cohort I, and at least 1 fully active drug was mandated for cohort II. The primary efficacy end point was the proportion of subjects on day 11 in whom the plasma HIV-1 RNA load decreased by ≥0.7 log10 copies/mL from baseline or was <400 copies/mL. Results. A rapid antiviral response was observed. More subjects achieved the primary end point in cohort II (23 of 24 [96%]), compared with cohort I (21 of 27 [78%]) at day 11. At week 24, 41% and 75% of subjects had an HIV-1 RNA load of <50 copies/mL in cohorts I and II, respectively. Further integrase genotypic evolution was uncommon. Dolutegravir had a good, similar safety profile with each dosing regimen. Conclusion. Dolutegravir 50 mg twice daily with an optimized background provided greater and more durable benefit than the once-daily regimen. These data are the first clinical demonstration of the activity of any integrase inhibitor in subjects with HIV-1 resistant to RAL. PMID:23225901
Pawar, Archana; Meier, Jeremy A; Dasgupta, Anwesha; Diwanji, Neha; Deshpande, Neha; Saxena, Kritika; Buwa, Natasha; Inchanalkar, Siddhi; Schwartz, Martin Alexander; Balasubramanian, Nagaraj
2016-09-01
Integrin dependent regulation of growth factor signalling confers anchorage dependence that is deregulated in cancers. Downstream of integrins and oncogenic Ras the small GTPase Ral is a vital mediator of adhesion dependent trafficking and signalling. This study identifies a novel regulatory crosstalk between Ral and Arf6 that controls Ral function in cells. In re-adherent mouse fibroblasts (MEFs) integrin dependent activation of RalA drives Arf6 activation. Independent of adhesion constitutively active RalA and RalB could both however activate Arf6. This is further conserved in oncogenic H-Ras containing bladder cancer T24 cells, which express anchorage independent active Ral that supports Arf6 activation. Arf6 mediates active Ral-exocyst dependent delivery of raft microdomains to the plasma membrane that supports anchorage independent growth signalling. Accordingly in T24 cells the RalB-Arf6 crosstalk is seen to preferentially regulate anchorage independent Erk signalling. Active Ral we further find uses a Ral-RalBP1-ARNO-Arf6 pathway to mediate Arf6 activation. This study hence identifies Arf6, through this regulatory crosstalk, to be a key downstream mediator of Ral isoform function along adhesion dependent pathways in normal and cancer cells. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Mass spectroscopic phosphoprotein mapping of Ral Binding protein 1 (RalBP1/Rip1/RLIP76)
Herlevsen, Mikael C; Theodorescu, Dan
2009-01-01
RalBP1, a multifunctional protein implicated in cancer cell proliferation, radiation and chemoresistance and ligand dependent receptor internalization, is upregulated in bladder cancer and is a downstream effector of RalB, a GTPase associated with metastasis. RalBP1 can be regulated by phosphorylation by protein kinase C (PKC). No studies have comprehensively mapped RalBP1 phosphorylation sites or whether RalB affects these. We identified fourteen phosphorylation sites of RalBP1 in human bladder carcinoma UMUC-3 and embryonic kidney derived 293T cells. The phosphorylated residues are concentrated at the N-terminus. Ten of the first 100 amino acids of the primary structure were phosphorylated. Nine were serine residues, and one a threonine. We evaluated the effect of RalB overexpression on RalBP1 phosphorylation and found the largest change in phosphorylation status at S463 and S645. Further characterization of these sites will provide novel insights on RalBP1 biology, its functional relationship to RalB and possible avenues for therapeutic intervention. PMID:17706599
Cytotoxicity of All-Trans-Retinal Increases Upon Photodegradation†
Różanowska, Małgorzata; Handzel, Kinga; Boulton, Michael E.; Różanowski, Bartosz
2013-01-01
All-trans-retinal (AtRal) can accumulate in the retina as a result of excessive exposure to light. The purpose of this study was to compare cytotoxicity of AtRal and photodegraded AtRal (dAtRal) on cultured human retinal pigment epithelial cells in dark and upon exposure to visible light. AtRal was degraded by exposure to visible light. Cytotoxicity was monitored by imaging of cell morphology, propidium iodide staining of cells with permeable plasma membrane and measurements of reductive activity of cells. Generation of singlet oxygen photosensitized by AtRal and dAtRal was monitored by time-resolved measurements of characteristic singlet oxygen phosphorescence. Photodegradation of AtRal resulted in a decrease in absorption of visible light and accumulation of the degradation products with absorption maximum at ~330 nm. Toxicity of dAtRal was concentration-dependent and was greater during irradiation with visible light than in dark. DAtRal was more cytotoxic than AtRal both in dark and during exposure to visible light. Photochemical properties of dAtRal indicate that it may be responsible for the maximum in the action spectra of retinal photodamage recorded in animals. In conclusion, photodegradation products of AtRal may impose a significant threat to the retina and therefore their roles in retinal pathology need to be explored. PMID:22515697
Baldelli, Sara; Cerea, Matteo; Landonio, Simona; Meraviglia, Paola; Simioni, Emanuela; Cozzi, Valeria; Fucile, Serena; Gazzaniga, Andrea; Clementi, Emilio; Galli, Massimo; Rizzardini, Giuliano; Gervasoni, Cristina
2012-01-01
The pharmacokinetics of raltegravir (RAL) in HIV patients is characterized by high interpatient/intrapatient variability. We investigated the potential contribution of the drug pharmaceutical formulation to RAL pharmacokinetics. We first compared in vivo the pharmacokinetics of RAL for 67 patients to whom the drug was administered by swallowing the intact tablet with those obtained from 13 HIV-infected patients who chewed the RAL tablet due to swallowing difficulties. Subsequently, we evaluated in vitro the dissolution of RAL tablets under different conditions. In the in vivo study, we found that patients given RAL by chewing the tablets presented pharmacokinetic profiles characterized by significantly higher RAL absorption than did patients receiving the drug by swallowing. The in vitro studies showed that when the whole tablets were exposed to an acidic medium, the release of RAL was very low, whereas when the tablets were crushed, the profiles presented significantly higher concentrations of RAL. Crushed tablets tested in water or in a pH 6.8 buffer exhibited prompt and complete dissolution of RAL. HIV-infected patients receiving RAL by chewing the tablet showed higher drug absorption and reduced pharmacokinetic variability compared with patients swallowing the intact tablet. This is related to problems in tablet disintegration and to erratic drug absorption. The amelioration of the RAL pharmaceutical formulation could improve drug pharmacokinetics. PMID:22964253
Which Way In? The RalF Arf-GEF Orchestrates Rickettsia Host Cell Invasion
Rennoll-Bankert, Kristen E.; Rahman, M. Sayeedur; Gillespie, Joseph J.; Guillotte, Mark L.; Kaur, Simran J.; Lehman, Stephanie S.; Beier-Sexton, Magda; Azad, Abdu F.
2015-01-01
Bacterial Sec7-domain-containing proteins (RalF) are known only from species of Legionella and Rickettsia, which have facultative and obligate intracellular lifestyles, respectively. L. pneumophila RalF, a type IV secretion system (T4SS) effector, is a guanine nucleotide exchange factor (GEF) of ADP-ribosylation factors (Arfs), activating and recruiting host Arf1 to the Legionella-containing vacuole. In contrast, previous in vitro studies showed R. prowazekii (Typhus Group) RalF is a functional Arf-GEF that localizes to the host plasma membrane and interacts with the actin cytoskeleton via a unique C-terminal domain. As RalF is differentially encoded across Rickettsia species (e.g., pseudogenized in all Spotted Fever Group species), it may function in lineage-specific biology and pathogenicity. Herein, we demonstrate RalF of R. typhi (Typhus Group) interacts with the Rickettsia T4SS coupling protein (RvhD4) via its proximal C-terminal sequence. RalF is expressed early during infection, with its inactivation via antibody blocking significantly reducing R. typhi host cell invasion. For R. typhi and R. felis (Transitional Group), RalF ectopic expression revealed subcellular localization with the host plasma membrane and actin cytoskeleton. Remarkably, R. bellii (Ancestral Group) RalF showed perinuclear localization reminiscent of ectopically expressed Legionella RalF, for which it shares several structural features. For R. typhi, RalF co-localization with Arf6 and PI(4,5)P2 at entry foci on the host plasma membrane was determined to be critical for invasion. Thus, we propose recruitment of PI(4,5)P2 at entry foci, mediated by RalF activation of Arf6, initiates actin remodeling and ultimately facilitates bacterial invasion. Collectively, our characterization of RalF as an invasin suggests that, despite carrying a similar Arf-GEF unknown from other bacteria, different intracellular lifestyles across Rickettsia and Legionella species have driven divergent roles for RalF during infection. Furthermore, our identification of lineage-specific Arf-GEF utilization across some rickettsial species illustrates different pathogenicity factors that define diverse agents of rickettsial diseases. PMID:26291822
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zhu, Xue; Wang, Ke, E-mail: wangke@jsinm.org; Zhang, Kai
Delayed clearance of free form all-trans-retinal (atRAL) is estimated be the key cause of retinal pigment epithelium (RPE) cells injury during the pathogenesis of retinopathies such as age-related macular degeneration (AMD), however, the underlying molecular mechanisms are far from clear. In this study, we investigated the cytotoxicity effect and underlying molecular mechanism of atRAL on human retinal pigment epithelium ARPE-19 cells. The results indicated that atRAL could cause cell dysfunction by inducing oxidative and nitrosative stresses in ARPE-19 cells. The oxidative stress induced by atRAL was mediated through up-regulation of reactive oxygen species (ROS) generation, activating mitochondrial-dependent and MAPKs signalingmore » pathways, and finally resulting in apoptosis of ARPE-19 cells. The NADPH oxidase inhibitor apocynin could partly attenuated ROS generation, indicating that NADPH oxidase activity was involved in atRAL-induced oxidative stress in ARPE-19 cells. The nitrosative stress induced by atRAL was mainly reflected in increasing nitric oxide (NO) production, enhancing iNOS, ICAM-1 and VCAM-1 expressions, and promoting monocyte adhesion. Furthermore, above effects could be dramatically blocked by using a nuclear factor kappa B (NF-κB) inhibitor SN50, indicated that atRAL-induced oxidative and nitrosative stresses were mediated by NF-κB. The results provide better understanding of atRAL-induced toxicity in human RPE cells. - Highlights: • atRAL induces oxidative stress-mediated apoptosis in ARPE-19 cells. • atRAL induces oxidative stress-mediated inflammation in ARPE-19 cells. • NF-κB is involved in atRAL-induced oxidative and nitrosative stresses.« less
Zago, Giulia; Biondini, Marco; Camonis, Jacques; Parrini, Maria Carla
2017-05-12
Cell migration is central to many developmental, physiologic and pathological processes, including cancer progression. The Ral GTPases (RalA and RalB) which act down-stream the Ras oncogenes, are key players in the coordination between membrane trafficking and actin polymerization. A major direct effector of Ral, the exocyst complex, works in polarized exocytosis and is at the center of multiple protein-protein interactions that support cell migration by promoting protrusion formation, front-rear polarization, and extra-cellular matrix degradation. In this review we describe the recent advancements in deciphering the molecular mechanisms underlying this role of Ral via exocyst on cell migration. Among others, we will discuss the recently identified cross-talk between Ral and Rac1 pathways: exocyst binds to a negative regulator (the RacGAP SH3BP1) and to the major effector (the Wave Regulatory Complex, WRC) of Rac1, the master regulator of protrusions. Next challenge will be to better characterize the dynamics in space and in time of these molecular interplays, to better understand the pleiotropic functions of Ral in both normal and cancer cells.
Robotic Versus Video-assisted Lobectomy/Segmentectomy for Lung Cancer: A Meta-analysis.
Liang, Hengrui; Liang, Wenhua; Zhao, Lei; Chen, Difei; Zhang, Jianrong; Zhang, Yiyin; Tang, Shiyan; He, Jianxing
2017-06-16
: Objective: To compare the safety/efficacy of the robotic-assisted lobectomy/segmentectomy (RAL/S) with the video-assisted lobectomy/segmentectomy (VAL/S) for radical lung cancer resection. It remains uncertain whether the newly developed RAL/S is comparable with the VAL/S. A comprehensive search of online databases was performed. Perioperative outcomes were synthesized. Cumulative meta-analysis was performed to evaluate the temporal trend of pooled outcomes. Specific subgroups (propensity score matching studies, pure lobectomy studies) were examined. Analysis of 14 studies including a total of 7438 patients was performed. RAL/S was performed on 3239 patients, whereas the other 4199 patients underwent VAL/S. The 30-day mortality [0.7% vs 1.1%; odds ratio (OR) 0.53, P = 0.045] and conversion rate to open surgery (10.3% vs 11.9%; OR 0.57, P < 0.001) were significantly lower in patients who underwent RAL/S than VAL/S. Meanwhile, the postoperative complications (27.5% vs 28.2%; OR 0.95, P = 0.431), operation time [176.63 vs 162.74 min; standardized mean difference (SMD) 0.30, P = 0.086], duration of hospitalization (4.90 vs 5.23 days; SMD -0.08, P = 0.292), days to tube removal (4.10 vs 3.53 days; SMD 0.25, P = 0.120), retrieved lymph node (11.96 vs 10.67; SMD 0.46, P = 0.381), and retrieved lymph node station (4.98 vs 4.32; SMD 0.83, P = 0.261) were similar between the 2 groups. The cumulative meta-analyses suggested that the relative effects between 2 groups have already stabilized. All outcomes of subgroup and overall analyses were similar. This up-to-date meta-analysis confirms that RAL/S is a feasible and safe alternative to VAL/S for radical resection of lung cancer. Future studies should focus on the long-term benefits and cost effectiveness of RAL/S compared with VAL/S.
Integrase mutations can reduce the effectiveness of the first-generation FDA-approved integrase strand transfer inhibitors (INSTIs), raltegravir (RAL) and elvitegravir (EVG). The second-generation agent, dolutegravir (DTG), has enjoyed considerable clinical success; however, resistancecausing mutations that diminish the efficacy of DTG have appeared. Our current findings
Kirks, Russell C; Lorimer, Patrick D; Fruscione, Michael; Cochran, Allyson; Baker, Erin H; Iannitti, David A; Vrochides, Dionisios; Martinie, John B
2017-09-01
This study compares clinical and cost outcomes of robot-assisted laparoscopic (RAL) and open longitudinal pancreaticojejunostomy (LPJ) for chronic pancreatitis. Clinical and cost data were retrospectively compared between open and RAL LPJ performed at a single center from 2008-2015. Twenty-six patients underwent LPJ: 19 open and 7 RAL. Two robot-assisted cases converted to open were included in the open group for analysis. Patients undergoing RAL LPJ had less intraoperative blood loss, a shorter surgical length of stay, and lower medication costs. Operation supply cost was higher in the RAL group. No difference in hospitalization cost was found. Versus the open approach, RAL LPJ performed for chronic pancreatitis shortens hospitalization and reduces medication costs; hospitalization costs are equivalent. A higher operative cost for RAL LPJ is mitigated by a shorter hospitalization. Decreased morbidity and healthcare resource economy support use of the robotic approach for LPJ when appropriate. Copyright © 2017 John Wiley & Sons, Ltd.
Ral GTPase and the exocyst regulate autophagy in a tissue-specific manner.
Tracy, Kirsten; Velentzas, Panagiotis D; Baehrecke, Eric H
2016-01-01
Autophagy traffics cellular components to the lysosome for degradation. Ral GTPase and the exocyst have been implicated in the regulation of stress-induced autophagy, but it is unclear whether they are global regulators of this process. Here, we investigate Ral function in different cellular contexts in Drosophila and find that it is required for autophagy during developmentally regulated cell death in salivary glands, but does not affect starvation-induced autophagy in the fat body. Furthermore, knockdown of exocyst subunits has a similar effect, preventing autophagy in dying cells but not in cells of starved animals. Notch activity is elevated in dying salivary glands, this change in Notch signaling is influenced by Ral, and decreased Notch function influences autophagy. These data indicate that Ral and the exocyst regulate autophagy in a context-dependent manner, and that in dying salivary glands, Ral mediates autophagy, at least in part, by regulation of Notch. © 2015 The Authors.
Ral signaling pathway in health and cancer.
Moghadam, Adel Rezaei; Patrad, Elham; Tafsiri, Elham; Peng, Warner; Fangman, Benjamin; Pluard, Timothy J; Accurso, Anthony; Salacz, Michael; Shah, Kushal; Ricke, Brandon; Bi, Danse; Kimura, Kyle; Graves, Leland; Najad, Marzieh Khajoie; Dolatkhah, Roya; Sanaat, Zohreh; Yazdi, Mina; Tavakolinia, Naeimeh; Mazani, Mohammad; Amani, Mojtaba; Ghavami, Saeid; Gartell, Robyn; Reilly, Colleen; Naima, Zaid; Esfandyari, Tuba; Farassati, Faris
2017-12-01
The Ral (Ras-Like) signaling pathway plays an important role in the biology of cells. A plethora of effects is regulated by this signaling pathway and its prooncogenic effectors. Our team has demonstrated the overactivation of the RalA signaling pathway in a number of human malignancies including cancers of the liver, ovary, lung, brain, and malignant peripheral nerve sheath tumors. Additionally, we have shown that the activation of RalA in cancer stem cells is higher in comparison with differentiated cancer cells. In this article, we review the role of Ral signaling in health and disease with a focus on the role of this multifunctional protein in the generation of therapies for cancer. An improved understanding of this pathway can lead to development of a novel class of anticancer therapies that functions on the basis of intervention with RalA or its downstream effectors. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Molecular pharmacodynamics of emixustat in protection against retinal degeneration
Zhang, Jianye; Kiser, Philip D.; Badiee, Mohsen; Palczewska, Grazyna; Dong, Zhiqian; Golczak, Marcin; Tochtrop, Gregory P.; Palczewski, Krzysztof
2015-01-01
Emixustat is a visual cycle modulator that has entered clinical trials as a treatment for age-related macular degeneration (AMD). This molecule has been proposed to inhibit the visual cycle isomerase RPE65, thereby slowing regeneration of 11-cis-retinal and reducing production of retinaldehyde condensation byproducts that may be involved in AMD pathology. Previously, we reported that all-trans-retinal (atRAL) is directly cytotoxic and that certain primary amine compounds that transiently sequester atRAL via Schiff base formation ameliorate retinal degeneration. Here, we have shown that emixustat stereoselectively inhibits RPE65 by direct active site binding. However, we detected the presence of emixustat-atRAL Schiff base conjugates, indicating that emixustat also acts as a retinal scavenger, which may contribute to its therapeutic effects. Using agents that lack either RPE65 inhibitory activity or the capacity to sequester atRAL, we assessed the relative importance of these 2 modes of action in protection against retinal phototoxicity in mice. The atRAL sequestrant QEA-B-001-NH2 conferred protection against phototoxicity without inhibiting RPE65, whereas an emixustat derivative incapable of atRAL sequestration was minimally protective, despite direct inhibition of RPE65. These data indicate that atRAL sequestration is an essential mechanism underlying the protective effects of emixustat and related compounds against retinal phototoxicity. Moreover, atRAL sequestration should be considered in the design of next-generation visual cycle modulators. PMID:26075817
Jiang, Ying; Sverdlov, Maria S; Toth, Peter T; Huang, Long Shuang; Du, Guangwei; Liu, Yiyao; Natarajan, Viswanathan; Minshall, Richard D
2016-09-23
Caveolae are the primary route for internalization and transendothelial transport of macromolecules, such as insulin and albumin. Caveolae-mediated endocytosis is activated by Src-dependent caveolin-1 (Cav-1) phosphorylation and subsequent recruitment of dynamin-2 and filamin A (FilA), which facilitate vesicle fission and trafficking, respectively. Here, we tested the role of RalA and phospholipase D (PLD) signaling in the regulation of caveolae-mediated endocytosis and trafficking. The addition of albumin to human lung microvascular endothelial cells induced the activation of RalA within minutes, and siRNA-mediated down-regulation of RalA abolished fluorescent BSA uptake. Co-immunoprecipitation studies revealed that albumin induced the association between RalA, Cav-1, and FilA; however, RalA knockdown with siRNA did not affect FilA recruitment to Cav-1, suggesting that RalA was not required for FilA and Cav-1 complex formation. Rather, RalA probably facilitates caveolae-mediated endocytosis by activating downstream effectors. PLD2 was shown to be activated by RalA, and inhibition of PLD2 abolished Alexa-488-BSA uptake, indicating that phosphatidic acid (PA) generated by PLD2 may facilitate caveolae-mediated endocytosis. Furthermore, using a PA biosensor, GFP-PASS, we observed that BSA induced an increase in PA co-localization with Cav-1-RFP, which could be blocked by a dominant negative PLD2 mutant. Total internal reflection fluorescence microscopy studies of Cav-1-RFP also showed that fusion of caveolae with the basal plasma membrane was dependent on PLD2 activity. Thus, our results suggest that the small GTPase RalA plays an important role in promoting invagination and trafficking of caveolae, not by potentiating the association between Cav-1 and FilA but by stimulating PLD2-mediated generation of phosphatidic acid. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Prolonged lobar hypoxia in vivo enhances the responsivity of isolated pulmonary veins to hypoxia
NASA Technical Reports Server (NTRS)
Sheehan, D. W.; Farhi, L. E.; Russell, J. A.
1992-01-01
The hypoxic response of pulmonary vessels isolated from eight sheep whose right apical lobes (RAL) had inspired 100% N2 for 20 h was studied. The RAL of these conscious sheep inspired hypoxic gas and the remainder of the lung inspired air. During hypoxia, RAL perfusion was 33 +/- 3% of its air value, carotid arterial PO2 averaged 86 +/- 3 mm Hg and pulmonary perfusion pressure was not significantly different from the initial control period when the RAL inspired air. At the end of the hypoxic exposure, the sheep were killed, and pulmonary artery and vein rings (0.5 to 2 mm inner diameter) were isolated from both the RAL and the right cardiac lobe, which served as the control lobe (CL). Arteries from the RAL and CL did not contract in response to 6% O2/6% CO2/88% N2 (hypoxia). In contrast, RAL veins did contract vigorously in response to hypoxia, whereas CL veins did not contract or contracted only minimally. Rubbing of the endothelium or prior incubation of RAL veins with catalase (1,200 units/ml), indomethacin (10(-5) M), or the thromboxane A2/prostaglandin H2 (TxA2/PGH2) receptor antagonist, SQ 29,548 (3 X 10(-6) M) each significantly reduced the response to hypoxia. RAL veins were also found to be more reactive than CL veins to the prostaglandin endoperoxide analogue U46619. We conclude that prolonged lobar hypoxia in vivo increases the responsivity of isolated pulmonary veins to hypoxia. These contractions may result from an increase in reactive O2 species, which in turn modify production of, metabolism of, and/or tissue responsivity to TxA2/PGH2.
Styrene maleic acid encapsulated raloxifene micelles for management of inflammatory bowel disease.
Greish, Khaled; Taha, Safa; Jasim, Anfal; Elghany, Sara Abd; Sultan, Ameera; AlKhateeb, Ali; Othman, Manal; Jun, Fang; Taurin, Sebastien; Bakhiet, Moiz
2017-12-01
Inflammatory bowel disease (IBD) comprises a group of disorders that manifest through chronic inflammation of the colon and small intestine. Although the exact cause of IBD is still unclear, dysfunctional immunoregulation involving overproduction of inflammatory cytokines such as TNF-α, and IL-6 have been implicated in pathogenesis. Current therapy relies on immunosuppression, cytotoxic drugs, and monoclonal antibodies against TNF-α. These classes of drugs have severe side-effects, especially when used for long duration. Our previous work with raloxifene, a selective estrogen receptor modulator, has shown that the drug, and to a greater extent its micellar formulation, has a significant suppressive effect on NF-κB, an essential immune-regulator. This finding directed the current work towards testing the anti-inflammatory and immunomodulatory effects of raloxifene using cell lines, as well as testing the potential use of the styrene maleic acid (SMA) micelles loaded with raloxifene (SMA-Ral) against dextran sulfate sodium (DSS) induced colitis in an in vivo model of IBD. Treatment of MCF-7 cells with TNF-α was shown to protect the cells from the cytotoxic effect of raloxifene (42 vs. 10% cell death, with TNF-α. Treating CaCo-2 cells with both free and SMA-Ral improved cell survival after exposure to 2% DDS with significantly higher protection with SMA-Ral. Treatment of U-937 with SMA-Ral and free-Ral resulted in down-regulation of TNF-α, IL-1β, IL-6, and MIP1α, with greater inhibition of the SMA-Ral, compared to free Ral. Balb/c mice treated with raloxifene and SMA-Ral showed weight gain at 14 days, compared to the control group (122, and 115% respectively). Treatment with raloxifene prevented DSS-induced diarrhea in 6/6 of free raloxifene treated mice and in 5/6 mice treated with SMA-Ral. Control group of DSS-treated mice showed average colon length of 7.4 cm compared to 13 cm in the control group. The average colon length was 12.3 and 11.5 cm for raloxifene and SMA-Ral treated groups, respectively. Furthermore, inflammatory cytokines such as IL-6 and TNF-α were reduced in serum of animals treated with free-Ral and SMA-Ral. Raloxifene and its micellar formulation warrants further studies to understand their effect on the treatment of colitis. Graphical abstract SMA-Raloxifene preparation and its in vivo and in vitro effect on colitis.
Frische, Ester W; Pellis-van Berkel, Wendy; van Haaften, Gijs; Cuppen, Edwin; Plasterk, Ronald H A; Tijsterman, Marcel; Bos, Johannes L; Zwartkruis, Fried J T
2007-01-01
The small Ras-like GTPase Rap1 has been identified as a regulator of integrin activation and cadherin-mediated cell–cell contacts. Surprisingly, null mutants of RAP-1 in Caenorhabditis elegans are viable and fertile. In a synthetic lethal RNAi screen with C. elegans rap-1 mutants, the Ras-like GTPase ral-1 emerged as one of seven genes specifically required for viability. Depletion of exoc-8 and sec-5, encoding two putative RAL-1 effectors and members of the exocyst complex, also caused lethality of rap-1 mutants, but did not affect wild-type worms. The RAP-1 and the RAL-1/exocyst pathway appear to coordinate hypodermal cell movement and elongation during embryonic development. They mediate their effect in part through targeting the α-catenin homologue HMP-1 to the lateral membrane. Genetic interactions show that the RAP-1 and RAL-1/exocyst pathway also act in parallel during larval stages. Together these data provide in vivo evidence for the exocyst complex as a downstream RAL-1 effector in cell migration. PMID:17989692
Frische, Ester W; Pellis-van Berkel, Wendy; van Haaften, Gijs; Cuppen, Edwin; Plasterk, Ronald H A; Tijsterman, Marcel; Bos, Johannes L; Zwartkruis, Fried J T
2007-12-12
The small Ras-like GTPase Rap1 has been identified as a regulator of integrin activation and cadherin-mediated cell-cell contacts. Surprisingly, null mutants of RAP-1 in Caenorhabditis elegans are viable and fertile. In a synthetic lethal RNAi screen with C. elegans rap-1 mutants, the Ras-like GTPase ral-1 emerged as one of seven genes specifically required for viability. Depletion of exoc-8 and sec-5, encoding two putative RAL-1 effectors and members of the exocyst complex, also caused lethality of rap-1 mutants, but did not affect wild-type worms. The RAP-1 and the RAL-1/exocyst pathway appear to coordinate hypodermal cell movement and elongation during embryonic development. They mediate their effect in part through targeting the alpha-catenin homologue HMP-1 to the lateral membrane. Genetic interactions show that the RAP-1 and RAL-1/exocyst pathway also act in parallel during larval stages. Together these data provide in vivo evidence for the exocyst complex as a downstream RAL-1 effector in cell migration.
Imkamp, Florian; Herrmann, Thomas R W; Tolkach, Yuri; Dziuba, Sebastian; Stolzenburg, Jens U; Rassweiler, Jens; Sulser, Tullio; Zimmermann, Uwe; Merseburger, Axel S; Kuczyk, Markus A; Burchardt, Martin
2015-01-01
Robotic-assisted laparoscopy (RAL) is being widely accepted in the field of urology as a replacement for conventional laparoscopy (CL). Nevertheless, the process of its integration in clinical routines has been rather spontaneous. To determine the prevalence of robotic systems (RS) in urological clinics in Germany, Austria and Switzerland, the acceptance of RAL among urologists as a replacement for CL and its current use for 25 different urological indications. To elucidate the practice patterns of RAL, a survey at hospitals in Germany, Austria and Switzerland was conducted. All surgically active urology departments in Germany (303), Austria (37) and Switzerland (84) received a questionnaire with questions related to the one-year period prior to the survey. The response rate was 63%. Among the participants, 43% were universities, 45% were tertiary care centres, and 8% were secondary care hospitals. A total of 60 RS (Germany 35, Austria 8, Switzerland 17) were available, and the majority (68%) were operated under public ownership. The perception of RAL and the anticipated superiority of RAL significantly differed between robotic and non-robotic surgeons. For only two urologic indications were more than 50% of the procedures performed using RAL: pyeloplasty (58%) and transperitoneal radical prostatectomy (75%). On average, 35% of robotic surgeons and only 14% of non-robotic surgeons anticipated RAL superiority in some of the 25 indications. This survey provides a detailed insight into RAL implementation in Germany, Austria and Switzerland. RAL is currently limited to a few urological indications with a small number of high-volume robotic centres. These results might suggest that a saturation of clinics using RS has been achieved but that the existing robotic capacities are being utilized ineffectively. The possible reasons for this finding are discussed, and certain strategies to solve these problems are offered. © 2015 S. Karger AG, Basel.
Critical Contribution of RAL GTPases to Growth and Survival of Breast Cancer Cells
2007-04-01
similar to the NFkB p50 dimerization domain that falls into the IPT/TIG family of protein domains (Fukai et al., 2003). Given that GTP-bound RalB and TBK1...RalB and Sec5 are required for IRF-3 but not p65 responsiveness to TLR3 activation. HBECs were cotransfected with a plasmid expressing GFP together with...RalA andSec8 were not limiting for this response (Figures 6D and 6E). Poly(I:C)-induced mobilization of p65 NFkB nuclear accumulation is independent of
Walker, David M; Hayes, Ellen C; Webb, Lauren J
2013-08-07
Electrostatic fields at the interface of the GTPase H-Ras (Ras) docked with the Ras binding domain of the protein Ral guanine nucleoside dissociation stimulator (Ral) were measured with vibrational Stark effect (VSE) spectroscopy. Nine residues on the surface of Ras that participate in the protein-protein interface were systematically mutated to cysteine and subsequently converted to cyanocysteine in order to introduce a nitrile VSE probe into the protein-protein interface. The absorption energy of the nitrile was measured both on the surface of Ras in its monomeric state, then after incubation with the Ras binding domain of Ral to form the docked complex. Boltzmann-weighted structural snapshots of the nitrile-labeled Ras protein were generated both in monomeric and docked configurations from molecular dynamics simulations using enhanced sampling of the cyanocysteine side chain's χ2 dihedral angle. These snapshots were used to determine that on average, most of the nitrile probes were aligned along the Ras surface, parallel to the Ras-Ral interface. The average solvent-accessible surface areas (SASA) of the cyanocysteine side chain were found to be <60 Å(2) for all measured residues, and was not significantly different whether the nitrile was on the surface of the Ras monomer or immersed in the docked complex. Changes in the absorption energy of the nitrile probe at nine positions along the Ras-Ral interface were compared to results of a previous study examining this interface with Ral-based probes, and found a pattern of low electrostatic field in the core of the interface surrounded by a ring of high electrostatic field around the perimeter of the interface. These data are used to rationalize several puzzling features of the Ras-Ral interface.
A one-year follow-up on the effects of raloxifene on thyroid function in postmenopausal women.
Ceresini, Graziano; Morganti, Simonetta; Rebecchi, Isabella; Bertone, Luca; Ceda, Gian Paolo; Bacchi-Modena, Alberto; Sgarabotto, Mariapaola; Baldini, Monica; Ablondi, Fabrizio; Valenti, Giorgio; Braverman, Lewis E
2004-01-01
Estrogens increase serum thyroxine-binding globulin (TBG) and total thyroxine (TT4) concentrations. Serum free thyroxine (FT4) concentrations, however, remain normal. Raloxifene (RAL) is a selective estrogen receptor modulator used to treat postmenopausal osteoporosis. Data on the long-term effects of RAL on thyroid physiology are scanty. We evaluated the effects of RAL administration for 1 year on thyroid function in osteopenic, postmenopausal women. Fifty osteopenic, postmenopausal women were randomly assigned to receive either RAL (60 mg/day, n = 25) or placebo (PL, n = 25) for 1 year, in a double-blind study. Measurements of serum TBG, TT4, FT4, thyroid-stimulating hormone (TSH), thyroid hormone-binding ratio (THBR), FT4 index (FT4-I) and TT4/TBG ratio were carried out at baseline and after 4 and 12 months of therapy. Baseline values were similar in both treatment groups. Serum TBG concentrations were increased during RAL treatment from baseline values of 29.60 +/- 0.9 microg/mL to 31.45 +/- 1.33 and 32.34 +/- 1.37 microg/mL at 4 months and 1 year, respectively (P < 0.05, baseline v 1-year values) but were unchanged during PL treatment. A small, insignificant increase in TT4 and TSH concentrations occurred in the RAL group and no changes in the PL group. All other values were unchanged during either treatment. These results demonstrate that RAL significantly increased serum TBG levels, but the changes were small and not accompanied by changes in FT4-I, FT4, or TSH concentrations, suggesting that long-term RAL treatment is unlikely to clinically affect the thyroid status in euthyroid, postmenopausal women.
Cozzi-Lepri, A; Zangerle, R; Machala, L; Zilmer, K; Ristola, M; Pradier, C; Kirk, O; Sambatakou, H; Fätkenheuer, G; Yust, I; Schmid, P; Gottfredsson, M; Khromova, I; Jilich, D; Flisiak, R; Smidt, J; Rozentale, B; Radoi, R; Losso, M H; Lundgren, J D; Mocroft, A
2018-02-01
There are currently few data on the long-term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. The EuroSIDA cohort was divided into three groups: those starting RAL-based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression. The RAL cohort included 1470 individuals [with 4058 person-years of follow-up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non-AIDS-related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95-1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37-2.61). In intention-to-treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84-1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90-1.61) and 0.83 (95% CI 0.70-0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47-1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65-1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53-1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76-1.72 for RALvs. CONC). We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups. © 2017 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.
Minimally invasive colorectal surgery: status and technical specifications.
Keller, D S; Ibarra, S; Haas, E M
2015-10-01
Laparoscopy was the most significant technologic advance in colorectal surgery in the last quarter century. The safety, feasibility and oncologic equivalence have been proven, and undisputed clinical benefits have also been demonstrated over open approaches. Despite proven benefits, laparoscopic has not dominated the market, especially for colon and rectal cancer cases. Adaptations in laparoscopic technique were developed to increase use of minimally invasive surgery. Concurrently, there has been a paradigm shift toward less invasive technologies to further optimize patient outcomes. From these needs, hand assisted laparoscopic surgery (HALS), single incision laparoscopic surgery (SILS), and robotic assisted laparoscopic surgery (RALS) were applied to colorectal surgery. Each platform has unique costs and benefits, and similar outcomes when likened to each other in comparative studies. However, conventional laparoscopy, HALS, SILS, and RALS actually serve a complementary role as tools to increase the use of minimally invasive colorectal surgery. The goal of this paper is to review the history, current status, technical specifications, and evolution of the major minimally invasive platforms for colorectal surgery.
TD-60 links RalA GTPase function to the CPC in mitosis
Papini, Diana; Langemeyer, Lars; Abad, Maria A.; Kerr, Alastair; Samejima, Itaru; Eyers, Patrick A.; Jeyaprakash, A. Arockia; Higgins, Jonathan M. G.; Barr, Francis A.; Earnshaw, William C.
2015-01-01
TD-60 (also known as RCC2) is a highly conserved protein that structurally resembles the Ran guanine exchange factor (GEF) RCC1, but has not previously been shown to have GEF activity. TD-60 has a typical chromosomal passenger complex (CPC) distribution in mitotic cells, but associates with integrin complexes and is involved in cell motility during interphase. Here we show that TD-60 exhibits GEF activity, in vitro and in cells, for the small GTPase RalA. TD-60 or RalA depletion causes spindle abnormalities in prometaphase associated with abnormal centromeric accumulation of CPC components. TD-60 and RalA apparently work together to contribute to the regulation of kinetochore–microtubule interactions in early mitosis. Importantly, several mitotic phenotypes caused by TD-60 depletion are reverted by the expression of a GTP-locked mutant, RalA (Q72L). The demonstration that a small GTPase participates in the regulation of the CPC reveals a level of mitotic regulation not suspected in previous studies. PMID:26158537
Robot-assisted laparoscopic (RAL) procedures in general surgery.
Alimoglu, Orhan; Sagiroglu, Julide; Atak, Ibrahim; Kilic, Ali; Eren, Tunc; Caliskan, Mujgan; Bas, Gurhan
2016-09-01
Robotics was introduced in clinical practice more than two decades ago, and it has gained remarkable popularity for a wide variety of laparoscopic procedures. We report our results of robot-assisted laparoscopic surgery (RALS) in the most commonly applied general surgical procedures. Ninety seven patients underwent RALS from 2009 to 2012. Indications for RALS were cholelithiasis, gastric carcinoma, splenic tumors, colorectal carcinoma, benign colorectal diseases, non-toxic nodular goiter and incisional hernia. Records of patients were analyzed for demographic features, intraoperative and postoperative complications and conversion to open surgery. Forty six female and 51 male patients were operated and mean age was 58,4 (range: 25-88). Ninety three out of 97 procedures (96%) were completed robotically, 4 were converted to open surgery and there were 15 postoperative complications. There was no mortality. Wide variety of procedures of general surgery can be managed safely and effectively by RALS. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Amor,J.; Swails, J.; Zhu, X.
2005-01-01
The Legionella pneumophila protein RalF is secreted into host cytosol via the Dot/Icm type IV transporter where it acts to recruit ADP-ribosylation factor (Arf) to pathogen-containing phagosomes in the establishment of a replicative organelle. The presence in RalF of the Sec7 domain, present in all Arf guanine nucleotide exchange factors, has suggested that recruitment of Arf is an early step in pathogenesis. We have determined the crystal structure of RalF and of the isolated Sec7 domain and found that RalF is made up of two domains. The Sec7 domain is homologous to mammalian Sec7 domains. The C-terminal domain forms amore » cap over the active site in the Sec7 domain and contains a conserved folding motif, previously observed in adaptor subunits of vesicle coat complexes. The importance of the capping domain and of the glutamate in the 'glutamic finger,' conserved in all Sec7 domains, to RalF functions was examined using three different assays. These data highlight the functional importance of domains other than Sec7 in Arf guanine nucleotide exchange factors to biological activities and suggest novel mechanisms of regulation of those activities.« less
Remote access laboratories in Australia and Europe
NASA Astrophysics Data System (ADS)
Ku, H.; Ahfock, T.; Yusaf, T.
2011-06-01
Remote access laboratories (RALs) were first developed in 1994 in Australia and Switzerland. The main purposes of developing them are to enable students to do their experiments at their own pace, time and locations and to enable students and teaching staff to get access to facilities beyond their institutions. Currently, most of the experiments carried out through RALs in Australia are heavily biased towards electrical, electronic and computer engineering disciplines. However, the experiments carried out through RALs in Europe had more variety, in addition to the traditional electrical, electronic and computer engineering disciplines, there were experiments in mechanical and mechatronic disciplines. It was found that RALs are now being developed aggressively in Australia and Europe and it can be argued that RALs will develop further and faster in the future with improving Internet technology. The rising costs of real experimental equipment will also speed up their development because by making the equipment remotely accessible, the cost can be shared by more universities or institutions and this will improve their cost-effectiveness. Their development would be particularly rapid in large countries with small populations such as Australia, Canada and Russia, because of the scale of economy. Reusability of software, interoperability in software implementation, computer supported collaborative learning and convergence with learning management systems are the required development of future RALs.
Macías, Juan; Mancebo, María; Merino, Dolores; Téllez, Francisco; Montes-Ramírez, M Luisa; Pulido, Federico; Rivero-Juárez, Antonio; Raffo, Miguel; Pérez-Pérez, Montserrat; Merchante, Nicolás; Cotarelo, Manuel; Pineda, Juan A
2017-09-15
Antiretroviral drugs with a lower potential to induce hepatic steatosis in human immunodeficiency virus (HIV) infection need to be identified. We compared the effect of switching efavirenz (EFV) to raltegravir (RAL) on hepatic steatosis among HIV-infected patients with nonalcoholic fatty liver disease (NAFLD) receiving EFV plus 2 nucleoside analogues. HIV-infected patients on EFV plus tenofovir/emtricitabine or abacavir/lamivudine with NAFLD were randomized 1:1 to switch from EFV to RAL (400 mg twice daily), maintaining nucleoside analogues unchanged, or to continue with EFV plus 2 nucleoside analogues. At baseline, eligible patients should show controlled attenuation parameter (CAP) values ≥238 dB/m. Changes in hepatic steatosis at 48 weeks of follow-up over baseline levels were measured by CAP. Overall, 39 patients were included, and 19 of them were randomized to switch to RAL. At week 48, median CAP for the RAL group was 250 (Q1-Q3, 221-277) dB/m and 286 (Q1-Q3, 269-314) dB/m for the EFV group (P = .035). The median decrease in CAP values was -20 (Q1-Q3, -67 to 15) dB/m for the RAL arm and 30 (Q1-Q3, -17 to 49) dB/m for the EFV group (P = .011). CAP values <238 dB/m at week 48 were observed in 9 (47%) patients on RAL and 3 (15%) individuals on EFV (P = .029). After 48 weeks, HIV-infected individuals switching EFV to RAL showed decreases in the degree of hepatic steatosis, as measured by CAP, compared with those continuing with EFV. In addition, the proportion of patients without significant hepatic steatosis after 48 weeks was greater for those who switched to RAL. NCT01900015. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Croteau, David; Letendre, Scott; Best, Brookie M.; Ellis, Ronald J.; Breidinger, Sheila; Clifford, David; Collier, Ann; Gelman, Benjamin; Marra, Christina; Mbeo, Gilbert; McCutchan, Allen; Morgello, Susan; Simpson, David; Way, Lauren; Vaida, Florin; Ueland, Susan; Capparelli, Edmund; Grant, Igor
2010-01-01
HIV-associated neurocognitive disorders continue to be common. Antiretrovirals that achieve higher concentrations in cerebrospinal fluid (CSF) are associated with better control of HIV and improved cognition. The objective of this study was to measure total raltegravir (RAL) concentrations in CSF and to compare them with matched concentrations in plasma and in vitro inhibitory concentrations. Eighteen subjects with HIV-1 infection were enrolled based on the use of RAL-containing regimens and the availability of CSF and matched plasma samples. RAL was measured in 21 CSF and plasma pairs by liquid chromatography-tandem mass spectrometry, and HIV RNA was detected by reverse transcription-PCR (RT-PCR). RAL concentrations were compared to the 50% inhibitory concentration (IC50) for wild-type HIV-1 (3.2 ng/ml). Volunteers were predominantly middle-aged white men with AIDS and without hepatitis C virus (HCV) coinfection. The median concurrent CD4+ cell count was 276/μl, and 28% of CD4+ cell counts were below 200/μl. HIV RNA was detectable in 38% of plasma specimens and 4% of CSF specimens. RAL was present in all CSF specimens, with a median total concentration of 14.5 ng/ml. The median concentration in plasma was 260.9 ng/ml, with a median CSF-to-plasma ratio of 0.058. Concentrations in CSF correlated with those in with plasma (r2, 0.24; P, 0.02) but not with the postdose sampling time (P, >0.50). RAL concentrations in CSF exceeded the IC50 for wild-type HIV in all specimens by a median of 4.5-fold. RAL is present in CSF and reaches sufficiently high concentrations to inhibit wild-type HIV in all individuals. As a component of effective antiretroviral regimens or as the main antiretroviral, RAL likely contributes to the control of HIV replication in the nervous system. PMID:20876368
Cancer du sein bilatéral synchrone au Maroc: caractéristiques épidémiologiques et cliniques
Boufettal, Houssine; Samouh, Naïma
2015-01-01
Préciser la fréquence, les facteurs de risque et le pronostic du cancer du sein bilatéral, à partir d'une étude rétrospective de 22 cas de cancer du sein bilatéral synchrone dans un pays du Maghreb. De 2002 à 2010, 625 patientes étaient prises en charge pour cancer du sein au service de Gynécologie-Obstétrique «C» du centre hospitalier universitaire de Casablanca. 22 cas de cancer bilatéral synchrone étaient diagnostiqués. Nos résultats sont comparés avec ceux de la littérature. La fréquence de la bilatéralité du cancer du sein synchrone était de 3,52% (22/625). L'intervalle de temps moyen entre les deux cancers est de 4 mois (0 à 6 mois). Les patientes âgées de moins de 40 ans lors du premier cancer avaient six fois plus de risque de développer un cancer au niveau du sein controlatéral que les femmes âgées de plus de 40 ans. Les patientes atteintes d'une tumeur T3 ou T4 avaient un risque neuf fois plus élevé que les autres. 90,9% (2/22) des cas des premiers cancers sont des adénocarcinomes infiltrants. Les types histologiques du premier et du douzième cancer étaient identiques dans 86,4% (19/22) des cas. Quant au pronostic, il dépend à la fois du stade du premier et du deuxième cancer et le traitement de ce dernier doit obéir aux mêmes règles du traitement du premier cancer. L'incidence du cancer bilatéral synchrone du sein est de 3,52% dans notre série. Le cancer du sein unilatéral constitue un facteur de risque de développement d'un cancer du sein controlatéral. Une surveillance à vie est nécessaire au cours d'un cancer du sein pour détecter un cancer controlatéral. PMID:26090066
[Arf6, RalA and BIRC5 protein expression in non small cell lung cancer].
Knizhnik, A V; Kovaleva, O B; Laktionov, K K; Mochal'nikova, V V; Komel'kov, A V; Chevkina, E M; Zborovskaia, I B
2011-01-01
Evaluation of tumor markers expression pattern which determines individual progression parameters is one of the major topics in molecular oncopathology research. This work presents research on expression analysis of several Ras-Ral associated signal transduction pathway proteins (Arf6, RalA and BIRC5) in accordance with clinical criteria in non small cell lung cancer patients. Using Western-blot analysis and RT-PCR Arf6, RalA and BIRC5 expression has been analyzed in parallel in 53 non small cell lung cancer samples of different origin. Arf6 protein expression was elevated in 55% non small cell lung cancer tumor samples in comparison with normal tissue. In the group of squamous cell lung cancer Arf6 expression elevation was observed more often. RalA protein expression was decreased in comparison to normal tissue samples in 64% of non small cell lung cancer regardless to morphological structure. Correlation between RalA protein expression decrease and absence of regional metastases was revealed for squamous cell lung cancer. BIRC5 protein expression in tumor samples versus corresponding normal tissue was 1.3 times more often elevated in the squamous cell lung cancer group (in 76% tumor samples). At the same time elevation of BIRC5 expression was fixed only in 63% of adenocarcinoma tumor samples. A statistically significant decrease (p = 0.0158) of RalA protein expression and increase (p = 0.0498) of Arf6 protein expression in comparison with normal tissue was found for T1-2N0M0 and T1-2N1-2M0 groups of squamous cell lung cancer correspondingly.
Impact of resistance mutations on inhibitor binding to HIV-1 integrase
DOE Office of Scientific and Technical Information (OSTI.GOV)
Chen, Qi; Buolamwini, John K.; Smith, Jeremy C.
2013-11-08
Here, HIV-1 integrase (IN) is essential for HIV-1 replication, catalyzing two key reaction steps termed 3' processing and strand transfer. Therefore, IN has become an important target for antiviral drug discovery. However, mutants have emerged, such as E92Q/N155H and G140S/Q148H, which confer resistance to raltegravir (RAL), the first IN strand transfer inhibitor (INSTI) approved by the FDA, and to the recently approved elvitegravir (EVG). To gain insights into the molecular mechanisms of ligand binding and drug resistance, we performed molecular dynamics (MD) simulations of homology models of the HIV-1 IN and four relevant mutants complexed with viral DNA and RAL.more » The results show that the structure and dynamics of the 140s loop, comprising residues 140 to 149, are strongly influenced by the IN mutations. In the simulation of the G140S/Q148H double mutant, we observe spontaneous dissociation of RAL from the active site, followed by an intrahelical swing-back of the 3' -OH group of nucleotide A17, consistent with the experimental observation that the G140S/Q148H mutant exhibits the highest resistance to RAL compared to other IN mutants. An important hydrogen bond between residues 145 and 148 is present in the wild-type IN but not in the G140S/Q148H mutant, accounting for the structural and dynamical differences of the 140s' loop and ultimately impairing RAL binding in the double mutant. End-point free energy calculations that broadly capture the experimentally known RAL binding profiles elucidate the contributions of the 140s' loop to RAL binding free energies and suggest possible approaches to overcoming drug resistance.« less
Cardozo, Erwing Fabian; Andrade, Adriana; Mellors, John W.; ...
2017-07-05
The kinetics of HIV-1 decay under treatment depends on the class of antiretrovirals used. Mathematical models are useful to interpret the different profiles, providing quantitative information about the kinetics of virus replication and the cell populations contributing to viral decay. We modeled proviral integration in short- and long-lived infected cells to compare viral kinetics under treatment with and without the integrase inhibitor raltegravir (RAL). We fitted the model to data obtained from participants treated with RAL-containing regimes or with a four-drug regimen of protease and reverse transcriptase inhibitors. Our model explains the existence and quantifies the three phases of HIV-1more » RNA decay in RAL-based regimens vs. the two phases observed in therapies without RAL. Our findings indicate that HIV-1 infection is mostly sustained by short-lived infected cells with fast integration and a short viral production period, and by long-lived infected cells with slow integration but an equally short viral production period. We propose that these cells represent activated and resting infected CD4+ T-cells, respectively, and estimate that infection of resting cells represent ~4% of productive reverse transcription events in chronic infection. RAL reveals the kinetics of proviral integration, showing that in short-lived cells the pre-integration population has a half-life of ~7 hours, whereas in long-lived cells this half-life is ~6 weeks. We also show that the efficacy of RAL can be estimated by the difference in viral load at the start of the second phase in protocols with and without RAL. Altogether, we provide a mechanistic model of viral infection that parsimoniously explains the kinetics of viral load decline under multiple classes of antiretrovirals.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cardozo, Erwing Fabian; Andrade, Adriana; Mellors, John W.
The kinetics of HIV-1 decay under treatment depends on the class of antiretrovirals used. Mathematical models are useful to interpret the different profiles, providing quantitative information about the kinetics of virus replication and the cell populations contributing to viral decay. We modeled proviral integration in short- and long-lived infected cells to compare viral kinetics under treatment with and without the integrase inhibitor raltegravir (RAL). We fitted the model to data obtained from participants treated with RAL-containing regimes or with a four-drug regimen of protease and reverse transcriptase inhibitors. Our model explains the existence and quantifies the three phases of HIV-1more » RNA decay in RAL-based regimens vs. the two phases observed in therapies without RAL. Our findings indicate that HIV-1 infection is mostly sustained by short-lived infected cells with fast integration and a short viral production period, and by long-lived infected cells with slow integration but an equally short viral production period. We propose that these cells represent activated and resting infected CD4+ T-cells, respectively, and estimate that infection of resting cells represent ~4% of productive reverse transcription events in chronic infection. RAL reveals the kinetics of proviral integration, showing that in short-lived cells the pre-integration population has a half-life of ~7 hours, whereas in long-lived cells this half-life is ~6 weeks. We also show that the efficacy of RAL can be estimated by the difference in viral load at the start of the second phase in protocols with and without RAL. Altogether, we provide a mechanistic model of viral infection that parsimoniously explains the kinetics of viral load decline under multiple classes of antiretrovirals.« less
Kinsella, B T; Erdman, R A; Maltese, W A
1991-05-25
Membrane localization of p21ras is dependent upon its posttranslational modification by a 15-carbon farnesyl group. The isoprenoid is linked to a cysteine located within a conserved carboxyl-terminal sequence termed the "CAAX" box (where C is cysteine, A is an aliphatic amino acid, and X is any amino acid). We now show that three GTP-binding proteins encoded by the recently identified rac1, rac2, and ralA genes also undergo isoprenoid modification. cDNAs coding for each protein were transcribed in vitro, and the RNAs were translated in reticulocyte lysates. Incorporation of isoprenoid precursors, [3H]mevalonate or [3H]farnesyl pyrophosphate, indicated that the translation products were modified by isoprenyl groups. A protein recognized by an antibody to rac1 also comigrated with a protein metabolically labeled by a product of [3H] mevalonate in cultured cells. Gel permeation chromatography of radiolabeled hydrocarbons released from the rac1, rac2, and ralA proteins by reaction with Raney nickel catalyst indicated that unlike p21Hras, which was modified by a 15-carbon moiety, the rac and ralA translation products were modified by 20-carbon isoprenyl groups. Site-directed mutagenesis established that the isoprenylated cysteines in the rac1, rac2, and ralA proteins were located in the fourth position from the carboxyl terminus. The three-amino acid extension distal to the cysteine was required for this modification. The isoprenylation of rac1 (CSLL), ralA (CCIL), and the site-directed mutants rac1 (CRLL) and ralA (CSIL), demonstrates that the amino acid adjacent to the cysteine need not be aliphatic. Therefore, proteins with carboxyl-terminal CXXX sequences that depart from the CAAX motif should be considered as potential targets for isoprenoid modification.
Current controversies in pediatric urologic robotic surgery.
Trevisani, Lorenzo F M; Nguyen, Hiep T
2013-01-01
Minimally invasive surgeries such as conventional laparoscopic surgery and robotic assisted laparoscopic surgery (RALS) have significant advantages over the traditional open surgical approach including lower pain medication requirements and decreased length of hospitalization. However, open surgery has demonstrated better success rates and shorter surgery time when compared to the other modalities. Currently, it is unclear which approach has better long-term clinical outcomes, greater benefits and less cost. There are limited studies in the literature comparing these three different surgical approaches. In this review, we will evaluate the advantages and disadvantages of RALS compared to conventional laparoscopic surgery and open surgery for commonly performed pediatric urological procedures such as pyeloplasty, ureteral reimplantation, complete and partial nephrectomy, bladder augmentation and creation of continent catheterizable channels. Although it is not yet possible to demonstrate the superiority of one single surgical modality over another, RALS has been shown to be feasible, well tolerated and advantageous in reconstructive urological procedures. With experience, the outcomes of RALS are improving, justifying its usage. However, cost remains a significant issue, limiting the accessibility of RALS, which in the future may improve with market competition and device innovation.
Richhariya, Shlesha; Jayakumar, Siddharth; Abruzzi, Katharine; Rosbash, Michael; Hasan, Gaiti
2017-02-14
Transcriptional regulation by Store-operated Calcium Entry (SOCE) is well studied in non-excitable cells. However, the role of SOCE has been poorly documented in neuronal cells with more complicated calcium dynamics. Previous reports demonstrated a requirement for SOCE in neurons that regulate Drosophila flight bouts. We refine this requirement temporally to the early pupal stage and use RNA-sequencing to identify SOCE mediated gene expression changes in the developing Drosophila pupal nervous system. Down regulation of dStim, the endoplasmic reticular calcium sensor and a principal component of SOCE in the nervous system, altered the expression of 131 genes including Ral, a small GTPase. Disruption of Ral function in neurons impaired flight, whereas ectopic expression of Ral in SOCE-compromised neurons restored flight. Through live imaging of calcium transients from cultured pupal neurons, we confirmed that Ral does not participate in SOCE, but acts downstream of it. These results identify neuronal SOCE as a mechanism that regulates expression of specific genes during development of the pupal nervous system and emphasizes the relevance of SOCE-regulated gene expression to flight circuit maturation.
77 FR 62231 - Excelerate Liquefaction Solutions I, LLC, Nutreco Canada Inc., JM & RAL Energy Inc...
Federal Register 2010, 2011, 2012, 2013, 2014
2012-10-12
... During August 2012 AGENCY: Office of Fossil Energy, Department of Energy (DOE). ACTION: Notice of orders. SUMMARY: The Office of Fossil Energy (FE) of the Department of Energy gives notice that during August 2012... Web site at http://www.fossil.energy.gov/programs/gasregulation/authorizations/Orders-2012.html . They...
The effects of strength training and raloxifene on bone health in aging ovariectomized rats.
Stringhetta-Garcia, Camila Tami; Singulani, Monique Patrício; Santos, Leandro Figueiredo; Louzada, Mário Jefferson Quirino; Nakamune, Ana Cláudia Stevanato; Chaves-Neto, Antonio Hernandes; Rossi, Ana Cláudia; Ervolino, Edilson; Dornelles, Rita Cássia Menegati
2016-04-01
The aim of this study was to investigate the effects of strength training (ST) and raloxifene (Ral), alone or in combination, on the prevention of bone loss in an aging estrogen-deficient rat model. Aging Wistar female rats were ovariectomized at 14months and allocated to four groups: (1) non-trained and treated with vehicle, NT-Veh; (2) strength training and treated with vehicle, ST-Veh; (3) non-trained and treated with raloxifene, NT-Ral; and (4) strength training and treated with raloxifene, ST-Ral. ST was performed on a ladder three times per week and Ral was administered daily by gavage (1mg/kg/day), both for 120days. Areal bone mineral density (aBMD), strength, microarchitecture, and biomarkers (osteocalcin, OCN; osteoprotegerin, OPG; and tartrate-resistant acid phosphatase, TRAP) were assessed. Immunohistochemistry was performed for runt-related transcription factor 2 (RUNX2), osterix (OSX), OCN, OPG, TRAP, and receptor activator of nuclear factor kappa-B ligand (RANKL). The rats that performed ST (ST-Veh) or were treated with Ral (NT-Ral) showed significant improvements in aBMD (p=0.001 and 0.004), bone strength (p=0.001), and bone microarchitecture, such as BV/TV (%) (p=0.001), BS/TV (mm(2)/mm(3)) (p=0.023 and 0.002), Conn.Dn (1/mm(3)) (p=0.001), Tb.N (1/mm) (p=0.012 and 0.011), Tb.Th (1/mm) (p=0.001), SMI (p=0.001 and 0.002), Tb.Sp (p=0.001), and DA (p=0.002 and 0.007); there was also a significant decrease in plasma levels of OCN (p=0.001 and 0.002) and OPG (p=0.003 and 0.014), compared with animals in the NT-Veh group. Ral, with or without ST, promoted an increased immunolabeling pattern for RUNX2 (p=0.0105 and p=0.0006) and OSX (p=0.0105), but a reduced immunolabeling pattern for TRAP (p=0.0056) and RANKL (p=0.033 and 0.004). ST increased the immunolabeling pattern for RUNX2 (p=0.0105), and association with Ral resulted in an increased immunolabeling pattern for OPG (p=0.0034) and OCN (p=0.0024). In summary, ST and Ral administration in aged, estrogen-deficient Wistar female rats is associated with a decrease in bone turnover marker plasma levels, increased activity of cells that promote osteoblastogenesis, and decreased activity of cells that promote osteoclastogenesis; these are correlated with higher aBMD, bone strength, and bone microarchitecture at the femoral neck. The results indicate that strength training and Ral are potential tools to reduce the risk of fractures at clinically relevant sites. Copyright © 2016 Elsevier Inc. All rights reserved.
Wang, Hongren; Huang, Xiaojun; Qin, Zhen; Deng, Zhaomin; Luo, Jun; Wang, Baoning; Li, Mingyuan
2016-01-01
Background Integrase strand transfer inhibitors (INSTIs) are a novel class of anti-HIV agents that show high activity in inhibiting HIV-1 replication. Currently, licensed INSTIs include raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG); these drugs have played a critical role in AIDS therapy, serving as additional weapons in the arsenal for treating patients infected with HIV-1. To date, long-term data regarding clinical experience with INSTI use and the emergence of resistance remain scarce. However, the literature is likely now sufficiently comprehensive to warrant a meta-analysis of resistance to INSTIs. Methods Our team implemented a manuscript retrieval protocol using Medical Subject Headings (MeSH) via the Web of Science, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases. We screened the literature based on inclusion and exclusion criteria and then performed a quality analysis and evaluation using RevMan software, Stata software, and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). We also performed a subgroup analysis. Finally, we calculated resistance rates and risk ratios (RRs) for the three types of drugs. Results We identified 26 references via the database search. A meta-analysis of the RAL data revealed that the resistance rate was 3.9% (95% CI = 2.9%-4.9%) for the selected randomized controlled trials (RCTs). However, the RAL resistance rate reached 40.9% (95% CI = 8.8%-72.9%) for the selected observational studies (OBSs). The rates of resistance to RAL that were associated with HIV subtypes A, B, and C as well as with more complex subtypes were 0.1% (95% CI = -0.7%-0.9%), 2.5% (95% CI = 0.5%-4.5%), 4.6% (95% CI = 2.7%-6.6%) and 2.2% (95% CI = 0.7%-3.7%), respectively. The rates of resistance to EVG and DTG were 1.2% (95% CI = 0.2%-2.2%) and 0.1% (95% CI = -0.2%-0.5%), respectively. Furthermore, we found that the RRs for antiviral resistance were 0.414 (95% CI = 0.210–0.816) between DTG and RAL and 0.499 (95% CI = 0.255–0.977) between EVG and RAL. When RAL was separately co-administered with nuclear nucleoside reverse transcriptase inhibitors (NRTIs) or protease inhibitors (PIs), the rates of resistance to RAL were 0.2% (95% CI = -0.1%-0.5%) and 0.2% (95% CI = -0.2%-0.6%), respectively. The ten major integrase mutations (including N155H, Y143C/R, Q148H/R, Y143Y/H, L74L/M, E92Q, E138E/A, Y143C, Q148Q and Y143S) can reduce the sensitivity of RAL and EVG. The resistance of DTG is mainly shown in 13 integrase mutations (including T97T/A, E138E/D, V151V/I, N155H, Q148, Y143C/H/R, T66A and E92Q). Conclusions Our results reveal that the DTG resistance rate was lower than the RAL resistance rate in a head-to-head comparison. Moreover, we confirmed that the EVG resistance rate was lower than the RAL resistance rate. In addition, our results revealed that the resistance rate of RAL was lower than that of efavirenz. The rates of resistance to RAL, EVG and DTG were specifically 3.9%, 1.2% and 0.1%, respectively. Compared with other types of antiviral drugs, the rates of resistance to INSTIs are generally lower. Unfortunately, the EVG and DTG resistance rates could not be compared because of a lack of data. PMID:27532886
Passerotti, Carlo C; Franco, Felipe; Bissoli, Julio C C; Tiseo, Bruno; Oliveira, Caio M; Buchalla, Carlos A O; Inoue, Gustavo N C; Sencan, Arzu; Sencan, Aydin; do Pardo, Rogerio Ruscitto; Nguyen, Hiep T
2015-07-01
Robotic assistance may provide for distinct technical advantages over conventional laparoscopic technique. The goals of this study were (1) to objectively evaluate the difference in the learning curves by novice and expert surgeons in performing fundamental laparoscopic skills using conventional laparoscopic surgery (CLS) and robotic-assisted laparoscopic surgery (RALS) and (2) to evaluate the surgeons' frustration level in performing these tasks. Twelve experienced and 31 novices in laparoscopy were prospectively evaluated in performing three standardized laparoscopic tasks in five consecutive, weekly training sessions. Analysis of the learning curves was based on the magnitude, rate, and quickness in performance improvement. The participant's frustration and mood were also evaluated during and after every session. For the novice participants, RALS allowed for shorter time to task completion and greater accuracy. However, significant and rapid improvement in performance as measured by magnitude, rate, and quickness at each session was also seen with CLS. For the experienced surgeons, RALS only provided a slight improvement in performance. For all participants, the use of RALS was associated with less number of sessions in which they felt frustrated, less number of frustration episodes during a session, lower frustration score during and after the session, and higher good mood score. The advantages of RALS may be of most benefit when doing more complex tasks and by less experienced surgeons. RALS should not be used as a replacement for CLS but rather in specific situations in which it has the greatest advantages.
Richhariya, Shlesha; Jayakumar, Siddharth; Abruzzi, Katharine; Rosbash, Michael; Hasan, Gaiti
2017-01-01
Transcriptional regulation by Store-operated Calcium Entry (SOCE) is well studied in non-excitable cells. However, the role of SOCE has been poorly documented in neuronal cells with more complicated calcium dynamics. Previous reports demonstrated a requirement for SOCE in neurons that regulate Drosophila flight bouts. We refine this requirement temporally to the early pupal stage and use RNA-sequencing to identify SOCE mediated gene expression changes in the developing Drosophila pupal nervous system. Down regulation of dStim, the endoplasmic reticular calcium sensor and a principal component of SOCE in the nervous system, altered the expression of 131 genes including Ral, a small GTPase. Disruption of Ral function in neurons impaired flight, whereas ectopic expression of Ral in SOCE-compromised neurons restored flight. Through live imaging of calcium transients from cultured pupal neurons, we confirmed that Ral does not participate in SOCE, but acts downstream of it. These results identify neuronal SOCE as a mechanism that regulates expression of specific genes during development of the pupal nervous system and emphasizes the relevance of SOCE-regulated gene expression to flight circuit maturation. PMID:28195208
Mourik, Sarah L; Martens, Jolise E; Aktas, Mustafa
2012-11-01
Measuring quality of life of women with disorders of the pelvic floor is crucial when evaluating a therapy. The aim of this study is to profile health related quality of life of women with pelvic organ prolapse who are treated with robot assisted laparoscopic sacrohysteropexy (RALS). We also compare the operative characteristics and learning curve in this study with the current literature and describe the surgical technique. A prospective cohort study in a teaching hospital in The Netherlands. Fifty women with uterovaginal prolapse were treated with RALS. This study presents the largest cohort in Europe treated by RALS to date. Quality of life was assessed pre- and post-operatively using the UDI/IIQ validated self-questionnaire designed for Dutch-speaking patients. Clinical and operative data were prospectively collected up to 29 months. RALS was performed with preservation of the uterus. Statistical analysis of categorical data was performed with the paired T-test. Descriptive statistics were computed with the use of standard methods for means, median and proportions. Before operation, overall wellbeing was scored at 67.7% and after surgery this improved to 82.1% (p=0.03). Feelings of nervousness, frustration and embarrassment reduced significantly. Sexual functioning improved, but not significantly. The mean operative time was 223 (103-340) min. Operative time decreased significantly with gained experience and became comparable to the operative time for abdominal sacrocolpopexy and classic laparoscopy. Average blood loss was less than 50 ml and patients had a mean hospital stay of 2 days. Of all women, 95.2% were very satisfied with the result after RALS. Health related quality of life improves significantly after RALS. There are high rates of patient satisfaction. RALS proves to be a safe and effective treatment of pelvic organ prolapse. Operative time is comparable to abdominal sacrocolpopexy and classic laparoscopy in the current literature. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Raloxifene reduces skeletal fractures in an animal model of osteogenesis imperfecta.
Berman, Alycia G; Wallace, Joseph M; Bart, Zachary R; Allen, Matthew R
2016-01-01
Osteogenesis imperfecta (OI) is a genetic disease of Type I collagen and collagen-associated pathways that results in brittle bone behavior characterized by fracture and reduced mechanical properties. Based on previous work in our laboratory showing that raloxifene (RAL) can significantly improve bone mechanical properties through non-cellular mechanisms, we hypothesized that raloxifene would improve the mechanical properties of OI bone. In experiment 1, tibiae from female wild type (WT) and homozygous oim mice were subjected to in vitro soaking in RAL followed by mechanical tests. RAL soaking resulted in significantly higher post-yield displacement (+75% in WT, +472% in oim; p<0.004), with no effect on ultimate load or stiffness, in both WT and oim animals. In experiment 2, eight-week old WT and oim male mice were treated for eight weeks with saline vehicle (VEH) or RAL. Endpoint measures included assessment of in vivo skeletal fractures, bone density/geometry and mechanical properties. In vivo skeletal fractures of the femora, assessed by micro CT imaging, were significantly lower in oim-RAL (20%) compared to oim-VEH (48%, p=0.047). RAL led to significantly higher DXA-based BMD (p<0.01) and CT-based trabecular BV/TV in both WT and oim animals compared to those treated with VEH. Fracture toughness of the femora was lower in oim mice compared to WT and improved with RAL in both genotypes. These results suggest that raloxifene reduces the incidence of fracture in this mouse model of oim. Furthermore, they suggest that raloxifene's effects may be the result of both cellular (increased bone mass) and non-cellular (presumably changes in hydration) mechanisms, raising the possibility of using raloxifene, or related compounds, as a new approach for treating bone fragility associated with OI. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.
Stafford, Amy J; Ensign, Daniel L; Webb, Lauren J
2010-11-25
Electrostatic fields at the interface of the Ras binding domain of the protein Ral guanine nucleotide dissociation stimulator (RalGDS) with the structurally analogous GTPases Ras and Rap1A were measured with vibrational Stark effect (VSE) spectroscopy. Eleven residues on the surface of RalGDS that participate in this protein-protein interaction were systematically mutated to cysteine and subsequently converted to cyanocysteine in order to introduce a nitrile VSE probe in the form of the thiocyanate (SCN) functional group. The measured SCN absorption energy on the monomeric protein was compared with solvent-accessible surface area (SASA) calculations and solutions to the Poisson-Boltzmann equation using Boltzmann-weighted structural snapshots from molecular dynamics simulations. We found a weak negative correlation between SASA and measured absorption energy, indicating that water exposure of protein surface amino acids can be estimated from experimental measurement of the magnitude of the thiocyanate absorption energy. We found no correlation between calculated field and measured absorption energy. These results highlight the complex structural and electrostatic nature of the protein-water interface. The SCN-labeled RalGDS was incubated with either wild-type Ras or wild-type Rap1A, and the formation of the docked complex was confirmed by measurement of the dissociation constant of the interaction. The change in absorption energy of the thiocyanate functional group due to complex formation was related to the change in electrostatic field experienced by the nitrile functional group when the protein-protein interface forms. At some locations, the nitrile experiences the same shift in field when bound to Ras and Rap1A, but at others, the change in field is dramatically different. These differences identify residues on the surface of RalGDS that direct the specificity of RalGDS binding to its in vivo binding partner, Rap1A, through an electrostatic mechanism.
Frantzell, Arne; Fransen, Signe; Petropoulos, Christos J.
2013-01-01
Y143C,R substitutions in HIV-1 integrase define one of three primary raltegravir (RAL) resistance pathways. Here we describe clinical isolates with alternative substitutions at position 143 (Y143A, Y143G, Y143H, and Y143S [Y143A,G,H,S]) that emerge less frequently, and we compare the genotypic and phenotypic profiles of these viruses to Y143C,R viruses to reconcile the preferential selection of Y143C,R variants during RAL treatment. Integrase amino acid sequences and RAL susceptibility were characterized in 117 patient isolates submitted for drug resistance testing and contained Y143 amino acid changes. The influence of specific Y143 substitutions on RAL susceptibility and their preferential association with particular secondary substitutions were further defined by evaluating the composition of patient virus populations along with a large panel of site-directed mutants. Our observations demonstrate that the RAL resistance profiles of Y143A,G,H,S viruses and their association with specific secondary substitutions are similar to the well-established Y143C profile but distinct from the Y143R profile. Y143R viruses differ from Y143A,C,G,H,S viruses in that Y143R confers a greater reduction in RAL susceptibility as a single substitution, consistent with a lower resistance barrier. Among Y143A,C,G,H,S viruses, the higher prevalence of Y143C viruses is the result of a lower genetic barrier than that of the Y143A,G,S viruses and a lower resistance barrier than that of the Y143H viruses. In addition, Y143A,C,G,H,S viruses require multiple secondary substitutions to develop large reductions in RAL susceptibility. Patient-derived viruses containing Y143 substitutions exhibit cross-resistance to elvitegravir. PMID:23733474
R&D Toward a Neutrino Factory and Muon Collider
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zisman, Michael S
2011-03-20
Significant progress has been made in recent years in R&D towards a neutrino factory and muon collider. The U.S. Muon Accelerator Program (MAP) has been formed recently to expedite the R&D efforts. This paper will review the U.S. MAP R&D programs for a neutrino factory and muon collider. Muon ionization cooling research is the key element of the program. The first muon ionization cooling demonstration experiment, MICE (Muon Ionization Cooling Experiment), is under construction now at RAL (Rutherford Appleton Laboratory) in the UK. The current status of MICE will be described.
Mata-Marín, José Antonio; Smeke, Ariane Estrella Weiser; Rodriguez, Mariana Rotzinger; Chávez-García, Marcelino; Banda-Lara, Marco Isaac; Rios, Alma Minerva Pérez; Nuñez-Rodríguez, Nohemí; Domínguez-Hermosillo, Juan Carlos; Sánchez, Alberto Chaparro; Juarez-Kasusky, Irene; Herrera, Javier Enrique Cruz; Ramírez, Jorge Luis Sandoval; Gaytán-Martínez, Jesús
2017-03-01
We evaluated the effectiveness of a raltegravir (RAL)-containing regimen plus an optimized background regimen in HIV-1 highly treatment-experienced patients. A retrospective cohort, multicentre study was conducted. Adult (>16 years old) HIV treatment-experience patients starting therapy with a RAL-containing regimen were included. Effectiveness was evaluated as the percentage of patients with an undetectable HIV-1 RNA viral load (<50 and <200 copies/mL) after 48 weeks, and changes in CD4+ cell counts. We evaluated the risk factors associated with treatment failure. Of the 107 patients in the cohort, 86% were men, the median age was 45 years [interquartile range (IQR) 40-52] and the median number of previous regimens was six (IQR 4-7). After 48 weeks of treatment, 73% (IQR 63-80%) of patients (n = 78) had a viral load of <50 copies/mL and 85% (IQR 77-90%) (n = 91) had <200 copies/mL. In a logistic regression model, risk factors associated with a virological outcome of HIV-1 RNA of <200 copies/mL were age >40 years [odds ratio (OR) 5.61; 95% confidence interval (CI) 1.61-18.84; P = 0.006] and use of tenofovir in the regimen (OR 0.16; 95% CI 0.03-0.80; P = 0.026). In this Mexican cohort, RAL achieved high rates of virological suppression and an increase in CD4+ cell count in highly treatment-experienced patients infected with HIV-1. Age >40 years was associated with a good virological outcome, contrary to tenofovir use, which was associated with a poor virological outcome.
Theoretical study on phase-locking of a radial array CO2 laser
NASA Astrophysics Data System (ADS)
Xu, Yonggen
2014-11-01
The phase-locking of the radial array CO2 laser (RAL) is introduced based on the injection-locking principle. The characteristic parameters of laser beams used in the phase-locking are described, and the coupling coefficient c00 between the injected mode and the eigenmode of RAL is calculated. The laser modes from RAL are the low-order Hermite Gaussian modes due to the diffraction loss. The analytical formula for the output beam through an ABCD optical system is derived according Collins formula. The numerical examples are given to illustrate our analytical results.
NASA Astrophysics Data System (ADS)
Clayton, Steven; Chupp, Tim; Cude-Woods, Christopher; Currie, Scott; Ito, Takeyasu; Liu, Chen-Yu; Long, Joshua; MacDonald, Stephen; Makela, Mark; O'Shaughnessy, Christopher; Plaster, Brad; Ramsey, John; Saunders, Andy; LANL nEDM Collaboration
2017-09-01
The Los Alamos National Laboratory ultracold neutron (UCN) source was recently upgraded for a factor of 5 improvement in stored density, providing the statistical precision needed for a room temperature neutron electric dipole moment measurement with sensitivity 3 ×10-27 e . cm, a factor 10 better than the limit set by the Sussex-RAL-ILL experiment. Here, we show results of a demonstration of Ramsey's separated oscillatory fields method on stored UCNs at the LANL UCN source and in a geometry relevant for a nEDM measurement. We argue a world-leading nEDM experiment could be performed at LANL with existing technology and a short lead time, providing a physics result with sensitivity intermediate between the current limit set by Sussex-RAL-ILL, and the anticipated limit from the complex, cryogenic nEDM experiment planned for the next decade at the ORNL Spallation Neutron Source (SNS-nEDM). This work was supported by the Los Alamos LDRD Program, Project 20140015DR.
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
Patterson, Kristine B.; Prince, Heather A.; Stevens, Trenton; Shaheen, Nicholas J.; Dellon, Evan S.; Madanick, Ryan D.; Jennings, Steven; Cohen, Myron S.; Kashuba, Angela D.M.
2014-01-01
Objective To investigate the concentration of the integrase strand inhibitor raltegravir (RAL) throughout gastrointestinal (GI) tissue, especially gutassociated lymphoid tissue (GALT), as an adjunct to current prevention and cure strategies. Design Open-label pharmacokinetic study Methods HIV-negative men received RAL 400 mg twice daily for 7 days. Seven blood plasma (BP) specimens were collected over 12-hr intervals; timed tissue specimens from terminal ileum, splenic flexure, and rectum were also obtained by colonoscopy following the first dose (FD) and on Day 7 [Multiple Dose (MD)]. RAL concentrations were measured by validated LC-MS assay with 1 ng/mL lower limit of detection. Data were analyzed by noncompartmental methods (WinNonlin 6). Tissue exposures are reported as composite medians and tissue density of 1.04 g/mL is assumed for comparisons. Results Fourteen men completed evaluations. Median (range) age was 24 (19–49) yrs and BMI 25 (19–31) kg/m2. After the FD, AUC-0-12h was highest in the terminal ileum (594 μg*h/mL). Exposures were 160, 68 and 39-fold greater than BP at the terminal ileum, splenic flexure and rectum, respectively. After multiple doses, exposure was highest at the splenic flexure (2240 μg*h/mL); exposure at the terminal ileum and rectum were equivalent (both 788 μg*h/mL). Following multiple doses, exposures were 160–650-fold greater than BP throughout the colon. Conclusions RAL rapidly disseminates into GI tissue and concentrations remain significantly higher than BP. RAL exposure in GI tissue remains higher than any ARV investigated to date. These data suggest that RAL should result in full suppression of viral replication in GI tissue and GALT. PMID:23945503
Klose, Markus; Duvall, Laura; Li, Weihua; Liang, Xitong; Ren, Chi; Steinbach, Joe Henry; Taghert, Paul H
2016-05-18
The neuropeptide PDF promotes the normal sequencing of circadian behavioral rhythms in Drosophila, but its signaling mechanisms are not well understood. We report daily rhythmicity in responsiveness to PDF in critical pacemakers called small LNvs. There is a daily change in potency, as great as 10-fold higher, around dawn. The rhythm persists in constant darkness and does not require endogenous ligand (PDF) signaling or rhythmic receptor gene transcription. Furthermore, rhythmic responsiveness reflects the properties of the pacemaker cell type, not the receptor. Dopamine responsiveness also cycles, in phase with that of PDF, in the same pacemakers, but does not cycle in large LNv. The activity of RalA GTPase in s-LNv regulates PDF responsiveness and behavioral locomotor rhythms. Additionally, cell-autonomous PDF signaling reversed the circadian behavioral effects of lowered RalA activity. Thus, RalA activity confers high PDF responsiveness, providing a daily gate around the dawn hours to promote functional PDF signaling. Copyright © 2016 Elsevier Inc. All rights reserved.
Liang, Xitong; Ren, Chi; Steinbach, Joe Henry; Taghert, Paul H.
2016-01-01
The neuropeptide PDF promotes the normal sequencing of circadian behavioral rhythms in Drosophila, but its signaling mechanisms are not well understood. We report daily rhythmicity in responsiveness to PDF in critical pacemakers called small LNvs. There is a daily change in potency, as great as 10-fold higher, around dawn. The rhythm persists in constant darkness, does not require endogenous ligand (PDF) signaling, or rhythmic receptor gene transcription. Furthermore, rhythmic responsiveness reflects the properties of the pacemaker cell type, not the receptor. Dopamine responsiveness also cycles, in phase with that of PDF, in the same pacemakers, but does not cycle in large LNv. The activity of RalA GTPase in s-LNv regulates PDF responsiveness and behavioral locomotor rhythms. Additional, cell autonomous PDF signaling reversed the circadian behavioral effects of lowered RalA activity. Thus RalA activity confers high PDF responsiveness, providing a daily gate around the dawn hours to promote functional PDF signaling. PMID:27161526
Ito, Kyoko; Hao, Lei; Wray, Amanda E.; Ross, A. Catharine
2013-01-01
The accumulation of hepatic TG and development of hepatic steatosis (HS) is a serious complication of the use of parenteral nutrition (PN) formulas containing a high percentage of dextrose. But whether fat emulsions or other nutrients can ameliorate the induction of HS by high-carbohydrate diets is still uncertain. We hypothesized that administration of a lipid emulsion (LE; Intralipid) and/or the vitamin A metabolite retinal (RAL) will reduce hepatic TG accumulation and attenuate indicators of inflammation. C57BL/6 male mice were fed PN formula as their only source of hydration and nutrition for 4–5 wk. In Expt. 1, mice were fed PN only or PN plus treatment with RAL (1 μg/g orally), LE (200 μL i.v.), or both LE and RAL. In Expt. 2, LE was orally administered at 4 and 13.5% of energy to PN-fed mice. All PN mice developed HS compared with mice fed normal chow (NC) and HS was reduced by LE. The liver TG mass was lower in the PN+LE and PN+RAL+LE groups compared with the PN and PN+RAL groups (P < 0.01) and in the 4% and 13.5% PN+LE groups compared with PN alone. Hepatic total retinol was higher in the RAL-fed mice (P < 0.0001), but RAL did not alter TG mass. mRNA transcripts for fatty acid synthase (Fasn) and sterol regulatory element-binding protein-1c (Srebpf1) were higher in the PN compared with the NC mice, but FAS protein and Srebpf1 mRNA were lower in the PN+LE groups compared with PN alone. The inflammation marker serum amyloid P component was also reduced. In summary, LE given either i.v. or orally may be sufficient to reduce the steatotic potential of orally fed high-dextrose formulas and may suppress the early development of HS during PN therapy. PMID:23325918
Sun, Dongxiao; Jones, Nathan R; Manni, Andrea; Lazarus, Philip
2014-01-01
Raloxifene is a 2nd-generation selective estrogen receptor modulator used for the prevention and treatment of osteoporosis and the prevention of breast cancer in postmenopausal women. Raloxifene is extensively metabolized by glucuronidation to form raloxifene-6-glucuronide (ral-6-Gluc) and raloxifene-4′-glucuronide (ral-4′-Gluc). The goal of the present study was to determine whether functional polymorphisms in active UGTs could play a role in altered raloxifene glucuronidation in vivo. Using homogenates from HEK293 UGT-overexpressing cell lines, raloxifene was shown to be glucuronidated primarily by the hepatic UGTs 1A1 and 1A9 and the extra-hepatic UGTs 1A8 and 1A10; no detectable raloxifene glucuronidation activity was found for UGT2B enzymes. Functional UGT1A1 transcriptional promoter genotypes were significantly (ptrend=0.005) associated with ral-6-Gluc formation in human liver microsomes, and, consistent with the decreased raloxifene glucuronidation activities observed in vitro with cell line over-expressing UGT1A8 variants, the UGT1A8*2 variant was significantly (p=0.023) correlated with total raloxifene glucuronide formation in human jejunum homogenates. While ral-4′-Gluc exhibited 1/100th the anti-estrogenic activity of raloxifene itself as measured by binding to the estrogen receptor, raloxifene glucuronides comprised ∼99% of the circulating raloxifene dose in raloxifene-treated subjects, with ral-4′-Gluc comprising ∼70% of raloxifene glucuronides. Plasma ral-6-Gluc (ptrend=0.0025), ral-4′-Gluc (ptrend=0.001), and total raloxifene glucuronides (ptrend=0.001) were increased in raloxifene-treated subjects who were predicted slow metabolizers [UGT1A8 (*1/*3)] vs intermediate metabolizers [UGT1A8 (*1/*1) or UGT1A8 (*1/*2)] vs fast metabolizers [UGT1A8 (*2/*2). These data suggest that raloxifene metabolism may be dependent on UGT1A8 genotype and that UGT1A8 genotype may play an important role in overall response to raloxifene. PMID:23682072
Rétinoschisis maculaire bilatéral associé à un rétinoschisis périphérique unilatéral
Oummad, Hanane; Elkaddoumi, Maryama; Maré, Josiane; Lezrek, Mounir; Cherkaoui, Ouafae
2017-01-01
Le retinoschisis juvénile lié au chromosome X est une affection héréditaire qui affecte habituellement les garçons avec de rare cas d’atteinte du sexe féminin. Les premières manifestations cliniques apparaissent généralement au cours de la première décennie. Il est responsable d’une baisse d’acuité visuelle d’importance variable et lentement progressive. Cette évolution peut être émaillée d’hémorragies dans le vitré et de décollements de rétine volontiers récidivants. Nous présentons le cas d’un patient âgé de 17ans. Au fond d'œil on retrouve remaniement maculaire microkystique stellaire bilatéral, centré sur la fovéola, associé à des schisis périphériques avec décollement de rétine et déchirure des feuillets interne et externe unilatéral. PMID:29158861
Hess, Jessica A; Zhan, Bin; Torigian, April R; Patton, John B; Petrovsky, Nikolai; Zhan, Tingting; Bottazzi, Maria Elena; Hotez, Peter J; Klei, Thomas R; Lustigman, Sara; Abraham, David
2016-07-01
In some regions in Africa, elimination of onchocerciasis may be possible with mass drug administration, although there is concern based on several factors that onchocerciasis cannot be eliminated solely through this approach. A vaccine against Onchocerca volvulus would provide a critical tool for the ultimate elimination of this infection. Previous studies have demonstrated that immunization of mice with Ov-103 and Ov-RAL-2, when formulated with alum, induced protective immunity. It was hypothesized that the levels of protective immunity induced with the two recombinant antigens formulated with alum would be improved by formulation with other adjuvants known to enhance different types of antigen-specific immune responses. Immunizing mice with Ov-103 and Ov-RAL-2 in conjunction with alum, Advax 2 and MF59 induced significant levels of larval killing and host protection. The immune response was biased towards Th2 with all three of the adjuvants, with IgG1 the dominant antibody. Improved larval killing and host protection was observed in mice immunized with co-administered Ov-103 and Ov-RAL-2 in conjunction with each of the three adjuvants as compared to single immunizations. Antigen-specific antibody titers were significantly increased in mice immunized concurrently with the two antigens. Based on chemokine levels, it appears that neutrophils and eosinophils participate in the protective immune response induced by Ov-103, and macrophages and neutrophils participate in immunity induced by Ov-RAL-2. The mechanism of protective immunity induced by Ov-103 and Ov-RAL-2, with the adjuvants alum, Advax 2 and MF59, appears to be multifactorial with roles for cytokines, chemokines, antibody and specific effector cells. The vaccines developed in this study have the potential of reducing the morbidity associated with onchocerciasis in humans.
Bowman, A R; Sass, D A; Marshall, I; Ma, Y F; Liang, H; Jee, W S; Epstein, S
1996-08-01
Cyclosporin A (CsA) administered to the oophorectomized (Ox) rat exacerbates the high turnover osteopenia associated with estrogen deficiency. 17 beta-estradiol replacement therapy prevent this bone loss. The aim of this study was to see whether an estrogen-like compound, Raloxifene analog (LY117018 HCL, Ral) could likewise ameliorate CsA-induced osteopenia in the Ox rat. Sixty 6-month-old Sprague-Dawley rats, divided into five groups, underwent oophorectomy. One group acted as a basal group and the others received either vehicle (group B), CsA 15 mg/kg/day (group C), Ral 3 mg/kg/day (group D), or CsA 15 mg/kg/day and Ral 3 mg/kg/day (group E) for 28 days by gavage. A sixth sham operated group of 12 rats received vehicle only (group A). Rats were weighed and bled on days 0, 14, and 28 for measurement of ionized calcium, glucose, osteocalcin (BGP), 17 beta-estradiol, and 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Tibiae were removed on day 28 for bone histomorphometry after double tetracycline and calcein labeling. Oophorectomy caused a significant gain in weight in groups B and C which was prevented by Ral in groups D and E. Randomized blood glucose levels and 1,25(OH)2D3 levels were elevated in both CsA-treated groups. Blood ionized calcium levels were lower in vehicle (group B) compared with sham (group A) on day 28. Ox (group B) had significantly higher serum BGP levels compared with sham-operated rats. Serum BGP levels were further elevated in group C compared with vehicle and were lowered in both Ral-treated groups to vehicle levels by day 28. Bone histomorphometry revealed a high turnover osteopenia with increased parameters of bone formation and resorption and loss of cancellous bone volume postoophorectomy (group B). CsA (group C) exacerbated the effects of oophorectomy. Ral (group D) completely prevented the high turnover osteopenia caused by oophorectomy and was able to attenuate substantially the effects of CsA in the Ox rat (group E). Ral therapy ameliorated CsA-induced osteopenia in the Ox rat and might prove a useful agent in preventing bone loss in postmenopausal women receiving CsA.
Communicating Science; a collaborative approach through Art, Dance, Music and Science
NASA Astrophysics Data System (ADS)
Smart, Sarah-Jane; Mortimer, Hugh
2016-04-01
A collaborative approach to communicating our amazing science. RAL Space at the Rutherford Appleton Lab, has initiated a unique collaboration with a team of award-winning performing artists with the aim of making space science research engaging and accessible to a wide audience. The collaboration has two distinct but connected strands one of which is the development of a contemporary dance work inspired by solar science and including images and data from the Space Physics Division of STFC RAL Space. The work has been commissioned by Sadler's Wells, one of the world's leading dance venues. It will be created by choreographer Alexander Whitley, video artist Tal Rosner and composers Ella Spira and Joel Cadbury and toured throughout the UK and internationally by the Alexander Whitley Dance Company (AWDC). The work will come about through collaboration with the work of the scientists of RAL Space and in particular the SOHO, CDS and STEREO missions, taking a particular interest in space weather. Choreographer Alexander Whitley and composers Ella Spira and Joel Cadbury will take their inspiration from the images and data that are produced by the solar science within RAL Space. Video artist Tal Rosner will use these spectacular images to create an atmospheric backdrop to accompany the work, bringing the beauty and wonder of space exploration to new audiences. Funding for the creation and touring of the work will be sought from Arts Council England, the British Council, partner organisations, trusts and foundations and private donors.The world premiere of the work will take place at Sadler's Wells in June 2017. It will then tour throughout the UK and internationally to theatres, science conferences and outreach venues with the aim of bringing the work of STFC RAL Space and the science behind solar science and space weather to new audiences. An education programme will combine concepts of choreography and space science aimed at young people in year 5 Key Stage 2 and be developed by a Creative Learning specialist with input from RAL Space scientists and engineers, the RAL Space communication and outreach group and Alexander Whitley Dance Company. The programme will be piloted in selected East London schools and then, following evaluation, be rolled out to several schools across the UK.
Using container orchestration to improve service management at the RAL Tier-1
NASA Astrophysics Data System (ADS)
Lahiff, Andrew; Collier, Ian
2017-10-01
In recent years container orchestration has been emerging as a means of gaining many potential benefits compared to a traditional static infrastructure, such as increased utilisation through multi-tenancy, improved availability due to self-healing, and the ability to handle changing loads due to elasticity and auto-scaling. To this end we have been investigating migrating services at the RAL Tier-1 to an Apache Mesos cluster. In this model the concept of individual machines is abstracted away and services are run in containers on a cluster of machines, managed by schedulers, enabling a high degree of automation. Here we describe Mesos, the infrastructure deployed at RAL, and describe in detail the explicit example of running a batch farm on Mesos.
Study of turbine bypass remote augmentor lift system for V/STOL aircraft
NASA Technical Reports Server (NTRS)
Sheridan, A. E.
1985-01-01
The airframe design and engine/aircraft integration were emphasized in a NASA comparative study of turbofan and turbine bypass engine (TBE) with remote augmentor lift systems (RALS) for supersonic V/STOL aircraft. Functional features of the TBE are reviewed, noting the enhanced cycle efficiency and reduced afterbody drag compared to the turbojets. The present studies examied performance levels for aircraft with fleet defense and secondary anti-surface warfare roles, carrying AMRAAM and AIM missiles. TBE engine cycles were configured for hover and up-and-away flight from deck launch, and all tests were done from a conceptual design viewpoint. The results indicate that the TBE-RALS is superior to turbofan-RALS aircraft in both gross take-off weight and life cycle cost.
Development of a gas-pressurized high-pressure μSR setup at the RIKEN-RAL Muon Facility
NASA Astrophysics Data System (ADS)
Watanabe, I.; Ishii, Y.; Kawamata, T.; Suzuki, T.; Pratt, F. L.; Done, R.; Chowdhury, M.; Goodway, C.; Dreyer, J.; Smith, C.; Southern, M.
2009-04-01
The development and testing of a gas-pressurized μSR setup for the RIKEN-RAL Muon Facility is reported. In collaboration with the high-pressure group of the ISIS Facility at the Rutherford Appleton Laboratory, a gas-pressurized setup for a pulsed muon beam at the RIKEN-RAL Muon Facility has been constructed in 2008. The sample is pressurized by helium gas and the designed maximum pressure is 6.4 kbar. The high-pressure cell can be cooled down to 2 K using an existing cryostat. Tests were made injecting the double-pulsed muon beam into a high-purity sample of Sn powder, which confirmed that the maximum pressure achieved at 2 K was close to the designed pressure.
U.S. Security Assistance Programs in Southern Africa: Are They Supporting National Objectives?
1985-04-01
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The error analysis of Lobular and segmental division of right liver by volume measurement.
Zhang, Jianfei; Lin, Weigang; Chi, Yanyan; Zheng, Nan; Xu, Qiang; Zhang, Guowei; Yu, Shengbo; Li, Chan; Wang, Bin; Sui, Hongjin
2017-07-01
The aim of this study is to explore the inconsistencies between right liver volume as measured by imaging and the actual anatomical appearance of the right lobe. Five healthy donated livers were studied. The liver slices were obtained with hepatic segments multicolor-infused through the portal vein. In the slices, the lobes were divided by two methods: radiological landmarks and real anatomical boundaries. The areas of the right anterior lobe (RAL) and right posterior lobe (RPL) on each slice were measured using Photoshop CS5 and AutoCAD, and the volumes of the two lobes were calculated. There was no statistically significant difference between the volumes of the RAL or RPL as measured by the radiological landmarks (RL) and anatomical boundaries (AB) methods. However, the curves of the square error value of the RAL and RPL measured using CT showed that the three lowest points were at the cranial, intermediate, and caudal levels. The U- or V-shaped curves of the square error rate of the RAL and RPL revealed that the lowest value is at the intermediate level and the highest at the cranial and caudal levels. On CT images, less accurate landmarks were used to divide the RAL and RPL at the cranial and caudal layers. The measured volumes of hepatic segments VIII and VI would be less than their true values, and the measured volumes of hepatic segments VII and V would be greater than their true values, according to radiological landmarks. Clin. Anat. 30:585-590, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Spacecraft Environmental Interactions Technology 1983
1985-01-01
sr. 144 S+ +. + ’ J9 • "=• _Z7 `16~ r’r f,"::,irC 14 0 ral Irl -r -4: 3J’ r. .4 1 .. i. . Figure 3. - Isocontour maps as in figiire 1 for the average ...Geophysics Laboratory ....... . . . . . . . . . .. 125 AVERAGE AND WORST-CASE SPECIFICATIONS OF PRECIPITATING AURORAL ELECTRON ENVIRONMENT David A...force now, In volume S we d( ’elop a road- map of how a technology program would co-tinue to develop the technology base required for the specific
Restelli, Umberto; Rizzardini, Giuliano; Antinori, Andrea; Lazzarin, Adriano; Bonfanti, Marzia; Bonfanti, Paolo; Croce, Davide
2017-01-01
In January 2014, the European Medicines Agency issued a marketing authorization for dolutegravir (DTG), a second-generation integrase strand transfer inhibitor for HIV treatment. The study aimed at determining the incremental cost-effectiveness ratio (ICER) of the use of DTG+backbone compared with raltegravir (RAL)+backbone, darunavir (DRV)+ritonavir(r)+backbone and efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC) in HIV-positive treatment-naïve patients and compared with RAL+backbone in treatment-experienced patients, from the Italian National Health Service's point of view. A published Monte Carlo Individual Simulation Model (ARAMIS-DTG model) was used to perform the analysis. Patients pass through mutually exclusive health states (defined in terms of diagnosis of HIV with or without opportunistic infections [OIs] and cardiovascular disease [CVD]) and successive lines of therapy. The model considers costs (2014) and quality of life per monthly cycle in a lifetime horizon. Costs and quality-adjusted life years (QALYs) are dependent on OI, CVD, AIDS events, adverse events and antiretroviral therapies. In treatment-naïve patients, DTG dominates RAL; compared with DRV/r, the ICER obtained is of 38,586 €/QALY (6,170 €/QALY in patients with high viral load) and over EFV/TDF/FTC, DTG generates an ICER of 33,664 €/QALY. In treatment-experienced patients, DTG compared to RAL leads to an ICER of 12,074 €/QALY. The use of DTG+backbone may be cost effective in treatment-naïve and treatment-experienced patients compared with RAL+backbone and in treatment-naïve patients compared with DRV/r+backbone and EFV/TDF/FTC considering a threshold of 40,000 €/QALY.
Blakney, Anna K.; Jiang, Yonghou; Whittington, Dale; Woodrow, Kim A.
2016-01-01
Etravirine (ETR), maraviroc (MVC) and raltegravir (RAL) are promising antiretroviral drugs being used in HIV treatment and may be interesting for prevention applications such as oral or topical pre-exposure prophylaxis. Here we describe a sensitive and accurate method for the simultaneous detection of ETR, MVC and RAL from pigtail macaque plasma, vaginal secretions, and vaginal tissue. This method is characterized by a straightforward precipitation extraction method, a limit of quantification <0.5 ng mL−1 for all three antiretrovirals bolstered by a corresponding internal standard for each drug analyte, and short run time. Quantification is performed using positive ion electrospray triple quadrupole mass spectrometry. This method was validated over clinically relevant ranges for the three ARV drugs in all three matrices: 0.1–100 ng mL−1 for ETR, 0.05–100 ng mL−1 for MVC and 1–100 ng mL−1 for RAL. Our method is accurate and precise, with measured mean inter-assay precision (%CV) and accuracy (% bias) of 5.08% and 1.96%, respectively, while the mean intra-assay precision and accuracy were 3.44% and 1.08 %. The overall post-extraction recovery for ETR, MVC and RAL was >94% in all cases. We also show that extracted biological samples are stable after storage at room temperature or 4 °C and after three freeze/thaw cycles. This is the first analytical method capable of quantifying ETR, MVC and RAL in biological matrices relevant for pre-clinical testing of oral or topical HIV prevention methods in pigtailed macaques. PMID:27236000
Evolution and the origin of the visual retinoid cycle in vertebrates.
Kusakabe, Takehiro G; Takimoto, Noriko; Jin, Minghao; Tsuda, Motoyuki
2009-10-12
Absorption of a photon by visual pigments induces isomerization of 11-cis-retinaldehyde (RAL) chromophore to all-trans-RAL. Since the opsins lacking 11-cis-RAL lose light sensitivity, sustained vision requires continuous regeneration of 11-cis-RAL via the process called 'visual cycle'. Protostomes and vertebrates use essentially different machinery of visual pigment regeneration, and the origin and early evolution of the vertebrate visual cycle is an unsolved mystery. Here we compare visual retinoid cycles between different photoreceptors of vertebrates, including rods, cones and non-visual photoreceptors, as well as between vertebrates and invertebrates. The visual cycle systems in ascidians, the closest living relatives of vertebrates, show an intermediate state between vertebrates and non-chordate invertebrates. The ascidian larva may use retinochrome-like opsin as the major isomerase. The entire process of the visual cycle can occur inside the photoreceptor cells with distinct subcellular compartmentalization, although the visual cycle components are also present in surrounding non-photoreceptor cells. The adult ascidian probably uses RPE65 isomerase, and trans-to-cis isomerization may occur in distinct cellular compartments, which is similar to the vertebrate situation. The complete transition to the sophisticated retinoid cycle of vertebrates may have required acquisition of new genes, such as interphotoreceptor retinoid-binding protein, and functional evolution of the visual cycle genes.
Raloxifene therapy interacts with serum osteoprotegerin in postmenopausal women.
Messalli, Enrico M; Mainini, Giampaolo; Scaffa, Cono; Cafiero, Angela; Salzillo, Pier Luigi; Ragucci, Angelo; Cobellis, Luigi
2007-01-20
Osteoprotegerin (OPG) is a protein expressed by osteoblasts that, linking the receptor activator of nuclear factor kappaB (RANK) ligand (RANKL), produced by osteoblasts, blocks the process of osteoclastic differentiation and modulates osteoclastic apoptosis. Raloxifene (RAL) stimulates the production of OPG from osteoblasts, as demonstrated in vitro, carring out their antiresorption activity, at least in part, as means of the OPG/RANK/RANKL system. The aim of this study was to evaluate in vivo if the RAL treatment of postmenopausal women was associated to changes in serum OPG; moreover, to evaluate the serum changes of bone turnover modulators interleukin-6 (IL-6) and C-telopeptides of type-1 collagen (CrossLaps). A prospective, randomized, placebo-controlled study was designed. A group of consecutive healthy postmenopausal women (n=40) referred to II Menopause Centre of the Department of Gynaecology of Second University of Naples for climacteric syndrome was enrolled and divided in two groups: (n=20) postmenopausal women received for 6 months oral raloxifene (60 mg/day) versus (n=20) postmenopausal women received placebo tablets. Serum OPG levels in postmenopausal women after RAL treatment are statistically significant increased (P<0.001) versus baseline (P=0.007) versus placebo. These in vivo data demonstrate that RAL could improve osteoporosis, also through an increase of OPG production by osteoblasts.
HPLC/UV quantitation of retinal, retinol, and retinyl esters in serum and tissues
Kane, Maureen A.; Folias, Alexandra E.; Napoli, Joseph L.
2008-01-01
We report robust HPLC/UV methods for quantifying retinyl esters (RE), retinol (ROL) and retinal (RAL) applicable to diverse biological samples, with lower limits of detection of 0.7 pmol, 0.2 pmol, and 0.2 pmol, respectively, and linear ranges >3 orders of magnitude. These assays function well with small, complex biological samples (10–20 mg tissue). Coefficients of variation range from: intra-day, 5.9–10.0%; inter-day, 5.9–11.0%. Quantification of endogenous RE, ROL, and RAL in mouse serum and tissues (liver, kidney, adipose, muscle, spleen, testis, skin, brain, and brain regions) reveals utility. Ability to discriminate spatial concentrations of ROL and RE is illustrated with C57BL/6 mouse brain loci (hippocampus, cortex, olfactory bulb, thalamus, cerebellum, and striatum.) We also developed a method to distinguish isomeric forms of ROL to investigate precursors of retinoic acid. The ROL isomer assay has limits of detection between 3.5–4.5 pmol and a similar linear range and % CV as the ROL/RE and RAL assays. The assays described here provide for sensitive and rigorous quantification of endogenous RE, ROL, and RAL to elucidate retinoid homeostasis in disease states, such as Alzheimer’s disease, type 2 diabetes, obesity, and cancer. PMID:18410739
Public Outreach at RAL: Engaging the Next Generation of Scientists and Engineers
NASA Astrophysics Data System (ADS)
Corbett, G.; Ryall, G.; Palmer, S.; Collier, I. P.; Adams, J.; Appleyard, R.
2015-12-01
The Rutherford Appleton Laboratory (RAL) is part of the UK's Science and Technology Facilities Council (STFC). As part of the Royal Charter that established the STFC, the organisation is required to generate public awareness and encourage public engagement and dialogue in relation to the science undertaken. The staff at RAL firmly support this activity as it is important to encourage the next generation of students to consider studying Science, Technology, Engineering, and Mathematics (STEM) subjects, providing the UK with a highly skilled work-force in the future. To this end, the STFC undertakes a variety of outreach activities. This paper will describe the outreach activities undertaken by RAL, particularly focussing on those of the Scientific Computing Department (SCD). These activities include: an Arduino based activity day for 12-14 year-olds to celebrate Ada Lovelace day; running a centre as part of the Young Rewired State - encouraging 11-18 year-olds to create web applications with open data; sponsoring a team in the Engineering Education Scheme - supporting a small team of 16-17 year-olds to solve a real world engineering problem; as well as the more traditional tours of facilities. These activities could serve as an example for other sites involved in scientific computing around the globe.
1992-05-22
ABSTRACT (Maximum 200 worch) A carpact sOtt X-ray laser (SXL) can be designed combining results of Princeton Plasma Physics Laboratory ( PPPL ) and Rutherford...Appleton Laboratory (RAL). At PPPL , gain at 18.2nm was dem- onstrated in a carbon plasma pumped by a low energy laser, with no mag- netic field. The...Physics Laboratory ( PPPL ) and Rutherford Appleton Laboratory (RAL). In the PPPL experiment, gain at a wavelength of 18.2 nm was demonstrated in a
The effect of tamoxifen and raloxifene on estrogen metabolism and endometrial cancer risk.
Williams-Brown, Marian Y; Salih, Sana M; Xu, Xia; Veenstra, Timothy D; Saeed, Muhammad; Theiler, Shaleen K; Diaz-Arrastia, Concepcion R; Salama, Salama A
2011-09-01
Selective estrogen receptor modulators (SERMs) demonstrate differential endometrial cancer (EC) risk. While tamoxifen (TAM) use increases the risk of endometrial hyperplasia and malignancy, raloxifene (RAL) has neutral effects on the uterus. How TAM increases the risk of EC and why TAM and RAL differentially modulate the risk for EC, however, remain elusive. Here, we tested the hypothesis that TAM increases the risk for EC, at least in part, by enhancing the local estrogen biosynthesis and directing estrogen metabolism towards the formation of genotoxic and hormonally active estrogen metabolites. In addition, the differential effects of TAM and RAL in EC risk are attributed to their differential effect on estrogen metabolism/metabolites. The endometrial cancer cell line (Ishikawa cells) and the nonmalignant immortalized human endometrial glandular cell line (EM1) were used for the study. The profile of estrogen/estrogen metabolites (EM), depurinating estrogen-DNA adducts, and the expression of estrogen-metabolizing enzymes in cells treated with 17β-estradiol (E2) alone or in combination with TAM or RAL were investigated using high performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS(2)), ultraperformance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS), and Western blot analysis, respectively. TAM significantly increased the total EM and enhanced the formation of hormonally active and carcinogenic estrogen metabolites, 4-hydroxestrone (4-OHE1) and 16α-hydroxyestrone, with concomitant reduction in the formation of antiestrogenic and anticarcinogenic 2-hydroxyestradiol and 2-methoxyestradiol. Furthermore, TAM increased the formation of depurinating estrogen-DNA adducts 4-OHE1 [2]-1-N7Guanine and 4-OHE1 [2]-1-N3 Adenine. TAM-induced alteration in EM and depurinating DNA adduct formation is associated with altered expression of estrogen metabolizing enzymes CYP1A1, CYP1B1, COMT, NQO1, and SF-1 as revealed by Western blot analysis. In contrast to TAM, RAL has minimal effect on EM, estrogen-DNA adduct formation, or estrogen-metabolizing enzymes expression. These data show that TAM perturbs the balance of estrogen-metabolizing enzymes and alters the disposition of estrogen metabolites, which can explain, at least in part, the mechanism for TAM-induced EC. These results also implicate the differential effect of TAM and RAL on estrogen metabolism/metabolites as a potential mechanism for their disparate effects on the endometrium. Copyright © 2011 Elsevier Ltd. All rights reserved.
Lu, Pei; Yue, Huifang; Xing, Yi; Wei, Jianjun; Zeng, Zheng; Li, Rui; Wu, Wanrong
2018-05-11
In this study, series of Ce x Zr y Mn z O 2 /r-Al 2 O 3 catalysts were prepared by impregnation method and explored to co-purification of NO x and Hg 0 at low temperature. The physical and chemical properties of the catalysts were investigated by XRD, BET, FTIR, NH 3 -TPD, H 2 -TPR, and XPS. The experimental results showed that 10% Ce 0.2 Zr 0.3 Mn 0.5 O 2 /r-Al 2 O 3 yielded higher conversion on co-purification of NO x and Hg 0 than the other prepared catalysts at low temperature, especially at 200-300 °C. 91% and 97% convert rate of NO x and Hg 0 were obtained, respectively, when 10% Ce 0.2 Zr 0.3 Mn 0.5 O 2 /r-Al 2 O 3 catalyst was used at 250 °C. Moreover, the presence of H 2 O slightly decreased the removal of NO x and Hg 0 owing to the competitive adsorption of H 2 O and Hg 0 . When SO 2 was added, the removal of Hg 0 first increased slightly and then presented a decrease due to the generation of SO 3 and (NH 4 ) 2 SO 4 . The results of NH 3 -TPD indicated that the strong acid of 10% Ce 0.2 Zr 0.3 Mn 0.5 O 2 /r-Al 2 O 3 improved its high-temperature activity. XPS and H 2 -TPR results showed there were high-valence Mn and Ce species in 10% Ce 0.2 Zr 0.3 Mn 0.5 O 2 /r-Al 2 O 3 , which could effectively promote the removal of NO x and Hg 0 . Therefore, the mechanisms of Hg 0 and NO x removal were proposed as Hg (ad) + [O] → HgO (ad), and 2NH 3 /NH 4 + (ad) + NO 2 (ad) + NO (g) → 2 N 2 + 3H 2 O/2H + , respectively. Graphical abstract ᅟ.
The Selection of a Marine Artillery Battery Fire Direction Computer System.
1982-12-01
yhsical Characteristics: Tbe VI provi-ds s h gen er al physical characteri-sti-cs of the BCS. The total weight of the BCS is based on ti,: eg’±ipment...twenty special fanc -tion keys. Six of the special function keys arc- currently spares and will be programmed -o support the P31 software aiditions...close to the weapon or mounted on the weapon. Phs- ga C aacteri sti cs: Table XIV provides the gen e ral physical charactaristics of the FCC. The act
Retinaldehyde/hyaluronic acid fragments: a synergistic association for the management of skin aging.
Cordero, Andres; Leon-Dorantes, Gladys; Pons-Guiraud, Annick; Di Pietro, Anonio; Asensi, Santiago Vidal; Walkiewicz-Cyraska, Barbara; Litvik, Radek; Turlier, Virginie; Mery, Sophie; Merial-Kieny, Christelle
2011-06-01
Retinaldehyde (RAL) was proven effective in treating photodamaged skin. Topical treatments with specific intermediate-size hyaluronate fragments (HAFi, 50-400 kDa) have been shown to stimulate keratinocytes proliferation and epidermal hyperplasia. The aim of this open, multicentric, international study was to assess the efficacy of the combination RAL-HAFi in the correction of skin photoaging. Either RAL 0.05%-HAFi 0.5% (Eluage® cream; group 1) or RAL 0.05%-HAFi 1% (Eluage® antiwrinkle concentrate; group 2) or both products (group 3) were applied daily to the 1462 subjects during 90 days. Overall photoaging severity was evaluated in the three groups by the dermatologists at D0, D30, and D90 based on the Larnier's scale. Wrinkles and/or furrows and clinical signs of aging were evaluated using a 4-point scale. The skin microrelief of the crow's feet, evaluated by optical profilometry, was performed in subjects from group 3. The 3-month application significantly improved overall photoaging through decrease of the Larnier's score in the three groups (P<0.001). At D90, significant improvement of wrinkles was shown in groups 2 and 3 [forehead wrinkles (-19% and -10%, respectively, P<0.001), nasolabial folds (-20% and -16%, P<0.001), crow's feet (-27% in the two groups, P<0.001), and perioral wrinkles (-34% and -23%, P<0.001)]. Clinical signs of photoaging on the entire face improved significantly in groups 1 and 3 [elasticity (-32% and -33%, respectively, P<0.001), hyperpigmentation (-34% and -31%, P<0.001), and ptosis (-18% and -22%; P<0.001)]. Results were confirmed using an optical profilometry technique. Products were very well tolerated. This clinical study showed the efficacy and value of the RAL-HAFi combination in the management of aging skin in a large cohort of patients. © 2011 Wiley Periodicals, Inc.
Kaylor, Joanna J.; Cook, Jeremy D.; Makshanoff, Jacob; Bischoff, Nicholas; Yong, Jennifer; Travis, Gabriel H.
2014-01-01
Absorption of a photon by a rhodopsin or cone-opsin pigment isomerizes its 11-cis-retinaldehyde (11-cis-RAL) chromophore to all-trans-retinaldehyde (all-trans-RAL), which dissociates after a brief period of activation. Light sensitivity is restored to the resulting apo-opsin when it recombines with another 11-cis-RAL. Conversion of all-trans-RAL to 11-cis-RAL is carried out by an enzyme pathway called the visual cycle in cells of the retinal pigment epithelium. A second visual cycle is present in Müller cells of the retina. The retinol isomerase for this noncanonical pathway is dihydroceramide desaturase (DES1), which catalyzes equilibrium isomerization of retinol. Because 11-cis-retinol (11-cis-ROL) constitutes only a small fraction of total retinols in an equilibrium mixture, a subsequent step involving selective removal of 11-cis-ROL is required to drive synthesis of 11-cis-retinoids for production of visual chromophore. Selective esterification of 11-cis-ROL is one possibility. Crude homogenates of chicken retinas rapidly convert all-trans-ROL to 11-cis-retinyl esters (11-cis-REs) with minimal formation of other retinyl-ester isomers. This enzymatic activity implies the existence of an 11-cis-specific retinyl-ester synthase in Müller cells. Here, we evaluated multifunctional O-acyltransferase (MFAT) as a candidate for this 11-cis-RE-synthase. MFAT exhibited much higher catalytic efficiency as a synthase of 11-cis-REs versus other retinyl-ester isomers. Further, we show that MFAT is expressed in Müller cells. Finally, homogenates of cells coexpressing DES1 and MFAT catalyzed the conversion of all-trans-ROL to 11-cis-RP, similar to what we observed with chicken-retina homogenates. MFAT is therefore an excellent candidate for the retinyl-ester synthase that cooperates with DES1 to drive synthesis of 11-cis-retinoids by mass action. PMID:24799687
Restelli, Umberto; Rizzardini, Giuliano; Antinori, Andrea; Lazzarin, Adriano; Bonfanti, Marzia; Bonfanti, Paolo; Croce, Davide
2017-01-01
Background In January 2014, the European Medicines Agency issued a marketing authorization for dolutegravir (DTG), a second-generation integrase strand transfer inhibitor for HIV treatment. The study aimed at determining the incremental cost-effectiveness ratio (ICER) of the use of DTG+backbone compared with raltegravir (RAL)+backbone, darunavir (DRV)+ritonavir(r)+backbone and efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC) in HIV-positive treatment-naïve patients and compared with RAL+backbone in treatment-experienced patients, from the Italian National Health Service’s point of view. Materials and methods A published Monte Carlo Individual Simulation Model (ARAMIS-DTG model) was used to perform the analysis. Patients pass through mutually exclusive health states (defined in terms of diagnosis of HIV with or without opportunistic infections [OIs] and cardiovascular disease [CVD]) and successive lines of therapy. The model considers costs (2014) and quality of life per monthly cycle in a lifetime horizon. Costs and quality-adjusted life years (QALYs) are dependent on OI, CVD, AIDS events, adverse events and antiretroviral therapies. Results In treatment-naïve patients, DTG dominates RAL; compared with DRV/r, the ICER obtained is of 38,586 €/QALY (6,170 €/QALY in patients with high viral load) and over EFV/TDF/FTC, DTG generates an ICER of 33,664 €/QALY. In treatment-experienced patients, DTG compared to RAL leads to an ICER of 12,074 €/QALY. Conclusion The use of DTG+backbone may be cost effective in treatment-naïve and treatment-experienced patients compared with RAL+backbone and in treatment-naïve patients compared with DRV/r+backbone and EFV/TDF/FTC considering a threshold of 40,000 €/QALY. PMID:28721059
Opticien Célèbre. André Maréchal
NASA Astrophysics Data System (ADS)
Haidar, Riad
2017-12-01
Physicien français spécialisé en optique, professeur à la faculté des sciences de l'université de Paris, André Maréchal a également été délégué général à la recherche scientifique et technique, et directeur général de l'Institut d'Optique. On lui doit notamment des résultats remarquables sur la théorie des aberrations et de la diffraction.
Lawrie, S R; Faircloth, D C; Letchford, A P; Perkins, M; Whitehead, M O; Wood, T; Gabor, C; Back, J
2014-02-01
The ISIS pulsed spallation neutron and muon facility at the Rutherford Appleton Laboratory (RAL) in the UK uses a Penning surface plasma negative hydrogen ion source. Upgrade options for the ISIS accelerator system demand a higher current, lower emittance beam with longer pulse lengths from the injector. The Front End Test Stand is being constructed at RAL to meet the upgrade requirements using a modified ISIS ion source. A new 10% duty cycle 25 kV pulsed extraction power supply has been commissioned and the first meter of 3 MeV radio frequency quadrupole has been delivered. Simultaneously, a Vessel for Extraction and Source Plasma Analyses is under construction in a new laboratory at RAL. The detailed measurements of the plasma and extracted beam characteristics will allow a radical overhaul of the transport optics, potentially yielding a simpler source configuration with greater output and lifetime.
Takenaka, Nobuyuki; Nihata, Yuma; Ueda, Sho; Satoh, Takaya
2017-11-01
Rac1 has been implicated in insulin-dependent glucose uptake by mechanisms involving plasma membrane translocation of the glucose transporter GLUT4 in skeletal muscle. Although the uptake of glucose is also stimulated by insulin in adipose tissue, the role for Rac1 in adipocyte insulin signaling remains controversial. As a step to reveal the role for Rac1 in adipocytes, we aimed to establish immunofluorescent microscopy to detect the intracellular distribution of activated Rac1. The epitope-tagged Rac1-binding domain of a Rac1-specific target was utilized as a probe that specifically recognizes the activated form of Rac1. Rac1 activation in response to ex vivo and in vivo insulin stimulations in primary adipocyte culture and mouse white adipose tissue, respectively, was successfully observed by immunofluorescent microscopy. These Rac1 activations were mediated by phosphoinositide 3-kinase. Another small GTPase RalA has also been implicated in insulin-stimulated glucose uptake in skeletal muscle and adipose tissue. Similarly to Rac1, immunofluorescent microscopy using an activated RalA-specific polypeptide probe allowed us to detect intracellular distribution of insulin-activated RalA in adipocytes. These novel approaches to visualize the activation status of small GTPases in adipocytes will largely contribute to the understanding of signal transduction mechanisms particularly for insulin action. Copyright © 2017 Elsevier Inc. All rights reserved.
Canadian Civil-Military Relations, 1939-1941: A Case Study in Strategic Dialogue
2011-07-01
second case study, and the subject of a companion Technical Memorandum, will examine the debates about military power in 1940 in the context of the...their influence in national strategic discussions. The second case study, and the subject of a companion Technical Memorandum, examines the...comprendre ce qui arrive ou devrait arriver. Un examen du rôle joué par le Général H.D.G. Crerar, le chef d’état-major général en 1940-1941, dans les
Chemical analysis of acoustically levitated drops by Raman spectroscopy.
Tuckermann, Rudolf; Puskar, Ljiljana; Zavabeti, Mahta; Sekine, Ryo; McNaughton, Don
2009-07-01
An experimental apparatus combining Raman spectroscopy with acoustic levitation, Raman acoustic levitation spectroscopy (RALS), is investigated in the field of physical and chemical analytics. Whereas acoustic levitation enables the contactless handling of microsized samples, Raman spectroscopy offers the advantage of a noninvasive method without complex sample preparation. After carrying out some systematic tests to probe the sensitivity of the technique to drop size, shape, and position, RALS has been successfully applied in monitoring sample dilution and preconcentration, evaporation, crystallization, an acid-base reaction, and analytes in a surface-enhanced Raman spectroscopy colloidal suspension.
Installation Restoration Program for Eglin AFB, Florida. Phase 2. Field Evaluation
1984-09-01
of t jest l-iianja-erent pra-ct ices w .hien are discussed in Section D.5 5.1.4 Landfill L)-26 In Dotn NoveM( Der and tebruary samplI igs, ioX" results...to analy.ze 6rounawater samp los tronm La’nd ti I v)-ZIt for organional I ides in the base/ neut ral extractaLeI, organics section of the priority...the gasoline tank was not filled near wells or the van and any spillage was allowed to evaporate before moving the pump. During use, the pump was
Offor, Obiageli; Utay, Netanya; Reynoso, David; Somasunderam, Anoma; Currier, Judith; Lake, Jordan
2018-01-01
People with HIV are at for metabolic syndrome (MetS) and fatty liver disease, but the role of Antiretroviral therapy (ART) is poorly understood. MetS and fatty liver disease been associated with changes in adiponectin, soluble ST2 (sST2), chitinase 3-like 1 (Chi3L1), hyaluronic acid (HA), tissue inhibitor of metalloproteinase-1 (TIMP-1), lysyl oxidase-like-2 (LOXL2) and transforming growth factor β (TGF-β) concentrations in HIV-uninfected populations. Protease (PI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) may contribute to these comorbidities, but the effects of switching from PI- or NNRTI to raltegravir (RAL) on these biomarkers is unknown. Cryopreserved plasma was obtained from a completed, prospective trial of HIV-infected women with central adiposity on NNRTI- or PI-based ART during which they were randomized to remain on their current ART or switch to a RAL based regimen. Biomarker concentrations were quantified using ELISA and Multiplex assays at baseline and 24 weeks after randomization. Wilcoxon-signed rank test evaluated within-group changes, Spearman and linear regression models evaluated correlations between biomarkers and clinical covariates. Participants had a median age of 43 years, CD4+ T lymphocyte count 558 cells/mm3 and BMI 32 kg/m2; 35% met criteria for MetS. At baseline, higher adiponectin levels correlated with higher Chi3L1 levels (r = 0.42, p = 0.02), as did declines after 24 weeks (r = 0.40, p = 0.03). Changes in sST2 correlated with changes in Chi3L1 (r = 0.43, p = 0.02) and adiponectin (r = 0.40, p = 0.03). Adiponectin and Chi3L1 levels decreased significantly in women switched to RAL vs continue PI/NNRTI. In women with HIV and central obesity, the hepatic steatosis/fibrosis marker Chi3L1 and adiponectin decrease in conjunction with sST2 decreases following switch to RAL. Whether switching from NNRTI/PI-based regimens to RAL can improve hepatic steatosis and dysmetabolism requires further study. Clinicaltrials.gov NCT00656175.
Chandra, Chetan; Valavalkar, Narayan; Vandana, K. L.
2011-01-01
Background and Objectives: Prevention of the periodontal disease progression is the primary goal of periodontal therapy. When conventional therapy is found inadequate to attain periodontal health in chronic periodontitis, local antimicrobial agents have been used as an adjunct with scaling and root planning (SRP) which has reproduced encouraging results. Hence, this study was undertaken to evaluate the new sustained released local drug Chlosite clinically and microbiologically in smokers and non-smokers. Materials and Methods: The patients were grouped into experimental group A treated with SRP plus Chlosite (SRP + CHL), experimental group B treated with Chlosite alone (CHL), and control group C treated only with SRP alone. A total number of 141 sites from six patients (67 sites from three non-smoker patients and 74 sites from three smoker patients) participated in this study. The clinical parameters, Plaque index (PI), Gingival index (GI), Bleeding index (BI), and Relative attachment level (RAL), were recorded and subgingival plaque samples were collected and subjected to microbiological analysis. Results: On comparison of smokers and non-smokers, in SRP group, non-smokers showed a higher reduction in BI and GI and smokers showed a higher reduction in PI. There was no significant gain in RAL of both smokers and non-smokers. In SRP + CHL group, non-smokers showed a higher reduction in relation to BI and GI and smokers showed a higher reduction in relation to PI. There was no significant gain in RAL of both smokers and non-smokers. In CHL group, both smokers and non-smokers showed a nonsignificant reduction in BI, GI, and RAL, but smokers showed a significant reduction in PI as compared with non-smokers. All the groups showed reduction in the microbial count of Fusobacterium nucleatum, Porphyromonas gingivalis, and Tannerella forsythia which were found to be statistically not significant when it was compared between non-smokers and smokers. Interpretation and Conclusion: In this study, all treatment groups were found to be efficacious in the treatment of periodontal disease as demonstrated by improvement in PI, GI, BI, and RAL. Combination of SRP and Chlosite resulted in added benefits compared with the two treatment groups. PMID:22028508
Cook, Paul P; Stang, Alexandra Te; Walker, Lia R; Akula, Shaw M; Cook, Fiona J
2016-11-01
Treatment of human immunodeficiency virus (HIV)-infected patients with tenofovir disoproxil fumarate is associated with a decrease in bone mineral density (BMD). Treatment with efavirenz is associated with vitamin D deficiency. We compared the effects of efavirenz, emtricitabine, and tenofovir disoproxil fumarate (EFV/FTC/TDF) with the effects of raltegravir, darunavir, and ritonavir (RAL/DRV/r) on BMD and 25-hydroxyvitamin D (25[OH]D) levels in HIV-infected, antiretroviral treatment-naïve African American subjects. This was a pilot study at a single HIV clinic. Forty HIV treatment-naïve African American subjects were screened, 35 of whom were randomized to receive either EFV/FTC/TDF or RAL/DRV/r. All of the subjects received supplemental vitamin D 3 and calcium. CD4 counts, HIV RNA, parathyroid hormone, osteocalcin, N-telopeptide, and 25(OH)D levels were obtained at baseline and at 8, 24, 36, and 48 weeks. Dual-energy x-ray absorptiometry of the spine and hip was performed at baseline and at week 48. Of the 35 subjects enrolled, 10 patients receiving each regimen completed the study. Median baseline 25(OH)D levels were decreased and similar in both groups. All of the patients had plasma HIV RNA <50 copies per milliliter by week 24. By week 48, there was a sustained increase in 25(OH)D in the RAL/DRV/r group ( P = 0.0004) but not in the EFV/FTC/TDF group ( P = 0.78). There were reductions in BMD of the mean total hip ( P = 0.002) and the mean femoral neck ( P = 0.004) in the EFV/FTC/TDF group but not in the RAL/DRV/r group. Treatment of African American patients with HIV using EFV/FTC/TDF is associated with a reduction in BMD of the hip and sustained reductions of 25(OH)D not seen in the group that received RAL/DRV/r. This phenomenon may have long-term consequences on bone integrity in this population.
2015-01-01
The phytotoxic fungal polyketides lasiodiplodin and resorcylide inhibit human blood coagulation factor XIIIa, mineralocorticoid receptors, and prostaglandin biosynthesis. These secondary metabolites belong to the 12-membered resorcylic acid lactone (RAL12) subclass of the benzenediol lactone (BDL) family. Identification of genomic loci for the biosynthesis of lasiodiplodin from Lasiodiplodia theobromae and resorcylide from Acremonium zeae revealed collaborating iterative polyketide synthase (iPKS) pairs whose efficient heterologous expression in Saccharomyces cerevisiae provided a convenient access to the RAL12 scaffolds desmethyl-lasiodiplodin and trans-resorcylide, respectively. Lasiodiplodin production was reconstituted in the heterologous host by co-expressing an O-methyltransferase also encoded in the lasiodiplodin cluster, while a glutathione-S-transferase was found not to be necessary for heterologous production. Clarification of the biogenesis of known resorcylide congeners in the heterologous host helped to disentangle the roles that biosynthetic irregularities and chemical interconversions play in generating chemical diversity. Observation of 14-membered RAL homologues during in vivo heterologous biosynthesis of RAL12 metabolites revealed “stuttering” by fungal iPKSs. The close global and domain-level sequence similarities of the orthologous BDL synthases across different structural subclasses implicate repeated horizontal gene transfers and/or cluster losses in different fungal lineages. The absence of straightforward correlations between enzyme sequences and product structural features (the size of the macrocycle, the conformation of the exocyclic methyl group, or the extent of reduction by the hrPKS) suggest that BDL structural variety is the result of a select few mutations in key active site cavity positions. PMID:24597618
MICE data handling on the Grid
NASA Astrophysics Data System (ADS)
Martyniak, J.; Mice Collaboration
2014-06-01
The international Muon Ionisation Cooling Experiment (MICE) is designed to demonstrate the principle of muon ionisation cooling for the first time, for application to a future Neutrino factory or Muon Collider. The experiment is currently under construction at the ISIS synchrotron at the Rutherford Appleton Laboratory (RAL), UK. In this paper we present a system - the Raw Data Mover, which allows us to store and distribute MICE raw data - and a framework for offline reconstruction and data management. The aim of the Raw Data Mover is to upload raw data files onto a safe tape storage as soon as the data have been written out by the DAQ system and marked as ready to be uploaded. Internal integrity of the files is verified and they are uploaded to the RAL Tier-1 Castor Storage Element (SE) and placed on two tapes for redundancy. We also make another copy at a separate disk-based SE at this stage to make it easier for users to access data quickly. Both copies are check-summed and the replicas are registered with an instance of the LCG File Catalog (LFC). On success a record with basic file properties is added to the MICE Metadata DB. The reconstruction process is triggered by new raw data records filled in by the mover system described above. Off-line reconstruction jobs for new raw files are submitted to RAL Tier-1 and the output is stored on tape. Batch reprocessing is done at multiple MICE enabled Grid sites and output files are shipped to central tape or disk storage at RAL using a custom File Transfer Controller.
Pulsed source of ultra low-energy muons at RIKEN-RAL
NASA Astrophysics Data System (ADS)
Bakule, Pavel; Matsuda, Yasuyuki; Iwasaki, Masahiko; Miyake, Yasuhiro; Nagamine, Kanetada; Ikedo, Yutaka; Shimomura, Koichiro; Strasser, Patrick
2006-03-01
At RIKEN-RAL muon facility of the Rutherford Appleton Laboratory (UK) we have produced a pulsed LE-μ + beam with pulse duration of only 10 ns and performed μSR experiments to demonstrate the capability to measure high spin precession frequency signals. The yield of pulsed LE-μ + has been steadily improving over the past 3 years and currently rates of up to 20 μ + per second are observed at the sample position. The overall cooling efficiency from the surface muon beam is now comparable to moderating the muon beam to epithermal energies in simple van der Waals bound solids.
The President’s Identity Theft Task Force Report
2008-09-01
effeCtIve, RISk-BASed ReSPOnSeS tO dAtA BReACheS SUffeRed By fedeRAl AGenCIeS Issue Data Breach Guidance to Agencies Publish a “Routine Use...and developing a data breach response plan. The FTC will continue to seek opportunities to work with state and local officials and policymakers...of fiscal year 2008. ReCOMMendAtIOn 4: enSURe effeCtIve, RISk-BASed ReSPOnSeS tO dAtA BReACheS SUffeRed By fedeRAl AGenCIeS The Task Force
Walker, David M; Wang, Ruifei; Webb, Lauren J
2014-10-07
Vibrational Stark effect (VSE) spectroscopy was used to measure the electrostatic fields present at the interface of the human guanosine triphosphatase (GTPase) Ras docked with the Ras binding domain (RBD) of the protein kinase Raf. Nine amino acids located on the surface of Raf were selected for labeling with a nitrile vibrational probe. Eight of the probe locations were situated along the interface of Ras and Raf, and one probe was 2 nm away on the opposite side of Raf. Vibrational frequencies of the nine Raf nitrile probes were compared both in the monomeric, solvated protein and when docked with wild-type (WT) Ras to construct a comprehensive VSE map of the Ras-Raf interface. Molecular dynamics (MD) simulations employing an umbrella sampling strategy were used to generate a Boltzmann-weighted ensemble of nitrile positions in both the monomeric and docked complexes to determine the effect that docking has on probe location and orientation and to aid in the interpretation of VSE results. These results were compared to an identical study that was previously conducted on nine nitrile probes on the RBD of Ral guanidine dissociation stimulator (RalGDS) to make comparisons between the docked complexes formed when either of the two effectors bind to WT Ras. This comparison finds that there are three regions of conserved electrostatic fields that are formed upon docking of WT Ras with both downstream effectors. Conservation of this pattern in the docked complex then results in different binding orientations observed in otherwise structurally similar proteins. This work supports an electrostatic cause of the known binding tilt angle between the Ras-Raf and Ras-RalGDS complexes.
Is robotic sacrocolpopexy a marketing gimmick or a technological advancement?
Kim, Ja-Hong; Anger, Jennifer T
2010-07-01
Robot-assisted laparoscopic sacrocolpopexy (RALS) is a new surgical technique for the treatment of symptomatic vaginal vault prolapse that is rapidly gaining popularity among both urologists and gynecologists. This article will summarize the available published data to assess the potential advantages and disadvantages of this new procedure and its current role in female pelvic floor reconstruction. The literature on RALS is limited mainly to single-institution retrospective studies, which suggest minimal morbidity, technical feasibility, and short-term efficacy comparable to open abdominal sacrocolpopexy. What remains uncertain is whether this approach will be superior to the other established minimally invasive transvaginal and laparoscopic approaches in terms of subjective and objective outcomes and quality of life. Other relevant issues, such as overall cost-effectiveness and extended application for multicompartment defects and uterine-sparing procedures, remain largely unexplored. The use of RALS will likely continue to expand secondary to increased access and the popularity of the robotic apparatus among both surgeons and patients. Well designed large randomized multicenter comparative studies based on validated measurement instruments are needed to evaluate its advantage over conventional approaches, including open abdominal sacrocolpopexy and various transvaginal and laparoscopic techniques.
The deployment of a large scale object store at the RAL Tier-1
NASA Astrophysics Data System (ADS)
Dewhurst, A.; Johnson, I.; Adams, J.; Canning, B.; Vasilakakos, G.; Packer, A.
2017-10-01
Since 2014, the RAL Tier-1 has been working on deploying a Ceph backed object store. The aim is to replace Castor for disk-only storage. This new service must be scalable to meet the data demands of the LHC to 2020 and beyond. As well as offering access protocols the LHC experiments currently use, it must also provide industry standard access protocols. In order to keep costs down the service must use erasure coding rather than replication to ensure data reliability. This paper will present details of the storage service setup, which has been named Echo, as well as the experience gained from running it. The RAL Tier-1 has also been developing XrootD and GridFTP plugins for Ceph. Both plugins are built on top of the same libraries that write striped data into Ceph and therefore data written by one protocol will be accessible by the other. In the long term we hope the LHC experiments will migrate to industry standard protocols, therefore these plugins will only provide the features needed by the LHC experiments. This paper will report on the development and testing of these plugins.
Towards a true aerosol-and-cloud retrieval scheme
NASA Astrophysics Data System (ADS)
Thomas, Gareth; Poulsen, Caroline; Povey, Adam; McGarragh, Greg; Jerg, Matthias; Siddans, Richard; Grainger, Don
2014-05-01
The Optimal Retrieval of Aerosol and Cloud (ORAC) - formally the Oxford-RAL Aerosol and Cloud retrieval - offers a framework that can provide consistent and well characterised properties of both aerosols and clouds from a range of imaging satellite instruments. Several practical issues stand in the way of achieving the potential of this combined scheme however; in particular the sometimes conflicting priorities and requirements of aerosol and cloud retrieval problems, and the question of the unambiguous identification of aerosol and cloud pixels. This presentation will present recent developments made to the ORAC scheme for both aerosol and cloud, and detail how these are being integrated into a single retrieval framework. The implementation of a probabilistic method for pixel identification will also be presented, for both cloud detection and aerosol/cloud type selection. The method is based on Bayesian methods applied the optimal estimation retrieval output of ORAC and is particularly aimed at providing additional information in the so-called "twilight zone", where pixels can't be unambiguously identified as either aerosol or cloud and traditional cloud or aerosol products do not provide results.
Prospects for a Muon Spin Resonance Facility in the Fermilab MuCool Test Area
DOE Office of Scientific and Technical Information (OSTI.GOV)
Johnstone, John A.; Johnstone, Carol
This paper investigates the feasibility of re-purposing the MuCool Test Area (MTA) beamline and experimental hall to support a Muon Spin Resonance (MuSR) facility, which would make it the only such facility in the US. This report reviews the basic muon production concepts studied and operationally implemented at TRIUMF, PSI, and RAL and their application in the context of the MTA facility. Two scenarios were determined feasible. One, an initial minimal-shielding and capital-cost investment stage with a single secondary muon beamline that utilizes an existing high- intensity beam absorber and, another, upgraded stage, that implements an optimized production target pile,more » a proximate high-intensity absorber, and optimized secondary muon lines. A unique approach is proposed which chops or strips a macropulse of H$^-$ beam into a micropulse substructure – a muon creation timing scheme – which allows Muon Spin Resonance experiments in a linac environment. With this timing scheme, and attention to target design and secondary beam collection, the MTA can host enabling and competitive Muon Spin Resonance experiments.« less
Might dolutegravir be part of a functional cure for HIV?
Wainberg, Mark A; Han, Ying-Shan; Mesplède, Thibault
2016-05-01
Antiretroviral therapy (ART) has greatly decreased HIV-related morbidity and mortality. However, HIV can establish viral reservoirs that evade both the immune system and ART. Dolutegravir (DTG) is a second-generation integrase strand transfer inhibitor (INSTI) related to the first-generation INSTIs raltegravir (RAL) and elvitegravir (EVG). DTG shows a higher genetic barrier to the development of HIV-1 resistance than RAL and EVG. More interestingly, clinical resistance mutations to DTG in treatment-naïve patients have not been observed to date. This review summarizes recent studies on strategies toward a cure for HIV, explores resistance profiles of DTG, and discusses how DTG might help in finding a functional cure for HIV.
Applying Convergent Immunity to Innovative Vaccines Targeting Staphylococcus aureus
Yeaman, Michael R.; Filler, Scott G.; Schmidt, Clint S.; Ibrahim, Ashraf S.; Edwards, John E.; Hennessey, John P.
2014-01-01
Recent perspectives forecast a new paradigm for future “third generation” vaccines based on commonalities found in diverse pathogens or convergent immune defenses to such pathogens. For Staphylococcus aureus, recurring infections and a limited success of vaccines containing S. aureus antigens imply that native antigens induce immune responses insufficient for optimal efficacy. These perspectives exemplify the need to apply novel vaccine strategies to high-priority pathogens. One such approach can be termed convergent immunity, where antigens from non-target organisms that contain epitope homologs found in the target organism are applied in vaccines. This approach aims to evoke atypical immune defenses via synergistic processes that (1) afford protective efficacy; (2) target an epitope from one organism that contributes to protective immunity against another; (3) cross-protect against multiple pathogens occupying a common anatomic or immunological niche; and/or (4) overcome immune subversion or avoidance strategies of target pathogens. Thus, convergent immunity has a potential to promote protective efficacy not usually elicited by native antigens from a target pathogen. Variations of this concept have been mainstays in the history of viral and bacterial vaccine development. A more far-reaching example is the pre-clinical evidence that specific fungal antigens can induce cross-kingdom protection against bacterial pathogens. This trans-kingdom protection has been demonstrated in pre-clinical studies of the recombinant Candida albicans agglutinin-like sequence 3 protein (rAls3) where it was shown that a vaccine containing rAls3 provides homologous protection against C. albicans, heterologous protection against several other Candida species, and convergent protection against several strains of S. aureus. Convergent immunity reflects an intriguing new approach to designing and developing vaccine antigens and is considered here in the context of vaccines to target S. aureus. PMID:25309545
Al x Ga1‑ x N-based semipolar deep ultraviolet light-emitting diodes
NASA Astrophysics Data System (ADS)
Akaike, Ryota; Ichikawa, Shuhei; Funato, Mitsuru; Kawakami, Yoichi
2018-06-01
Deep ultraviolet (UV) emission from Al x Ga1‑ x N-based light-emitting diodes (LEDs) fabricated on semipolar (1\\bar{1}02) (r-plane) AlN substrates is presented. The growth conditions are optimized. A high NH3 flow rate during metalorganic vapor phase epitaxy yields atomically flat Al y Ga1‑ y N (y > x) on which Al x Ga1‑ x N/Al y Ga1‑ y N multiple quantum wells with abrupt interfaces and good periodicity are fabricated. The fabricated r-Al x Ga1‑ x N-based LED emits at 270 nm, which is in the germicidal wavelength range. Additionally, the emission line width is narrow, and the peak wavelength is stable against the injection current, so the semipolar LED shows promise as a UV emitter.
Xie, Li; Zhu, Dan; Kang, Youhou; Liang, Tao; He, Yu; Gaisano, Herbert Y
2013-01-01
The exocyst complex subunit Sec5 is a downstream effector of RalA-GTPase which promotes RalA-exocyst interactions and exocyst assembly, serving to tether secretory granules to docking sites on the plasma membrane. We recently reported that RalA regulates biphasic insulin secretion in pancreatic islet β cells in part by tethering insulin secretory granules to Ca(2+) channels to assist excitosome assembly. Here, we assessed β cell exocytosis by patch clamp membrane capacitance measurement and total internal reflection fluorescence microscopy to investigate the role of Sec5 in regulating insulin secretion. Sec5 is present in human and rodent islet β cells, localized to insulin granules. Sec5 protein depletion in rat INS-1 cells inhibited depolarization-induced release of primed insulin granules from both readily-releasable pool and mobilization from the reserve pool. This reduction in insulin exocytosis was attributed mainly to reduction in recruitment and exocytosis of newcomer insulin granules that undergo minimal docking time at the plasma membrane, but which encompassed a larger portion of biphasic glucose stimulated insulin secretion. Sec5 protein knockdown had little effect on predocked granules, unless vigorously stimulated by KCl depolarization. Taken together, newcomer insulin granules in β cells are more sensitive than predocked granules to Sec5 regulation.
Saotome, Yasuhiko; Tada, Akio; Hanada, Nobuhiro; Yoshihara, Akihiro; Uematsu, Hiroshi; Miyazaki, Hideo; Senpuku, Hidenobu
2006-12-01
The relationship of the levels of cariogenic bacterial species with periodontal status and decayed root surfaces was investigated in elderly Japanese subjects. Three hundred and sixty-eight individuals (each 75 years old) were examined for periodontal status (pocket depth, attachment loss), root surface caries and salivary levels of mutans streptococci (MS) and lactobacilli (LB). Values >4 mm of attachment loss (rAL4) and for average attachment loss (aAL) of sites measured were significantly higher in subjects with LB than those without. Multiple regression analysis also showed a correlation between aAL and rAL4 values with the presence of LB (aAL p = 0.003; rAL4 p = 0.002). Further, multiple regression analysis of interacting factors regarding decayed root surfaces showed that LB carriers had a greater incidence of decayed root surface caries (p = 0.003), while MS and LB levels were correlated to the number of decayed root surfaces (LB p = 0.010; MS p = 0.026). Our results indicate that considerable attachment loss elevates the possibility of having LB, thus increasing the risk of root surface caries. It was also found that LB and MS measurements may be useful indicators of decayed root surfaces in elderly individuals with attachment loss.
Blasco, Antonio Javier; Llibre, Josep M; Arribas, José Ramón; Boix, Vicente; Clotet, Bonaventura; Domingo, Pere; González-García, Juan; Knobel, Hernando; López, Juan Carlos; Lozano, Fernando; Miró, José M; Podzamczer, Daniel; Santamaría, Juan Miguel; Tuset, Montserrat; Zamora, Laura; Lázaro, Pablo; Gatell, Josep M
2013-11-01
The GESIDA and National AIDS Plan panel of experts have proposed "preferred regimens" of antiretroviral treatment (ART) as initial therapy in HIV infected patients for 2013. The objective of this study is to evaluate the costs and effectiveness of initiating treatment with these "preferred regimens". An economic assessment of costs and effectiveness (cost/effectiveness) was performed using decision tree analysis models. Effectiveness was defined as the probability of having viral load <50copies/mL at week48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regime was defined as the costs of ART and its consequences (adverse effects, changes of ART regime and drug resistance analyses) during the first 48weeks. The perspective of the analysis is that of the National Health System was applied, only taking into account differential direct costs: ART (official prices), management of adverse effects, resistance studies, and determination of HLA B*5701. The setting is Spain and the costs are those of 2013. A sensitivity deterministic analysis was performed, constructing three scenarios for each regimen: baseline, most favourable, and most unfavourable cases. In the baseline case scenario, the cost of initiating treatment ranges from 6,747euros for TDF/FTC+NVP to 12,059euros for TDF/FTC+RAL. The effectiveness ranges between 0.66 for ABC/3TC+LPV/r and ABC/3TC+ATV/r, and 0.87 for TDF/FTC+RAL and ABC/3TC+RAL. Effectiveness, in terms of cost/effectiveness, varies between 8,396euros and 13,930euros per responder at 48weeks, for TDF/FTC/RPV and TDF/FTC+RAL, respectively. Taking ART at official prices, the most effective regimen was TDF/FTC/RPV, followed by the rest of non-nucleoside containing regimens. The sensitivity analysis confirms the robustness of these findings. Copyright © 2013 Elsevier España, S.L. All rights reserved.
Shiotsu, Yoko; Yanagita, Masahiko
2018-06-01
This study aimed to examine the effects of exercise order of combined aerobic and low- or moderate-intensity resistance training into the same session on body composition, functional performance, and muscle strength in healthy older women. Furthermore, this study compared the effects of different (low- vs moderate-) intensity combined training. A total of 60 healthy older women (age 61-81 y) were randomly assigned to five groups that performed aerobic exercise before low-intensity resistance training (AR-L, n = 12) or after resistance training (RA-L, n = 12), performed aerobic exercise before moderate-intensity resistance training (AR-M, n = 12) or after resistance training (RA-M, n = 12), or nonintervention control conditions (CON, n = 12). Body composition, functional performance, and muscle strength were evaluated before and after the 10-week training. No effects of exercise order of combined aerobic and low- or moderate-intensity resistance training (AR-L vs RA-L, AR-M vs RA-M) were observed in body composition, functional performance, or muscle strength, whereas the effects of training intensity of combined training (AR-L vs AR-M, RA-L vs RA-M) were observed on functional performance. All combined trainings significantly increased muscle strength and gait ability (P < 0.01, respectively). Functional reach test significantly increased in the AR-M and RA-M groups (P < 0.01, respectively), and there were significant group differences between AR-L and AR-M (P = 0.002), RA-L and RA-M (P = 0.014). Preliminary findings suggest that combined aerobic and low- or moderate-intensity resistance training increases muscle strength and improves gait ability, regardless of the exercise order. Also, greater improvement in dynamic balance capacity, a risk factor associated with falling, is observed in moderate-intensity combined training.
Somjen, D; Katzburg, S; Sharon, O; Grafi-Cohen, M; Knoll, E; Stern, N
2011-02-01
In cultured human osteoblasts estradiol-17β (E2) modulated DNA synthesis, the specific activity of creatine kinase BB (CK), 12 and 15 lipoxygenase (LO) mRNA expression and formation of 12- and 15-hydroxyeicosatetraenoic acid (HETE). We now investigate the response of human bone cell line (SaOS2) to phytoestrogens and estrogen receptors (ER)-specific agonists and antagonists. Treatment of SaSO2 with E2, 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN; ERβ-specific agonist), 4,4',4″-[4-propyl-(1H)-pyrazol-1,3,5-triyl] tris-phenol (PPT; ERα-specific agonist), biochainin A (BA), daidzein (D), genistein (G) and raloxifene (Ral) showed increased DNA synthesis and CK. Ral inhibited completely all stimulations except DPN and to some extent D. The ERα-specific antagonist methyl-piperidino-pyrazole (MPP) and the ERβ-specific antagonist 4-[2-phenyl-5,7-bis (tri-fluoro-methyl) pyrazolo [1,5-a]pyrimidin-3-yl] phenol (PTHPP) inhibited DNA synthesis, CK and reactive oxygen species (ROS) formation induced by estrogens according to their receptors affinity. The LO inhibitor baicaleine inhibited only E2, DPN and G's effects. E2 and Ral unlike all other compounds had no effect on ERα mRNA expression, while ERβ mRNA expression was stimulated by all compounds. All compounds modulated the expression of 12LO and 15LO mRNA, except E2, PPT and Ral for 12LO, and 12- and 15-HETE productions and stimulated ROS formation which was inhibited by NADPH oxidase inhibitors diphenyleneiodonium chloride (DPI) and N-acetyl cysteine and the estrogen inhibitor ICI. DPI did not affect hormonal-induced DNA and CK. In conclusion, we provide evidence for the separation of mediation via ERα and ERβ pathways in the effects of estrogenic compounds on osteoblasts, but the role of LO/HETE/ROS is unclear. Copyright © 2010 Wiley-Liss, Inc.
Pavan, Nicola; Autorino, Riccardo; Lee, Hak; Porpiglia, Francesco; Sun, Yinghao; Greco, Francesco; Jeff Chueh, S; Han, Deok Hyun; Cindolo, Luca; Ferro, Matteo; Chen, Xiang; Branco, Anibal; Fornara, Paolo; Liao, Chun-Hou; Miyajima, Akira; Kyriazis, Iason; Puglisi, Marco; Fiori, Cristian; Yang, Bo; Fei, Guo; Altieri, Vincenzo; Jeong, Byong Chang; Berardinelli, Francesco; Schips, Luigi; De Cobelli, Ottavio; Chen, Zhi; Haber, Georges-Pascal; He, Yao; Oya, Mototsugu; Liatsikos, Evangelos; Brandao, Luis; Challacombe, Benjamin; Kaouk, Jihad; Darweesh, Ithaar
2016-10-01
To evaluate contemporary international trends in the implementation of minimally invasive adrenalectomy and to assess contemporary outcomes of different minimally invasive techniques performed at urologic centers worldwide. A retrospective multinational multicenter study of patients who underwent minimally invasive adrenalectomy from 2008 to 2013 at 14 urology institutions worldwide was included in the analysis. Cases were categorized based on the minimally invasive adrenalectomy technique: conventional laparoscopy (CL), robot-assisted laparoscopy (RAL), laparoendoscopic single-site surgery (LESS), and mini-laparoscopy (ML). The rates of the four treatment modalities were determined according to the year of surgery, and a regression analysis was performed for trends in all surgical modalities. Overall, a total of 737 adrenalectomies were performed across participating institutions and included in this analysis: 337 CL (46 % of cases), 57 ML (8 %), 263 LESS (36 %), and 80 RA (11 %). Overall, 204 (28 %) operations were performed with a retroperitoneal approach. The overall number of adrenalectomies increased from 2008 to 2013 (p = 0.05). A transperitoneal approach was preferred in all but the ML group (p < 0.001). European centers mostly adopted CL and ML techniques, whereas those from Asia and South America reported the highest rate in LESS procedures, and RAL was adopted to larger extent in the USA. LESS had the fastest increase in utilization at 6 %/year. The rate of RAL procedures increased at slower rates (2.2 %/year), similar to ML (1.7 %/year). Limitations of this study are the retrospective design and the lack of a cost analysis. Several minimally invasive surgical techniques for the management of adrenal masses are successfully implemented in urology institutions worldwide. CL and LESS seem to represent the most commonly adopted techniques, whereas ML and RAL are growing at a slower rate. All the MIS techniques can be safely and effectively performed for a variety of adrenal disease.
Selected CNS Outcomes Among INSTI Antiretrovirals
Wohl, David; Mills, Anthony; Mera, Robertino; Piontkowsky, David
2017-01-01
Abstract Background Higher rates of neuropsychiatric events among patients on dolutegravir (DTG) compared with other integrase inhibitors (INSTIs) have been reported from clinic cohorts and one blinded trial. We compared select neurological and psychiatric events in a large sample of patients treated with different INSTIs. Methods The Quintiles IMS database, which includes pharmacy and medical claims records, was examined for HIV infected patients treated from 2006 to 2016 with DTG (TIVICAY/TRIUMEQ), elvitegravir (EVG, STRIBILD), or raltegravir (RAL, ISENTRESS). The dependent variable outcomes were insomnia/sleep disturbance and depression. A propensity score was created to adjust for variables associated with treatment with a particular INSTI including age, gender, year of initial INSTI exposure, and enrollment time. Multivariate Poisson mixed models were used to generate incidence rate ratios (IRRs). Results Records for 54,151 distinct HIV-infected patients treated with DTG, EVG, or RAL were identified. In the multivariate model the rate of insomnia/sleep disturbance events was significantly higher for patients treated with DTG vs. EVG (IRR 1.21 [95% CI 1.09–1.33, P < 0.001]), but was not significantly different when comparing DTG to RAL (IRR 1.04 [95% CI 0.94–1.14, P = 0.459]). Likewise, the rate of incident depression was significantly higher for patients treated with DTG vs. EVG (IRR 1.18 [95% CI 1.09–1.27, P < 0.001], but not when comparing DTG to RAL (IRR 0.93 [95% CI 0.87 – 1.01, P = 0.068]). Conclusion In this analysis using a large healthcare database, significantly higher adjusted rates of both incident insomnia/sleep disturbances (21% more) and depression (18% more) were found among patients treated with DTG compared with EVG. In contrast, a significant difference in the rates of either outcome was not observed when comparing DTG and RAL. Further studies are warranted to determine the risk of neuropsychiatric events in patients treated with different INSTIs. Disclosures D. Wohl, Gilead Sciences: Consultant and Investigator, Consulting fee and Research grant; Viiv: Consultant and Investigator, Consulting fee and Research grant; Janssen: Consultant, Consulting fee; Bristol-Myers Squibb: Consultant, Consulting fee; A. Mills, Gilead Sciences: Consultant, Investigator and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium; Viiv: Consultant and Investigator, Consulting fee and Research grant; Merck: Consultant, Investigator and Speaker’s Bureau, Consulting fee, Research grant and Speaker honorarium; Janssen: Investigator, Research grant; Bristol-Myers Squibb: Investigator, Research grant; Sangamo Bio Sciences: Investigator, Research grant; R. Mera, Gilead Sciences: Employee and Shareholder, Salary; D. Piontkowsky, Gilead Sciences: Employee and Shareholder, Salary
[Difficulties medical care of persons placed under hand of justice].
Brahmy, Betty
2013-01-01
The "contrôleur général des lieux de privation de liberté", french, national mechanism of prevention is an independant authorithy in charge of making sure since 2008 that rights of deprivation of freedom people--particularly access to health--are respected, in any place they are in captivity. The reports of the controllers present that the care of these persons is still a subject of concern as well for them--as the number of letters received by the Contrôleur général shows--as for professionals working in these places. The exercising of these health professionals in these institutions is a care mission to be done in a real partnership with the other actors.
Ensign, Daniel L; Webb, Lauren J
2011-12-01
Using molecular dynamics simulations, we explore geometric and physical factors contributing to calculated electrostatic fields at the binding surface of the GTPase Ras with a spectroscopically labeled variant of a downstream effector, the Ras-binding domain of Ral guanine nucleotide dissociation stimulator (RalGDS). A related system (differing by mutation of one amino acid) has been studied in our group using vibrational Stark effect spectroscopy, a technique sensitive to electrostatic fields. Electrostatic fields were computed using the AMBER 2003 force field and averaged over snapshots from molecular dynamics simulation. We investigate geometric factors by exploring how the orientation of the spectroscopic probe changes on Ras-effector binding. In addition, we explore the physical origin of electrostatic fields at our spectroscopic probe by comparing contributions to the field from discrete components of the system, such as explicit solvent, residues on the Ras surface, and residues on the RalGDS surface. These models support our experimental hypothesis that vibrational Stark shifts are caused by Ras binding to its effector and not the structural rearrangements of the effector surface or probe reorientation on Ras-effector binding, for at least some of our experimental probes. These calculations provide physical insight into the origin, magnitude, and importance of electrostatic fields in protein-protein interactions and suggest new experiments to probe the field's role in protein docking. Copyright © 2011 Wiley-Liss, Inc.
Baek, Minki; Au, Jason; Huang, Gene O; Koh, Chester J
2017-04-01
We describe our experience with robot-assisted laparoscopic (RAL) pyeloureterostomy in infants with duplex systems and upper pole hydronephrosis with an emphasis on the various double J (DJ) ureteral stent placement techniques. We used our RAL pyeloureterostomy technique in two female infants with duplex systems and upper pole hydronephrosis. For case 1, we introduced the DJ stent and placed it in the recipient lower pole ureter during the robotic operation in an antegrade fashion. For case 2, we inserted the DJ stent during retrograde pyelography prior to the robotic procedure in a retrograde fashion, and the proximal portion of the stent was placed across the anastomosis into the upper pole renal pelvis. Postoperatively, each of the patients were discharged on postoperative day 1 without complications. The postoperative renal ultrasound at 3 months demonstrated marked improvement of the right upper pole hydronephrosis in both patients. RAL pyeloureterostomy represents a minimally invasive option for upper tract reconstruction of duplex systems with upper pole hydronephrosis in infants. The DJ stent can be placed at the beginning or during the procedure. The stent can be placed in the lower pole ureter or across the anastomosis into the upper pole renal pelvis. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.
First results from the TOPSAT camera
NASA Astrophysics Data System (ADS)
Greenway, Paul; Tosh, Ian; Morris, Nigel; Burton, Gary; Cawley, Steve
2017-11-01
The TopSat camera is a low cost remote sensing imager capable of producing 2.5 metre resolution panchromatic imagery, funded by the British National Space Centre's Mosaic programme. The instrument was designed and assembled at the Space Science & Technology Department of the CCLRC's Rutherford Appleton Laboratory (RAL) in the UK, and was launched on the 27th October 2005 from Plesetsk Cosmodrome in Northern Russia on a Kosmos-3M. The camera utilises an off-axis three mirror system, which has the advantages of excellent image quality over a wide field of view, combined with a compactness that makes its overall dimensions smaller than its focal length. Keeping the costs to a minimum has been a major design driver in the development of this camera. The camera is part of the TopSat mission, which is a collaboration between four UK organisations; QinetiQ, Surrey Satellite Technology Ltd (SSTL), RAL and Infoterra. Its objective is to demonstrate provision of rapid response high resolution imagery to fixed and mobile ground stations using a low cost minisatellite. The paper "Development of the TopSat Camera" presented by RAL at the 5th ICSO in 2004 described the opto-mechanical design, assembly, alignment and environmental test methods implemented. Now that the spacecraft is in orbit and successfully acquiring images, this paper presents the first results from the camera and makes an initial assessment of the camera's in-orbit performance.
Prospects for a Muon Spin Resonance Facility in the MuCool Test Area
DOE Office of Scientific and Technical Information (OSTI.GOV)
Johnstone, John A.
2017-04-12
This paper investigates the feasibility of re-purposing the MuCool Test Area beamline and experimental hall to support a Muon Spin Resonance facility, which would make it the only such facility in the US. This report reviews the basic muon production concepts studied and operationally implemented at TRIUMF, PSI, and RAL and their application to the MTA facility. Two scenarios were determined feasible. One represents an initial minimal-shielding and capital-cost investment stage with a single secondary muon beamline that transports the primary beam to an existing high-intensity beam absorber located outside of the hall. Another, upgraded stage, involves an optimized productionmore » target pile and high-intensity absorber installed inside the experimental hall and potentially multiple secondary muon lines. In either scenario, with attention to target design, the MTA can host enabling and competitive Muon Spin Resonance experiments« less
Droplet heteroepitaxy of zinc-blende vs. wurtzite GaN quantum dots
NASA Astrophysics Data System (ADS)
Reese, C.; Jeon, S.; Hill, T.; Jones, C.; Shusterman, S.; Yacoby, Y.; Clarke, R.; Deng, H.; Goldman, Rs
We have developed a GaN droplet heteroepitaxy process based upon plasma-assisted molecular-beam epitaxy. Using various surface treatments and Ga deposition parameters, we have demonstrated polycrystalline, zinc-blende (ZB), and wurtzite (WZ) GaN quantum dots (QDs) on Si(001), r-Al2O3, Si(111), and c-GaN substrates. For the polar substrates (i.e. Si(111) and c-GaN), high-resolution transmission electron microscopy and coherent Bragg rod analysis reveals the formation of coherent WZ GaN QDs with nitridation-temperature-dependent sizes and densities. For the non-polar substrates (i.e. Si(001) and r-Al2O3) , QDs with strong near-band photoluminescence emission are observed and ZB GaN QD growth on Si(001) is demonstrated for the first time.
Yunus, Sara; Pieper, Stephanie; Kolve, Hedwig; Goletz, Grazyna; Jürgens, Heribert; Groll, Andreas H
2014-03-01
Children and adolescents with acute myeloid leukaemia (AML) and recurrent acute leukaemias (RALs) are at high risk of life-threatening invasive fungal infections (IFIs). We analysed implementation, safety and efficacy of a standard operating procedure for oral, azole-based, mould-active antifungal prophylaxis. Patients with AML and RALs aged ≥13 years received 200 mg of posaconazole three times daily and patients aged 2-12 years received 200 mg of voriconazole two times daily from the completion of chemotherapy until haematopoietic recovery. Algorithms for fever or focal findings in all patients with haematological malignancies included blood cultures, high-resolution CT and other appropriate imaging, serial serum galactomannan, invasive diagnostics and pre-emptive therapy with change in class if on antifungal medication. From 2006 to 2010, 40 patients (0.8-17 years; 21 males) with newly diagnosed AML (n = 31) or RAL (n = 9) were admitted, of whom 36 received a total of 149 courses of chemotherapy (reasons for exclusion: contraindications and early death ≤3 days). Azole prophylaxis was given in 87.2% (n = 130/149) of episodes. Pre-emptive antifungal therapy for pulmonary infiltrates was initiated in 5/36 (13.9%) patients or 6/130 (4.6%) episodes for a duration of 3-22 days. No proven or probable IFIs occurred. Adverse events (AEs) were common but mostly low grade and reversible. Three courses (2.3%) were discontinued due to AEs. In simultaneously admitted new patients with acute lymphatic leukaemia (ALL; n = 101) and paediatric lymphomas (n = 29) not receiving standard antifungal prophylaxis, proven/probable IFIs occurred in 4 patients with ALL (4.0%) and 7/130 patients (5.4%) received pre-emptive therapy. Azole-based, mould-active antifungal prophylaxis in high-risk paediatric patients with AML and RALs was satisfactorily implemented, well tolerated and effective. The low rate of IFIs in patients with ALL/lymphoma supports the lack of a general indication for prophylaxis in this population in the presence of a diagnostic and therapeutic algorithm.
Puthanakit, Thanyawee; Thepnarong, Nattawan; Chaithongwongwatthana, Surasith; Anugulruengkitt, Suvaporn; Anunsittichai, Orawan; Theerawit, Tuangtip; Ubolyam, Sasiwimol; Pancharoen, Chitsanu; Phanuphak, Praphan
2018-04-01
Objectives: The rate of vertical HIV transmission for women at high risk of HIV transmission stands at approximately 7.6%. In the present study we describe infant infection rates in women who had received raltegravir (RAL) intensification during pregnancy to a standard three-drug antiretroviral (ART) regimen in Thailand. Methods: This prospective cohort study enrolled HIV-1-positive pregnant women at high risk of vertical transmission, as defined by (1) ART initiation at a gestational age (GA) ≥32 weeks or (2) HIV-1 RNA >1000 copies/mL at GA of 32-38 weeks while on ART. Women received a standard three-drug ART regimen with RAL intensification (400 mg twice daily) until delivery and continued on a three-drug ART regimen after delivery. Plasma HIV-1 RNA testing was performed before intensification and at delivery. Infant HIV-1 status was determined using DNA PCR at birth, and at 1, 2 and 4 months of life. Results: Between February 2016 and November 2017, 154 pregnant women on ART were enrolled into the study with a median CD4 cell count and plasma HIV-1 RNA level of 382 cells/mm 3 and 4.0 log 10 copies/mL, respectively. The three-drug combination consisted of either a lopinavir/ritonavir- (53%) or efavirenz-based (43%) regimen. Median GA at time of RAL initiation was 34 weeks (interquartile range [IQR] 33-36) and median duration was 21 days (IQR 8-34). The proportion of women who had a plasma HIV-1 RNA <50 and <1000 copies/mL at delivery was 45% and 76%, respectively. There were six infants with HIV infection, three in utero and three peripartum. Overall vertical transmission rate was 3.9% (95% confidence interval [CI] 1.4-8.2). Conclusion: The majority of high-risk pregnant women living with HIV-1 who had received RAL intensification achieved viral suppression at delivery with a relatively low rate of vertical transmission. This intensification strategy represents an option for prevention in HIV-positive women at high risk of vertical transmission.
... side or close that eye. This is called Bell's palsy, or facial nerve paralysis (say: puh-RAL-uh- ... purposes only. For specific medical advice, diagnoses, and treatment, consult your doctor. © 1995- The Nemours Foundation. All ...
Halperin-Sternfeld, Michal; Zigdon-Giladi, Hadar; Machtei, Eli E
2016-03-01
The aim of this study was to retrospectively evaluate the association between shallow vestibular depth (VD) and peri-implant parameters. Peri-implant parameters were evaluated in 61 periodontal patients under regular supportive periodontal therapy. Clinical parameters included gingival index (GI), plaque index (PI), bleeding on probing (BOP), peri-implant pocket depths (PPD), mucosal recession (MR), relative attachment level (RAL), width and thickness of keratinized mucosa (KMW, KMT) and VD. Radiographic bone level (RBL) was measured on peri-apical radiographs. Sites with shallow VD (≤ 4 mm) were associated with higher MR (0.91 mm versus 0.47 mm, p ≤ 0.009), higher RAL (4.23 mm versus 3.59 mm, p ≤ 0.0001) and higher RBL (2.18 mm versus 1.7 mm, p = 0.05) when compared with adequate vestibular depth sites (VD > 4 mm). Moreover, sites with shallow VD presented lower KMW compared with sites with adequate VD (1.24 mm versus 2.38 mm, respectively, p ≤ 0.0001). Slightly greater BOP, and GI were recorded for the shallow VD compared with adequate sites. According to multivariate analysis, factors that could predict RAL included: VD, GI, age, supporting periodontal therapy, implant type and design. Based on this study, inadequate vestibular depth around dental implants may be associated with increased peri-implant bone loss and mucosal recession. Further prospective and intervention studies will be required to fully understand this phenomenon. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
MAGNETIC PROPERTIES OF RARE EARTH ALUMINUM COMPOUNDS WITH MgCu$sub 2$ STRUCTURE
DOE Office of Scientific and Technical Information (OSTI.GOV)
Williams, H.J.; Wernick, J.H.; Nesbitt, E.A.
1962-03-01
The magnetic moments of some RAl/sub 2/ (R = rare earth element) cubic Laves phase compounds were measured at temperatures from 1.4 to 300 deg K. The measurements indicate that the spin moments of the rare earth ions are coupled ferromagnetically. The Curie points of the RAl/sub 2/ compounds are found to be uniformly higher than the corresponding Laves compounds, ROs/sub 2/, Rlr/sub 2/ and RRu/sub 2/. Solid solutions of some of the compounds were also investigated. For example, in the Gd/sub x/Pr/sub (1-x)/Al/sub 2/ compounds, the magnetic moments of the Gd ions are antiparallel to those of the Prmore » ions because J is antiparallel to S in the ground state of the Pr ion. Compensation points were observed in this system. (auth)« less
Selected retinoids: determination by isocratic normal-phase HPLC.
Klvanova, J; Brtko, J
2002-09-01
Retinol (ROL), retinal (RAL) and retinoic acid (RA) are physiologically active forms of vitamin A. All-trans retinoic acid (ATRA) can be formed by oxidation from all-trans retinal (ATRAL). Isomerization of RA is considered to be an important metabolic pathway of retinoids. RA isomers transactivate various response pathways via their cognate nuclear receptors that act as ligand inducible transcription factors. The aim of this study was to establish a rapid and simple method for determination of ATRA, 13-cis retinoic acid (13CRA) and ATRAL by HPLC. In our laboratory, we slightly modified the method of Miyagi et al. (2001) and separated ATRA, 13CRA and ATRAL by simple isocratic normal phase HPLC. Both retinoic acid isomers and ATRAL were eluted within 13 min and all components were well resolved. The coefficients of variation (C.V.) for RAs and RAL were from 3.0 to 5.4 %.
Asp, Michelle L.; Martindale, Joshua J.; Metzger, Joseph M.
2013-01-01
Tamoxifen (Tam), a selective estrogen receptor modulator, is in wide clinical use for the treatment and prevention of breast cancer. High Tam doses have been used for treatment of gliomas and cancers with multiple drug resistance, but long QT Syndrome is a side effect. Tam is also used experimentally in mice for inducible gene knockout in numerous tissues, including heart; however, the potential direct effects of Tam on cardiac myocyte mechanical function are not known. The goal of this study was to determine the direct, acute effects of Tam, its active metabolite 4-hydroxytamoxifen (4OHT), and related drug raloxifene (Ral) on isolated rat cardiac myocyte mechanical function and calcium handling. Tam decreased contraction amplitude, slowed relaxation, and decreased Ca2+ transient amplitude. Effects were primarily observed at 5 and 10 μM Tam, which is relevant for high dose Tam treatment in cancer patients as well as Tam-mediated gene excision in mice. Myocytes treated with 4OHT responded similarly to Tam-treated cells with regard to both contractility and calcium handling, suggesting an estrogen-receptor independent mechanism is responsible for the effects. In contrast, Ral increased contraction and Ca2+ transient amplitudes. At 10 μM, all drugs had a time-dependent effect to abolish cellular contraction. In conclusion, Tam, 4OHT, and Ral adversely and differentially alter cardiac myocyte contractility and Ca2+ handling. These findings have important implications for understanding the Tam-induced cardiomyopathy in gene excision studies and may be important for understanding effects on cardiac performance in patients undergoing high-dose Tam therapy. PMID:24205315
Multilabel learning via random label selection for protein subcellular multilocations prediction.
Wang, Xiao; Li, Guo-Zheng
2013-01-01
Prediction of protein subcellular localization is an important but challenging problem, particularly when proteins may simultaneously exist at, or move between, two or more different subcellular location sites. Most of the existing protein subcellular localization methods are only used to deal with the single-location proteins. In the past few years, only a few methods have been proposed to tackle proteins with multiple locations. However, they only adopt a simple strategy, that is, transforming the multilocation proteins to multiple proteins with single location, which does not take correlations among different subcellular locations into account. In this paper, a novel method named random label selection (RALS) (multilabel learning via RALS), which extends the simple binary relevance (BR) method, is proposed to learn from multilocation proteins in an effective and efficient way. RALS does not explicitly find the correlations among labels, but rather implicitly attempts to learn the label correlations from data by augmenting original feature space with randomly selected labels as its additional input features. Through the fivefold cross-validation test on a benchmark data set, we demonstrate our proposed method with consideration of label correlations obviously outperforms the baseline BR method without consideration of label correlations, indicating correlations among different subcellular locations really exist and contribute to improvement of prediction performance. Experimental results on two benchmark data sets also show that our proposed methods achieve significantly higher performance than some other state-of-the-art methods in predicting subcellular multilocations of proteins. The prediction web server is available at >http://levis.tongji.edu.cn:8080/bioinfo/MLPred-Euk/ for the public usage.
García-Mayoral, María Flor; Treviño, Miguel Angel; Pérez-Piñar, Teresa; Caballero, María Luisa; Knaute, Tobias; Umpierrez, Ana
2014-01-01
Background Anisakiasis is a re-emerging global disease caused by consumption of raw or lightly cooked fish contaminated with L3 Anisakis larvae. This zoonotic disease is characterized by severe gastrointestinal and/or allergic symptoms which may misdiagnosed as appendicitis, gastric ulcer or other food allergies. The Anisakis allergen Ani s 5 is a protein belonging to the SXP/RAL-2 family; it is detected exclusively in nematodes. Previous studies showed that SXP/RAL-2 proteins are active antigens; however, their structure and function remain unknown. The aim of this study was to elucidate the three-dimensional structure of Ani s 5 and its main IgE and IgG4 binding regions. Methodology/Principal Findings The tertiary structure of recombinant Ani s 5 in solution was solved by nuclear magnetic resonance. Mg2+, but not Ca2+, binding was determined by band shift using SDS-PAGE. IgE and IgG4 epitopes were elucidated by microarray immunoassay and SPOTs membranes using sera from nine Anisakis allergic patients. The tertiary structure of Ani s 5 is composed of six alpha helices (H), with a Calmodulin like fold. H3 is a long, central helix that organizes the structure, with H1 and H2 packing at its N-terminus and H4 and H5 packing at its C-terminus. The orientation of H6 is undefined. Regarding epitopes recognized by IgE and IgG4 immunoglobulins, the same eleven peptides derived from Ani s 5 were bound by both IgE and IgG4. Peptides 14 (L40-K59), 26 (A76-A95) and 35 (I103-D122) were recognized by three out of nine sera. Conclusions/Significance This is the first reported 3D structure of an Anisakis allergen. Magnesium ion binding and structural resemblance to Calmodulin, suggest some putative functions for SXP/RAL-2 proteins. Furthermore, the IgE/IgG4 binding regions of Ani s 5 were identified as segments localized on its surface. These data will contribute towards a better understanding of the interactions that occur between immunoglobulins and allergens and, in turn, facilitate the design of novel diagnostic tests and immunotherapeutic strategies. PMID:24603892
Martin, Allison; Moore, Cecilia L; Mallon, Patrick W G; Hoy, Jennifer F; Emery, Sean; Belloso, Waldo H; Phanuphak, Praphan; Ferret, Samuel; Cooper, David A; Boyd, Mark A
2013-01-01
To compare changes over 48 weeks in body fat, lipids, Metabolic Syndrome and cardiovascular disease risk between patients randomised 1:1 to lopinavir/ritonavir (r/LPV) plus raltegravir (RAL) compared to r/LPV plus 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) as second-line therapy. Participants were HIV-1 positive (>16 years) failing first-line treatment (2 consecutive HIV RNA >500 copies/mL) of NNRTI +2N(t)RTI. Whole body dual energy x-ray absorptiometry was performed at baseline and week 48. Data were obtained to calculate the Metabolic Syndrome and Framingham cardiovascular disease (CVD) risk score. Linear regression was used to compare mean differences between arms. Logistic regression compared incidence of metabolic syndrome. Associations between percent limb fat changes at 48 weeks with baseline variables were assessed by backward stepwise multivariate linear regression. Analyses were adjusted for gender, body mass index and smoking status. 210 participants were randomised. The mean (95% CI) increase in limb fat over 48 weeks was 15.7% (5.3, 25.9) or 0.9 kg (0.2, 1.5) in the r/LPV+N(t)RTI arm and 21.1% (11.1, 31,1) or 1.3 kg (0.7, 1.9) in the r/LPV+RAL arm, with no significant difference between treatment arms (-5.4% [-0.4 kg], p>0.1). Increases in total body fat mass (kg) and trunk fat mass (kg) were also similar between groups. Total:HDL cholesterol ratio was significantly higher in the RAL arm (mean difference -0.4 (1.4); p = 0.03), there were no other differences in lipid parameters between treatment arms. There were no statistically significant differences in CVD risk or incidence of Metabolic Syndrome between the two treatment arms. The baseline predictors of increased limb fat were high viral load, high insulin and participant's not taking lipid lowering treatment. In patients switching to second line therapy, r/LPV combined with RAL demonstrated similar improvements in limb fat as an N(t)RTI + r/LPV regimen, but a worse total:HDL cholesterol ratio over 48 weeks. This clinical trial is registered on Clinicaltrials.gov, registry number NCT00931463 http://clinicaltrials.gov/ ct2/show/NCT00931463?term = NCT00931463&rank = 1.
Marchetti, Pablo; Razmaria, Aria; Zagaja, Greg P; Gundeti, Mohan S
2011-02-01
Infection or malfunction of ventriculo-peritoneal (VP) shunts is a severe complication during laparoscopic surgery involving the gastrointestinal or urinary tract. It has been recently suggested to externalize the shunt or convert into a ventriculo-atrial shunt to prevent this complication with laparoscopic approach. Herein, we present a novel technique for management of the VP shunt during robot-assisted laparoscopic (RAL) urologic procedures. After port placement and diagnostic peritoneoscopy, an Endopouch bag (Ethicon Endo-Surgery) was inserted into the peritoneal cavity and the distal end of the shunt was placed into the pouch. The Endopouch suture was synched around the shunt and the pouch was placed in the subhepatic space during the surgery. The intraperitoneal pressure was maintained at 12 mm Hg during the entire procedure. Metronidazole, gentamicin, and vancomycin were administered as prophylaxis. Following the completion of the surgery and profuse irrigation of the peritoneal cavity, the shunt was repositioned within the peritoneum. We evaluated perioperative shunt-related complications. We used this technique in four patients with VP shunt undergoing RAL cystoplasty and appendicovesicostomy and/or colonic enema channel formation. The average age of the patient at surgery was 10.8 (7-14) years. One patient was converted to open because of failure to progress due to multiple adhesions and the shunt was externalized temporarily. At a mean follow-up of 13 (3-20) months, no shunt-related complications were seen. In our preliminary experience, the use of an intracorporeal Endopouch bag with controlled pneumoperitoneal pressure to protect the VP shunt may be an effective alternative to prevent complications related to it during RAL urologic surgery involving the gastrointestinal or urinary tract. Further studies will be needed to confirm our results.
Singh, Abhilasha; Sridhar, Raja; Shrihatti, Ravi; Mandloy, Akash
2018-01-01
The aim of this study was to evaluate and compare the effect of chlorhexidine (CHX) chip and turmeric chip as a local drug delivery (LDD) agent in the treatment of patients with chronic periodontitis. A total of 120 sites with pocket depths 5-8 mm were chosen as a split mouth design at 3 sites in the same patient. Selected sites were randomly divided into three groups to receive CHX chip in addition to scaling and root planing (SRP) in group A, turmeric chip in addition to SRP in group B, and SRP only in group C. Clinical parameters, that is, plaque index (PI), gingival index (GI), probing pocket depth (PPD), and relative attachment level (RAL) were recorded at baseline, 1 month, and 3 months interval. On applying statistical analysis, results revealed that there was a significant reduction in all the clinical parameters, that is, PI, GI, PPD, and gain in RAL from baseline to 1 month and 3 months in all the three groups. These results were found to be significantly high in the CHX group and turmeric group than in the SRP group. Also, the results in both the test groups were maintained till the end of the study periods, but SRP group showed a significant deterioration after 1 month as was seen by increase in PPD and decrease in RAL scores after 3 months in the SRP group. Both the treatment modalities with the application of LDD as an adjunct to SRP proved to be equally beneficial in the treatment of chronic periodontitis.
NASA Astrophysics Data System (ADS)
Mahoney, W. P., III
2015-12-01
For more than 30 years, the Research Applications Laboratory (RAL) of the National Center for Atmospheric Research (NCAR) has conducted fundamental and applied research focused on developing decision support tools spanning multiple end-user groups representing a variety of economic sectors. Technology transfer is a primary mission of the laboratory where innovation is a key attribute and multidisciplinary research and development are the norm. Application areas include, aviation, surface transportation, wind and solar energy prediction, climate, weather and health, numerical weather prediction, biological and chemical plume dispersion for homeland security, flood prediction and water resource management, soil condition and crop maturity prediction among other application areas. The majority of the developed capabilities have been operationalized by the public, private, and academic sectors. Several commercial companies have been successfully formed around the technologies (e.g., Weather Information Technologies, Inc., Peak Weather Resources, Inc., and Global Weather Corporation) and many existing companies have improved their products by utilizing the RAL-developed weather system advancements (The Weather Channel, WSI, Schneider Electric, Xcel Energy, United Airlines, Vaisala, Panasonic, Idaho Power, etc.). The economic benefit estimates of implementing these technologies have ranged from billions of dollars in avoided commercial aircraft accidents over the last 30 years to 10s of millions of dollars of annual savings by state departments of transportation via more efficient ice and snow maintenance operations. Research and development at RAL is connected to the Broader Impacts Criterion of NSF and its focus on research that results in significant economic or societal impact. This talk will describe our research-to-operations process and discuss several technology transfer examples that have led to commercial opportunities.
Fresh from the Ornamental Garden: Hips of Selected Rose Cultivars Rich in Phytonutrients.
Cunja, Vlasta; Mikulic-Petkovsek, Maja; Weber, Nika; Jakopic, Jerneja; Zupan, Anka; Veberic, Robert; Stampar, Franci; Schmitzer, Valentina
2016-02-01
Morphological parameters (size, weight, color), the content of sugars, organic acids, lycopene, β-carotene, and phenolics were determined in hips of Rosa canina (RCA), Rosa sweginzowii (RSW), Rosa rugosa (RUG), and selected ornamental Rosa cultivars Fru Dagmar Hastrup (FDH), Repandia (REP), Veilchenblau (RVB), Aloha (RAL), Bonica (BON), and Golden Gate (RGG). Although traditionally used RCA hips contained the highest amount of cyanidin-3-glucoside (83 μg/g DW) and were the reddest (h° = 17.5), they did not stand out in other analyzed parameters. RGG climber had the biggest hips (8.86 g), which also contained highest sugar levels (50.9 g/100 g DW). RAL stood out as the cultivar rich in organic acids (33.9 g/100 g DW), mainly because of high quinic acid content (17.6 g/100g DW). FDH and RSW hips were characterized by particularly high ascorbic acid levels (4325 mg/100 g DW and 4711 mg/100 g DW). Other ornamental cultivars contained low amounts of ascorbic acid compared to the analyzed species. The phenolic profile was species/cultivars-specific. The greatest diversity of phenolic compounds was detected in RUG and FDH hips (55 and 54 different tentatively identified compounds with HPLC/MS). Flavanols represented the main phenolic class in most of the investigated species/cultivars and RGG hips contained the highest amount of catechin and proanthocyandin derivatives (15855 μg/g DW). Altogether RAL hips contained the highest quantity of phenolics (44746 μg/g DW) mainly due to high levels of hydrolysable tannins compared to other species/cultivars. Although small, hips of BON and REP were most abundant regarding β-carotene and lycopene content, respectively. © 2016 Institute of Food Technologists®
Díaz, Nicolás M; Morera, Luis P; Tempesti, Tomas; Guido, Mario E
2017-05-01
The vertebrate retina contains typical photoreceptor (PR) cones and rods responsible for day/night vision, respectively, and intrinsically photosensitive retinal ganglion cells (ipRGCs) involved in the regulation of non-image-forming tasks. Rhodopsin/cone opsin photopigments in visual PRs or melanopsin (Opn4) in ipRGCs utilizes retinaldehyde as a chromophore. The retinoid regeneration process denominated as "visual cycle" involves the retinal pigment epithelium (RPE) or Müller glial cells. Opn4, on the contrary, has been characterized as a bi/tristable photopigment, in which a photon of one wavelength isomerizes 11-cis to all-trans retinal (Ral), with a second photon re-isomerizing it back. However, it is unknown how the chromophore is further metabolized in the inner retina. Nor is it yet clear whether an alternative secondary cycle occurs involving players such as the retinal G-protein-coupled receptor (RGR), a putative photoisomerase of unidentified inner retinal activity. Here, we investigated the role of RGR in retinoid photoisomerization in Opn4x (Xenopus ortholog) (+) RGC primary cultures free of RPE and other cells from chicken embryonic retinas. Opn4x (+) RGCs display significant photic responses by calcium fluorescent imaging and photoisomerize exogenous all-trans to 11-cis Ral and other retinoids. RGR was found to be expressed in developing retina and in primary cultures; when its expression was knocked down, the levels of 11-cis, all-trans Ral, and all-trans retinol in cultures exposed to light were significantly higher and those in all-trans retinyl esters lower than in dark controls. The results support a novel role for RGR in ipRGCs to modulate retinaldehyde levels in light, keeping the balance of inner retinal retinoid pools.
Chandradas, Nikhil D.; Ravindra, Shivamurthy; Rangaraju, Vivekananda M.; Jain, Sheetal; Dasappa, Shivaprasad
2016-01-01
Aim: To evaluate the efficacy of platelet rich fibrin (PRF) with or without bone graft [demineralized bone matrix (DBM) graft] in the treatment of intrabony defects based on clinical and radiographic parameters. Materials and Methods: Thirty six intrabony defects in 36 patients were randomly divided into three different groups and were treated with group A (PRF with DBM) or group B (PRF alone) or group C [open flap debridement (OFD)]. Clinical parameters such as plaque index (PI), gingival index (GI), probing depth (PD), relative attachment level (RAL), and gingival recession (GR) were assessed at baseline and 9 months postoperatively; radiographic parameters such as linear bone growth (LBG) and percentage in bone fill (%BF) were calculated by using the image analysis software. Comparisons of groups were analyzed using Kruskal–Wallis analysis of variance test. Pair-wise comparison of groups was done by Mann-Whitney U test. Results: Mean PD reduction and RAL gain were greater in group A (4.25 ± 1.48, 3.92 ± 0.90) and group B (3.82 ± 0.75, 3.27 ± 0.65) than control (3.00 ± 1.21, 2.25 ± 0.62). Furthermore, statistically significant improvement in LBG and %BF was found in group A (3.47 ± 0.53, 61.53 ± 4.54) compared to group B (2.55 ± 0.61, 49.60 ± 14.08) and group C (1.21 ± 0.80, 24.69 ± 15.59). Conclusions: The study demonstrated that PRF improves clinical and radiological parameters compared to OFD alone in intrabony defects. Addition of DBM enhances the effects of PRF in RAL gain and radiographic defect fill. PMID:27652249
Investigation of Mesospheric Metal Emission Signals from SCIAMACHY Limb Measurements
2013-10-31
Mg seasonal variations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 5.3 Mg annual mean...19 5.4 Mg+ monthly means . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 5.5 Mg+ seasonal variations ...ground, which have a good vertical and tempo - ral resolution. Valuable information on mesospheric temperatures, wind speeds and wave propagation effects
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lawrie, Scott R., E-mail: scott.lawrie@stfc.ac.uk; John Adams Institute for Accelerator Science, Department of Physics, University of Oxford; Faircloth, Daniel C.
2015-04-08
In order to facilitate the testing of advanced H{sup −} ion sources for the ISIS and Front End Test Stand (FETS) facilities at the Rutherford Appleton Laboratory (RAL), a Vessel for Extraction and Source Plasma Analyses (VESPA) has been constructed. This will perform the first detailed plasma measurements on the ISIS Penning-type H{sup −} ion source using emission spectroscopic techniques. In addition, the 30-year-old extraction optics are re-designed from the ground up in order to fully transport the beam. Using multiple beam and plasma diagnostics devices, the ultimate aim is improve H{sup −} production efficiency and subsequent transport for eithermore » long-term ISIS user operations or high power FETS requirements. The VESPA will also accommodate and test a new scaled-up Penning H{sup −} source design. This paper details the VESPA design, construction and commissioning, as well as initial beam and spectroscopy results.« less
Pulmonary hypoxic vasoconstriction: how strong? How fast?
NASA Technical Reports Server (NTRS)
Sheehan, D. W.; Klocke, R. A.; Farhi, L. E.
1992-01-01
We have developed a minimally invasive technique for studying regional blood flow in conscious sheep, bypassing the complications of open-chest surgery, flow probes and tracer infusion. We quantitate regional perfusion continuously on the basis of regional clearance of methane (methane is produced in the sheep rumen, enters the circulation and is eliminated nearly completely (greater than 95%) in the lung). Tracheal intubation with a dual-lumen catheter isolates the gas exchange of the right apical lobe (RAL; less than 15% of the lung) from that of the remainder of the lung, which serves as a control (CL). We measure RAL and CL methane elimination by entraining expirates in constant flows, sampled continuously for methane. Results obtained with this technique and from regional oxygen uptake are in excellent agreement. We have found that hypoxic vasoconstriction is far more potent and stable during eucapnic hypoxia than during hypocapnic hypoxia. The time course of the vasoconstriction suggests that many of the data in the literature may have been obtained prior to steady state.
Medicine patent pool--pharma philanthropy or PR?
De Luca, Carmela
2015-01-01
Merck recently signed an agreement with The Medicines Patent Pool (MPP) to license intellectual property relating to pediatric formulations of its integrase HIV drug, raltegravir (Ral) (the 'Agreement'). The Agreement is alleged to clear the way for cheaper formulations for use in developing and some middle income countries and allows for the development of novel pediatric formulations of Ral as well as novel combinations. Merck's license is royalty free and under the terms of the Agreement, manufacturers anywhere in the world who meet the quality assurance criteria, can manufacture and sell pediatric versions of the drug in the licensed countries under the agreed conditions without paying a royalty to Merck. The Agreement covers at least 92 countries and MPP reports that 98.1% of children with HIV in the developing world live in the included countries. The Agreement has been criticized as a public relations exercise. The article asks if the criticism is justified and explores several aspects of the Agreement in addressing the question.
NASA Astrophysics Data System (ADS)
Mosleh, A.; Ehteshamzadeh, M.; Taherzadeh Mousavian, R.
2014-10-01
In this study, a powder mixture with an Al/TiO2 molar ratio of 10/3 was used to form an r-Al2Ti intermetallic matrix composite (IMC) reinforced with α-Al2O3 ceramic by a novel milling technique, called discontinuous mechanical milling (DMM) instead of milling and ignition of the produced thermite. The results of energy dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD) of samples with varying milling time indicate that this fabrication process requires considerable mechanical energy. It is shown that Al2Ti-Al2O3 IMC with small grain size was produced by DMM after 15 h of ball milling. Peaks for γ-TiAl as well as Al2Ti and Al2O3 are observed in XRD patterns after DMM followed by heat treatment. The microhardness of the DMM-treated composite produced after heat treatment was higher than Hv 700.
MACROMOLECULAR ADDUCTION BY TRICHLOROACETONITRILE IN THE FISCHER 344 RAT FOLLOWING ORAL GAVAGE
Male Fischer 344 rats were administered 1- or 2-[14C]-trichloroacetonitrile (TCAN) by ral gavage. NA was isolated from the liver, kidneys and stomach and several protein fractions (globin, albumin and blobulins) were isolated from blood. CAN binds to both the DNA and the blood pr...
Three-Dimensional Evolution of Erupted Flux Ropes from the Sun (2-20 Solar Radii) to 1 AU
2012-12-01
public release; distribution unlimited 13. SUPPLEMENTARY NOTES Preprint, Solar Phys., 2013 14. ABSTRACT 15. SUBJECT TERMS 16. SECURITY ...NASA GSFC (USA), RAL and University of Birmingham (UK), MPS(Germany), CSL (Belgium), IOTA and IAS (France). References Brueckner, G.E., Howard, R.A
Tracking Streamer Blobs Into the Heliosphere
2010-05-20
SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT Same as Report (SAR) 18. NUMBER OF PAGES 10 19a. NAME OF RESPONSIBLE PERSON a. REPORT...NASA/GSFC (US), RAL (UK), UB- HAM (UK), MPS (Germany), CSL (Belgium), IOTA (France), and IAS (France). In the US, funding was provided by NASA, in the
The Temperature-Dependent Nature of Coronal Dimmings
2010-07-01
opening-up, of flux and can be observed both off-limb and on-disk. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT...international consortium of the NRL, LMSAL and NASA GSFC (USA), RAL and U. Bham (UK), MPS (Germany), CSL (Belgium), IOTA and IAS (France). This work was
Benchmarking Glucose Results through Automation: The 2009 Remote Automated Laboratory System Report
Anderson, Marcy; Zito, Denise; Kongable, Gail
2010-01-01
Background Hyperglycemia in the adult inpatient population remains a topic of intense study in U.S. hospitals. Most hospitals have established glycemic control programs but are unable to determine their impact. The 2009 Remote Automated Laboratory System (RALS) Report provides trends in glycemic control over 4 years to 576 U.S. hospitals to support their effort to manage inpatient hyperglycemia. Methods A proprietary software application feeds de-identified patient point-of-care blood glucose (POC-BG) data from the Medical Automation Systems RALS-Plus data management system to a central server. Analyses include the number of tests and the mean and median BG results for intensive care unit (ICU), non-ICU, and each hospital compared to the aggregate of the other hospitals. Results More than 175 million BG results were extracted from 2006–2009; 25% were from the ICU. Mean range of BG results for all inpatients in 2006, 2007, 2008, and 2009 was 142.2–201.9, 145.6–201.2, 140.6–205.7, and 140.7–202.4 mg/dl, respectively. The range for ICU patients was 128–226.5, 119.5–219.8, 121.6–226.0, and 121.1–217 mg/dl, respectively. The range for non-ICU patients was 143.4–195.5, 148.6–199.8, 145.2–201.9, and 140.7–203.6 mg/dl, respectively. Hyperglycemia rates of >180 mg/dl in 2008 and 2009 were examined, and hypoglycemia rates of <40 mg/dl (severe) and <70 mg/dl (moderate) in both 2008 and 2009 were calculated. Conclusions From these data, hospitals can determine the current state of glycemic control in their hospital and in comparison to other hospitals. For many, glycemic control has improved. Automated POC-BG data management software can assist in this effort. PMID:21129348
NASA Astrophysics Data System (ADS)
Bonesini, Maurizio
2017-12-01
The FAMU (Fisica degli Atomi Muonici) experiment has the goal to measure precisely the proton Zemach radius, thus contributing to the solution of the so-called proton radius "puzzle". To this aim, it makes use of a high-intensity pulsed muon beam at RIKEN-RAL impinging on a cryogenic hydrogen target with an high-Z gas admixture and a tunable mid-IR high power laser, to measure the hyperfine (HFS) splitting of the 1S state of the muonic hydrogen. From the value of the exciting laser frequency, the energy of the HFS transition may be derived with high precision ( 10-5) and thus, via QED calculations, the Zemach radius of the proton. The experimental apparatus includes a precise fiber-SiPMT beam hodoscope and a crown of eight LaBr3 crystals and a few HPGe detectors for detection of the emitted characteristic X-rays. Preliminary runs to optimize the gas target filling and its operating conditions have been taken in 2014 and 2015-2016. The final run, with the pump laser to drive the HFS transition, is expected in 2018.
9 CFR 72.13 - Permitted dips and procedures.
Code of Federal Regulations, 2010 CFR
2010-01-01
... proprietary brands of permitted dips—as well the use of compressed air, vat management techniques, and other... proprietary brands of a Dioxathion (Delnav ®) emulsifiable concentrate used at a concentration of 0.125 to 0.150 percent. 4 (2) Approved proprietary brands of coumaphos (Co-Ral ®), 25 percent wettable powder or...
None
2017-12-09
J.Luns des Pays-Bas, ancien sécétaire général de NATO (OTAN=Organisation du traité de l'Atlantique Nord) parle du passé, présent et future de la défense européenne et des relations est et ouest
Performance of Hearing Protectors in Impulse Noise
2000-09-01
report: ADPO10340 thru ADP010346 UNCLASSIFIED 3-1 Performance of Hearing Protectors in Impulse Noise K. Buck French German Research Institute BP 34...5 rue du G6n~ral Cassagnou 68301 Saint-Louis CEDEX France Summary adapted to the high levels to which the devices will The present paper describes the
Examining the Antecedents of Social Networking Sites Use among CEGEP Students
ERIC Educational Resources Information Center
Doleck, Tenzin; Bazelais, Paul; Lemay, David John
2017-01-01
Investigations in technology acceptance in education has largely overlooked certain unique populations like students from the "Collège d'enseignement général et professionnel" (CEGEP) system. In studies examining CEGEP students' use of technology, the Technology Acceptance Model (TAM) perspective has not been taken into account, nor have…
Institutionalizing Community-Based Learning and Research: The Case for External Networks
ERIC Educational Resources Information Center
Shrader, Elizabeth; Saunders, Mary Anne; Marullo, Sam; Benatti, Sylvia; Weigert, Kathleen Maas
2008-01-01
Conversations continue as to whether and how community-based learning and research (CBLR) can be most effectively integrated into the mission and practice of institutions of higher education (IHEs). In 2005, eight District of Columbia- (DC-) area universities affiliated with the Community Research and Learning (CoRAL) Network engaged in a planning…
Remote Access Laboratories in Australia and Europe
ERIC Educational Resources Information Center
Ku, H.; Ahfock, T.; Yusaf, T.
2011-01-01
Remote access laboratories (RALs) were first developed in 1994 in Australia and Switzerland. The main purposes of developing them are to enable students to do their experiments at their own pace, time and locations and to enable students and teaching staff to get access to facilities beyond their institutions. Currently, most of the experiments…
Theoretical Investigation of Optical Computing Based on Neural Network Models.
1987-09-29
34 Cognitive and Psychological Computation with Neu- ral Models," IEEE Trans. Sys., Man, and cyber., SMC-13, p. 799, 1983. 20’ K. Nakano, "Association-A...7),482(1986). 211 F. Rosenblatt, Principles of Neurodynamics : Perceptron and the The- ory of Brain Mechanisms, Spartan Books, Washington,(1961). 22
2012-06-10
and white light) and the longitudinal extent of the SEP event in the heliosphere. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION...The STEREO SECCHI data are pro- duced by a consortium of RAL (UK), NRL (USA), LMSAL (USA), GSFC (USA), MPS (Germany), CSL (Belgium), IOTA (France
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bogomilov, M.; Karadzhov, Y.; Kolev, D.
2012-05-01
The international Muon Ionization Cooling Experiment (MICE), which is under construction at the Rutherford Appleton Laboratory (RAL), will demonstrate the principle of ionization cooling as a technique for the reduction of the phase-space volume occupied by a muon beam. Ionization cooling channels are required for the Neutrino Factory and the Muon Collider. MICE will evaluate in detail the performance of a single lattice cell of the Feasibility Study 2 cooling channel. The MICE Muon Beam has been constructed at the ISIS synchrotron at RAL, and in MICE Step I, it has been characterized using the MICE beam-instrumentation system. In thismore » paper, the MICE Muon Beam and beam-line instrumentation are described. The muon rate is presented as a function of the beam loss generated by the MICE target dipping into the ISIS proton beam. For a 1 V signal from the ISIS beam-loss monitors downstream of our target we obtain a 30 KHz instantaneous muon rate, with a neglible pion contamination in the beam.« less
Kumari, Minal; Martande, Santosh S; Pradeep, A R; Naik, Savitha B
2016-11-01
The present study was designed to evaluate effectiveness of 1.2% atorvastatin (ATV) gel, as an adjunct to scaling and root planing (SRP) in the treatment of intrabony defects in chronic periodontitis (CP) in patients with type 2 diabetes mellitus (t2DM). Seventy-five patients were categorized into two treatment groups: 1) SRP plus 1.2% ATV and 2) SRP plus placebo. Clinical parameters including modified sulcus bleeding index, probing depth (PD), and relative attachment level (RAL) were recorded at baseline and 3, 6, and 9 months. Percentage radiographic defect depth reduction was evaluated using computer-aided software at baseline and 6 and 9 months. Mean PD reduction and mean RAL gain was greater in the ATV group than the placebo group at 3, 6, and 9 months. Furthermore, ATV group sites presented with a significantly greater percentage of radiographic defect depth reduction at 6 and 9 months. Locally delivered ATV was found to be effective in treatment of intrabony defects in CP in patients with t2DM.
A remote augmentor lift system with a turbine bypass engine
NASA Technical Reports Server (NTRS)
Fishbach, L. H.; Franciscus, L. C.
1982-01-01
Two supersonic vertical takeoff or landing (VTOL) aircraft engine types, a conventional medium bypass ratio turbofan, and a turbine bypass turbojet were studied. The aircraft assumed was a clipped delta wing with canard configuration. A VTOL deck launched intercept, DLI, mission with Mach 1.6 dash and cruise segments was used as the design mission. Several alternate missions requiring extended subsonic capabilities were analyzed. Comparisons were made between the turbofan (TF) and the turbine bypass turbojet (TBE) engines in airplane types using a Remote Augmented Lift Systems, RALS and a Lift plus Lift Cruise system (L+LC). The figure of merit was takeoff gross weight for the VTOL DLI mission. The results of the study show that the turbine bypass turbojet and the conventional turbofan are competitive engines for both type of aircraft in terms of takeoff gross weight and range. However, the turbine bypass turbojet would be a simpler engine and may result in more attractive life cycle costs and reduced maintenance. The RALS and L+LC airplane types with either TBE or TF engines have approximately the same aircraft takeoff gross weight.
Complex robotic reconstructive surgical procedures in children with urologic abnormalities.
Orvieto, Marcelo A; Gundeti, Mohan S
2011-07-01
Robot-assisted laparoscopic surgery (RALS) is evolving rapidly in the pediatric surgical field. The unique attributes of the robotic interface makes this technology ideal for children with congenital anomalies who often require reconstructive procedures. Furthermore, the system can generate extremely delicate movements in a confined working space such as the one generally found in the pediatric population. Herein, we critically review the current experience with RALS placing a special emphasis in children undergoing complex reconstructive surgical procedures worldwide. A total of 42 original manuscripts on a variety of robot-assisted urologic surgical procedures in children were identified from a MEDLINE database search. Complex reconstructive procedures that are being currently performed include reoperative pyeloplasty, pyeloplasty in infants, pyelolithotomy, ureteropyelostomy/ureterostomy, bladder augmentation with or without appendico-vesicostomy, bladder neck sling procedure, among others. Initial results with robot assistance are encouraging and have demonstrated safety comparable to open procedures and outcomes at least equivalent to standard laparoscopy. Future development of smaller instruments, incorporating tactile feedback, will likely overcome current limitations and spread out the use of this technique in younger children and more advanced procedures.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Heuer, Rolf; Catherin, Anne-Sylvie; Vuillemin, Vin
2010-06-25
Cher(e)s collègues, En collaboration avec le Département HR, le Directeur général a le plaisir de vous convier à une réunion publique qui se tiendra le vendredi 25 juin 2010 à 9h30 dans l’Amphithéâtre principal (Bâtiment 500)*. Un café d’accueil y sera servi à partir de 9h. Cette réunion abordera les thèmes suivants : • Valeurs de l’Organisation (Directeur général) • Code de Conduite (Directeur général / Anne-Sylvie Catherin) • Création du nouveau rôle d’Ombudsperson (Vincent Vuillemin); Ces présentations seront suivies d’une séance de questions-réponses. Nous espérons vous retrouver nombreux le 25 juin ! Meilleures salutations, Anne-Sylvie Catherin Chef du Départementmore » des Ressources humaines *Cette réunion sera retransmise simultanément dans l’Amphithéâtre BE de Prévessin (Bâtiment 864) et également disponible à l’adresse suivante : http://webcast.cern.ch. Dear colleagues, In collaboration with HR Department, the Director-General would like to invite you to an information meeting which will be held on Friday 25 June 2010 at 9:30 am in the Main Auditorium (Building 500)*. A welcome coffee will be available from 9:00 am. During this meeting, information will be given about: • Organization’s values (Director-General) • Code of Conduct (Director-General / Anne-Sylvie Catherin) • New Ombudsperson role (Vincent Vuillemin) These presentations will be followed by a questions & answers session. We look forward to seeing you all on 25 June! Best regards, Anne-Sylvie Catherin Head, Human Resources Department. This meeting will be simultaneously retransmitted in BE Auditorium (Building 864) and available at the following address: http://webcast.cern.ch.« less
DOE Office of Scientific and Technical Information (OSTI.GOV)
None
2010-10-12
Cher(e)s collègues, En collaboration avec le Département HR, le Directeur général a le plaisir de vous convier à une réunion publique qui se tiendra le vendredi 25 juin 2010 à 9h30 dans l’Amphithéâtre principal (Bâtiment 500)*. Un café d’accueil y sera servi à partir de 9h. Cette réunion abordera les thèmes suivants : Valeurs de l’Organisation (Directeur général); Code de Conduite (Directeur général / Anne-Sylvie Catherin); Création du nouveau rôle d’Ombudsperson (Vincent Vuillemin) Ces présentations seront suivies d’une séance de questions-réponses. Nous espérons vous retrouver nombreux le 25 juin ! Meilleures salutations, Anne-Sylvie Catherin Chef du Département des Ressources humainesmore » *Cette réunion sera retransmise simultanément dans l’Amphithéâtre BE de Prévessin (Bâtiment 864) et également disponible à l’adresse suivante : http://webcast.cern.ch [Dear colleagues, In collaboration with HR Department, the Director-General would like to invite you to an information meeting which will be held on Friday 25 June 2010 at 9:30 am in the Main Auditorium (Building 500)*. A welcome coffee will be available from 9:00 am. During this meeting, information will be given about: Organization’s values (Director-General); Code of Conduct (Director-General / Anne-Sylvie Catherin); New Ombudsperson role (Vincent Vuillemin); These presentations will be followed by a questions & answers session. We look forward to seeing you all on 25 June! Best regards, Anne-Sylvie Catherin Head, Human Resources Department *This meeting will be simultaneously retransmitted in BE Auditorium (Building 864) and available at the following address: http://webcast.cern.ch.« less
Syndrome de poland: à propos d’un cas et revue de la litterature
Benzalim, Meriam; Berghalout, Laila; Elfakir, Sophia; Jalal, Hicham
2017-01-01
Le syndrome de Poland est une malformation congénitale rare associant à des degrés divers des anomalies thoraciques et du membre supérieur homolatéral. Nous rapportons le cas d'une fillette de 7 ans, explorée pour dépression de l'hémithorax gauche avec masse sous claviculaire homolatérale. La tomodensitométrie a montré que la déformation de la paroi thoracique était liée à l'absence des chefs à insertion sterno-costale du muscle pectoralis major gauche avec agénésie du pectoralis minor et hypoplasie des arcs antérieurs des six premières côtes correspondantes. Ces anomalies étaient rapportées à un syndrome de Poland. Un bilan général fait d'échographie abdominale, radiographies des deux mains, a été réalisé chez la patiente n'ayant révélé aucune malformation associée. Le syndrome de Poland résulte d'un défaut d'approvisionnement sanguin des éléments musculosquelettiques de la paroi thoracique pendant la vie fœtale. Il existe de nombreuses variantes du syndrome de Poland qui peuvent être mieux détectées par la TDM qui doit être réalisée chaque fois qu'il est disponible, sans omettre le rôle de la radiologie général dans la détection des malformations associées. La caractéristique de ce syndrome est l'agénésie des faisceaux sternocostaux du muscle pectoralis major. Son étiologie reste inconnue et discutée. Une anomalie vasculaire en serait la cause, sans que le primum movens de cette anomalie vasculaire soit connu. PMID:28450991
Troya, Jesús; Montejano, Rocio; Ryan, Pablo; Gómez, Cristina; Matarranz, Mariano; Cabello, Alfonso; Vera, Francisco; Sepúlveda, María Antonia; Santos, Ignacio; Samperiz, Gloria; Bachiller, Pablo; Boix, Vicente; Barrufet, Pilar; Cervero, Miguel; Sanz, José; Solís, Javier; Yllescas, María; Valencia, Eulalia
2018-01-01
Long-term combination antiretroviral therapy often results in toxicity/tolerability problems, which are one of the main reasons for switching treatment. Despite the favorable profile of raltegravir (RAL), data on its combination with abacavir/lamivudine (ABC/3TC) are scarce. Based on clinical data, we evaluated this regimen as a switching strategy. Multicenter, non-controlled, retrospective study including all virologically suppressed HIV-1-infected patients who had switched to RAL+ABC/3TC. We evaluated effectiveness (defined as maintenance of HIV-1-RNA <50 copies/mL at 48 weeks) safety, tolerability, laboratory data, and CD4+ count at week 48 of this switching strategy. The study population comprised 467 patients. Median age was 49 years (IQR: 45-53). Males accounted for 75.4%. Median CD4+ count at baseline was 580 cells/μL (IQR, 409). The main reasons for switching were toxicity/tolerability problems (197; 42.2%) and physician's criteria (133; 28.5%). At week 48, HIV-1 RNA remained at <50 copies/mL in 371/380 (97.6%; 95%CI: 96.4-99.0) when non-virological failure was censured. Virological failure was recorded in 1.9% patients and treatment failure in 20.5% of patients (96/467 [95%CI, 16.9-24.2]). The main reasons for treatment failure included switch to fixed-dose combination regimens (31; 6.6%), toxicity/poor tolerability (27; 5.8%), and physician's decision (17; 3.6%). A total of 73 adverse events were detected in 64 patients (13.7%). These resolved in 43 patients (67.2%). Of the 33 cases related or likely related to treatment, 30 were Grade-1 (90.9%). CD4+ count and renal, hepatic, and lipid profiles remained clinically stable over the 48 weeks. Our findings suggest that RAL+ABC/3TC could be an effective, safe/tolerable, and low-toxicity option for virologically suppressed HIV-1-infected patients.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kotova, Irina Yu.; Buryat State University, Smolin St. 24a, Ulan-Ude 670000, Buryat Republic; Solodovnikov, Sergey F.
Triple molybdates AgA{sub 3}R(MoO{sub 4}){sub 5} (A=Mg, R=Cr, Fe; A=Mn, R=Al, Cr, Fe, Sc, In) of the NaMg{sub 3}In(MoO{sub 4}){sub 5} type were synthesized and single crystals of AgMg{sub 3}R(MoO{sub 4}){sub 5} (R=Cr, Fe) were grown. In their structures, the MoO{sub 4} tetrahedra, pairs and trimers of edge-shared (Mg, R)O{sub 6} octahedra are connected by common vertices to form a 3D framework. Large framework cavities involve Ag{sup +} cations disordered on three nearby positions with CN=3+1 or 4+1. Alternating (Mg, R)O{sub 6} octahedra and MoO{sub 4} tetrahedra in the framework form quadrangular windows penetrable for Ag{sup +} at elevated temperatures.more » Above 653–673 K, the newly obtained molybdates demonstrate abrupt reduction of the activation energy to 0.4–0.6 eV. At 773 K, AgMg{sub 3}Al(MoO{sub 4}){sub 5} shows electric conductivity 2.5·10{sup −2} S/cm and E{sub a}=0.39 eV compatible with characteristics of the best ionic conductors of the NASICON type. - Graphical abstract: Triple molybdates AgA{sub 3}R(MoO{sub 4}){sub 5} (A=Mg, R=Cr, Fe; A=Mn, R=Al, Cr, Fe, Sc, In) of the NaMg{sub 3}In(MoO{sub 4}){sub 5} type were synthesized, AgMg{sub 3}R(MoO{sub 4}){sub 5} (R=Cr, Fe) were structurally characterized, ion-conductive properties of AgMg{sub 3}Al(MoO{sub 4}){sub 5} were measured. Display Omitted - Highlights: • Triple molybdates AgA{sub 3}R(MoO{sub 4}){sub 5} (A=Mg, R=Cr, Fe; A=Mn, R=Al, Cr, Fe, Sc, In) of the NaMg{sub 3}In(MoO{sub 4}){sub 5} type were synthesized. • Single crystals of AgMg{sub 3}R(MoO{sub 4}){sub 5} (R=Cr, Fe) were grown and their crystal structures were determined. • Disordering Ag{sup +} ions and penetrable framework structures of AgMg{sub 3}R(MoO{sub 4}){sub 5} (R=Cr, Fe) suggest 2D-character of silver-ion mobility. • Measured ion-conductive properties of AgMg{sub 3}Al(MoO{sub 4}){sub 5} are compatible with characteristics of the best ionic conductors of the NASICON type.« less
U.S. EPA, Pesticide Product Label, RL 2 DUST CONTAINS CO-RAL, 03/02/1987
2011-04-21
... rul .. · orT dato 1. ';1:i~ oi'r1' ('atiar. ;-'. r ti.Cf' r:'·-3 I"~"rt."Ij ranI"! C"''''i"1! "!lr:,.,t i (~:'J i!1 ,.,r;' 'ct j Vf" ,~, :u;mi t:t('.4 u.,r( r "';, ~i'· n"' ... r,...( I)!",' ...
U. S. Naval Forces, Vietnam Monthly Historical Supplement for August 1969
1969-11-01
not called on for fire support. The ground troops kiled seven VC., captured two VC suspects and ibherated 17 civilian prisoners. In aditonairsupport... kiled j .0 in July!, eighteen 7C were ca-turcd, "" and one VS ralIlied. Yarire casualties were almost identical to those 4 of July .- th fifteen
The Role of Attachment in Facebook Usage: A Study of Canadian College Students
ERIC Educational Resources Information Center
Teo, Timothy; Doleck, Tenzin; Bazelais, Paul
2018-01-01
Considering the increasingly ubiquitous and frequent use of Facebook among college students, this study sought to explicate and unravel the salient determinants of Facebook use. Specifically, the main goal was to ascertain the factors influencing "Collège d'enseignement général et professionnel" (CEGEP) students' Facebook use, for which…
Analysis of Androgen- and EGF-Receptor Expression in the Fetal Rat Phallus After Exposure to Vinclozolin
Cynthia Wolf1,2, Barbara Abbott1, Gerald A. LeBlanc2, and L. Earl Gray, Jr.1
1USEPA, ORD, NHEERL, RTD, RTP, NC 27711, 2NCSU, Environmental and Molecular Toxicology, Ral...
2011-07-29
SPECIAL INSPE CTOR GENE RAL FOR IRAQ RECONSTRUCTION 400 Army Navy Drive • Arlington, Virginia 22202 July 29, 2011 LETTER FOR...11-019) In September 2007, Blackwater , Inc., a private security contractor (PSC) under contract with the Department of State (DoS), was involved in
46 CFR Appendix A to Part 520 - Standard Terminology and Codes
Code of Federal Regulations, 2011 CFR
2011-10-01
... DTB Firkin FIR Flo-Bin FLO Frame FRM Flask FSK Forward Reel FWR Garment on Hanger GOH Heads of Beef... Private Vehicle POV Pipe Rack PRK Quarters of Beef QTR Rail (semiconductor) RAL Rack RCK Reel REL Roll ROL Reverse Reel RVR Sack SAK Shook SHK Sides of Beef SID Skid SKD Skid, Elev, Lift Trk SKE Sleeve SLV Spin...
46 CFR Appendix A to Part 520 - Standard Terminology and Codes
Code of Federal Regulations, 2012 CFR
2012-10-01
... DTB Firkin FIR Flo-Bin FLO Frame FRM Flask FSK Forward Reel FWR Garment on Hanger GOH Heads of Beef... Private Vehicle POV Pipe Rack PRK Quarters of Beef QTR Rail (semiconductor) RAL Rack RCK Reel REL Roll ROL Reverse Reel RVR Sack SAK Shook SHK Sides of Beef SID Skid SKD Skid, Elev, Lift Trk SKE Sleeve SLV Spin...
46 CFR Appendix A to Part 520 - Standard Terminology and Codes
Code of Federal Regulations, 2013 CFR
2013-10-01
... DTB Firkin FIR Flo-Bin FLO Frame FRM Flask FSK Forward Reel FWR Garment on Hanger GOH Heads of Beef... Private Vehicle POV Pipe Rack PRK Quarters of Beef QTR Rail (semiconductor) RAL Rack RCK Reel REL Roll ROL Reverse Reel RVR Sack SAK Shook SHK Sides of Beef SID Skid SKD Skid, Elev, Lift Trk SKE Sleeve SLV Spin...
46 CFR Appendix A to Part 520 - Standard Terminology and Codes
Code of Federal Regulations, 2014 CFR
2014-10-01
... DTB Firkin FIR Flo-Bin FLO Frame FRM Flask FSK Forward Reel FWR Garment on Hanger GOH Heads of Beef... Private Vehicle POV Pipe Rack PRK Quarters of Beef QTR Rail (semiconductor) RAL Rack RCK Reel REL Roll ROL Reverse Reel RVR Sack SAK Shook SHK Sides of Beef SID Skid SKD Skid, Elev, Lift Trk SKE Sleeve SLV Spin...
46 CFR Appendix A to Part 520 - Standard Terminology and Codes
Code of Federal Regulations, 2010 CFR
2010-10-01
... DTB Firkin FIR Flo-Bin FLO Frame FRM Flask FSK Forward Reel FWR Garment on Hanger GOH Heads of Beef... Private Vehicle POV Pipe Rack PRK Quarters of Beef QTR Rail (semiconductor) RAL Rack RCK Reel REL Roll ROL Reverse Reel RVR Sack SAK Shook SHK Sides of Beef SID Skid SKD Skid, Elev, Lift Trk SKE Sleeve SLV Spin...
CSIR Contribution to Defining Adaptive Capacity in the Context of Environmental Change
2014-03-31
Pollution rates Cultural norms Roads Agricultu ral practises / norms Level of Income Access to safe water Gender based discriminati on Fear of...internal conflicts Civil rights Quality of nutrition Status of environm ental policies Spiritual practises Dams Food for sale ... Fertility rates Literacy rates These developed categories are currently being tested by using both qualitative and
U.S. EPA, Pesticide Product Label, VETERINARIAN TYPE DISINFECTANT, 10/22/1980
2011-04-14
nlR[< I Itl'\\S fOJ;: !'S! GENER,\\l CI ,\\SSl F IrATI,·" i t ',j 3 It is ;1 viol"t{"l' tf r .. rl"ral ,.~". fl' ., .. pl'~duct in aI I9I11:nnf"r in.''1l ... • . t.·:1t '.·It" It l.ht"'liny. L ...
The Validation of Cloud Retrieval Algorithms Using Synthetic Datasets
NASA Astrophysics Data System (ADS)
Kokhanovsky, Alexander; Fischer, Jurgen; Linstrot, Rasmus; Meirink, Jan Fokke; Poulsen, Caroline; Preusker, Rene; Siddans, Richard; Thomas, Gareth; Arnold, Chris; Grainger, Roy; Lilli, Luca; Rozanov, Vladimir
2012-11-01
We have performed the inter-comparison study of cloud property retrievals using algorithms initially developed for AATSR (ORAC, RAL-Oxford University), AVHRR and SEVIRI (CPP, KNMI), SCIAMACHY/GOME (SACURA, University of Bremen), and MERIS (ANNA, Free University of Berlin). The accuracy of retrievals of cloud optical thickness (COT), effective radius (ER) of droplets, and cloud top height (CTH) is discussed.
ERIC Educational Resources Information Center
Bazelais, Paul; Doleck, Tenzin; Lemay, David John
2018-01-01
The purpose of this research is to investigate pre-university science "Collège d'enseignement général et professionnel" (CEGEP) students' behavioral intentions towards using online learning technologies. Heretofore, CEGEP students' use of technology has received scant attention, yet online learning technologies are found to play an…
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Chen; Shen, Xuan; Yang, Yurong
Perovskite RAlO 3 (R = La, Nd, Sm, and Gd) films have been deposited epitaxially on (001) TiO 2-terminated SrTiO 3 substrates. In this paper, it is observed that the two-dimensional transport characteristics at the RAlO 3/SrTiO 3 interfaces are very sensitive to the species of rare-earth element, that is to chemical strain. Although electron energy loss spectroscopy measurements show that electron transfer occurs in all the four polar/nonpolar heterostructures, the amount of electrons transferred across SmAlO 3/SrTiO 3 and GdAlO 3/SrTiO 3 interfaces are much less than those across LaAlO 3/SrTiO 3 and NdAlO 3/SrTiO 3 interfaces. First-principles calculationsmore » reveal the competition between ionic polarization and electronic polarization in the polar layers in compensating the build-in polarization due to the polar discontinuity at the interface. Finally, in particular, a large ionic polarization is found in SmAlO 3/SrTiO 3 and GdAlO 3/SrTiO 3 systems (which experience the largest tensile epitaxial strain), hence reducing the amount of electrons transferred.« less
Identification of Tetranectin as a Potential Biomarker for Metastatic Oral Cancer
Arellano-Garcia, Martha E.; Li, Roger; Liu, Xiaojun; Xie, Yongming; Yan, Xiaofei; Loo, Joseph A.; Hu, Shen
2010-01-01
Lymph node involvement is the most important predictor of survival rates in patients with oral squamous cell carcinoma (OSCC). A biomarker that can indicate lymph node metastasis would be valuable to classify patients with OSCC for optimal treatment. In this study, we have performed a serum proteomic analysis of OSCC using 2-D gel electrophoresis and liquid chromatography/tandem mass spectrometry. One of the down-regulated proteins in OSCC was identified as tetranectin, which is a protein encoded by the CLEC3B gene (C-type lectin domain family 3, member B). We further tested the protein level in serum and saliva from patients with lymph-node metastatic and primary OSCC. Tetranectin was found significantly under-expressed in both serum and saliva of metastatic OSCC compared to primary OSCC. Our results suggest that serum or saliva tetranectin may serve as a potential biomarker for metastatic OSCC. Other candidate serum biomarkers for OSCC included superoxide dismutase, ficolin 2, CD-5 antigen-like protein, RalA binding protein 1, plasma retinol-binding protein and transthyretin. Their clinical utility for OSCC detection remains to be further tested in cancer patients. PMID:20957082
None
2018-05-24
Cher(e)s collègues, En collaboration avec le Département HR, le Directeur général a le plaisir de vous convier à une réunion publique qui se tiendra le vendredi 25 juin 2010 à 9h30 dans lâAmphithéâtre principal (Bâtiment 500)*. Un café dâaccueil y sera servi à partir de 9h. Cette réunion abordera les thèmes suivants : Valeurs de lâOrganisation (Directeur général); Code de Conduite (Directeur général / Anne-Sylvie Catherin); Création du nouveau rôle dâOmbudsperson (Vincent Vuillemin) Ces présentations seront suivies dâune séance de questions-réponses. Nous espérons vous retrouver nombreux le 25 juin ! Meilleures salutations, Anne-Sylvie Catherin Chef du Département des Ressources humaines *Cette réunion sera retransmise simultanément dans lâAmphithéâtre BE de Prévessin (Bâtiment 864) et également disponible à lâadresse suivante : http://webcast.cern.ch [Dear colleagues, In collaboration with HR Department, the Director-General would like to invite you to an information meeting which will be held on Friday 25 June 2010 at 9:30 am in the Main Auditorium (Building 500)*. A welcome coffee will be available from 9:00 am. During this meeting, information will be given about: Organizationâs values (Director-General); Code of Conduct (Director-General / Anne-Sylvie Catherin); New Ombudsperson role (Vincent Vuillemin); These presentations will be followed by a questions & answers session. We look forward to seeing you all on 25 June! Best regards, Anne-Sylvie Catherin Head, Human Resources Department *This meeting will be simultaneously retransmitted in BE Auditorium (Building 864) and available at the following address: http://webcast.cern.ch.
PRIVACYGRID: Supporting Anonymous Location Queries in Mobile Environments
2007-01-01
continued price reduction of location tracking de- vices, location - based services (LBSs) are widely recognized as an important feature of the future computing... location - based services can operate completely anonymously, such as “when I pass a gas station, alert me with the unit price of the gas”. Others can...Anonymous Usage of Location - Based Services Through Spatial and Tempo- ral Cloaking. In Proceedings of the International Con- ference on Mobile
Surface Hardening by Laser Skin Melting
1979-07-01
typical cross-sectional view of a melt region. Various solutions includina Murakami’s reaqent, Vilella’s reagent and an oxalic acid solution were used...each type selectively revealinq different microstructu- ral features. A second etch in an oxalic acid/hydrochloric acid solution was used in the...genization due to vigorous hydrothermal mixing and liquid super- heating. Computations by Greenwald (13) from a heat flow model are graphically represented
Learned Tactics for Asset Allocation
2013-06-01
based on off-policy and on-policy tempo - ral difference learning [6, 31, 47]. The basic prin- ciple that unifies MARL techniques is to identify and...patterns with regu- larities such as symmetry, repetition, and repetition with variation [49, 50, 54]. For example, simply by in- cluding a Gaussian...tactics and policies while still exhibiting variation across the policy geometry. In other words, policies are spread across the substrate in a
Bogren, Anna; Teles, Ricardo P; Torresyap, Gay; Haffajee, Anne D; Socransky, Sigmund S; Jönsson, Kerstin; Wennström, Jan L
2008-02-01
To test the hypothesis of a superior clinical and microbiological effect of the combined use of powered toothbrush+triclosan-containing dentifrice compared with manual toothbrush+regular fluoride-containing dentifrice in periodontal maintenance patients. A total of 128 periodontitis subjects involved in recall programmes were randomized to use either powered toothbrush with triclosan-dentifrice (test) or manual toothbrush and standard dentifrice (control). Supportive periodontal treatment was provided at baseline and every 6 months. Plaque, bleeding on probing (BoP), probing pocket depth (PPD) and relative attachment level (RAL) were scored at baseline, 1, 2 and 3 years. Subgingival plaque samples were taken and analysed for their content of 40 bacterial species at each examination interval. All analyses were performed by "intention-to-treat" protocol. Both groups showed significant reduction in BoP, PPD and in mean total counts of the 40 bacterial species between baseline and 3 years, while plaque score and RAL remained almost unchanged. No significant differences between the two prevention programmes were found for any of the clinical outcome variables or in mean counts of the various bacterial species. The study failed to demonstrate superior clinical and microbiological effects of powered toothbrush+triclosan dentifrice compared with manual toothbrush+standard fluoride-dentifrice in periodontitis-susceptible patients on regular maintenance therapy.
Li, Chen; Shen, Xuan; Yang, Yurong; ...
2016-12-27
Perovskite RAlO 3 (R = La, Nd, Sm, and Gd) films have been deposited epitaxially on (001) TiO 2-terminated SrTiO 3 substrates. In this paper, it is observed that the two-dimensional transport characteristics at the RAlO 3/SrTiO 3 interfaces are very sensitive to the species of rare-earth element, that is to chemical strain. Although electron energy loss spectroscopy measurements show that electron transfer occurs in all the four polar/nonpolar heterostructures, the amount of electrons transferred across SmAlO 3/SrTiO 3 and GdAlO 3/SrTiO 3 interfaces are much less than those across LaAlO 3/SrTiO 3 and NdAlO 3/SrTiO 3 interfaces. First-principles calculationsmore » reveal the competition between ionic polarization and electronic polarization in the polar layers in compensating the build-in polarization due to the polar discontinuity at the interface. Finally, in particular, a large ionic polarization is found in SmAlO 3/SrTiO 3 and GdAlO 3/SrTiO 3 systems (which experience the largest tensile epitaxial strain), hence reducing the amount of electrons transferred.« less
NASA Astrophysics Data System (ADS)
Giltrap, Samuel; Stuart, Nick; Robinson, Tim; Armstrong, Chris; Hicks, George; Eardley, Sam; Gumbrell, Ed; Smith, Roland
2016-10-01
Here we report on the development of an optical levitation based x-ray and proton source, motivated by the requirement for a debris free, high spatial resolution, and low EMP source for x-ray radiography and proton production. Research at Imperial College has led to the development of a feedback controlled optical levitation trap which is capable of holding both solid (Glass beads) and liquid (silicon based oil) micro-targets ( 3-10um). The optical levitation trap has been successfully fielded in a high-intensity laser interaction experiment at Imperial College London and at the Vulcan Petawatt Laser system at the Rutherford Appleton Laboratory (RAL). Here we report on the results from that RAL run including; an x-ray source size of 10-15um with very good spherical symmetry when compared to wire targets, secondly very low EMP signal from isolated levitated targets (9 times less RF signal than a comparable wire target). At Imperial College we were also able to record an x-ray energy spectrum which produced an electron temperature of 0.48KeV, and performed interferometry of a shock evolving into a blast wave off an optically levitated droplet which allowed us to infer the electron density within the shock front.
V/STOL propulsion control analysis: Phase 2, task 5-9
NASA Technical Reports Server (NTRS)
1981-01-01
Typical V/STOL propulsion control requirements were derived for transition between vertical and horizontal flight using the General Electric RALS (Remote Augmented Lift System) concept. Steady-state operating requirements were defined for a typical Vertical-to-Horizontal transition and for a typical Horizontal-to-Vertical transition. Control mode requirements were established and multi-variable regulators developed for individual operating conditions. Proportional/Integral gain schedules were developed and were incorporated into a transition controller with capabilities for mode switching and manipulated variable reassignment. A non-linear component-level transient model of the engine was developed and utilized to provide a preliminary check-out of the controller logic. An inlet and nozzle effects model was developed for subsequent incorporation into the engine model and an aircraft model was developed for preliminary flight transition simulations. A condition monitoring development plan was developed and preliminary design requirements established. The Phase 1 long-range technology plan was refined and restructured toward the development of a real-time high fidelity transient model of a supersonic V/STOL propulsion system and controller for use in a piloted simulation program at NASA-Ames.
International Aviation (Selected Articles).
1982-04-12
and advanced quality control. ,onclusions 10 ____ -c ’~-, nznu i’’ hrm ,~ :~~r i f aviation rcli~cts and ral-eLn -ecr 7conomld ethe’ :’orlnnzs and...have basically attained or approached .he level of foreign countries. The successful development of directional conden- sation technique means that...attenuation, softness , and light weight in addition to an advantage that no metal reflection lining is required. Once such materials are developed, radar
Relating Sensitivity and Criterion Effects to the Internal Mechanisms of Visual Spatial Attention
1988-04-30
Hughes & Zimba , 1987; Rizzolatti, Riggio, Descola & *, .. Umilta, 1987). Further, deficits for uncued locations are a function 4. of the distance...Wilson, 1986; Rizzolatti, et. al., 1987; Hughes & Zimba , 1987, argue that this effect depends upon the use of an articulated visual field). Distance...Hughes, H. & Zimba , L. (1987) Nat,ral boundaries for the spatial spread of directed visual attention. Neuropsychologia, 25, 5-18. O Jonides, J. (1976
Differential Effector Engagement by Oncogenic KRAS. | Office of Cancer Genomics
KRAS can bind numerous effector proteins, which activate different downstream signaling events. The best known are RAF, phosphatidylinositide (PI)-3' kinase, and RalGDS families, but many additional direct and indirect effectors have been reported. We have assessed how these effectors contribute to several major phenotypes in a quantitative way, using an arrayed combinatorial siRNA screen in which we knocked down 41 KRAS effectors nodes in 92 cell lines.
Army Logistician. Volume 35, Issue 5, September-October 2003
2003-10-01
Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is estimated to average 1 hour per...and reviewing the collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information...designed to deliver performance-enhancing natu- ral food elements to troops in the field. The gel con- tains a mixture of glucose and maltodextrin —a
World Epidemiology Review, Number 104
1978-09-06
EL DIA in Spanish 26 Jul 78 p 10 [Text] Canelones—A meeting held at the premises of the Commercial and Social Center was attended by members of the...and dis- cussions on subjects of the specialty, as well as receptions in the Argen- tine Embassy and a series of social activities for those attending...courses and gene- ral activities. At times, use is made of infrastructures of the Ministry of Public Health or of other organizations. Social
Williams AFB, Arizona Revised Uniform Summary of Surface Weather Observations (RUSSWO) Parts A-F.
1981-10-21
N;I 1-L 9AL CLIMATOLOGY BRANCH ~.w~ .’ ETAC LJS. H A~(I EATV UMDT 2 f wEATHER SERVICE/MAC SEE FIRST HUMDIT 2 114 1 LLIAMS AFB AZ 69-70,73-80 JUL...4622 USAPETAC ’ol 0-87-5(01.A) , I roFql CL,-RAL CLIMATOLOGY BRANCH EATV 2 AFETAC SRVIE/ACATIVE UUTO HUMIDITY SEE FIRST PAGE Z Cl)4 AILLIAMS AFS AZ
Factors Required for Successful Future Research in Decision Making
1999-06-01
to democracy and a market economy. The characteristics that this transition has in common with a complex system operating in its chaotic regime i...the Center for Science and Industrial Policy, Moscow. 4 T. J. Gordon and R. Pratt ! r • � .... 11ral Scanning, The� Hill Encyclopedia of Market ...foresight successful if it helped a firm beat a competitor or to secure greater market share. Some organizations rely on external futures
Reptiles and Amphibians of Fairchild Air Force Base, WA
2013-05-10
calling, free swimming larvae, and metamorph emer- gence, respectively. General survey methods included the use of timed au- ral surveys, automated...influence metamorph success or use . Although the majority of adult spotted frogs were found in ditches, it is inter- esting to note that a large...number of metamorphs were found within a pond (at UTM 451650 5272683) that had not had any prior evidence of amphibian use . This pond had very little
Program Aids Analysis And Optimization Of Design
NASA Technical Reports Server (NTRS)
Rogers, James L., Jr.; Lamarsh, William J., II
1994-01-01
NETS/ PROSSS (NETS Coupled With Programming System for Structural Synthesis) computer program developed to provide system for combining NETS (MSC-21588), neural-network application program and CONMIN (Constrained Function Minimization, ARC-10836), optimization program. Enables user to reach nearly optimal design. Design then used as starting point in normal optimization process, possibly enabling user to converge to optimal solution in significantly fewer iterations. NEWT/PROSSS written in C language and FORTRAN 77.
Integrated Payload Data Handling Systems Using Software Partitioning
NASA Astrophysics Data System (ADS)
Taylor, Alun; Hann, Mark; Wishart, Alex
2015-09-01
An integrated Payload Data Handling System (I-PDHS) is one in which multiple instruments share a central payload processor for their on-board data processing tasks. This offers a number of advantages over the conventional decentralised architecture. Savings in payload mass and power can be realised because the total processing resource is matched to the requirements, as opposed to the decentralised architecture here the processing resource is in effect the sum of all the applications. Overall development cost can be reduced using a common processor. At individual instrument level the potential benefits include a standardised application development environment, and the opportunity to run the instrument data handling application on a fully redundant and more powerful processing platform [1]. This paper describes a joint program by SCISYS UK Limited, Airbus Defence and Space, Imperial College London and RAL Space to implement a realistic demonstration of an I-PDHS using engineering models of flight instruments (a magnetometer and camera) and a laboratory demonstrator of a central payload processor which is functionally representative of a flight design. The objective is to raise the Technology Readiness Level of the centralised data processing technique by address the key areas of task partitioning to prevent fault propagation and the use of a common development process for the instrument applications. The project is supported by a UK Space Agency grant awarded under the National Space Technology Program SpaceCITI scheme. [1].
NASA Technical Reports Server (NTRS)
Laird, Philip
1992-01-01
We distinguish static and dynamic optimization of programs: whereas static optimization modifies a program before runtime and is based only on its syntactical structure, dynamic optimization is based on the statistical properties of the input source and examples of program execution. Explanation-based generalization is a commonly used dynamic optimization method, but its effectiveness as a speedup-learning method is limited, in part because it fails to separate the learning process from the program transformation process. This paper describes a dynamic optimization technique called a learn-optimize cycle that first uses a learning element to uncover predictable patterns in the program execution and then uses an optimization algorithm to map these patterns into beneficial transformations. The technique has been used successfully for dynamic optimization of pure Prolog.
Heuer, Rolf; Catherin, Anne-Sylvie; Vuillemin, Vin
2018-05-25
Cher(e)s collègues, En collaboration avec le Département HR, le Directeur général a le plaisir de vous convier à une réunion publique qui se tiendra le vendredi 25 juin 2010 à 9h30 dans lâAmphithéâtre principal (Bâtiment 500)*. Un café dâaccueil y sera servi à partir de 9h. Cette réunion abordera les thèmes suivants : ⢠Valeurs de lâOrganisation (Directeur général) ⢠Code de Conduite (Directeur général / Anne-Sylvie Catherin) ⢠Création du nouveau rôle dâOmbudsperson (Vincent Vuillemin); Ces présentations seront suivies dâune séance de questions-réponses. Nous espérons vous retrouver nombreux le 25 juin ! Meilleures salutations, Anne-Sylvie Catherin Chef du Département des Ressources humaines *Cette réunion sera retransmise simultanément dans lâAmphithéâtre BE de Prévessin (Bâtiment 864) et également disponible à lâadresse suivante : http://webcast.cern.ch. Dear colleagues, In collaboration with HR Department, the Director-General would like to invite you to an information meeting which will be held on Friday 25 June 2010 at 9:30 am in the Main Auditorium (Building 500)*. A welcome coffee will be available from 9:00 am. During this meeting, information will be given about: ⢠Organizationâs values (Director-General) ⢠Code of Conduct (Director-General / Anne-Sylvie Catherin) ⢠New Ombudsperson role (Vincent Vuillemin) These presentations will be followed by a questions & answers session. We look forward to seeing you all on 25 June! Best regards, Anne-Sylvie Catherin Head, Human Resources Department. This meeting will be simultaneously retransmitted in BE Auditorium (Building 864) and available at the following address: http://webcast.cern.ch.
Phase and structural behavior of SmAlO{sub 3}–RAlO{sub 3} (R = Eu, Gd) systems
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ohon, N.; Vasylechko, L., E-mail: crystal-lov@polynet.lviv.ua; Prots, Yu.
2014-02-01
Highlights: • Continuous solid solutions exist in the SmAlO{sub 3}–RAlO{sub 3} (R = Eu, Gd) systems. • Lattice parameter crossover was found in solid solutions Sm{sub 1−x}R{sub x}AlO{sub 3} (R = Eu, Gd). • Thermally induced lattice crossovers occur in Sm{sub 0.9}R{sub 0.1}AlO{sub 3} at elevated temperatures. • First-order structural phase transition Pbnm↔R3{sup ¯}c was found in Sm{sub 1−x}R{sub x}AlO{sub 3} (R = Eu, Gd). • Phase diagram of the systems SmAlO{sub 3}–EuAlO{sub 3} and SmAlO{sub 3}–GdAlO{sub 3} has been constructed. - Abstract: Phase and structural behavior in the SmAlO{sub 3}–RAlO{sub 3} (R = Eu, Gd) systems has been studiedmore » in a whole concentration range by means of laboratory X-ray diffraction, in situ synchrotron powder diffraction and differential thermal analysis techniques. Continuous solid solutions with orthorhombic perovskite structure have been found in both systems. Peculiarity of the solid solutions of Sm{sub 1−x}Eu{sub x}AlO{sub 3} and Sm{sub 1−x}Gd{sub x}AlO{sub 3} is the existence of two lattice parameter crossovers in each system occurred at x{sub Eu} = 0.07 and 0.62 and at x{sub Gd} = 0.04 and 0.33, respectively. The temperature induced lattice crossovers in the Sm{sub 0.9}Eu{sub 0.1}AlO{sub 3} and Sm{sub 0.9}Gd{sub 0.1}AlO{sub 3} samples have been found at 387 and 922 K and at 501 and 894 K. First-order reversible structural phase transformations Pbnm↔R3{sup ¯}c have been detected in both systems at the elevated temperatures. The temperatures of these transitions increase linearly with the decreasing of the samarium content. Phase diagrams of the pseudo-binary systems SmAlO{sub 3}–EuAlO{sub 3} and SmAlO{sub 3}–GdAlO{sub 3} have been constructed.« less
A New Therapeutic Paradigm for Breast Cancer Exploiting Low Dose Estrogen-Induce Apoptosis
2008-09-01
pulmonary embolism , DVT, transient ischemic attack, osteoporotic fractures , cataracts, death and quality of life (Vogel, Costantino et al. 2006...transplanting 1 mm3 tumor pieces (from other tumor bearing animals) into recipient mouse axillary mammary fat pads. This procedure was also used to...per site into the axillary mammary fat pads to generate tumors. In culture, MCF-7/RAL2 were maintained in phenol red-free MEM supplemented with 1 µM
Two-photon exchange correction to the hyperfine splitting in muonic hydrogen
NASA Astrophysics Data System (ADS)
Tomalak, Oleksandr
2017-12-01
We reevaluate the Zemach, recoil and polarizability corrections to the hyperfine splitting in muonic hydrogen expressing them through the low-energy proton structure constants and obtain the precise values of the Zemach radius and two-photon exchange (TPE) contribution. The uncertainty of TPE correction to S energy levels in muonic hydrogen of 105 ppm exceeds the ppm accuracy level of the forthcoming 1S hyperfine splitting measurements at PSI, J-PARC and RIKEN-RAL.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jeon, Hyejin; Zheng, Long Tai; Lee, Shinrye
2011-08-15
Small G protein superfamily consists of more than 150 members, and is classified into six families: the Ras, Rho, Rab, Arf, Ran, and RGK families. They regulate a wide variety of cell functions such as cell proliferation/differentiation, cytoskeletal reorganization, vesicle trafficking, nucleocytoplasmic transport and microtubule organization. The small G proteins have also been shown to regulate cell death/survival and cell shape. In this study, we compared the role of representative members of the six families of small G proteins in cell migration and cell death/survival, two cellular phenotypes that are associated with inflammation, tumorigenesis, and metastasis. Our results show thatmore » small G proteins of the six families differentially regulate cell death and cell cycle distribution. In particular, our results indicate that Rho family of small G proteins is antiapoptotic. Ras, Rho, and Ran families promoted cell migration. There was no significant correlation between the cell death- and cell migration-regulating activities of the small G proteins. Nevertheless, RalA was not only cytoprotective against multiple chemotherapeutic drugs, but also promigratory inducing stress fiber formation, which was accompanied by the activation of Akt and Erk pathways. Our study provides a framework for further systematic investigation of small G proteins in the perspectives of cell death/survival and motility in inflammation and cancer.« less
The Effect of Magnetic Field on HTS Leads What Happens when thePower Fails at RAL?
DOE Office of Scientific and Technical Information (OSTI.GOV)
Green, Michael A.
2007-02-14
The key to being able to operate the MICE superconducting solenoids on small coolers is the use of high temperature superconducting (HTS) leads between the first stage of the cooler and the magnet, which operates at around 4.2 K. Because MICE magnets are not shielded, all of the MICE magnets have a stray magnetic field in the region where the coolers and the HTS leads are located. The behavior of the HTS leads in a magnetic field depends strongly on the HTS material used for the leads and the temperature of the cooler first stage temperature. The HTS leads canmore » be specified to operate at the maximum current for the magnet. This report shows how the HTS leads can be specified for use the MICE magnets. MICE magnets take from 1.3 hours (the tracker solenoids) to 3.7 hours (the coupling magnet) to charge to the highest projected operating currents. If the power fails, the cooler and the upper ends of the HTS leads warm up. The question is how one can discharge the magnet to protect the HTS leads without quenching the MICE magnets. This report describes a method that one can use to protect the HTS leads in the event of a power failure at the Rutherford Appleton Laboratory (RAL).« less
Ptosis congénital: expérience d'un centre de soins tertiaires Marocain et mise au point
Handor, Hanan; Hafidi, Zouheir; Bencherif, Moulayzahid; Amrani, Youssef; Belmokhtar, Adil; Laghmari, Mina; Daoudi, Rajae
2014-01-01
Le ptosis congénital constitue la malposition palpébrale la plus fréquente de l'enfant. Le but de ce travail est de rapporter l'expérience de notre service dans la prise en charge de cette affection. Cette étude analyse les données épidémiologiques, cliniques et thérapeutiques des patients opérés pour ptosis congénital dans notre service entre Janvier 2005 et Décembre 2012. 44 patients (48 yeux) ont été opérés. La médiane d'âge était de 10 ans et une prédominance masculine a été retrouvée. Le ptosis était unilatéral et isolé dans 40 cas (90,90 %), bilatéral et associé à un syndrome de blépharophimosis dans 3 cas et à un syndrome de fibrose congénitale des muscles oculomoteurs dans un cas. Une amblyopie a été notée dans 11 cas (25%). La résection du muscle releveur de la paupière supérieure était la technique chirurgicale la plus utilisée (81,81%). Les résultats postopératoires étaient bons dans 33 cas (75%). PMID:25767669
Coupling Bacterial Activity Measurements with Cell Sorting by Flow Cytometry.
Servais; Courties; Lebaron; Troussellier
1999-08-01
> Abstract A new procedure to investigate the relationship between bacterial cell size and activity at the cellular level has been developed; it is based on the coupling of radioactive labeling of bacterial cells and cell sorting by flow cytometry after SYTO 13 staining. Before sorting, bacterial cells were incubated in the presence of tritiated leucine using a procedure similar to that used for measuring bacterial production by leucine incorporation and then stained with SYTO 13. Subpopulations of bacterial cells were sorted according to their average right-angle light scatter (RALS) and fluorescence. Average RALS was shown to be significantly related to the average biovolume. Experiments were performed on samples collected at different times in a Mediterranean seawater mesocosm enriched with nitrogen and phosphorus. At four sampling times, bacteria were sorted in two subpopulations (cells smaller and larger than 0.25 µm(3)). The results indicate that, at each sampling time, the growth rate of larger cells was higher than that of smaller cells. In order to confirm this tendency, cell sorting was performed on six subpopulations differing in average biovolume during the mesocosm follow-up. A clear increase of the bacterial growth rates was observed with increasing cell size for the conditions met in this enriched mesocosm.http://link.springer-ny.com/link/service/journals/00248/bibs/38n2p180.html
Optimization Research of Generation Investment Based on Linear Programming Model
NASA Astrophysics Data System (ADS)
Wu, Juan; Ge, Xueqian
Linear programming is an important branch of operational research and it is a mathematical method to assist the people to carry out scientific management. GAMS is an advanced simulation and optimization modeling language and it will combine a large number of complex mathematical programming, such as linear programming LP, nonlinear programming NLP, MIP and other mixed-integer programming with the system simulation. In this paper, based on the linear programming model, the optimized investment decision-making of generation is simulated and analyzed. At last, the optimal installed capacity of power plants and the final total cost are got, which provides the rational decision-making basis for optimized investments.
Press briefing on results from the solar spacecraft SOHO
NASA Astrophysics Data System (ADS)
1998-04-01
After its launch on 2 December 1995, SOHO travelled to take up a special orbit 1.5 million kilometres away on the sunward side of the Earth, where the Sun never sets. The full scientific programme began in April 1996. The occasion for the briefing is the celebration of that second anniversary and of the mission's extension to 2003. Organized by the European Space Agency, the briefing will be hosted by the Rutherford Appleton Laboratory, which is near Oxford. Leading scientists associated with SOHO will announce to the press some remarkable new discoveries about the Sun's interior, atmosphere and solar wind. They will also briefly review the main achievements of the past two years. The role of SOHO as the chief watchdog for storms on the Sun that may affect the Earth will be demonstrated. Europe's creation of the finest spacecraft ever built to observe the Sun will be recalled by a top engineer from ESA. A speaker from NASA will explain transatlantic contributions to SOHO, which is a project of international cooperation between ESA and NASA. ESA's director of science will also be present, to relate SOHO to ESA's general science programme. A lunch-time talk by the BNSC's director of science completes the line-up of speakers. This is also an exceptional opportunity for the press to meet and interview scientists from all over Europe and the USA, who are attending a meeting at the Rutherford Appleton Laboratory of SOHO's Science Working Team (SWT). Journalists are usually excluded from such meetings. The Rutherford Appleton Laboratory plays a prominent part in SOHO, particularly through its provision of the CDS ultraviolet spectrometer. A visit to the CDS group will provide a chance to see what space research is really like. Please indicate your intention to attend, on the accreditation form that follows the schedule. Guidance on how to get to the Rutherford Appleton Laboratory is appended. PROGRAMME Rutherford Appleton Laboratory (RAL), 28 April 1998 10:30 Assembly of media representatives, with coffee 11:00 Press briefing starts: welcome to RAL and SOHO Richard Harrison, RAL, principal investigator for SOHO/CDS Congratulatory remarks Roger Bonnet, Director of Science, European Space Agency, Paris The watch on the Sun, including images of the day from SOHO Richard Harrison and link to Goddard Space Flight Center SOHO: technological highlights John Credland, Head of Scientific Projects, ESTEC, Noordwijk International cooperation David Bohlin, National Aeronautics and Space Administration, USA Scientific highlights and news from SOHO: Inside the Sun (helioseismology) :Douglas Gough, University of Cambridge The Sun's atmosphere : Eric Priest, University of St Andrews The solar wind and particles : Antoinette Galvin, University of New Hampshire ESA's science programme : Roger Bonnet, Director of Science, European Space Agency, Paris 12:00 Questions and answers 12:15 Press visit to the SOHO/CDS facility at RAL 12:45 Buffet lunch, with remarks by: Paul Murdin, Director of Science, British National Space Centre, and Head of Astronomy, PPARC 12:15-14:00 Opportunities for interviews 14:00 Resumption of Science Working Team technical meeting - Media representatives are welcome to attend. SOHO Science Presentations : D. Gough - Helioseismology E. Priest - Solar Atmosphere A. Galvin - Solar Wind and Particles 15:30-16:00 Discussion and closing remarks
Queiroz, Cleriston Farias; Lemos, Antonio Carlos Moreira; Bastos, Maria de Lourdes Santana; Neves, Margarida Célia Lima Costa; Camelier, Aquiles Assunção; Carvalho, Natália Barbosa; Carvalho, Edgar Marcelino de
2016-01-01
To determine whether COPD severity correlates with sputum cell counts, atopy, and asthma. This was a cross-sectional study involving 37 patients with COPD and 22 healthy subjects with normal lung function (controls). Sputum cell counts were determined by microscopy after centrifugation of samples. Skin prick tests were performed, and serum cytokines were determined by ELISA. Patients were stratified by bronchodilator response: a non-reversible airflow limitation (nonRAL) group comprised 24 patients showing no significant post-bronchodilator change in FEV1; and a partially reversible airflow limitation (partialRAL) group comprised 13 patients showing FEV1 reversibility (post-bronchodilator FEV1 increase ≥ 12%). The proportion of eosinophils in sputum was higher in the partialRAL group than in the nonRAL group (p < 0.01), and there was an inverse correlation between the proportion of eosinophils and FEV1 (p < 0.05). However, none of the patients had a history of asthma and skin prick test results did not differ between the two groups. In the patient sputum samples, neutrophils predominated. Serum levels of TNF, IL-6, IL-8, and RANTES (CCL5) were higher in patients than in controls (p < 0.001) but did not differ between the two patient groups. COPD patients with partial FEV1 reversibility appear to have higher sputum eosinophil counts and greater airway hyperresponsiveness than do those with no FEV1 reversibility. However, we found that COPD severity did not correlate with atopy or with the cytokine profile. Determinar se a gravidade da DPOC se correlaciona com a contagem de células no escarro, atopia e asma. Estudo transversal com 37 pacientes com DPOC e 22 indivíduos saudáveis com função pulmonar normal (controles). As contagens de células no escarro foram determinadas por microscopia após a centrifugação das amostras. Foram realizados testes cutâneos de puntura, e as citocinas séricas foram determinadas por ELISA. Os pacientes foram estratificados pela resposta ao broncodilatador: o grupo de limitação ao fluxo aéreo não reversível (LFAnr) envolveu 24 pacientes sem alteração significativa do VEF1 pós-broncodilatador, e o grupo de limitação ao fluxo aéreo parcialmente reversível (LFApr) envolveu 13 pacientes com reversibilidade do VEF1 (aumento do VEF1 pós-broncodilatador ≥ 12%). A proporção de eosinófilos no escarro foi maior no grupo LFApr do que no LFAnr (p < 0,01), e houve uma correlação inversa entre a proporção de eosinófilos e VEF1 (p < 0,05). Entretanto, nenhum dos pacientes apresentou histórico de asma e os resultados dos testes cutâneos não diferiram entre os dois grupos. Nas amostras de escarro dos pacientes, os neutrófilos predominaram. Os níveis séricos de TNF, IL-6, IL-8 e RANTES (CCL5) foram maiores nos pacientes que nos controles (p < 0,001), mas não diferiram entre os dois grupos de pacientes. Pacientes com DPOC e reversibilidade parcial do VEF1 parecem apresentar maiores contagens de eosinófilos no escarro e maior hiper-responsividade das vias aéreas que aqueles sem reversibilidade do VEF1. Entretanto, a gravidade da DPOC não se correlacionou com atopia ou perfil das citocinas.
Warrant Officer Senior Course WOSC Evaluation.
1981-07-01
Finance 2 Principles of Economics II I Managerial Accounting (Graduate) I Marketing Management (Graduate) I Principles of Biology 2 Number of Students...34? ’)rocesi, T he 3’’?~- ’ ADP.’- Gon~wcrslo, i li tAdniastr: ja-ln Cili- an Porsonel Management 7 Sl1pplV 0-: --i i 2 Li Support Structlirk! (,r,. ral L.~ i...ing, a ontapuivar* d Ar,2a Soviet Irw CiS Class 81-1 SUBJECT HOURS Techniques of Management I Transactional Analysis 2 Economic Approach and Linear
Non-kinetic Targeting Risk Assessment Methodology (NKTRAM)
2014-07-22
kinetic inetic Targe J TGTs & E ement of ris s and dama ian / non-co Treaty Orga kinetic enga rce ( IATF ) t of selecting perational and prioritiza c...t e activities. T c engagemen is often inapp of a tank, is and Major S ( IATF ). ssessm opose a non ral Damage / munitions ting Risk As ) staff...prototype stage and is classified. As such, it will not be discussed or identified within this SL. In November 2013, the IATF red teamed the prototype
2011-05-01
la scurit. Je vous remercie de votre temps et de votre contribution. Susan G. McIntyre Knowledge Management/ Gestion du savoir...National Defence, 2011 © Sa Majesté la Reine (en droit du Canada), telle que représentée par le ministre de la Défense nationale, 2011 DRDC CSS TR 2011...avantages du renforcement de la communication horizontale au sein du gouvernement fédéral, surtout en présence d’organismes de
What Should Users Expect from Information Storage and Retrieval Systems of the 1980’s
1981-12-01
cide dcentrer sur ls marchE de l1information secondaire, on doit d~finir Is secteur , rschercher des appuis (coop~rants) pour couvrir cc secteur ...inutiles. Ii appartient bien entendu chaque Gouvernemant dlapprdcier sea prioritds, mais en se plagant dans Is cadre tracE. GOUVERNEMENT ET SECTEUR PRIVE A...directive A76 salon laqualle le Gouvernament f~d~ral slappuiera sur Is secteur priv6 pour publiar at dissminar llinformation scientifique at technique
Hurricane Impact on Gulf Coast Barriers.
1982-01-01
advaince and huge late-ral extent, Frederic de- ye Ii ped a large ,.toriin so rge. After en is~.in g Dauphin [,land, Alabama, Fredi’ric made landfill near...stratification Each set is some 10 to 20 cr0 These fans are characterized byv wide con tinhi-its upper-flow thick . Tahular cross-stratif aioofviblthcnsisa...Note lth ndward mingration swash bars along the fan crest . (See fig 1:3 P’,intFtlicati)n of thi, oblique aerial photo). Photo taken March 12. 19N
2006-01-01
Willingness to Compromise •Risk Avoidance •Time to Decision •Etc. The “What” ral Variation Behaviors •Context Sensitivity Values •Individualism vs ...Collectivism •Power Distance •Formality vs . informality •Uncertainty Avoidance •Relationship vs . Deal Focus •Long-term vs . Short term orientation •Time...Orientation Cognition •Reasoning Styles Cultural Variations Behaviors •Context Sensitivity Values •Individualism vs . Collectivism •Power Distance •Formality
1989-12-27
is important to note also that as interdisciplinary studies have gained in -kj ’- popularity, theories incorporating physical and behavi6ral hypothesis...have gained strength due to approaches which focus multiple measures on single factors. Th( study of military sustained performance/operations...related fields of study . These environmental and interdisciplinary areas of study are typically sleep deprivation, work load, exercise physiology
Portfolio optimization by using linear programing models based on genetic algorithm
NASA Astrophysics Data System (ADS)
Sukono; Hidayat, Y.; Lesmana, E.; Putra, A. S.; Napitupulu, H.; Supian, S.
2018-01-01
In this paper, we discussed the investment portfolio optimization using linear programming model based on genetic algorithms. It is assumed that the portfolio risk is measured by absolute standard deviation, and each investor has a risk tolerance on the investment portfolio. To complete the investment portfolio optimization problem, the issue is arranged into a linear programming model. Furthermore, determination of the optimum solution for linear programming is done by using a genetic algorithm. As a numerical illustration, we analyze some of the stocks traded on the capital market in Indonesia. Based on the analysis, it is shown that the portfolio optimization performed by genetic algorithm approach produces more optimal efficient portfolio, compared to the portfolio optimization performed by a linear programming algorithm approach. Therefore, genetic algorithms can be considered as an alternative on determining the investment portfolio optimization, particularly using linear programming models.
Conjugate gradient optimization programs for shuttle reentry
NASA Technical Reports Server (NTRS)
Powers, W. F.; Jacobson, R. A.; Leonard, D. A.
1972-01-01
Two computer programs for shuttle reentry trajectory optimization are listed and described. Both programs use the conjugate gradient method as the optimization procedure. The Phase 1 Program is developed in cartesian coordinates for a rotating spherical earth, and crossrange, downrange, maximum deceleration, total heating, and terminal speed, altitude, and flight path angle are included in the performance index. The programs make extensive use of subroutines so that they may be easily adapted to other atmospheric trajectory optimization problems.
Efficient dynamic optimization of logic programs
NASA Technical Reports Server (NTRS)
Laird, Phil
1992-01-01
A summary is given of the dynamic optimization approach to speed up learning for logic programs. The problem is to restructure a recursive program into an equivalent program whose expected performance is optimal for an unknown but fixed population of problem instances. We define the term 'optimal' relative to the source of input instances and sketch an algorithm that can come within a logarithmic factor of optimal with high probability. Finally, we show that finding high-utility unfolding operations (such as EBG) can be reduced to clause reordering.
Surgeons' perceptions and injuries during and after urologic laparoscopic surgery.
Gofrit, Ofer N; Mikahail, Albert A; Zorn, Kevin C; Zagaja, Gregory P; Steinberg, Gary D; Shalhav, Arieh L
2008-03-01
The biomechanical and mental strains placed on the surgeon while performing laparoscopic procedures are significantly higher compared with open surgical techniques. We undertook this study to assess the prevalence of surgeons' deleterious perceptions or injuries related to laparoscopic urologic surgery. Members of endourological society were mailed a questionnaire evaluating their laparoscopic experience, total number of standard laparoscopic surgeries (SLS), hand-assisted laparoscopic surgeries (HALS), and robotic-assisted laparoscopic surgeries (RALS) they performed. The subjects reported any neuromuscular or arthritic injuries sustained during laparoscopic surgery, and graded the degree of pain, numbness, and fatigue they experienced. A total of 73 urologists completed the questionnaires. The average responder was 44 years old, had completed a median of 117 procedures, and was performing 3 laparoscopic surgeries per week. Neuromuscular or arthritic symptoms during surgery were reported by 22 responders (30%), the most common was finger paresthesia (18%). At the conclusion of HALS, 45% of the surgeons suffered from hand and wrist numbness and 37% reported pain in these areas. A significant association was observed between the risk of sustaining injury during surgery and the total number of laparoscopic procedures performed by the responder (P = 0.016). RALS was the procedure least associated with injuries, and HALS the most. The laparoscopic operating theater is a hostile ergonomic environment. Surgeons' awareness of the common injuries associated with laparoscopic surgery and careful equipment adjustments before surgery are mandatory to minimize injury. Future improvements in instrument design according to ergonomic principles are highly warranted.
Performance characterization of the EarthCARE BBR Detectors
NASA Astrophysics Data System (ADS)
Proulx, C.; Allard, M.; Pope, T.; Tremblay, B.; Williamson, F.; Julien, C.; Larouche, C.; Delderfield, J.; Parker, D.
2017-11-01
The Broadband Radiometer (BBR) is an instrument being developed for the ESA EarthCARE satellite. The BBR instrument objective is to provide measurements of the reflected short-wave (0.25-4.0 μm) and emitted long-wave (4.0-50 μm) top of the atmosphere (TOA) radiance over three along-track views (forward, nadir and backward). The instrument has three fixed telescopes, one for each view, each containing a broadband detector. The BBR instrument is led by SEA in the UK with RAL responsible for the BBR optics unit (OU) while EADS Astrium is the EarthCARE prime contractor. A detailed description of the instrument is provided in [1]. The BBR detectors consist in three dedicated assemblies under the responsibility of INO. The detectors development started in 2008 and led to the design and implementation of a new gold black deposition facility at INO [2], in parallel with the preliminary and detailed design phases of the detector assemblies. As of today, two breadboard models and one engineering model have been delivered to RAL. In the BBR OU each detector mechanically interfaces with the telescope and electrically with the front-end electronics (FEE). The detectors' development is now at the Critical Design Review (CDR) level. This paper first provides a description of the detector design along with its principles of operation. It further presents and discusses measurement and analysis results for the performance characterization of the engineering model in the context of the applicable requirements. Detector-level qualification planning is finally discussed.
Grover, Vishakha; Malhotra, Ranjan; Kapoor, Anoop; Bither, Rupika; Sachdeva, Sonia
2016-01-01
Current clinical periodontal diagnostic techniques emphasize the assessment of clinical and radiographic signs of periodontal diseases which can provide a measure of history of disease. Hence, new methodologies for early identification and determination of periodontal disease activity need to be explored which will eventually result in expedited treatment. To evaluate the correlation of alkaline phosphatase (ALP) activity in gingival crevicular fluid (GCF) to clinical parameters of periodontal inflammation in smokers with chronic periodontitis. Study population included 15 smoker male patients in the age group of 35-55 years suffering from moderate generalized chronic periodontitis with history of smoking present. Following parameters were evaluated at baseline, 1 month and 3 months after scaling and root planing: plaque index, bleeding index, probing pocket depth (PD), relative attachment level (RAL), and GCF ALP activity. Independent variables for measurements over time were analyzed by using Wilcoxon signed rank test. A statistically significant reduction in all the clinical parameters and GCF ALP activity was observed from baseline to 1 month and 3 months. A correlation was observed between change in GCF ALP activity and PD reduction as well as gain in RAL at 3 months. The present study emphasizes that total ALP activity could be used as a marker for periodontal disease activity in smokers. Estimation of changes in the levels of this enzyme has a potential to aid in the detection of progression of periodontal disease and monitoring the response to periodontal therapy.
A new implementation of the programming system for structural synthesis (PROSSS-2)
NASA Technical Reports Server (NTRS)
Rogers, James L., Jr.
1984-01-01
This new implementation of the PROgramming System for Structural Synthesis (PROSSS-2) combines a general-purpose finite element computer program for structural analysis, a state-of-the-art optimization program, and several user-supplied, problem-dependent computer programs. The results are flexibility of the optimization procedure, organization, and versatility of the formulation of constraints and design variables. The analysis-optimization process results in a minimized objective function, typically the mass. The analysis and optimization programs are executed repeatedly by looping through the system until the process is stopped by a user-defined termination criterion. However, some of the analysis, such as model definition, need only be one time and the results are saved for future use. The user must write some small, simple FORTRAN programs to interface between the analysis and optimization programs. One of these programs, the front processor, converts the design variables output from the optimizer into the suitable format for input into the analyzer. Another, the end processor, retrieves the behavior variables and, optionally, their gradients from the analysis program and evaluates the objective function and constraints and optionally their gradients. These quantities are output in a format suitable for input into the optimizer. These user-supplied programs are problem-dependent because they depend primarily upon which finite elements are being used in the model. PROSSS-2 differs from the original PROSSS in that the optimizer and front and end processors have been integrated into the finite element computer program. This was done to reduce the complexity and increase portability of the system, and to take advantage of the data handling features found in the finite element program.
Zhao, Bei-Bei; Li, Xiang-Hui; Zeng, Yong-Lun; Lu, Yong-Jun
2016-08-02
The opportunistic bacterial pathogen Legionella pneumophila uses substrate effectors of Dot/Icm type IVB secretion system (T4BSS) to accomplish survival and replication in amoebae cells and mammalian alveolar macrophages. During the conversion between its highly resistant, infectious dormant form and vigorously growing, uninfectious replicative form, L. pneumophila utilizes a complicated regulatory network in which proteolysis may play a significant role. As a highly conserved core protease, ClpP is involved in various cellular processes as well as virulence in bacteria, and has been proved to be required for the expression of transmission traits and cell division of L. pneumophila. The clpP-deficient L. pneumophila strain failed to replicate and was digested in the first 3 h post-infection in mammalian cells J774A.1. Further investigation demonstrates that the clpP deficient mutant strain was unable to escape the endosome-lysosomal pathway in host cells. We also found that the clpP deficient mutant strain still expresses T4BSS components, induces contact-dependent cytotoxicity and translocate effector proteins RalF and LegK2, indicating that its T4BSS was overall functional. Interestingly, we further found that the translocation of several effector proteins is significantly reduced without ClpP. The data indicate that ClpP plays an important role in regulating the virulence and effector translocation of Legionella pneumophila.
Madeddu, Giordano; Rusconi, Stefano; Cozzi-Lepri, Alessandro; Di Giambenedetto, Simona; Bonora, Stefano; Carbone, Alessia; De Luca, Andrea; Gianotti, Nicola; Di Biagio, Antonio; Antinori, Andrea
2017-08-01
Nucleos(t)ide reverse transcriptase inhibitors (NRTI) toxicity may represent a threat for long-term success of combined antiretroviral therapy. Some studies have suggested a possible improvement of NRTI-related toxicity after switching to NRTI-sparing regimens. We aimed to explore the efficacy and tolerability of switching to darunavir/ritonavir (DRV/r) plus raltegravir (RAL) while having a viral load (VL) ≤50 copies/mL in the clinical setting. Treatment-experienced HIV 1-infected patients enrolled in the ICONA Foundation Study cohort were included if they switched their current regimen to DRV/r + RAL with a HIV-RNA ≤50 copies/mL. Different definitions of virological failure (VF) and treatment failure (TF) were employed. Kaplan-Meier curves and Cox regression models were performed to estimate time to event probability. We included 72 HIV-infected patients, 22 (31%) of these were female, 31 (43%) men who have sex with men (MSM) amd 15 (21%) had hepatitis co-infections. Median age was 44 (IQR: 35-50) years amd CD4 count was 389 (IQR 283-606) cells/mmc. Median follow-up time for TF was 24 (IQR 9-31) months. Twenty-five discontinuations occurred (60% simplifications); only 2 (8%) were toxicity-driven (lipid elevations). The probability of VF (confirmed VL >50 copies/mL) was estimated at 7% [95% confidence interval (CI) 1-13%] by 12 and 9% (95% CI 2-16%) by 24 months. When considering TF, we found a probability of stop/intensification/single VL > 200 copies/mL of 13% (95% CI 1-17%) and 22% (95% CI 11-33%) by 12 and 24 months. Female gender (adjusted relative hazard, ARH = 0.10; 95% CI 0.01-0.74; p = 0.024) and older age (AHR = 0.50 per 10 years older; 95% CI 0.25-0.99; p = 0.045) were associated with a lower risk of TF. A previous PI failure was strongly associated with TF (AHR = 52.6, 95% CI 3.6-779; p = 0.004). DRV/r + RAL is a valuable NRTI-sparing option, especially in female and older patients, with a relatively low risk of VF and good tolerability after 2 years since start in an ART-experienced population. However, previous PI-failure should be a limiting factor for this strategy.
Moreno Guillen, Santiago; Losa García, Juan Emilio; Berenguer Berenguer, Juan; Martínez Sesmero, José Manuel; Cenoz Gomis, Santiago; Graefenhain, Ruth; Lopez Sanchez-Cambronero, David; Parrondo Garcia, Francisco Javier
2017-09-01
Fixed-dose combinations of antiretroviral drugs have meant an important step forward in simplifying treatment and improving compliance and has led to an increased effectiveness of therapy, a viral load decrease and improving the quality of life of patients. The single-table formulation of dolutegravir with abacavir and lamivudine (DTG/ABC/3TC) is a highly efficacious and well-tolerated once-daily regimen for HIV-infected patients. The objective of the study was to assess the incremental cost-utility ratio of the fixed-dose combination of (DTG/ABC/3TC) versus the combinations emtricitabine/tenofovir/efavirenz (FTC/TDF/EFV), and darunavir/r (DRV/r) or raltegravir (RAL) with emtricitabine/tenofovir (FTC/TDF) or abacavir/lamivudine (ABC/3TC) as initial antiretroviral therapy in patients infected with HIV-1 from the perspective of the Spanish National Health System. The ARAMIS model, which uses a microsimulation approach to simulate the individual changes in each patient from the start of treatment to death through a Markov chain of descriptive health states of the disease, was adapted to Spain. The alternatives used for comparison were the fixed-dose combination of emtricitabine/tenofovir/efavirenz (FTC/TDF/EFV), and the fixed- dose combinations of emtricitabine/tenofovir (FTC/TDF) or abacavir/lamivudine (ABC/3TC) with darunavir/r (DRV/r) or raltegravir (RAL). The probability of achieving virological suppression by the treatments included in the model was obtained from clinical trials SINGLE, SPRING-2 and FLAMINGO and the costs were expressed in € (2015). The model use the perspective of the Spanish National Health System, with a lifetime horizon and a discount rate of 3% was applied to cost and effectiveness. Treatment initiation with DTG/ABC/3TC was dominant when it was compared with treatment initiation with all the comparators: vs. FTC/TDF/EFV (-67 210.71€/QALY), vs. DRV/r + FTC/TDF or ABC/3TC (-1 787 341.44€/QALY), and vs. RAL + FTC/TDF or ABC/3TC (-1 005 117.13€/QALY). All the sensitivity analyses performed showed the consistency of these findings. With the premises considered, treatment initiation with DTG/ABC/3TC STR appears to be the most cost-effective option in ARTnaïve HIV infected patients from the Spanish Health System perspective. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.
1983-08-01
bedrock. Reservoir deposits are rich in silt and clay as shown by the plastic nature of material behind Cave Creek Dam. Recent alluvium is directly...formation and the zone I, impervious material. Then rolling with the rubber tired equipment would fill voids and small cracks with the clayey, plastic ...Assoclates US " 2 t 64urvey air J.1y 1969. ___OSOWRS g.Aorizatnfa( conirol ji 45 on G1A - EEA fSI Alaon~ral ieodtc Survey Dafum. Yerftci 4 1 -5 AtE
A New Optical Technique for Rapid Determination of Creep and Fatigue Thresholds at High Temperature.
1984-04-01
measurements, made far away from the crack tip, produced much smoother and more sensible results. Measurements by Macha et al (16) agree very well with...dependent upon the measurement positin. It becomes independent of position far enough away from the tip; this is consistent with the results of Macha , et...D. E. Macha , W. N. Sharpe, Jr., and A. P. ’ral(11, ’.., "A Laser Interferometry Method for ,xp.rim,-rit;a1 Stress Intensity Factor Calibration", AST
Artificial Intelligence -- Research and Applications.
1976-06-01
Determination of Minimum Cost Paths," IEEE Trans. Sys . Sci. Cybernetics, Vol. 4, No. 2, pp. 100-107. Hendrix, G. (1975), "Expanding the Utility of Semantic...PLANS E , IN, 7979 IZ)’. TE.R ATE RECOGNITION LASEHTAED LOCATION SENP PARTS ANO AAlYI CONIP E TELOMPL T FP NET SSTEMCOMPRS SY -STy 7974 ’T S ST7p -TO...EXTNDE 1: OUBLE -ETNE %AT,,RAL ~C’v LA ~t PB IV P6 TO T4 %~ ’ F" _______________________________________ SY ~STEM 7’j NTJt, E EPAk AAII IJ Aii SASSEVELY
In Situ/on-Site Biodegradation of Refined Oils and Fuels (A Technology Review). Volume 1.
1992-06-01
209. Atlas, R.M. and Bartha, R. 1972a. Biodegradation of petroleum in seawater at low temperatures. Can. J . Microbiol. 18:1851-1855. Atlas, R.M. and...Becking, L.G.M., Kaplan, I.R., and Moore, 0. 1960. Limits of the natu- ral environment in terms of pH and oxidation-reduction potentials. J . Geolo- gy. 68...of subsurface mi- croorganisms. Abstr. Ann. Mtg. Amer. Soc. Microbiol. p. 192. Ballester, A. and Castelvi, J . 1980. J . Invest. Pes. 44:1. 115
Spectroscopic Constants for Selected Homonuclear Diatomic Molecules. Volume 1. A through I
1976-02-16
n 00 ro O ro ro rg p - ro o in o o (M... P W en n ) + 3 W < n u + 13 W u ^ o o (M "*• tn en en TTT m in in o i n ^< •x) 00 < n I II in o >—i X oo - SO...00 —1 R) O •- 0 O n « .2 P A-25 I ^IIMHPWJ::"«!! As,. Perturbations and Genr ral Information Potential energy curves (67.10): State V
1994-05-01
actuel. Trois types de contraintes ont pu 8tre distingu6s A chaque avion pr6sent dans le secteur a~rien du contr~leur, on associe toutes les...assurant la s6curit6 des vols. simulateur implique en g6n6ral la prdsencc dc trois catdgories d’acteurs Los 6changyes entre contr~leur et pilote se...d’informations suivants interventions en phonic des pilotes d’avions presents dans le secteur de contr-blc. Pour cc faire, 1) utilisant des liaisons de donn
A Field Study of Air Force Organization Structures.
1984-05-01
t.ral 1z,,- contract . 66-1 and 66-5 are the numbered regulations ... eo coer’. , of design. Contract refers to the design used in a facility where...REPORT NUMBER (S) 5 MONITORING ORGANIZATION RLPORT NuMHLF1H’ LMDC-TR-34-4 6& NAME OF PERFORMING ORGANIZATION Fr. O IE SYMBOL 7a NAME OF MONITORING ORGANIZA...assi f ied 22& NAME OF RESPONSIBLE IN0IVIO~jA. 22t, TELEPHONE NUMBER 22c OFF ICE SY(MBOL Capt Jeffrey S. Austin (0)2373 MCA DOD FORM 1473,83 APR
1981-06-01
be Blow-off pipes in urban areas will be required to "clear" Cache Slough for the fenced to screen them from children , intake would be approximately...tip of Grand numbers of school-aged children . Island southeast of the intake locations. This disposal site, which would probably be best reached by...ind shel I h eads to Porno , Cent ral Wiat un , Wappo :in(I ’e()Ll! litrn Ma idu groups (Davis, 1974 :34-35). of the most distinctive asp~ect.,- of
1984-12-01
with more gene - ral arrival process or service-time distribution, with attention restricted to critical-number policies, have been studied by Adler...points of their respective intervals. This method proved quite satisfactory for df’s that possess no sharp peaks or severe skewness. The method is...then (animal is carnivore))) (rule id6 (if (animal has pointed teeth ) (animal has claws) (animal has forward eyes)) (then (animal is carnivore
Advanced Avionics and the Military Aircraft Man/Machine Interface.
1982-07-01
voiture au bas c~t6 de la route, angle d’incidence de l’aile, etc ... Le domaine de variation de chacun de ces param~tres de fonctionnement est en gdn6...ral limit6. Les limites, du domaine autoris6 sont bien souvent floues ; en toute rigueur il faut adniettre qu’au milieu du domaine autoristi, la...rapidement catastrophique 11 est n6anmoihs commode de parler de limite de domaine autoris6 pour chaque para- m~tre de fonctionnement tout en gardant A
Cache Locality Optimization for Recursive Programs
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lifflander, Jonathan; Krishnamoorthy, Sriram
We present an approach to optimize the cache locality for recursive programs by dynamically splicing--recursively interleaving--the execution of distinct function invocations. By utilizing data effect annotations, we identify concurrency and data reuse opportunities across function invocations and interleave them to reduce reuse distance. We present algorithms that efficiently track effects in recursive programs, detect interference and dependencies, and interleave execution of function invocations using user-level (non-kernel) lightweight threads. To enable multi-core execution, a program is parallelized using a nested fork/join programming model. Our cache optimization strategy is designed to work in the context of a random work stealing scheduler. Wemore » present an implementation using the MIT Cilk framework that demonstrates significant improvements in sequential and parallel performance, competitive with a state-of-the-art compile-time optimizer for loop programs and a domain- specific optimizer for stencil programs.« less
Review: Optimization methods for groundwater modeling and management
NASA Astrophysics Data System (ADS)
Yeh, William W.-G.
2015-09-01
Optimization methods have been used in groundwater modeling as well as for the planning and management of groundwater systems. This paper reviews and evaluates the various optimization methods that have been used for solving the inverse problem of parameter identification (estimation), experimental design, and groundwater planning and management. Various model selection criteria are discussed, as well as criteria used for model discrimination. The inverse problem of parameter identification concerns the optimal determination of model parameters using water-level observations. In general, the optimal experimental design seeks to find sampling strategies for the purpose of estimating the unknown model parameters. A typical objective of optimal conjunctive-use planning of surface water and groundwater is to minimize the operational costs of meeting water demand. The optimization methods include mathematical programming techniques such as linear programming, quadratic programming, dynamic programming, stochastic programming, nonlinear programming, and the global search algorithms such as genetic algorithms, simulated annealing, and tabu search. Emphasis is placed on groundwater flow problems as opposed to contaminant transport problems. A typical two-dimensional groundwater flow problem is used to explain the basic formulations and algorithms that have been used to solve the formulated optimization problems.
Performance Analysis and Design Synthesis (PADS) computer program. Volume 1: Formulation
NASA Technical Reports Server (NTRS)
1972-01-01
The program formulation for PADS computer program is presented. It can size launch vehicles in conjunction with calculus-of-variations optimal trajectories and can also be used as a general-purpose branched trajectory optimization program. In the former use, it has the Space Shuttle Synthesis Program as well as a simplified stage weight module for optimally sizing manned recoverable launch vehicles. For trajectory optimization alone or with sizing, PADS has two trajectory modules. The first trajectory module uses the method of steepest descent; the second employs the method of quasilinearization, which requires a starting solution from the first trajectory module.
A survey of compiler optimization techniques
NASA Technical Reports Server (NTRS)
Schneck, P. B.
1972-01-01
Major optimization techniques of compilers are described and grouped into three categories: machine dependent, architecture dependent, and architecture independent. Machine-dependent optimizations tend to be local and are performed upon short spans of generated code by using particular properties of an instruction set to reduce the time or space required by a program. Architecture-dependent optimizations are global and are performed while generating code. These optimizations consider the structure of a computer, but not its detailed instruction set. Architecture independent optimizations are also global but are based on analysis of the program flow graph and the dependencies among statements of source program. A conceptual review of a universal optimizer that performs architecture-independent optimizations at source-code level is also presented.
Federal Register 2010, 2011, 2012, 2013, 2014
2013-09-20
... (NOA) for Strategic Network Optimization (SNO) Program Environmental Assessment AGENCY: Defense Logistics Agency, DoD. ACTION: Notice of Availability (NOA) for Strategic Network Optimization (SNO) Program... implement the SNO initiative for improvements to material distribution network for the Department of Defense...
Program to Optimize Simulated Trajectories (POST). Volume 1: Formulation manual
NASA Technical Reports Server (NTRS)
Brauer, G. L.; Cornick, D. E.; Habeger, A. R.; Petersen, F. M.; Stevenson, R.
1975-01-01
A general purpose FORTRAN program for simulating and optimizing point mass trajectories (POST) of aerospace vehicles is described. The equations and the numerical techniques used in the program are documented. Topics discussed include: coordinate systems, planet model, trajectory simulation, auxiliary calculations, and targeting and optimization.
NASA Technical Reports Server (NTRS)
Pavarini, C.
1974-01-01
Work in two somewhat distinct areas is presented. First, the optimal system design problem for a Mars-roving vehicle is attacked by creating static system models and a system evaluation function and optimizing via nonlinear programming techniques. The second area concerns the problem of perturbed-optimal solutions. Given an initial perturbation in an element of the solution to a nonlinear programming problem, a linear method is determined to approximate the optimal readjustments of the other elements of the solution. Then, the sensitivity of the Mars rover designs is described by application of this method.
NASA Astrophysics Data System (ADS)
Wihartiko, F. D.; Wijayanti, H.; Virgantari, F.
2018-03-01
Genetic Algorithm (GA) is a common algorithm used to solve optimization problems with artificial intelligence approach. Similarly, the Particle Swarm Optimization (PSO) algorithm. Both algorithms have different advantages and disadvantages when applied to the case of optimization of the Model Integer Programming for Bus Timetabling Problem (MIPBTP), where in the case of MIPBTP will be found the optimal number of trips confronted with various constraints. The comparison results show that the PSO algorithm is superior in terms of complexity, accuracy, iteration and program simplicity in finding the optimal solution.
Duarte, Belmiro P.M.; Wong, Weng Kee; Atkinson, Anthony C.
2016-01-01
T-optimum designs for model discrimination are notoriously difficult to find because of the computational difficulty involved in solving an optimization problem that involves two layers of optimization. Only a handful of analytical T-optimal designs are available for the simplest problems; the rest in the literature are found using specialized numerical procedures for a specific problem. We propose a potentially more systematic and general way for finding T-optimal designs using a Semi-Infinite Programming (SIP) approach. The strategy requires that we first reformulate the original minimax or maximin optimization problem into an equivalent semi-infinite program and solve it using an exchange-based method where lower and upper bounds produced by solving the outer and the inner programs, are iterated to convergence. A global Nonlinear Programming (NLP) solver is used to handle the subproblems, thus finding the optimal design and the least favorable parametric configuration that minimizes the residual sum of squares from the alternative or test models. We also use a nonlinear program to check the global optimality of the SIP-generated design and automate the construction of globally optimal designs. The algorithm is successfully used to produce results that coincide with several T-optimal designs reported in the literature for various types of model discrimination problems with normally distributed errors. However, our method is more general, merely requiring that the parameters of the model be estimated by a numerical optimization. PMID:27330230
Duarte, Belmiro P M; Wong, Weng Kee; Atkinson, Anthony C
2015-03-01
T-optimum designs for model discrimination are notoriously difficult to find because of the computational difficulty involved in solving an optimization problem that involves two layers of optimization. Only a handful of analytical T-optimal designs are available for the simplest problems; the rest in the literature are found using specialized numerical procedures for a specific problem. We propose a potentially more systematic and general way for finding T-optimal designs using a Semi-Infinite Programming (SIP) approach. The strategy requires that we first reformulate the original minimax or maximin optimization problem into an equivalent semi-infinite program and solve it using an exchange-based method where lower and upper bounds produced by solving the outer and the inner programs, are iterated to convergence. A global Nonlinear Programming (NLP) solver is used to handle the subproblems, thus finding the optimal design and the least favorable parametric configuration that minimizes the residual sum of squares from the alternative or test models. We also use a nonlinear program to check the global optimality of the SIP-generated design and automate the construction of globally optimal designs. The algorithm is successfully used to produce results that coincide with several T-optimal designs reported in the literature for various types of model discrimination problems with normally distributed errors. However, our method is more general, merely requiring that the parameters of the model be estimated by a numerical optimization.
Christiaens, Véronique; De Bruyn, Hugo; Thevissen, Eric; Koole, Sebastiaan; Dierens, Melissa; Cosyn, Jan
2018-01-01
The accuracy of analogue and especially digital intra-oral radiography in assessing interdental bone level needs further documentation. The aim of this study was to compare clinical and radiographic bone level assessment to intra-surgical bone level registration (1) and to identify the clinical variables rendering interdental bone level assessment inaccurate (2). The study sample included 49 interdental sites in 17 periodontitis patients. Evaluation methods included vertical relative probing attachment level (RAL-V), analogue and digital intra-oral radiography and bone sounding without and with flap elevation. The latter was considered the true bone level. Five examiners evaluated all radiographs. Significant underestimation of the true bone level was observed for all evaluation methods pointing to 2.7 mm on average for analogue radiography, 2.5 mm for digital radiography, 1.8 mm for RAL-V and 0.6 mm for bone sounding without flap elevation (p < 0.001). Radiographic underestimation of the true bone level was higher in the (pre)molar region (p ≤ 0.047) and increased with defect depth (p < 0.001). Variation between clinicians was huge (range analogue radiography 2.2-3.2 mm; range digital radiography 2.1-3.0 mm). All evaluation methods significantly underestimated the true bone level. Bone sounding was most accurate, whereas intra-oral radiographs were least accurate. Deep periodontal defects in the (pre)molar region were most underrated by intra-oral radiography. Bone sounding had the highest accuracy in assessing interdental bone level.
The HEXITEC Hard X-Ray Pixelated CdTe Imager for Fast Solar Observations
NASA Technical Reports Server (NTRS)
Baumgartner, Wayne H.; Christe, Steven D.; Ryan, Daniel; Inglis, Andrew R.; Shih, Albert Y.; Gregory, Kyle; Wilson, Matt; Seller, Paul; Gaskin, Jessica; Wilson-Hodge, Colleen
2016-01-01
There is an increasing demand in solar and astrophysics for high resolution X-ray spectroscopic imaging. Such observations would present ground breaking opportunities to study the poorly understood high energy processes in our solar system and beyond, such as solar flares, X-ray binaries, and active galactic nuclei. However, such observations require a new breed of solid state detectors sensitive to high energy X-rays with fine independent pixels to sub-sample the point spread function (PSF) of the X-ray optics. For solar observations in particular, they must also be capable of handling very high count rates as photon fluxes from solar flares often cause pile up and saturation in present generation detectors. The Rutherford Appleton Laboratory (RAL) has recently developed a new cadmium telluride (CdTe) detector system, called HEXITEC (High Energy X-ray Imaging Technology). It is an 80 x 80 array of 250 micron independent pixels sensitive in the 2-200 keV band and capable of a high full frame read out rate of 10 kHz. HEXITEC provides the smallest independently read out CdTe pixels currently available, and are well matched to the few arcsecond PSF produced by current and next generation hard X-ray focusing optics. NASA's Goddard and Marshall Space Flight Centers are collaborating with RAL to develop these detectors for use on future space borne hard X-ray focusing telescopes. We show the latest results on HEXITEC's imaging capability, energy resolution, high read out rate, and reveal it to be ideal for such future instruments.
Maladie de Takayasu et polyarthrite rhumatoïde: une association rare - à propos d'une observation
Frikha, Faten; Maazoun, Fatma; Snoussi, Mouna; Abid, Leila; Abid, Hanen; Bouassida, Walid; Kaddour, Neila; Bahloul, Zouhir
2012-01-01
L'artérite de Takayasu ou maladie de Takayasu (MT) et la polyarthrite rhumatoïde (PR) et sont deux maladies inflammatoires chroniques et leur association a été rapportée dans la littérature à travers quelques observations de cas sporadiques. Nous rapportons une nouvelle observation d'une telle association. Une patiente âgée de 44 ans, diagnostiquée avec une polyarthrite rhumatoïde à facteur rhumatoïde positif, qui a développé des céphalées avec des vertiges de caractère permanent. L'examen révélait un pouls radial et huméral abolis à droite, un souffle carotidien bilatéral et une tension artérielle imprenable à droite. L'artériographie a confirmé la présence d'une atteinte de l'arc aortique type MT. Le diagnostic d'une maladie de Takayasu associée à une polyarthrite rhumatoïde était retenu. La patiente était traitée par une corticothérapie (prednisone à la dose de 0,5 mg/kg par jour) et un traitement de fond par Méthotrexate avec une bonne réponse initiale. A travers notre observation et une revue de la littérature, les caractéristiques épidémiologiques, étiopathogéniques, cliniques, thérapeutiques et évolutives de cette association seront discutées. PMID:22937201
Zaghloul, Mohamed A S; Wang, Mohan; Huang, Sheng; Hnatovsky, Cyril; Grobnic, Dan; Mihailov, Stephen; Li, Ming-Jun; Carpenter, David; Hu, Lin-Wen; Daw, Joshua; Laffont, Guillaume; Nehr, Simon; Chen, Kevin P
2018-04-30
This paper reports the testing results of radiation resistant fiber Bragg grating (FBG) in random air-line (RAL) fibers in comparison with FBGs in other radiation-hardened fibers. FBGs in RAL fibers were fabricated by 80 fs ultrafast laser pulse using a phase mask approach. The fiber Bragg gratings tests were carried out in the core region of a 6 MW MIT research reactor (MITR) at a steady temperature above 600°C and an average fast neutron (>1 MeV) flux >1.2 × 10 14 n/cm 2 /s. Fifty five-day tests of FBG sensors showed less than 5 dB reduction in FBG peak strength after over 1 × 10 20 n/cm 2 of accumulated fast neutron dose. The radiation-induced compaction of FBG sensors produced less than 5.5 nm FBG wavelength shift toward shorter wavelength. To test temporal responses of FBG sensors, a number of reactor anomaly events were artificially created to abruptly change reactor power, temperature, and neutron flux over short periods of time. The thermal sensitivity and temporal responses of FBGs were determined at different accumulated doses of neutron flux. Results presented in this paper reveal that temperature-stable Type-II FBGs fabricated in radiation-hardened fibers can survive harsh in-pile conditions. Despite large parameter drift induced by strong nuclear radiation, further engineering and innovation on both optical fibers and fiber devices could lead to useful fiber sensors for various in-pile measurements to improve safety and efficiency of existing and next generation nuclear reactors.
NASA Technical Reports Server (NTRS)
Mann, F. I.; Horsewood, J. L.
1974-01-01
Modifications and improvements are described that were made to the HILTOP electric propulsion trajectory optimization computer program during calendar years 1973 and 1974. New program features include the simulation of power degradation, housekeeping power, launch asymptote declination optimization, and powered and unpowered ballistic multiple swingby missions with an optional deep space burn.
Optimal Repair And Replacement Policy For A System With Multiple Components
2016-06-17
Numerical Demonstration To implement the linear program, we use the Python Programming Language (PSF 2016) with the Pyomo optimization modeling language...opre.1040.0133. Hart, W.E., C. Laird, J. Watson, D.L. Woodruff. 2012. Pyomo–optimization modeling in python , vol. 67. Springer Science & Business...Media. Hart, W.E., J. Watson, D.L. Woodruff. 2011. Pyomo: modeling and solving mathematical programs in python . Mathematical Programming Computation 3(3
A programing system for research and applications in structural optimization
NASA Technical Reports Server (NTRS)
Sobieszczanski-Sobieski, J.; Rogers, J. L., Jr.
1981-01-01
The paper describes a computer programming system designed to be used for methodology research as well as applications in structural optimization. The flexibility necessary for such diverse utilizations is achieved by combining, in a modular manner, a state-of-the-art optimization program, a production level structural analysis program, and user supplied and problem dependent interface programs. Standard utility capabilities existing in modern computer operating systems are used to integrate these programs. This approach results in flexibility of the optimization procedure organization and versatility in the formulation of contraints and design variables. Features shown in numerical examples include: (1) variability of structural layout and overall shape geometry, (2) static strength and stiffness constraints, (3) local buckling failure, and (4) vibration constraints. The paper concludes with a review of the further development trends of this programing system.
Structural optimization: Status and promise
NASA Astrophysics Data System (ADS)
Kamat, Manohar P.
Chapters contained in this book include fundamental concepts of optimum design, mathematical programming methods for constrained optimization, function approximations, approximate reanalysis methods, dual mathematical programming methods for constrained optimization, a generalized optimality criteria method, and a tutorial and survey of multicriteria optimization in engineering. Also included are chapters on the compromise decision support problem and the adaptive linear programming algorithm, sensitivity analyses of discrete and distributed systems, the design sensitivity analysis of nonlinear structures, optimization by decomposition, mixed elements in shape sensitivity analysis of structures based on local criteria, and optimization of stiffened cylindrical shells subjected to destabilizing loads. Other chapters are on applications to fixed-wing aircraft and spacecraft, integrated optimum structural and control design, modeling concurrency in the design of composite structures, and tools for structural optimization. (No individual items are abstracted in this volume)
NASA Technical Reports Server (NTRS)
1972-01-01
The Performance Analysis and Design Synthesis (PADS) computer program has a two-fold purpose. It can size launch vehicles in conjunction with calculus-of-variations optimal trajectories and can also be used as a general-purpose branched trajectory optimization program. In the former use, it has the Space Shuttle Synthesis Program as well as a simplified stage weight module for optimally sizing manned recoverable launch vehicles. For trajectory optimization alone or with sizing, PADS has two trajectory modules. The first trajectory module uses the method of steepest descent; the second employs the method of quasilinearization, which requires a starting solution from the first trajectory module. For Volume 1 see N73-13199.
Program manual for ASTOP, an Arbitrary space trajectory optimization program
NASA Technical Reports Server (NTRS)
Horsewood, J. L.
1974-01-01
The ASTOP program (an Arbitrary Space Trajectory Optimization Program) designed to generate optimum low-thrust trajectories in an N-body field while satisfying selected hardware and operational constraints is presented. The trajectory is divided into a number of segments or arcs over which the control is held constant. This constant control over each arc is optimized using a parameter optimization scheme based on gradient techniques. A modified Encke formulation of the equations of motion is employed. The program provides a wide range of constraint, end conditions, and performance index options. The basic approach is conducive to future expansion of features such as the incorporation of new constraints and the addition of new end conditions.
New reflective symmetry design capability in the JPL-IDEAS Structure Optimization Program
NASA Technical Reports Server (NTRS)
Strain, D.; Levy, R.
1986-01-01
The JPL-IDEAS antenna structure analysis and design optimization computer program was modified to process half structure models of symmetric structures subjected to arbitrary external static loads, synthesize the performance, and optimize the design of the full structure. Significant savings in computation time and cost (more than 50%) were achieved compared to the cost of full model computer runs. The addition of the new reflective symmetry analysis design capabilities to the IDEAS program allows processing of structure models whose size would otherwise prevent automated design optimization. The new program produced synthesized full model iterative design results identical to those of actual full model program executions at substantially reduced cost, time, and computer storage.
Scaling to Nanotechnology Limits with the PIMS Computer Architecture and a new Scaling Rule
DOE Office of Scientific and Technical Information (OSTI.GOV)
Debenedictis, Erik P.
2015-02-01
We describe a new approach to computing that moves towards the limits of nanotechnology using a newly formulated sc aling rule. This is in contrast to the current computer industry scali ng away from von Neumann's original computer at the rate of Moore's Law. We extend Moore's Law to 3D, which l eads generally to architectures that integrate logic and memory. To keep pow er dissipation cons tant through a 2D surface of the 3D structure requires using adiabatic principles. We call our newly proposed architecture Processor In Memory and Storage (PIMS). We propose a new computational model that integratesmore » processing and memory into "tiles" that comprise logic, memory/storage, and communications functions. Since the programming model will be relatively stable as a system scales, programs repr esented by tiles could be executed in a PIMS system built with today's technology or could become the "schematic diagram" for implementation in an ultimate 3D nanotechnology of the future. We build a systems software approach that offers advantages over and above the technological and arch itectural advantages. Firs t, the algorithms may be more efficient in the conventional sens e of having fewer steps. Second, the algorithms may run with higher power efficiency per operation by being a better match for the adiabatic scaling ru le. The performance analysis based on demonstrated ideas in physical science suggests 80,000 x improvement in cost per operation for the (arguably) gene ral purpose function of emulating neurons in Deep Learning.« less
Numerical optimization of Ignition and Growth reactive flow modeling for PAX2A
NASA Astrophysics Data System (ADS)
Baker, E. L.; Schimel, B.; Grantham, W. J.
1996-05-01
Variable metric nonlinear optimization has been successfully applied to the parameterization of unreacted and reacted products thermodynamic equations of state and reactive flow modeling of the HMX based high explosive PAX2A. The NLQPEB nonlinear optimization program has been recently coupled to the LLNL developed two-dimensional high rate continuum modeling programs DYNA2D and CALE. The resulting program has the ability to optimize initial modeling parameters. This new optimization capability was used to optimally parameterize the Ignition and Growth reactive flow model to experimental manganin gauge records. The optimization varied the Ignition and Growth reaction rate model parameters in order to minimize the difference between the calculated pressure histories and the experimental pressure histories.
Optimization Program for Drinking Water Systems
The Area-Wide Optimization Program (AWOP) provides tools and approaches for drinking water systems to meet water quality optimization goals and provide an increased – and sustainable – level of public health protection to their consumers.
2010-06-01
Journal of Kansas Herpetology Number 34 (June 2010) 11 www.cnah.org/khs ARtIClES tHE HERpEtofAUNA of lEttERKENNY ARMY dEpot, SoUtH-CENtRAl...compare the herpetological commu- nity currently present at the site with that expected from prior literature (felbaum, 1995; Hulse et al., 2001; tetra...Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Journal of Kansas Herpetology Number 34 (June 2010) 12 www.cnah.org/khs agricultural and other
1984-11-01
1,746 N. RAL HAZARDS AND RESEARCH NEEDS IN COASTAL AND OCEAN I ENEERING SUMMA..W NATIONAL SCIENCE FOUNDATION WA ;NG ON OC 1NAVE F AL NOV 84 FG02 N N...and Research Needs in Coastal and Ocean Engineering Summary and Recommendations to the National Science Foundation and the Office of Naval Research A T...Recommendations to the National Science Foundation and the Office of Naval Research by the Ad Hoc Committee for the Civil and Environmental Engineering
1979-10-01
obLrved in raLs treated it 500 mg/animal for three days. Produces cystic changes in rat kidneys. Vat Yellow 4 No definitive infrrmation retrieved on... pulmonary function, and oxygen consumption. Exposure to a nominal concentration of 2.5 mg/L (260 ppm) for B hours showed no toxic signs during exposure or for...to 260 ppmn icxachlzroethane showed severe s’gns of irritation, no changeq ii pulmonary function could be detectt-d.o4’ Six- tek exposure to 260 ppm
Transformation in the French Air Force in an Era of Change
2008-01-01
Abria.indd 6 10/30/08 1:15:37 PM Transformation in the French Air Force in an Era of Change Général d’armée aérienne Stéphane Abrial, chef...l’armée l’air,” sponsored by the Centre d’études stratégiques aérospatiales, 3 June 2008. The French Air Force, like all defense organizations...related to our equipment, because the French aircraft Gen Stéphane Abrial is the chief of staff of the French Air Force. He completed the French Air
NASA Astrophysics Data System (ADS)
Mendonça, J. T.; Shukla, P. K.; Eliasson, B.; Rodrigues, J. A.; Rodrigues
2013-08-01
The ``International Topical Conference on Plasma Science: Advanced Plasma Concepts'' was hosted by Instituto Superior Técnico, Lisbon and the University of Algarve, Faro, Portugal, during the period 24-28 September 2012. The conference was organized by Padma Kant Shukla, (Ruhr University Bochum, Germany), Robert Bingham (RAL, United Kingdom) and José Tito Mendonça, (IST, Portugal). The scientific activity belongs to a series of successful meetings, which started at the Abdus Salam International Centre for Theoretical Physics, Trieste, in 1989, and which has also been taking place at various other locations, including Faro and Lisbon in Portugal, and Santorini in Greece.
Etiologie Rare de Sinusites Nosocomiales en Milieu de Reanimation - A Propos d'une Observation
Messadi, A.A.; Oueslati, S.; Thabet, L.; Bousselmi, K.; Menif, E.
2006-01-01
Summary Les sinusites nosocomiales ne sont pas rares en réanimation. Elles surviennent en général dans les suites d'une intubation nasotrachéale voire même orotrachéale. Le tubage gastrique peut être à lui seul à l'origine d'une sinusite nosocomiale. Nous rapportons le cas d'une patiente hospitalisée qui a été victime de brûlures étendues chez qui la sonde nasogastrique a été à l'origine d'une pansinusite dont l'issue a été fatale. PMID:21991055
Demonstration of the Origin of Human Mast Cells from CD34+ Bone Marrow Progenitor Cells
1991-03-01
culture media sexi -ral tixixesovxer the agaxosc surf-~c. Total poured off, anid the reixiiig adherenxt cells were -cultured In cornm- cell counts were...ined bilue . Resi ills we-re explressed xis Itire percent Iage of cit her noxrmalx goat sern o xr gx xx IgGO (0,5 i, ’ ) I Ix at room cells st...hixIxri- aiixre - ;it ixialer lysis w%*is per-~- foxrmed ’loxverify the rcinxv~dl xIli- (1)2. (1119 ixx ("D2(1. 4A 17,oxr ()1. p it cells
Vibrationally Excited Ions: Quenching Reaction Enhancement, Lifetimes
1991-01-01
affinities in our lad- A,.=Af exp( - AS/IR) = I .IX 10 cm’ S_ with limits der . Any change it. P.A.(Br), ither due to a change in bet~een 7.Sx l3 9and...8217K P Huber and G Hereberg. C oeto of Drateooc Molecules ( Van "M Tubs’, G JasAay. N D Toeddy. and B. B. Fergusn. Ini J Mass Nostrand-Reinhold. New York...objectives and it seemed possible .aat neut - rals such as N,. Xe and CF, might provide suitable monitor gases for vibra- tionally excited HBr*. For HBr
Application of a neural network to simulate analysis in an optimization process
NASA Technical Reports Server (NTRS)
Rogers, James L.; Lamarsh, William J., II
1992-01-01
A new experimental software package called NETS/PROSSS aimed at reducing the computing time required to solve a complex design problem is described. The software combines a neural network for simulating the analysis program with an optimization program. The neural network is applied to approximate results of a finite element analysis program to quickly obtain a near-optimal solution. Results of the NETS/PROSSS optimization process can also be used as an initial design in a normal optimization process and make it possible to converge to an optimum solution with significantly fewer iterations.
ADS: A FORTRAN program for automated design synthesis: Version 1.10
NASA Technical Reports Server (NTRS)
Vanderplaats, G. N.
1985-01-01
A new general-purpose optimization program for engineering design is described. ADS (Automated Design Synthesis - Version 1.10) is a FORTRAN program for solution of nonlinear constrained optimization problems. The program is segmented into three levels: strategy, optimizer, and one-dimensional search. At each level, several options are available so that a total of over 100 possible combinations can be created. Examples of available strategies are sequential unconstrained minimization, the Augmented Lagrange Multiplier method, and Sequential Linear Programming. Available optimizers include variable metric methods and the Method of Feasible Directions as examples, and one-dimensional search options include polynomial interpolation and the Golden Section method as examples. Emphasis is placed on ease of use of the program. All information is transferred via a single parameter list. Default values are provided for all internal program parameters such as convergence criteria, and the user is given a simple means to over-ride these, if desired.
Parallelization of Program to Optimize Simulated Trajectories (POST3D)
NASA Technical Reports Server (NTRS)
Hammond, Dana P.; Korte, John J. (Technical Monitor)
2001-01-01
This paper describes the parallelization of the Program to Optimize Simulated Trajectories (POST3D). POST3D uses a gradient-based optimization algorithm that reaches an optimum design point by moving from one design point to the next. The gradient calculations required to complete the optimization process, dominate the computational time and have been parallelized using a Single Program Multiple Data (SPMD) on a distributed memory NUMA (non-uniform memory access) architecture. The Origin2000 was used for the tests presented.
A general-purpose optimization program for engineering design
NASA Technical Reports Server (NTRS)
Vanderplaats, G. N.; Sugimoto, H.
1986-01-01
A new general-purpose optimization program for engineering design is described. ADS (Automated Design Synthesis) is a FORTRAN program for nonlinear constrained (or unconstrained) function minimization. The optimization process is segmented into three levels: Strategy, Optimizer, and One-dimensional search. At each level, several options are available so that a total of nearly 100 possible combinations can be created. An example of available combinations is the Augmented Lagrange Multiplier method, using the BFGS variable metric unconstrained minimization together with polynomial interpolation for the one-dimensional search.
Interactive Implementation of the Optimal Systems Control Design Program (OPTSYSX) on the IBM 3033.
1984-03-01
DAS A44 159 INTERACTIVE IMPLEMENTATION OF THE OPTIMAL SYSTEMS I CONTROL DESIGN PROGRAM (OPTSYSX) ON THE 1DM 3033(U NAVAL POSTGRADUATE SCHOOL MONTEREY...noesear end idswtif’r b block number) Optimal Systems Control Systems Control Control Systems 10.; ABSTRACT (Continu an reveree side ff Roe684v ad Id yI...34 by block number) .- This thesis discusses the modification of an existing Optimal Systems Control FORTRAN program (OPTSYS) originally obtained from
Program document for Energy Systems Optimization Program 2 (ESOP2). Volume 1: Engineering manual
NASA Technical Reports Server (NTRS)
Hamil, R. G.; Ferden, S. L.
1977-01-01
The Energy Systems Optimization Program, which is used to provide analyses of Modular Integrated Utility Systems (MIUS), is discussed. Modifications to the input format to allow modular inputs in specified blocks of data are described. An optimization feature which enables the program to search automatically for the minimum value of one parameter while varying the value of other parameters is reported. New program option flags for prime mover analyses and solar energy for space heating and domestic hot water are also covered.
Elliptical varied line-space (EVLS) gratings
NASA Astrophysics Data System (ADS)
Thomas, Roger J.
2004-10-01
Imaging spectroscopy at wavelengths below 2000 Å offers an especially powerful method for studying many extended high-temperature astronomical objects, like the Sun and its outer layers. But the technology to make such measurements is also especially challenging, because of the poor reflectance of all standard materials at these wavelengths, and because the observation must be made from above the absorbing effects of the Earth's atmosphere. To solve these problems, single-reflection stigmatic spectrographs for XUV wavelengths have bee flown on several space missions based on designs with toroidal uniform line-space (TULS) or spherical varied line-space (SVLS) gratings that operate at near normal-incidence. More recently, three solar EUV/UV instruments have been selected that use toroidal varied line-space (TVLS) gratings; these are SUMI and RAISE, both sounding rocket payloads, and NEXUS, a SMEX satellite-mission. The next logical extension to such designs is the use of elliptical surfaces for varied line-space (EVLS) rulings. In fact, EVLS designs are found to provide superior imaging even at very large spectrograph magnifications and beam-speeds, permitting extremely high-quality performance in remarkably compact instrument packages. In some cases, such designs may be optimized even further by using a hyperbolic surface for the feeding telescope. The optical characteristics of two solar EUV spectrometers based on these concepts are described: EUS and EUI, both being developed as possible instruments for ESA's Solar Orbiter mission by consortia led by RAL and by MSSL, respectively.
[Assessment of the ICU stay from the point of view of patients and their relatives].
Gil-Juliá, Beatriz; Ballester-Arnal, Rafael; Bernat-Adell, M Desamparados; Giménez-García, Cristina; Castro-Calvo, Jesús
2018-05-31
The quality of care is a key aspect in the gene- ral hospital setting and particularly in ICU. The objective of this study was to analyze the assessment of ICU stay by patients and relatives, as well as the influence of socio-demographic/psycho- logical variables on this assessment. This study explores, conducting telephone surveys, the satisfaction71 critically ill patients and 89 relatives answered the Questionnaire of the ICU stay assessment and the Hospital Anxiety-Depression Scale. Descriptive and frequency analyzes were performed. Likewise, correlation coefficients (Pearson/ Spearman), Student's t test, ANOVA analysis and multiple re- gression equations were used. There were 4,486 hospital episodes, 1,108 due to complications of HCC, which generated 6,713 stays, readmission rate of 28.2% and mortality of 10.2%. The hospital cost amounted to 8,788,593EUR: 3,306,333EUR corresponded to Cirrhosis (5,273EUR/patient); 1,060,521EUR to Carcinoma (6,350EUR/ patient) and 2,962,873EUR to transplantation (70,544EUR/paciente. Comorbidity was 1,458,866EUR. These costs are maintai- ned for an average of 4 years once the cirrhosis decompensation begins. The general evaluation of the ICU stay was po- sitive, although with aspects susceptible to be improved. To know this reality is the prior step to the implementation of those measu- res that reinforce the well-valued issues and improve the worst- valued aspects in order to optimize the quality of the offered care.
Moore, J H
1995-06-01
A genetic algorithm for instrumentation control and optimization was developed using the LabVIEW graphical programming environment. The usefulness of this methodology for the optimization of a closed loop control instrument is demonstrated with minimal complexity and the programming is presented in detail to facilitate its adaptation to other LabVIEW applications. Closed loop control instruments have variety of applications in the biomedical sciences including the regulation of physiological processes such as blood pressure. The program presented here should provide a useful starting point for those wishing to incorporate genetic algorithm approaches to LabVIEW mediated optimization of closed loop control instruments.
Model-based optimal design of experiments - semidefinite and nonlinear programming formulations
Duarte, Belmiro P.M.; Wong, Weng Kee; Oliveira, Nuno M.C.
2015-01-01
We use mathematical programming tools, such as Semidefinite Programming (SDP) and Nonlinear Programming (NLP)-based formulations to find optimal designs for models used in chemistry and chemical engineering. In particular, we employ local design-based setups in linear models and a Bayesian setup in nonlinear models to find optimal designs. In the latter case, Gaussian Quadrature Formulas (GQFs) are used to evaluate the optimality criterion averaged over the prior distribution for the model parameters. Mathematical programming techniques are then applied to solve the optimization problems. Because such methods require the design space be discretized, we also evaluate the impact of the discretization scheme on the generated design. We demonstrate the techniques for finding D–, A– and E–optimal designs using design problems in biochemical engineering and show the method can also be directly applied to tackle additional issues, such as heteroscedasticity in the model. Our results show that the NLP formulation produces highly efficient D–optimal designs but is computationally less efficient than that required for the SDP formulation. The efficiencies of the generated designs from the two methods are generally very close and so we recommend the SDP formulation in practice. PMID:26949279
Model-based optimal design of experiments - semidefinite and nonlinear programming formulations.
Duarte, Belmiro P M; Wong, Weng Kee; Oliveira, Nuno M C
2016-02-15
We use mathematical programming tools, such as Semidefinite Programming (SDP) and Nonlinear Programming (NLP)-based formulations to find optimal designs for models used in chemistry and chemical engineering. In particular, we employ local design-based setups in linear models and a Bayesian setup in nonlinear models to find optimal designs. In the latter case, Gaussian Quadrature Formulas (GQFs) are used to evaluate the optimality criterion averaged over the prior distribution for the model parameters. Mathematical programming techniques are then applied to solve the optimization problems. Because such methods require the design space be discretized, we also evaluate the impact of the discretization scheme on the generated design. We demonstrate the techniques for finding D -, A - and E -optimal designs using design problems in biochemical engineering and show the method can also be directly applied to tackle additional issues, such as heteroscedasticity in the model. Our results show that the NLP formulation produces highly efficient D -optimal designs but is computationally less efficient than that required for the SDP formulation. The efficiencies of the generated designs from the two methods are generally very close and so we recommend the SDP formulation in practice.
Program to Optimize Simulated Trajectories (POST). Volume 3: Programmer's manual
NASA Technical Reports Server (NTRS)
Brauer, G. L.; Cornick, D. E.; Habeger, A. R.; Petersen, F. M.; Stevenson, R.
1975-01-01
Information pertinent to the programmer and relating to the program to optimize simulated trajectories (POST) is presented. Topics discussed include: program structure and logic, subroutine listings and flow charts, and internal FORTRAN symbols. The POST core requirements are summarized along with program macrologic.
AI-BL1.0: a program for automatic on-line beamline optimization using the evolutionary algorithm.
Xi, Shibo; Borgna, Lucas Santiago; Zheng, Lirong; Du, Yonghua; Hu, Tiandou
2017-01-01
In this report, AI-BL1.0, an open-source Labview-based program for automatic on-line beamline optimization, is presented. The optimization algorithms used in the program are Genetic Algorithm and Differential Evolution. Efficiency was improved by use of a strategy known as Observer Mode for Evolutionary Algorithm. The program was constructed and validated at the XAFCA beamline of the Singapore Synchrotron Light Source and 1W1B beamline of the Beijing Synchrotron Radiation Facility.
Systematic Propulsion Optimization Tools (SPOT)
NASA Technical Reports Server (NTRS)
Bower, Mark; Celestian, John
1992-01-01
This paper describes a computer program written by senior-level Mechanical Engineering students at the University of Alabama in Huntsville which is capable of optimizing user-defined delivery systems for carrying payloads into orbit. The custom propulsion system is designed by the user through the input of configuration, payload, and orbital parameters. The primary advantages of the software, called Systematic Propulsion Optimization Tools (SPOT), are a user-friendly interface and a modular FORTRAN 77 code designed for ease of modification. The optimization of variables in an orbital delivery system is of critical concern in the propulsion environment. The mass of the overall system must be minimized within the maximum stress, force, and pressure constraints. SPOT utilizes the Design Optimization Tools (DOT) program for the optimization techniques. The SPOT program is divided into a main program and five modules: aerodynamic losses, orbital parameters, liquid engines, solid engines, and nozzles. The program is designed to be upgraded easily and expanded to meet specific user needs. A user's manual and a programmer's manual are currently being developed to facilitate implementation and modification.
NASA Astrophysics Data System (ADS)
Fain, M. K.; Starinova, O. L.
2016-04-01
The paper outlines the method for determination of the locally optimal stepwise control structure in the problem of the low thrust spacecraft transfer optimization in the Earth-Moon system, including the L1-L2 transfer. The total flight time as an optimization criterion is considered. The optimal control programs were obtained by using the Pontryagin's maximum principle. As a result of optimization, optimal control programs, corresponding trajectories, and minimal total flight times were determined.
Ckmeans.1d.dp: Optimal k-means Clustering in One Dimension by Dynamic Programming.
Wang, Haizhou; Song, Mingzhou
2011-12-01
The heuristic k -means algorithm, widely used for cluster analysis, does not guarantee optimality. We developed a dynamic programming algorithm for optimal one-dimensional clustering. The algorithm is implemented as an R package called Ckmeans.1d.dp . We demonstrate its advantage in optimality and runtime over the standard iterative k -means algorithm.
DOT National Transportation Integrated Search
2003-01-01
This study evaluated existing traffic signal optimization programs including Synchro,TRANSYT-7F, and genetic algorithm optimization using real-world data collected in Virginia. As a first step, a microscopic simulation model, VISSIM, was extensively ...
NASA Technical Reports Server (NTRS)
Reichel, R. H.; Hague, D. S.; Jones, R. T.; Glatt, C. R.
1973-01-01
This computer program manual describes in two parts the automated combustor design optimization code AUTOCOM. The program code is written in the FORTRAN 4 language. The input data setup and the program outputs are described, and a sample engine case is discussed. The program structure and programming techniques are also described, along with AUTOCOM program analysis.
A programing system for research and applications in structural optimization
NASA Technical Reports Server (NTRS)
Sobieszczanski-Sobieski, J.; Rogers, J. L., Jr.
1981-01-01
The flexibility necessary for such diverse utilizations is achieved by combining, in a modular manner, a state-of-the-art optimization program, a production level structural analysis program, and user supplied and problem dependent interface programs. Standard utility capabilities in modern computer operating systems are used to integrate these programs. This approach results in flexibility of the optimization procedure organization and versatility in the formulation of constraints and design variables. Features shown in numerical examples include: variability of structural layout and overall shape geometry, static strength and stiffness constraints, local buckling failure, and vibration constraints.
A thermal vacuum test optimization procedure
NASA Technical Reports Server (NTRS)
Kruger, R.; Norris, H. P.
1979-01-01
An analytical model was developed that can be used to establish certain parameters of a thermal vacuum environmental test program based on an optimization of program costs. This model is in the form of a computer program that interacts with a user insofar as the input of certain parameters. The program provides the user a list of pertinent information regarding an optimized test program and graphs of some of the parameters. The model is a first attempt in this area and includes numerous simplifications. The model appears useful as a general guide and provides a way for extrapolating past performance to future missions.
Touati, Mohammed; Aljalil, Abdelfettah; Chihani, Mehdi; Bouchentouf, Rachid; Bouaity, Brahim; Ammar, Haddou
2013-01-01
La tuberculose primitive du nasopharynx est rare, nous présentons deux observations révélées par un aspect pseudo tumoral et à travers lesquelles nous soulevons le problème de diagnostic différentiel avec les lésions malignes du nasopharynx. La première observation concerne un jeune patient de 22 ans hospitalisé pour obstruction nasale bilatérale évoluant dans un contexte d'apyrexie et de conservation de l’état général. La nasofibrosopie et le scanner ont monté un processus tumoral évoquant une hypertrophie des végétations adénoïdes. Le deuxième cas est celui d'un homme de 45 ans tabagique chronique qui a présenté une adénopathie latérocervicale droite, une obstruction nasale et une otite séromuqueuse homolatérale. La nasophibroscopie et le scanner on montré un bourgeon tumoral postéro latéral droit du nasopharynx évoquant un carcinome nasopharyngé. Les biopsies du nasopharynx et les études histologiques, chez les deux patients, ont confirmé le diagnostic de tuberculose. La recherche d'autres localisations était négative. Le pronostic était favorable après 6 mois de traitement antibacillaire. La tuberculose primitive du cavum est rare, elle revêt le plus souvent des formes pseudotumorales et pose des problèmes de diagnostic différentiel avec les tumeurs nasopharyngées, son pronostic sous traitement antibacillaire est. PMID:23565310
NASA Astrophysics Data System (ADS)
Açıkgöz, Muhammed; Rudowicz, Czesław; Gnutek, Paweł
2017-11-01
Theoretical investigations are carried out to determine the temperature dependence of the local structural parameters of Cr3+ and Mn2+ ions doped into RAl3(BO3)4 (RAB, R = Y, Eu, Tm) crystals. The zero-field splitting (ZFS) parameters (ZFSPs) obtained from the spin Hamiltonian (SH) analysis of EMR (EPR) spectra serve for fine-tuning the theoretically predicted ZFSPs obtained using the semi-empirical superposition model (SPM). The SPM analysis enables to determine the local structure changes around Cr3+ and Mn2+ centers in RAB crystals and explain the observed temperature dependence of the ZFSPs. The local monoclinic C2 site symmetry of all Al sites in YAB necessitates consideration of one non-zero monoclinic ZFSP (in the Stevens notation, b21) for Cr3+ ions. However, the experimental second-rank ZFSPs (D =b20 , E = 1 / 3b22) were expressed in a nominal principal axis system. To provide additional insight into low symmetry aspects, the distortions (ligand's distances ΔRi and angular distortions Δθi) have been varied while preserving monoclinic site symmetry, in such way as to obtain the calculated values (D, E) close to the experimental ones, while keeping b21 close to zero. This procedure yields good matching of the calculated ZFSPs and the experimental ones, and enables determination of the corresponding local distortions. The present results may be useful in future studies aimed at technological applications of the Huntite-type borates with the formula RM3(BO3)4. The model parameters determined here may be utilized for ZFSP calculations for Cr3+ and Mn2+ ions at octahedral sites in single-molecule magnets and single-chain magnets.
Ras and relatives--job sharing and networking keep an old family together.
Ehrhardt, Annette; Ehrhardt, Götz R A; Guo, Xuecui; Schrader, John W
2002-10-01
Many members of the Ras superfamily of GTPases have been implicated in the regulation of hematopoietic cells, with roles in growth, survival, differentiation, cytokine production, chemotaxis, vesicle-trafficking, and phagocytosis. The well-known p21 Ras proteins H-Ras, N-Ras, K-Ras 4A, and K-Ras 4B are also frequently mutated in human cancer and leukemia. Besides the four p21 Ras proteins, the Ras subfamily of the Ras superfamily includes R-Ras, TC21 (R-Ras2), M-Ras (R-Ras3), Rap1A, Rap1B, Rap2A, Rap2B, RalA, and RalB. They exhibit remarkable overall amino acid identities, especially in the regions interacting with the guanine nucleotide exchange factors that catalyze their activation. In addition, there is considerable sharing of various downstream effectors through which they transmit signals and of GTPase activating proteins that downregulate their activity, resulting in overlap in their regulation and effector function. Relatively little is known about the physiological functions of individual Ras family members, although the presence of well-conserved orthologs in Caenorhabditis elegans suggests that their individual roles are both specific and vital. The structural and functional similarities have meant that commonly used research tools fail to discriminate between the different family members, and functions previously attributed to one family member may be shared with other members of the Ras family. Here we discuss similarities and differences in activation, effector usage, and functions of different members of the Ras subfamily. We also review the possibility that the differential localization of Ras proteins in different parts of the cell membrane may govern their responses to activation of cell surface receptors.
NASA Astrophysics Data System (ADS)
Donnadieu, Patricia
1994-05-01
The (Al6Li3Cu) (T2) quasicrystals are known to exhibit large deviations from the icosahedral symmetry. Series of electron diffraction patterns are used to investigate these imperfections in as-cast T, samples. A detailed analysis of the 5-fold and 3-fold symmetry diffraction patterns shows that they are compatible with the m3 point group instead of the m35 icosahedral group. This symmetry reduction is interprétéd as reminiscent of the cubic approximant phase (R-Al5Li3Cu) rather than of higher order approximant phases. This interpretation is supported by previous observations on crystal/quasicrystal phase transformation in the AlLiCu system. Les quasicristaux de phase T2(Al6Li3Cu) montrent d'importantes déviations à la symétrie icosaédrique. Ces imperfections sont mises en évidence par diffraction électronique dans des échantillons de phase T2 brut de coulée. Un examen détaillé des diagrammes de diffraction de symétrie d'ordre 3 et 5 révèle qu'ils sont compatibles avec le groupe ponctuel m3 au lieu du groupe de l'icosaèdre (m35). Cette réduction de symétrie est interprétée comme une réminiscence de la phase cubique approximante (R-Al5Li3Cu) et non l'apparition d'approximant d'ordre plus élevé. Cette interprétation est suggérée par des observations antérieures sur la transformation cristal/quasicristal dans le système AlLiCu.
Vasseur, Romain; Skrypek, Nicolas; Duchêne, Belinda; Renaud, Florence; Martínez-Maqueda, Daniel; Vincent, Audrey; Porchet, Nicole; Van Seuningen, Isabelle; Jonckheere, Nicolas
2015-12-01
The membrane-bound mucinMUC4 is a high molecularweight glycoprotein frequently deregulated in cancer. In pancreatic cancer, one of the most deadly cancers in occidental countries, MUC4 is neo-expressed in the preneoplastic stages and thereafter is involved in cancer cell properties leading to cancer progression and chemoresistance. K-ras oncogene is a small GTPase of the RAS superfamily, highly implicated in cancer. K-ras mutations are considered as an initiating event of pancreatic carcinogenesis and K-ras oncogenic activities are necessary components of cancer progression. However, K-ras remains clinically undruggable. Targeting early downstream K-ras signaling in cancer may thus appear as an interesting strategy and MUC4 regulation by K-ras in pancreatic carcinogenesis remains unknown. Using the Pdx1-Cre; LStopL-K-rasG12D mouse model of pancreatic carcinogenesis, we show that the in vivo early neo-expression of the mucin Muc4 in pancreatic intraepithelial neoplastic lesions (PanINs) induced by mutated K-ras is correlated with the activation of ERK, JNK and NF-κB signaling pathways. In vitro, transfection of constitutively activated K-rasG12V in pancreatic cancer cells led to the transcriptional upregulation of MUC4. This activation was found to be mediated at the transcriptional level by AP-1 and NF-κB transcription factors via MAPK, JNK and NF-κB pathways and at the posttranscriptional level by a mechanism involving the RalB GTPase. Altogether, these results identify MUC4 as a transcriptional and post-transcriptional target of K-ras in pancreatic cancer. This opens avenues in developing new approaches to target the early steps of this deadly cancer.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lee, C.K.; Brown, B.G.; Reed, E.A.
A prototype cigarette that heats tobacco (test cigarette), developed by R.J. Reynolds Tobacco Company, has yielded consistently negative results in several in vivo and in vitro genetic toxicology tests. The objective of the present study was to evaluate the potential of cigarette smoke condensate (CSC) from the test cigarette to induce DNA adducts in mouse tissues and compare the results with those obtained with CSC from a reference tobacco-burning cigarette (1R4F). CD-1 mice were skin-painted with CSF from reference and test cigarettes three times a week for 4 weeks. The highest mass of CSC applied was 180 mg tar permore » week per animal for both reference and test cigarette. DNA adducts were analyzed in skin and lung tissues using the [sup 32]P-postlabeling method with the P[sub 1] nuclease modification. Distinct diagonal radioactive zones (DRZ) were observed in the DNA from both skin and lung tissues of animals dosed with reference CSC, whereas no corresponding DRZ were observed from the DNA of animals dosed with either test CSC or acetone (solvent control). The relative adduct labeling (RAL) values of skin and lung DNA from reference CSC-treated animals were significantly greater than those of the test CSC-treated animals. The RAL values of the test CSC-treated animals were no greater than those of solvent controls. The negative results in DNA adduct assays with test CSC are consistent with all previous results of in vivo and in vitro genetic toxicology testing on this cigarette and provide additional evidence that smoke condensate from the test cigarette is not genotoxic. 31 refs., 4 figs., 2 tabs.« less
Krohn-Dale, Ivar; Bøe, Olav E; Enersen, Morten; Leknes, Knut N
2012-08-01
The objective of this randomized, controlled clinical trial was to compare the clinical and microbiological effects of pocket debridement using erbium-doped: yttrium, aluminium and garnet (Er:YAG) laser with conventional debridement in maintenance patients. Fifteen patients, all smokers, having at least four teeth with residual probing depth (PD) ≥ 5 mm were recruited. Two pockets in two jaw quadrants were randomly assigned to subgingival debridement using an Er:YAG laser (test) or ultrasonic scaler/curette (control) at 3-month intervals. Relative attachment level (RAL), PD, bleeding on probing and dental plaque were recorded at baseline and at 6 and 12 months. Microbiological subgingival samples were taken at the same time points and analysed using a checkerboard DNA-DNA hybridization technique. A significant decrease in PD took place in both treatments from baseline to 12 months (p < 0.01). In the control, the mean initial PD decreased from 5.4 to 4.0 mm at 12 months. For the test, a similar decrease occurred. No significant between-treatment differences were shown at any time point. The mean RAL showed no overall significant inter- or intra-treatment differences (p > 0.05). No significant between-treatment differences were observed in subgingival microbiological composition or total pathogens. The results failed to support that an Er:YAG laser may be superior to conventional debridement in the treatment of smokers with recurring chronic inflammation. This appears to be the first time that repeated Er-YAG laser instrumentation has been compared with mechanical instrumentation of periodontal sites with recurring chronic inflammation over a clinically relevant time period. © 2012 John Wiley & Sons A/S.
Structural basis of recognition of farnesylated and methylated KRAS4b by PDEδ.
Dharmaiah, Srisathiyanarayanan; Bindu, Lakshman; Tran, Timothy H; Gillette, William K; Frank, Peter H; Ghirlando, Rodolfo; Nissley, Dwight V; Esposito, Dominic; McCormick, Frank; Stephen, Andrew G; Simanshu, Dhirendra K
2016-11-01
Farnesylation and carboxymethylation of KRAS4b (Kirsten rat sarcoma isoform 4b) are essential for its interaction with the plasma membrane where KRAS-mediated signaling events occur. Phosphodiesterase-δ (PDEδ) binds to KRAS4b and plays an important role in targeting it to cellular membranes. We solved structures of human farnesylated-methylated KRAS4b in complex with PDEδ in two different crystal forms. In these structures, the interaction is driven by the C-terminal amino acids together with the farnesylated and methylated C185 of KRAS4b that binds tightly in the central hydrophobic pocket present in PDEδ. In crystal form II, we see the full-length structure of farnesylated-methylated KRAS4b, including the hypervariable region. Crystal form I reveals structural details of farnesylated-methylated KRAS4b binding to PDEδ, and crystal form II suggests the potential binding mode of geranylgeranylated-methylated KRAS4b to PDEδ. We identified a 5-aa-long sequence motif (Lys-Ser-Lys-Thr-Lys) in KRAS4b that may enable PDEδ to bind both forms of prenylated KRAS4b. Structure and sequence analysis of various prenylated proteins that have been previously tested for binding to PDEδ provides a rationale for why some prenylated proteins, such as KRAS4a, RalA, RalB, and Rac1, do not bind to PDEδ. Comparison of all four available structures of PDEδ complexed with various prenylated proteins/peptides shows the presence of additional interactions due to a larger protein-protein interaction interface in KRAS4b-PDEδ complex. This interface might be exploited for designing an inhibitor with minimal off-target effects.
Teshima, Teruki; Numasaki, Hodaka; Nishio, Masamichi; Ikeda, Hiroshi; Sekiguchi, Kenji; Kamikonya, Norihiko; Koizumi, Masahiko; Tago, Masao; Ando, Yutaka; Tsukamoto, Nobuhito; Terahara, Atsuro; Nakamura, Katsumasa; Murakami, Masao; Takahashi, Mitsuhiro; Nishimura, Tetsuo
2012-09-01
The ongoing structure of radiation oncology in Japan in terms of equipment, personnel, patient load and geographic distribution was evaluated in order to radiation identify and improve any deficiencies. A questionnaire-based national structure survey was conducted from March 2010 to January 2011 by the Japanese Society for Therapeutic Radiology and Oncology (JASTRO). These data were analyzed in terms of the institutional stratification of the Patterns of Care Study (PCS). The total numbers of new cancer patients and total of cancer patients (new and repeat) treated with radiation in 2009 were estimated at 201,000 and 240,000, respectively. The type and numbers of systems in actual use consisted of Linac (816), telecobalt (9), Gamma Knife (46), (60)Co remote afterloading system (RALS) (29) and (192)Ir RALS systems (130). The Linac systems used dual energy function for 586 (71.8%), 3DCRT for 663 (81.3%) and IMRT for 337 units (41.3%). There were 529 JASTRO-certified radiation oncologists (ROs), 939.4 full-time equivalent (FTE) ROs, 113.1 FTE medical physicists and 1836 FTE radiation therapists. The frequency of interstitial radiation therapy use for prostate and of intensity-modulated radiotherapy increased significantly. PCS stratification can clearly identify the maturity of structures based on their academic nature and caseload. Geographically, the more JASTRO-certified physicians there were in a given area, the more radiation therapy tended to be used for cancer patients. In conclusion, the Japanese structure has clearly improved during the past 19 years in terms of equipment and its use, although a shortage of manpower and variations in maturity disclosed by PCS stratification remained problematic in 2009.
Hefermehl, Lukas J; Largo, Remo A; Hermanns, Thomas; Poyet, Cédric; Sulser, Tullio; Eberli, Daniel
2014-08-01
To assess critical heat spread of cautery instruments used in robot-assisted laparoscopic (RAL) surgery. Thermal spread along bovine musculofascial tissues was examined by infrared camera, histology and enzyme assay. Currently used monopolar, bipolar and ultrasonic laparoscopic instruments were investigated at various power settings and application times. The efficacy of using an additional Maryland clamp as a heat sink was evaluated. A temperature of 45 °C was considered the threshold temperature for possible nerve damage. Monopolar instruments exhibited a mean (sem) critical thermal spread of 3.5 (2.3) mm when applied at 60 W for 1 s. After 2 s, the spread was >20 mm. For adjustable bipolar instruments the mean (sem) critical thermal spread was 2.2 (0.6) mm at 60 W and 1 s, and 3.6 (1.3) mm at 2 s. The PK and LigaSure forceps had mean (sem) critical thermal spreads of 3.9 (0.8) and 2.8 (0.6) mm respectively, whereas the ultrasonic instrument reached 2.9 (0.8) mm. Application of an additional Maryland clamp as a heat sink, significantly reduced the thermal spread. Histomorphometric analyses and enzyme assay supported these findings. All coagulation devices used in RAL surgery have distinct thermal spreads depending on power setting and application time. Cautery may be of concern due to lateral temperature spread, causing potential damage to sensitive structures including nerves. Our results provide surgeons with a resource for educated decision-making when using coagulation devices during robotic procedures. © 2013 The Authors. BJU International © 2013 BJU International.
New approach in the evaluation of a fitness program at a worksite.
Shirasaya, K; Miyakawa, M; Yoshida, K; Tanaka, C; Shimada, N; Kondo, T
1999-03-01
The most common methods for the economic evaluation of a fitness program at a worksite are cost-effectiveness, cost-benefit, and cost-utility analyses. In this study, we applied a basic microeconomic theory, "neoclassical firm's problems," as the new approach for it. The optimal number of physical-exercise classes that constitute the core of the fitness program are determined using the cubic health production function. The optimal number is defined as the number that maximizes the profit of the program. The optimal number corresponding to any willingness-to-pay amount of the participants for the effectiveness of the program is presented using a graph. For example, if the willingness-to-pay is $800, the optimal number of classes is 23. Our method can be applied to the evaluation of any health care program if the health production function can be estimated.
NASA Astrophysics Data System (ADS)
Lali, Mehdi
2009-03-01
A comprehensive computer program is designed in MATLAB to analyze, design and optimize the propulsion, dynamics, thermodynamics, and kinematics of any serial multi-staging rocket for a set of given data. The program is quite user-friendly. It comprises two main sections: "analysis and design" and "optimization." Each section has a GUI (Graphical User Interface) in which the rocket's data are entered by the user and by which the program is run. The first section analyzes the performance of the rocket that is previously devised by the user. Numerous plots and subplots are provided to display the performance of the rocket. The second section of the program finds the "optimum trajectory" via billions of iterations and computations which are done through sophisticated algorithms using numerical methods and incremental integrations. Innovative techniques are applied to calculate the optimal parameters for the engine and designing the "optimal pitch program." This computer program is stand-alone in such a way that it calculates almost every design parameter in regards to rocket propulsion and dynamics. It is meant to be used for actual launch operations as well as educational and research purposes.
User's guide to four-body and three-body trajectory optimization programs
NASA Technical Reports Server (NTRS)
Pu, C. L.; Edelbaum, T. N.
1974-01-01
A collection of computer programs and subroutines written in FORTRAN to calculate 4-body (sun-earth-moon-space) and 3-body (earth-moon-space) optimal trajectories is presented. The programs incorporate a variable step integration technique and a quadrature formula to correct single step errors. The programs provide capability to solve initial value problem, two point boundary value problem of a transfer from a given initial position to a given final position in fixed time, optimal 2-impulse transfer from an earth parking orbit of given inclination to a given final position and velocity in fixed time and optimal 3-impulse transfer from a given position to a given final position and velocity in fixed time.
SEEK: A FORTRAN optimization program using a feasible directions gradient search
NASA Technical Reports Server (NTRS)
Savage, M.
1995-01-01
This report describes the use of computer program 'SEEK' which works in conjunction with two user-written subroutines and an input data file to perform an optimization procedure on a user's problem. The optimization method uses a modified feasible directions gradient technique. SEEK is written in ANSI standard Fortran 77, has an object size of about 46K bytes, and can be used on a personal computer running DOS. This report describes the use of the program and discusses the optimizing method. The program use is illustrated with four example problems: a bushing design, a helical coil spring design, a gear mesh design, and a two-parameter Weibull life-reliability curve fit.
Program to Optimize Simulated Trajectories (POST). Volume 2: Utilization manual
NASA Technical Reports Server (NTRS)
Bauer, G. L.; Cornick, D. E.; Habeger, A. R.; Petersen, F. M.; Stevenson, R.
1975-01-01
Information pertinent to users of the program to optimize simulated trajectories (POST) is presented. The input required and output available is described for each of the trajectory and targeting/optimization options. A sample input listing and resulting output are given.
Combining analysis with optimization at Langley Research Center. An evolutionary process
NASA Technical Reports Server (NTRS)
Rogers, J. L., Jr.
1982-01-01
The evolutionary process of combining analysis and optimization codes was traced with a view toward providing insight into the long term goal of developing the methodology for an integrated, multidisciplinary software system for the concurrent analysis and optimization of aerospace structures. It was traced along the lines of strength sizing, concurrent strength and flutter sizing, and general optimization to define a near-term goal for combining analysis and optimization codes. Development of a modular software system combining general-purpose, state-of-the-art, production-level analysis computer programs for structures, aerodynamics, and aeroelasticity with a state-of-the-art optimization program is required. Incorporation of a modular and flexible structural optimization software system into a state-of-the-art finite element analysis computer program will facilitate this effort. This effort results in the software system used that is controlled with a special-purpose language, communicates with a data management system, and is easily modified for adding new programs and capabilities. A 337 degree-of-freedom finite element model is used in verifying the accuracy of this system.
Shuffle Optimizer: A Program to Optimize DNA Shuffling for Protein Engineering.
Milligan, John N; Garry, Daniel J
2017-01-01
DNA shuffling is a powerful tool to develop libraries of variants for protein engineering. Here, we present a protocol to use our freely available and easy-to-use computer program, Shuffle Optimizer. Shuffle Optimizer is written in the Python computer language and increases the nucleotide homology between two pieces of DNA desired to be shuffled together without changing the amino acid sequence. In addition we also include sections on optimal primer design for DNA shuffling and library construction, a small-volume ultrasonicator method to create sheared DNA, and finally a method to reassemble the sheared fragments and recover and clone the library. The Shuffle Optimizer program and these protocols will be useful to anyone desiring to perform any of the nucleotide homology-dependent shuffling methods.
FRANOPP: Framework for analysis and optimization problems user's guide
NASA Technical Reports Server (NTRS)
Riley, K. M.
1981-01-01
Framework for analysis and optimization problems (FRANOPP) is a software aid for the study and solution of design (optimization) problems which provides the driving program and plotting capability for a user generated programming system. In addition to FRANOPP, the programming system also contains the optimization code CONMIN, and two user supplied codes, one for analysis and one for output. With FRANOPP the user is provided with five options for studying a design problem. Three of the options utilize the plot capability and present an indepth study of the design problem. The study can be focused on a history of the optimization process or on the interaction of variables within the design problem.
Performance Analysis and Design Synthesis (PADS) computer program. Volume 3: User manual
NASA Technical Reports Server (NTRS)
1972-01-01
The two-fold purpose of the Performance Analysis and Design Synthesis (PADS) computer program is discussed. The program can size launch vehicles in conjunction with calculus-of-variations optimal trajectories and can also be used as a general purpose branched trajectory optimization program. For trajectory optimization alone or with sizing, PADS has two trajectory modules. The first trajectory module uses the method of steepest descent. The second module uses the method of quasi-linearization, which requires a starting solution from the first trajectory module.
Sears, Lindsay E; Coberley, Carter R; Pope, James E
2016-07-01
The aim of this study was to examine the direct and mediated effects of a telephonic health coaching program on changes to healthy behaviors, life satisfaction, and optimism. This longitudinal correlational study of 4881 individuals investigated simple and mediated relationships between participation in a telephonic health risk coaching program and outcomes from three annual Well-being Assessments. Program participation was directly related to improvements in healthy behaviors, life satisfaction and optimism, and indirect effects of coaching on these variables concurrently and over a one-year time lag were also supported. Given previous research that improvements to life satisfaction, optimism, and health behaviors are valuable for individuals, employers, and communities, a clearer understanding of intervention approaches that may impact these outcomes simultaneously can drive greater program effectiveness and value on investment.
NASA Astrophysics Data System (ADS)
Vasant, P.; Ganesan, T.; Elamvazuthi, I.
2012-11-01
A fairly reasonable result was obtained for non-linear engineering problems using the optimization techniques such as neural network, genetic algorithms, and fuzzy logic independently in the past. Increasingly, hybrid techniques are being used to solve the non-linear problems to obtain better output. This paper discusses the use of neuro-genetic hybrid technique to optimize the geological structure mapping which is known as seismic survey. It involves the minimization of objective function subject to the requirement of geophysical and operational constraints. In this work, the optimization was initially performed using genetic programming, and followed by hybrid neuro-genetic programming approaches. Comparative studies and analysis were then carried out on the optimized results. The results indicate that the hybrid neuro-genetic hybrid technique produced better results compared to the stand-alone genetic programming method.
Nichols, G; Mills, A; Grossberg, R; Lazzarin, A; Maggiolo, F; Molina, J; Pialoux, G; Wright, D; Ait-Khaled, M; Huang, J; Vavro, C; Wynne, B; Yeo, J
2012-01-01
Background VIKING-3 aimed to examine efficacy and safety of dolutegravir (DTG) 50 mg twice daily in patients with resistance to multiple ARV classes, including integrase inhibitors (INI). Methods RAL and/or EVG-resistant (current or historical) adult subjects with screening plasma HIV-1 RNA ≥500 c/mL and resistance to ≥2 other ART classes received open-label DTG 50 mg BID while continuing their failing regimen (without RAL/EVG). At Day 8 the background regimen was optimised and DTG continued. Activity of the optimized background regimen (OBR) was determined by Monogram Net Assessment. Primary endpoints were antiviral efficacy at Day 8 and Week 24. Results 183 subjects enrolled, 124 with INI-resistance at screening and 59 with historical (but no screening) resistance. Population was advanced: at BL, median CD4 140, prior ART 13 yrs, 56% CDC Class C; 79% had >2 NRTI, 75% >1 NNRTI, and 70% >2 PI resistance-associated mutations, and 61% had non-R5 HIV detected. Of the 114 subjects who had the opportunity to complete 24 weeks on study before data cutoff, 72 (63%) had <50 c/mL RNA at Week 24 (SNAPSHOT algorithm). Mean HIV RNA declined by 1.4 log10 c/mL (95% CI: 1.3, 1.5; p < 0.001) at Day 8; response differed by genotype pathway (Table). Primary INI mutations at BL N Mean HIV RNA (log 10) Change from BL (SD) at Day 8 %>1 log HIV RNA decline of <50 c/mL at Day 8 TOTAL 183 −1.4 (0.61) 82% T66 1 −1.9 100% Y143 28 −1.7 (0.42) 96% N155 33 −1.4 (0.51) 82% Q148 + ≤1 secondary mutation# 32 −1.1 (0.51) 69% Q148 + ≥2 secondary mutations# 20 −1.0 (0.81) 48% ≥2 primary mutations 8 −1.4 (0.76) 75% No primary mutations 60 −1.6 (0.55) 95% # Key secondary mutations comprised G140_ACS, L741, E138_AKT. In subjects with Q148 pathway mutations, virologic response decreased with increasing number of secondary mutations. Background overall susceptibility score (OSS) was not associated with Wk 24 response: % <50 c/mL were 83%, 63%, 59% and 69% for OSS 0, 1, 2 and >2, respectively. Discontinuations due to adverse events were uncommon (6/183, 3%); the most common drug-related AEs were diarrhoea, nausea and headache, each reported in only 5% of subjects. Conclusion A majority of the highly treatment-experienced subjects in VIKING-3 achieved suppression with DTG-based therapy. Responses were associated with Baseline IN genotype but not OSS, highlighting the importance and independence of DTG antiviral activity. DTG had a low rate of discontinuation due to adverse events at 50 mg BID in this advanced patient population.
Liu, Qingshan; Dang, Chuangyin; Huang, Tingwen
2013-02-01
This paper presents a decision-making model described by a recurrent neural network for dynamic portfolio optimization. The portfolio-optimization problem is first converted into a constrained fractional programming problem. Since the objective function in the programming problem is not convex, the traditional optimization techniques are no longer applicable for solving this problem. Fortunately, the objective function in the fractional programming is pseudoconvex on the feasible region. It leads to a one-layer recurrent neural network modeled by means of a discontinuous dynamic system. To ensure the optimal solutions for portfolio optimization, the convergence of the proposed neural network is analyzed and proved. In fact, the neural network guarantees to get the optimal solutions for portfolio-investment advice if some mild conditions are satisfied. A numerical example with simulation results substantiates the effectiveness and illustrates the characteristics of the proposed neural network.
On the Run-Time Optimization of the Boolean Logic of a Program.
ERIC Educational Resources Information Center
Cadolino, C.; Guazzo, M.
1982-01-01
Considers problem of optimal scheduling of Boolean expression (each Boolean variable represents binary outcome of program module) on single-processor system. Optimization discussed consists of finding operand arrangement that minimizes average execution costs representing consumption of resources (elapsed time, main memory, number of…
Final Report: Pilot Region-Based Optimization Program for Fund-Lead Sites, EPA Region III
This report describes a pilot study for a Region-based optimization program, implemented by a Regional Optimization Evaluation Team (ROET) that was conducted in U.S. EPA Region III at Fund-lead sites with pump-and-treat (P&T) systems.
A hybrid nonlinear programming method for design optimization
NASA Technical Reports Server (NTRS)
Rajan, S. D.
1986-01-01
Solutions to engineering design problems formulated as nonlinear programming (NLP) problems usually require the use of more than one optimization technique. Moreover, the interaction between the user (analysis/synthesis) program and the NLP system can lead to interface, scaling, or convergence problems. An NLP solution system is presented that seeks to solve these problems by providing a programming system to ease the user-system interface. A simple set of rules is used to select an optimization technique or to switch from one technique to another in an attempt to detect, diagnose, and solve some potential problems. Numerical examples involving finite element based optimal design of space trusses and rotor bearing systems are used to illustrate the applicability of the proposed methodology.
NASA Astrophysics Data System (ADS)
Li, Shuang; Zhu, Yongsheng; Wang, Yukai
2014-02-01
Asteroid deflection techniques are essential in order to protect the Earth from catastrophic impacts by hazardous asteroids. Rapid design and optimization of low-thrust rendezvous/interception trajectories is considered as one of the key technologies to successfully deflect potentially hazardous asteroids. In this paper, we address a general framework for the rapid design and optimization of low-thrust rendezvous/interception trajectories for future asteroid deflection missions. The design and optimization process includes three closely associated steps. Firstly, shape-based approaches and genetic algorithm (GA) are adopted to perform preliminary design, which provides a reasonable initial guess for subsequent accurate optimization. Secondly, Radau pseudospectral method is utilized to transcribe the low-thrust trajectory optimization problem into a discrete nonlinear programming (NLP) problem. Finally, sequential quadratic programming (SQP) is used to efficiently solve the nonlinear programming problem and obtain the optimal low-thrust rendezvous/interception trajectories. The rapid design and optimization algorithms developed in this paper are validated by three simulation cases with different performance indexes and boundary constraints.
NASA Technical Reports Server (NTRS)
1971-01-01
A modular program for design optimization of thermal protection systems is discussed. Its capabilities and limitations are reviewed. Instructions for the operation of the program, output, and the program itself are given.
Combating Narco-Terrorism in West Africa
2012-06-15
eral court for coordinating the ale of cocaine to Los Zeta" by w .. ing West A f1ica 10 lau nder drug IT’loney e~timated up to S200 million a month...allied \\\\ith al Queda. In Scplc tllbl’r ~01 1. Clcnl’ral Carter r. I lam . l ’ )t\\FR ICOM Commander. ’>latcd that he wu’> concerned uhnutlhrcc ,\\fri...ten.:~pt i n g. money lau ndering. ptlll’olthcir coa’t line. C\\ en Lhnugh rno’l ol 1hc counlric’ ;dung the cn:t’>t do not ha\\ L’ Guinea. The! L’ .S
Aura Satellite Mission: Oxford/RAL Spring School in Quantitative Earth Observation
NASA Technical Reports Server (NTRS)
Douglass, Anne
2005-01-01
The four instruments on Aura are providing new and exciting measurements of stratospheric and tropospheric ozone, species that contribute to ozone production and loss, and long-lived gases such as nitrous oxide and methane that provide information about atmospheric transport. These discussions of atmospheric chemistry will start with the basic principles of ozone production and loss. Aura data will be used where possible to illustrate the pertinent atmospheric processes. Three-dimensional model simulations will be used both to illustrate present capabilities in constituent modeling and to demonstrate how observations are used to evaluate and improve models and our ability to predict future ozone evolution.
2008-10-01
et planification en ressources humaines militaires a aboli la norme de taille minimum des Forces Canadiennes. On a conclu que "les...015; Defence R&D Canada – Toronto; October 2008. Introduction ou contexte : En février 2002, le directeur général – politiques et planification en...arming cables. ....................................................... 6 Figure 4 Reach of full throttle (left) and fire bottle T -handles (right
Production of pulsed ultra slow muons and first /μSR experiments on thin metallic and magnetic films
NASA Astrophysics Data System (ADS)
Träger, K.; Breitrück, A.; Trigo, M. Diaz; Grossmann, A.; Jungmann, K.; Merkel, J.; Meyer, V.; Neumayer, P.; Pachl, B.; zu Putlitz, G.; Santra, R.; William, L.; Allodi, G.; Bucci, C.; Renzi, R. De; Galli, F.; Guidi, G.; Shiroka, T.; Eaton, G. H.; King, P. J. C.; Scott, C. A.; Williams, G. W.; Roduner, E.; Scheuermann, R.; Charlton, M. C.; Donnelly, P.; Pareti, L.; Turilli, G.
2000-08-01
At ISIS, RAL (UK) we have produced a pulsed ultra-slow muon beam (E≲20 eV) and performed the first μSR experiments. Thanks to the pulsed feature, the implantation time is automatically determined and, by adjusting the final muon energy between ∼8 keV and 20 eV, depth slicing experiments are possible down to monolayers distances. We report slicing experiments across a 20 nm copper film on quartz substrate with evidence for a 2 nm copper oxide surface layer. A preliminary experiment on a hexagonal cobalt film suggests the existence of muon precession in the local magnetic field.
ERIC Educational Resources Information Center
Matzke, Orville R.
The purpose of this study was to formulate a linear programming model to simulate a foundation type support program and to apply this model to a state support program for the public elementary and secondary school districts in the State of Iowa. The model was successful in producing optimal solutions to five objective functions proposed for…
Software For Integer Programming
NASA Technical Reports Server (NTRS)
Fogle, F. R.
1992-01-01
Improved Exploratory Search Technique for Pure Integer Linear Programming Problems (IESIP) program optimizes objective function of variables subject to confining functions or constraints, using discrete optimization or integer programming. Enables rapid solution of problems up to 10 variables in size. Integer programming required for accuracy in modeling systems containing small number of components, distribution of goods, scheduling operations on machine tools, and scheduling production in general. Written in Borland's TURBO Pascal.
Variable-Metric Algorithm For Constrained Optimization
NASA Technical Reports Server (NTRS)
Frick, James D.
1989-01-01
Variable Metric Algorithm for Constrained Optimization (VMACO) is nonlinear computer program developed to calculate least value of function of n variables subject to general constraints, both equality and inequality. First set of constraints equality and remaining constraints inequalities. Program utilizes iterative method in seeking optimal solution. Written in ANSI Standard FORTRAN 77.
Optimal Assembly of Psychological and Educational Tests.
ERIC Educational Resources Information Center
van der Linden, Wim J.
1998-01-01
Reviews optimal test-assembly literature and introduces the contributions to this special issue. Discusses four approaches to computerized test assembly: (1) heuristic-based test assembly; (2) 0-1 linear programming; (3) network-flow programming; and (4) an optimal design approach. Contains a bibliography of 90 sources on test assembly.…
USASOC Injury Prevention/Performance Optimization Musculoskeletal Screening Initiative
2011-11-01
Tactical Human Optimization , Rapid Rehabilitation , and Reconditioning (THOR3) program to identify the...Special Operations Command (USASOC) to support development of USASOC’s Tactical Human Optimization , Rapid Rehabilitation , and Reconditioning (THOR3...biomechanical, musculoskeletal, physiological, tactical , and injury data and refine its current human performance program to address the
Li, Ji-Qing; Zhang, Yu-Shan; Ji, Chang-Ming; Wang, Ai-Jing; Lund, Jay R
2013-01-01
This paper examines long-term optimal operation using dynamic programming for a large hydropower system of 10 reservoirs in Northeast China. Besides considering flow and hydraulic head, the optimization explicitly includes time-varying electricity market prices to maximize benefit. Two techniques are used to reduce the 'curse of dimensionality' of dynamic programming with many reservoirs. Discrete differential dynamic programming (DDDP) reduces the search space and computer memory needed. Object-oriented programming (OOP) and the ability to dynamically allocate and release memory with the C++ language greatly reduces the cumulative effect of computer memory for solving multi-dimensional dynamic programming models. The case study shows that the model can reduce the 'curse of dimensionality' and achieve satisfactory results.
Deb, Kalyanmoy; Sinha, Ankur
2010-01-01
Bilevel optimization problems involve two optimization tasks (upper and lower level), in which every feasible upper level solution must correspond to an optimal solution to a lower level optimization problem. These problems commonly appear in many practical problem solving tasks including optimal control, process optimization, game-playing strategy developments, transportation problems, and others. However, they are commonly converted into a single level optimization problem by using an approximate solution procedure to replace the lower level optimization task. Although there exist a number of theoretical, numerical, and evolutionary optimization studies involving single-objective bilevel programming problems, not many studies look at the context of multiple conflicting objectives in each level of a bilevel programming problem. In this paper, we address certain intricate issues related to solving multi-objective bilevel programming problems, present challenging test problems, and propose a viable and hybrid evolutionary-cum-local-search based algorithm as a solution methodology. The hybrid approach performs better than a number of existing methodologies and scales well up to 40-variable difficult test problems used in this study. The population sizing and termination criteria are made self-adaptive, so that no additional parameters need to be supplied by the user. The study indicates a clear niche of evolutionary algorithms in solving such difficult problems of practical importance compared to their usual solution by a computationally expensive nested procedure. The study opens up many issues related to multi-objective bilevel programming and hopefully this study will motivate EMO and other researchers to pay more attention to this important and difficult problem solving activity.
The application of nonlinear programming and collocation to optimal aeroassisted orbital transfers
NASA Astrophysics Data System (ADS)
Shi, Y. Y.; Nelson, R. L.; Young, D. H.; Gill, P. E.; Murray, W.; Saunders, M. A.
1992-01-01
Sequential quadratic programming (SQP) and collocation of the differential equations of motion were applied to optimal aeroassisted orbital transfers. The Optimal Trajectory by Implicit Simulation (OTIS) computer program codes with updated nonlinear programming code (NZSOL) were used as a testbed for the SQP nonlinear programming (NLP) algorithms. The state-of-the-art sparse SQP method is considered to be effective for solving large problems with a sparse matrix. Sparse optimizers are characterized in terms of memory requirements and computational efficiency. For the OTIS problems, less than 10 percent of the Jacobian matrix elements are nonzero. The SQP method encompasses two phases: finding an initial feasible point by minimizing the sum of infeasibilities and minimizing the quadratic objective function within the feasible region. The orbital transfer problem under consideration involves the transfer from a high energy orbit to a low energy orbit.
A Language for Specifying Compiler Optimizations for Generic Software
DOE Office of Scientific and Technical Information (OSTI.GOV)
Willcock, Jeremiah J.
2007-01-01
Compiler optimization is important to software performance, and modern processor architectures make optimization even more critical. However, many modern software applications use libraries providing high levels of abstraction. Such libraries often hinder effective optimization — the libraries are difficult to analyze using current compiler technology. For example, high-level libraries often use dynamic memory allocation and indirectly expressed control structures, such as iteratorbased loops. Programs using these libraries often cannot achieve an optimal level of performance. On the other hand, software libraries have also been recognized as potentially aiding in program optimization. One proposed implementation of library-based optimization is to allowmore » the library author, or a library user, to define custom analyses and optimizations. Only limited systems have been created to take advantage of this potential, however. One problem in creating a framework for defining new optimizations and analyses is how users are to specify them: implementing them by hand inside a compiler is difficult and prone to errors. Thus, a domain-specific language for librarybased compiler optimizations would be beneficial. Many optimization specification languages have appeared in the literature, but they tend to be either limited in power or unnecessarily difficult to use. Therefore, I have designed, implemented, and evaluated the Pavilion language for specifying program analyses and optimizations, designed for library authors and users. These analyses and optimizations can be based on the implementation of a particular library, its use in a specific program, or on the properties of a broad range of types, expressed through concepts. The new system is intended to provide a high level of expressiveness, even though the intended users are unlikely to be compiler experts.« less
Final Report---Optimization Under Nonconvexity and Uncertainty: Algorithms and Software
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jeff Linderoth
2011-11-06
the goal of this work was to develop new algorithmic techniques for solving large-scale numerical optimization problems, focusing on problems classes that have proven to be among the most challenging for practitioners: those involving uncertainty and those involving nonconvexity. This research advanced the state-of-the-art in solving mixed integer linear programs containing symmetry, mixed integer nonlinear programs, and stochastic optimization problems. The focus of the work done in the continuation was on Mixed Integer Nonlinear Programs (MINLP)s and Mixed Integer Linear Programs (MILP)s, especially those containing a great deal of symmetry.
Computer-Aided Communication Satellite System Analysis and Optimization.
ERIC Educational Resources Information Center
Stagl, Thomas W.; And Others
Various published computer programs for fixed/broadcast communication satellite system synthesis and optimization are discussed. The rationale for selecting General Dynamics/Convair's Satellite Telecommunication Analysis and Modeling Program (STAMP) in modified form to aid in the system costing and sensitivity analysis work in the Program on…
OPTIMAL WELL LOCATOR (OWL): A SCREENING TOOL FOR EVALUATING LOCATIONS OF MONITORING WELLS
The Optimal Well Locator ( OWL) program was designed and developed by USEPA to be a screening tool to evaluate and optimize the placement of wells in long term monitoring networks at small sites. The first objective of the OWL program is to allow the user to visualize the change ...
NASA Astrophysics Data System (ADS)
Kalatzis, Fanis G.; Papageorgiou, Dimitrios G.; Demetropoulos, Ioannis N.
2006-09-01
The Merlin/MCL optimization environment and the GAMESS-US package were combined so as to offer an extended and efficient quantum chemistry optimization system, capable of implementing complex optimization strategies for generic molecular modeling problems. A communication and data exchange interface was established between the two packages exploiting all Merlin features such as multiple optimizers, box constraints, user extensions and a high level programming language. An important feature of the interface is its ability to perform dimer computations by eliminating the basis set superposition error using the counterpoise (CP) method of Boys and Bernardi. Furthermore it offers CP-corrected geometry optimizations using analytic derivatives. The unified optimization environment was applied to construct portions of the intermolecular potential energy surface of the weakly bound H-bonded complex C 6H 6-H 2O by utilizing the high level Merlin Control Language. The H-bonded dimer HF-H 2O was also studied by CP-corrected geometry optimization. The ab initio electronic structure energies were calculated using the 6-31G ** basis set at the Restricted Hartree-Fock and second-order Moller-Plesset levels, while all geometry optimizations were carried out using a quasi-Newton algorithm provided by Merlin. Program summaryTitle of program: MERGAM Catalogue identifier:ADYB_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADYB_v1_0 Program obtainable from: CPC Program Library, Queen's University of Belfast, N. Ireland Computer for which the program is designed and others on which it has been tested: The program is designed for machines running the UNIX operating system. It has been tested on the following architectures: IA32 (Linux with gcc/g77 v.3.2.3), AMD64 (Linux with the Portland group compilers v.6.0), SUN64 (SunOS 5.8 with the Sun Workshop compilers v.5.2) and SGI64 (IRIX 6.5 with the MIPSpro compilers v.7.4) Installations: University of Ioannina, Greece Operating systems or monitors under which the program has been tested: UNIX Programming language used: ANSI C, ANSI Fortran-77 No. of lines in distributed program, including test data, etc.:11 282 No. of bytes in distributed program, including test data, etc.: 49 458 Distribution format: tar.gz Memory required to execute with typical data: Memory requirements mainly depend on the selection of a GAMESS-US basis set and the number of atoms No. of bits in a word: 32 No. of processors used: 1 Has the code been vectorized or parallelized?: no Nature of physical problem: Multidimensional geometry optimization is of great importance in any ab initio calculation since it usually is one of the most CPU-intensive tasks, especially on large molecular systems. For example, the geometric and energetic description of van der Waals and weakly bound H-bonded complexes requires the construction of related important portions of the multidimensional intermolecular potential energy surface (IPES). So the various held views about the nature of these bonds can be quantitatively tested. Method of solution: The Merlin/MCL optimization environment was interconnected with the GAMESS-US package to facilitate geometry optimization in quantum chemistry problems. The important portions of the IPES require the capability to program optimization strategies. The Merlin/MCL environment was used for the implementation of such strategies. In this work, a CP-corrected geometry optimization was performed on the HF-H 2O complex and an MCL program was developed to study portions of the potential energy surface of the C 6H 6-H 2O complex. Restrictions on the complexity of the problem: The Merlin optimization environment and the GAMESS-US package must be installed. The MERGAM interface requires GAMESS-US input files that have been constructed in Cartesian coordinates. This restriction occurs from a design-time requirement to not allow reorientation of atomic coordinates; this rule holds always true when applying the COORD = UNIQUE keyword in a GAMESS-US input file. Typical running time: It depends on the size of the molecular system, the size of the basis set and the method of electron correlation. Execution of the test run took approximately 5 min on a 2.8 GHz Intel Pentium CPU.
Ammassari, Adriana; Abbate, Isabella; Orchi, Nicoletta; Pinnetti, Carmela; Rozera, Gabriella; Libertone, Raffaella; Pierro, Paola; Martini, Federico; Puro, Vincenzo; Girardi, Enrico; Antinori, Andrea; Capobianchi, Maria Rosaria
2014-01-01
Diagnosis of HIV infection during early stages is mandatory to catch up with the challenge of limiting HIV viral replication and reservoirs formation, as well as decreasing HIV transmissions by immediate cART initiation. Aims were to describe (a) virological characteristics of AHI identified, (b) epidemiological and clinical factors associated with being diagnosed with AHI. Cross-sectional, retrospective study. All individuals diagnosed with AHI according to Fiebig's staging between Jan 2013 and Mar 2014 at the INMI "L. Spallanzani" were included. Serum samples reactive to a fourth generation HIV-1/2 assay (Architect HIV Ag/Ab Combo, Abbott) were retested with another fourth generation assay (VIDAS DUO HIV Ultra, Biomérieux) and underwent confirmation with HIV-1 WB (New Lav I Bio-Rad) and/or with Geenius confirmatory assay (Bio-Rad). WHO criteria (two env products reactivity) were used to establish positivity of confirmatory assays. In case of clinically suspected AHI, HIV-1 RNA (Real time, Abbott) and p24 assay (VIDAS HIV P24 Bio-Rad) were also performed. Avidity test was carried out, on confirmed positive samples lacking p31 reactivity, to discriminate between recent (true Fiebig V phase) and late infections; to avoid possible misclassifications, clinical data were also used. Demographic, epidemiological, clinical and laboratory data are routinely, and anonymously recorded in the SENDIH and SIREA studies. During the study period, we observed 483 newly HIV diagnosed individuals, of whom 40 were identified as AHI (8.3%). Fiebig classification showed: 7 stage II/III, 13 stage IV, 20 stage V. Demographic, epidemiological, and clinical characteristics of patients are shown in the Table. Overall, the study population had a median S/Co ratio at fourth generation EIA (Architect) of 49.50 (IQR, 23.54-98.05): values were significantly lower in Fiebig II-IV than in Fiebig V (38.68 [IQR, 20.08-54.84] vs 75.72 [IQR, 42.66-249.80], p=0.01). Overall, median HIV-1 RNA was 5.44 log copies/mL (IQR, 4.29-6.18) and the value observed in Fiebig phase II-IV was higher than that found in Fiebig stage V (6.10 [IQR, 5.49-7.00] vs 4.69 [3.71-5.44], p<0.001). Median CD4+ cell count was 596/mmc (IQR, 410-737). cART was started in 26 patients: TDF/FTC/DRV/r/RAL=18; TDF/FTC/DRV/r=2; TDF/FTC/ATV/r=2; TDF+FTC+EFV=2; TDF/FTC/RAL=1; DRV/r+RAL=1. Integration of careful epidemiological investigation, partner notification, and technical advances in virological testing are key elements in AHI case-finding. Significant differences were found between Fiebig stages II-IV and Fiebig V with regard to virological exams.
Optimal blood glucose level control using dynamic programming based on minimal Bergman model
NASA Astrophysics Data System (ADS)
Rettian Anggita Sari, Maria; Hartono
2018-03-01
The purpose of this article is to simulate the glucose dynamic and the insulin kinetic of diabetic patient. The model used in this research is a non-linear Minimal Bergman model. Optimal control theory is then applied to formulate the problem in order to determine the optimal dose of insulin in the treatment of diabetes mellitus such that the glucose level is in the normal range for some specific time range. The optimization problem is solved using dynamic programming. The result shows that dynamic programming is quite reliable to represent the interaction between glucose and insulin levels in diabetes mellitus patient.
NASA Technical Reports Server (NTRS)
Brauer, G. L.; Cornick, D. E.; Stevenson, R.
1977-01-01
The capabilities and applications of the three-degree-of-freedom (3DOF) version and the six-degree-of-freedom (6DOF) version of the Program to Optimize Simulated Trajectories (POST) are summarized. The document supplements the detailed program manuals by providing additional information that motivates and clarifies basic capabilities, input procedures, applications and computer requirements of these programs. The information will enable prospective users to evaluate the programs, and to determine if they are applicable to their problems. Enough information is given to enable managerial personnel to evaluate the capabilities of the programs and describes the POST structure, formulation, input and output procedures, sample cases, and computer requirements. The report also provides answers to basic questions concerning planet and vehicle modeling, simulation accuracy, optimization capabilities, and general input rules. Several sample cases are presented.
Comparison of optimization algorithms in intensity-modulated radiation therapy planning
NASA Astrophysics Data System (ADS)
Kendrick, Rachel
Intensity-modulated radiation therapy is used to better conform the radiation dose to the target, which includes avoiding healthy tissue. Planning programs employ optimization methods to search for the best fluence of each photon beam, and therefore to create the best treatment plan. The Computational Environment for Radiotherapy Research (CERR), a program written in MATLAB, was used to examine some commonly-used algorithms for one 5-beam plan. Algorithms include the genetic algorithm, quadratic programming, pattern search, constrained nonlinear optimization, simulated annealing, the optimization method used in Varian EclipseTM, and some hybrids of these. Quadratic programing, simulated annealing, and a quadratic/simulated annealing hybrid were also separately compared using different prescription doses. The results of each dose-volume histogram as well as the visual dose color wash were used to compare the plans. CERR's built-in quadratic programming provided the best overall plan, but avoidance of the organ-at-risk was rivaled by other programs. Hybrids of quadratic programming with some of these algorithms seems to suggest the possibility of better planning programs, as shown by the improved quadratic/simulated annealing plan when compared to the simulated annealing algorithm alone. Further experimentation will be done to improve cost functions and computational time.
Portfolio optimization using fuzzy linear programming
NASA Astrophysics Data System (ADS)
Pandit, Purnima K.
2013-09-01
Portfolio Optimization (PO) is a problem in Finance, in which investor tries to maximize return and minimize risk by carefully choosing different assets. Expected return and risk are the most important parameters with regard to optimal portfolios. In the simple form PO can be modeled as quadratic programming problem which can be put into equivalent linear form. PO problems with the fuzzy parameters can be solved as multi-objective fuzzy linear programming problem. In this paper we give the solution to such problems with an illustrative example.
Research on numerical method for multiple pollution source discharge and optimal reduction program
NASA Astrophysics Data System (ADS)
Li, Mingchang; Dai, Mingxin; Zhou, Bin; Zou, Bin
2018-03-01
In this paper, the optimal method for reduction program is proposed by the nonlinear optimal algorithms named that genetic algorithm. The four main rivers in Jiangsu province, China are selected for reducing the environmental pollution in nearshore district. Dissolved inorganic nitrogen (DIN) is studied as the only pollutant. The environmental status and standard in the nearshore district is used to reduce the discharge of multiple river pollutant. The research results of reduction program are the basis of marine environmental management.
NASA Technical Reports Server (NTRS)
Hauser, F. D.; Szollosi, G. D.; Lakin, W. S.
1972-01-01
COEBRA, the Computerized Optimization of Elastic Booster Autopilots, is an autopilot design program. The bulk of the design criteria is presented in the form of minimum allowed gain/phase stability margins. COEBRA has two optimization phases: (1) a phase to maximize stability margins; and (2) a phase to optimize structural bending moment load relief capability in the presence of minimum requirements on gain/phase stability margins.
Optimization guide for programs compiled under IBM FORTRAN H (OPT=2)
NASA Technical Reports Server (NTRS)
Smith, D. M.; Dobyns, A. H.; Marsh, H. M.
1977-01-01
Guidelines are given to provide the programmer with various techniques for optimizing programs when the FORTRAN IV H compiler is used with OPT=2. Subroutines and programs are described in the appendices along with a timing summary of all the examples given in the manual.
Programmed Evolution for Optimization of Orthogonal Metabolic Output in Bacteria
Eckdahl, Todd T.; Campbell, A. Malcolm; Heyer, Laurie J.; Poet, Jeffrey L.; Blauch, David N.; Snyder, Nicole L.; Atchley, Dustin T.; Baker, Erich J.; Brown, Micah; Brunner, Elizabeth C.; Callen, Sean A.; Campbell, Jesse S.; Carr, Caleb J.; Carr, David R.; Chadinha, Spencer A.; Chester, Grace I.; Chester, Josh; Clarkson, Ben R.; Cochran, Kelly E.; Doherty, Shannon E.; Doyle, Catherine; Dwyer, Sarah; Edlin, Linnea M.; Evans, Rebecca A.; Fluharty, Taylor; Frederick, Janna; Galeota-Sprung, Jonah; Gammon, Betsy L.; Grieshaber, Brandon; Gronniger, Jessica; Gutteridge, Katelyn; Henningsen, Joel; Isom, Bradley; Itell, Hannah L.; Keffeler, Erica C.; Lantz, Andrew J.; Lim, Jonathan N.; McGuire, Erin P.; Moore, Alexander K.; Morton, Jerrad; Nakano, Meredith; Pearson, Sara A.; Perkins, Virginia; Parrish, Phoebe; Pierson, Claire E.; Polpityaarachchige, Sachith; Quaney, Michael J.; Slattery, Abagael; Smith, Kathryn E.; Spell, Jackson; Spencer, Morgan; Taye, Telavive; Trueblood, Kamay; Vrana, Caroline J.; Whitesides, E. Tucker
2015-01-01
Current use of microbes for metabolic engineering suffers from loss of metabolic output due to natural selection. Rather than combat the evolution of bacterial populations, we chose to embrace what makes biological engineering unique among engineering fields – evolving materials. We harnessed bacteria to compute solutions to the biological problem of metabolic pathway optimization. Our approach is called Programmed Evolution to capture two concepts. First, a population of cells is programmed with DNA code to enable it to compute solutions to a chosen optimization problem. As analog computers, bacteria process known and unknown inputs and direct the output of their biochemical hardware. Second, the system employs the evolution of bacteria toward an optimal metabolic solution by imposing fitness defined by metabolic output. The current study is a proof-of-concept for Programmed Evolution applied to the optimization of a metabolic pathway for the conversion of caffeine to theophylline in E. coli. Introduced genotype variations included strength of the promoter and ribosome binding site, plasmid copy number, and chaperone proteins. We constructed 24 strains using all combinations of the genetic variables. We used a theophylline riboswitch and a tetracycline resistance gene to link theophylline production to fitness. After subjecting the mixed population to selection, we measured a change in the distribution of genotypes in the population and an increased conversion of caffeine to theophylline among the most fit strains, demonstrating Programmed Evolution. Programmed Evolution inverts the standard paradigm in metabolic engineering by harnessing evolution instead of fighting it. Our modular system enables researchers to program bacteria and use evolution to determine the combination of genetic control elements that optimizes catabolic or anabolic output and to maintain it in a population of cells. Programmed Evolution could be used for applications in energy, pharmaceuticals, chemical commodities, biomining, and bioremediation. PMID:25714374
Programmed evolution for optimization of orthogonal metabolic output in bacteria.
Eckdahl, Todd T; Campbell, A Malcolm; Heyer, Laurie J; Poet, Jeffrey L; Blauch, David N; Snyder, Nicole L; Atchley, Dustin T; Baker, Erich J; Brown, Micah; Brunner, Elizabeth C; Callen, Sean A; Campbell, Jesse S; Carr, Caleb J; Carr, David R; Chadinha, Spencer A; Chester, Grace I; Chester, Josh; Clarkson, Ben R; Cochran, Kelly E; Doherty, Shannon E; Doyle, Catherine; Dwyer, Sarah; Edlin, Linnea M; Evans, Rebecca A; Fluharty, Taylor; Frederick, Janna; Galeota-Sprung, Jonah; Gammon, Betsy L; Grieshaber, Brandon; Gronniger, Jessica; Gutteridge, Katelyn; Henningsen, Joel; Isom, Bradley; Itell, Hannah L; Keffeler, Erica C; Lantz, Andrew J; Lim, Jonathan N; McGuire, Erin P; Moore, Alexander K; Morton, Jerrad; Nakano, Meredith; Pearson, Sara A; Perkins, Virginia; Parrish, Phoebe; Pierson, Claire E; Polpityaarachchige, Sachith; Quaney, Michael J; Slattery, Abagael; Smith, Kathryn E; Spell, Jackson; Spencer, Morgan; Taye, Telavive; Trueblood, Kamay; Vrana, Caroline J; Whitesides, E Tucker
2015-01-01
Current use of microbes for metabolic engineering suffers from loss of metabolic output due to natural selection. Rather than combat the evolution of bacterial populations, we chose to embrace what makes biological engineering unique among engineering fields - evolving materials. We harnessed bacteria to compute solutions to the biological problem of metabolic pathway optimization. Our approach is called Programmed Evolution to capture two concepts. First, a population of cells is programmed with DNA code to enable it to compute solutions to a chosen optimization problem. As analog computers, bacteria process known and unknown inputs and direct the output of their biochemical hardware. Second, the system employs the evolution of bacteria toward an optimal metabolic solution by imposing fitness defined by metabolic output. The current study is a proof-of-concept for Programmed Evolution applied to the optimization of a metabolic pathway for the conversion of caffeine to theophylline in E. coli. Introduced genotype variations included strength of the promoter and ribosome binding site, plasmid copy number, and chaperone proteins. We constructed 24 strains using all combinations of the genetic variables. We used a theophylline riboswitch and a tetracycline resistance gene to link theophylline production to fitness. After subjecting the mixed population to selection, we measured a change in the distribution of genotypes in the population and an increased conversion of caffeine to theophylline among the most fit strains, demonstrating Programmed Evolution. Programmed Evolution inverts the standard paradigm in metabolic engineering by harnessing evolution instead of fighting it. Our modular system enables researchers to program bacteria and use evolution to determine the combination of genetic control elements that optimizes catabolic or anabolic output and to maintain it in a population of cells. Programmed Evolution could be used for applications in energy, pharmaceuticals, chemical commodities, biomining, and bioremediation.
Structural optimization with approximate sensitivities
NASA Technical Reports Server (NTRS)
Patnaik, S. N.; Hopkins, D. A.; Coroneos, R.
1994-01-01
Computational efficiency in structural optimization can be enhanced if the intensive computations associated with the calculation of the sensitivities, that is, gradients of the behavior constraints, are reduced. Approximation to gradients of the behavior constraints that can be generated with small amount of numerical calculations is proposed. Structural optimization with these approximate sensitivities produced correct optimum solution. Approximate gradients performed well for different nonlinear programming methods, such as the sequence of unconstrained minimization technique, method of feasible directions, sequence of quadratic programming, and sequence of linear programming. Structural optimization with approximate gradients can reduce by one third the CPU time that would otherwise be required to solve the problem with explicit closed-form gradients. The proposed gradient approximation shows potential to reduce intensive computation that has been associated with traditional structural optimization.
Optimization applications in aircraft engine design and test
NASA Technical Reports Server (NTRS)
Pratt, T. K.
1984-01-01
Starting with the NASA-sponsored STAEBL program, optimization methods based primarily upon the versatile program COPES/CONMIN were introduced over the past few years to a broad spectrum of engineering problems in structural optimization, engine design, engine test, and more recently, manufacturing processes. By automating design and testing processes, many repetitive and costly trade-off studies have been replaced by optimization procedures. Rather than taking engineers and designers out of the loop, optimization has, in fact, put them more in control by providing sophisticated search techniques. The ultimate decision whether to accept or reject an optimal feasible design still rests with the analyst. Feedback obtained from this decision process has been invaluable since it can be incorporated into the optimization procedure to make it more intelligent. On several occasions, optimization procedures have produced novel designs, such as the nonsymmetric placement of rotor case stiffener rings, not anticipated by engineering designers. In another case, a particularly difficult resonance contraint could not be satisfied using hand iterations for a compressor blade, when the STAEBL program was applied to the problem, a feasible solution was obtained in just two iterations.
Huang, Kuo -Ling; Mehrotra, Sanjay
2016-11-08
We present a homogeneous algorithm equipped with a modified potential function for the monotone complementarity problem. We show that this potential function is reduced by at least a constant amount if a scaled Lipschitz condition (SLC) is satisfied. A practical algorithm based on this potential function is implemented in a software package named iOptimize. The implementation in iOptimize maintains global linear and polynomial time convergence properties, while achieving practical performance. It either successfully solves the problem, or concludes that the SLC is not satisfied. When compared with the mature software package MOSEK (barrier solver version 6.0.0.106), iOptimize solves convex quadraticmore » programming problems, convex quadratically constrained quadratic programming problems, and general convex programming problems in fewer iterations. Moreover, several problems for which MOSEK fails are solved to optimality. In addition, we also find that iOptimize detects infeasibility more reliably than the general nonlinear solvers Ipopt (version 3.9.2) and Knitro (version 8.0).« less
Mixed Integer Programming and Heuristic Scheduling for Space Communication Networks
NASA Technical Reports Server (NTRS)
Cheung, Kar-Ming; Lee, Charles H.
2012-01-01
We developed framework and the mathematical formulation for optimizing communication network using mixed integer programming. The design yields a system that is much smaller, in search space size, when compared to the earlier approach. Our constrained network optimization takes into account the dynamics of link performance within the network along with mission and operation requirements. A unique penalty function is introduced to transform the mixed integer programming into the more manageable problem of searching in a continuous space. The constrained optimization problem was proposed to solve in two stages: first using the heuristic Particle Swarming Optimization algorithm to get a good initial starting point, and then feeding the result into the Sequential Quadratic Programming algorithm to achieve the final optimal schedule. We demonstrate the above planning and scheduling methodology with a scenario of 20 spacecraft and 3 ground stations of a Deep Space Network site. Our approach and framework have been simple and flexible so that problems with larger number of constraints and network can be easily adapted and solved.
NASA Astrophysics Data System (ADS)
Chai, Runqi; Savvaris, Al; Tsourdos, Antonios
2016-06-01
In this paper, a fuzzy physical programming (FPP) method has been introduced for solving multi-objective Space Manoeuvre Vehicles (SMV) skip trajectory optimization problem based on hp-adaptive pseudospectral methods. The dynamic model of SMV is elaborated and then, by employing hp-adaptive pseudospectral methods, the problem has been transformed to nonlinear programming (NLP) problem. According to the mission requirements, the solutions were calculated for each single-objective scenario. To get a compromised solution for each target, the fuzzy physical programming (FPP) model is proposed. The preference function is established with considering the fuzzy factor of the system such that a proper compromised trajectory can be acquired. In addition, the NSGA-II is tested to obtain the Pareto-optimal solution set and verify the Pareto optimality of the FPP solution. Simulation results indicate that the proposed method is effective and feasible in terms of dealing with the multi-objective skip trajectory optimization for the SMV.
The Optimal Well Locator ( OWL) program was designed and developed by USEPA to be a screening tool to evaluate and optimize the placement of wells in long term monitoring networks at small sites. The first objective of the OWL program is to allow the user to visualize the change ...
Solving mixed integer nonlinear programming problems using spiral dynamics optimization algorithm
NASA Astrophysics Data System (ADS)
Kania, Adhe; Sidarto, Kuntjoro Adji
2016-02-01
Many engineering and practical problem can be modeled by mixed integer nonlinear programming. This paper proposes to solve the problem with modified spiral dynamics inspired optimization method of Tamura and Yasuda. Four test cases have been examined, including problem in engineering and sport. This method succeeds in obtaining the optimal result in all test cases.
OPTIMAL AIRCRAFT TRAJECTORIES FOR SPECIFIED RANGE
NASA Technical Reports Server (NTRS)
Lee, H.
1994-01-01
For an aircraft operating over a fixed range, the operating costs are basically a sum of fuel cost and time cost. While minimum fuel and minimum time trajectories are relatively easy to calculate, the determination of a minimum cost trajectory can be a complex undertaking. This computer program was developed to optimize trajectories with respect to a cost function based on a weighted sum of fuel cost and time cost. As a research tool, the program could be used to study various characteristics of optimum trajectories and their comparison to standard trajectories. It might also be used to generate a model for the development of an airborne trajectory optimization system. The program could be incorporated into an airline flight planning system, with optimum flight plans determined at takeoff time for the prevailing flight conditions. The use of trajectory optimization could significantly reduce the cost for a given aircraft mission. The algorithm incorporated in the program assumes that a trajectory consists of climb, cruise, and descent segments. The optimization of each segment is not done independently, as in classical procedures, but is performed in a manner which accounts for interaction between the segments. This is accomplished by the application of optimal control theory. The climb and descent profiles are generated by integrating a set of kinematic and dynamic equations, where the total energy of the aircraft is the independent variable. At each energy level of the climb and descent profiles, the air speed and power setting necessary for an optimal trajectory are determined. The variational Hamiltonian of the problem consists of the rate of change of cost with respect to total energy and a term dependent on the adjoint variable, which is identical to the optimum cruise cost at a specified altitude. This variable uniquely specifies the optimal cruise energy, cruise altitude, cruise Mach number, and, indirectly, the climb and descent profiles. If the optimum cruise cost is specified, an optimum trajectory can easily be generated; however, the range obtained for a particular optimum cruise cost is not known a priori. For short range flights, the program iteratively varies the optimum cruise cost until the computed range converges to the specified range. For long-range flights, iteration is unnecessary since the specified range can be divided into a cruise segment distance and full climb and descent distances. The user must supply the program with engine fuel flow rate coefficients and an aircraft aerodynamic model. The program currently includes coefficients for the Pratt-Whitney JT8D-7 engine and an aerodynamic model for the Boeing 727. Input to the program consists of the flight range to be covered and the prevailing flight conditions including pressure, temperature, and wind profiles. Information output by the program includes: optimum cruise tables at selected weights, optimal cruise quantities as a function of cruise weight and cruise distance, climb and descent profiles, and a summary of the complete synthesized optimal trajectory. This program is written in FORTRAN IV for batch execution and has been implemented on a CDC 6000 series computer with a central memory requirement of approximately 100K (octal) of 60 bit words. This aircraft trajectory optimization program was developed in 1979.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Arnis Judzis
2002-10-01
This document details the progress to date on the OPTIMIZATION OF MUD HAMMER DRILLING PERFORMANCE -- A PROGRAM TO BENCHMARK THE VIABILITY OF ADVANCED MUD HAMMER DRILLING contract for the quarter starting July 2002 through September 2002. Even though we are awaiting the optimization portion of the testing program, accomplishments include the following: (1) Smith International agreed to participate in the DOE Mud Hammer program. (2) Smith International chromed collars for upcoming benchmark tests at TerraTek, now scheduled for 4Q 2002. (3) ConocoPhillips had a field trial of the Smith fluid hammer offshore Vietnam. The hammer functioned properly, though themore » well encountered hole conditions and reaming problems. ConocoPhillips plan another field trial as a result. (4) DOE/NETL extended the contract for the fluid hammer program to allow Novatek to ''optimize'' their much delayed tool to 2003 and to allow Smith International to add ''benchmarking'' tests in light of SDS Digger Tools' current financial inability to participate. (5) ConocoPhillips joined the Industry Advisors for the mud hammer program. (6) TerraTek acknowledges Smith International, BP America, PDVSA, and ConocoPhillips for cost-sharing the Smith benchmarking tests allowing extension of the contract to complete the optimizations.« less
Lean and Efficient Software: Whole-Program Optimization of Executables
2015-09-30
libraries. Many levels of library interfaces—where some libraries are dynamically linked and some are provided in binary form only—significantly limit...software at build time. The opportunity: Our objective in this project is to substantially improve the performance, size, and robustness of binary ...executables by using static and dynamic binary program analysis techniques to perform whole-program optimization directly on compiled programs
NASA Astrophysics Data System (ADS)
Veerakamolmal, Pitipong; Lee, Yung-Joon; Fasano, J. P.; Hale, Rhea; Jacques, Mary
2002-02-01
In recent years, there has been increased focus by regulators, manufacturers, and consumers on the issue of product end of life management for electronics. This paper presents an overview of a conceptual study designed to examine the costs and benefits of several different Product Take Back (PTB) scenarios for used electronics equipment. The study utilized a reverse logistics supply chain model to examine the effects of several different factors in PTB programs. The model was done using the IBM supply chain optimization tool known as WIT (Watson Implosion Technology). Using the WIT tool, we were able to determine a theoretical optimal cost scenario for PTB programs. The study was designed to assist IBM internally in determining theoretical optimal Product Take Back program models and determining potential incentives for increasing participation rates.
Optimization techniques applied to passive measures for in-orbit spacecraft survivability
NASA Technical Reports Server (NTRS)
Mog, Robert A.; Price, D. Marvin
1987-01-01
Optimization techniques applied to passive measures for in-orbit spacecraft survivability, is a six-month study, designed to evaluate the effectiveness of the geometric programming (GP) optimization technique in determining the optimal design of a meteoroid and space debris protection system for the Space Station Core Module configuration. Geometric Programming was found to be superior to other methods in that it provided maximum protection from impact problems at the lowest weight and cost.
Social Emotional Optimization Algorithm for Nonlinear Constrained Optimization Problems
NASA Astrophysics Data System (ADS)
Xu, Yuechun; Cui, Zhihua; Zeng, Jianchao
Nonlinear programming problem is one important branch in operational research, and has been successfully applied to various real-life problems. In this paper, a new approach called Social emotional optimization algorithm (SEOA) is used to solve this problem which is a new swarm intelligent technique by simulating the human behavior guided by emotion. Simulation results show that the social emotional optimization algorithm proposed in this paper is effective and efficiency for the nonlinear constrained programming problems.
Robust Neighboring Optimal Guidance for the Advanced Launch System
NASA Technical Reports Server (NTRS)
Hull, David G.
1993-01-01
In recent years, optimization has become an engineering tool through the availability of numerous successful nonlinear programming codes. Optimal control problems are converted into parameter optimization (nonlinear programming) problems by assuming the control to be piecewise linear, making the unknowns the nodes or junction points of the linear control segments. Once the optimal piecewise linear control (suboptimal) control is known, a guidance law for operating near the suboptimal path is the neighboring optimal piecewise linear control (neighboring suboptimal control). Research conducted under this grant has been directed toward the investigation of neighboring suboptimal control as a guidance scheme for an advanced launch system.
A robust optimization methodology for preliminary aircraft design
NASA Astrophysics Data System (ADS)
Prigent, S.; Maréchal, P.; Rondepierre, A.; Druot, T.; Belleville, M.
2016-05-01
This article focuses on a robust optimization of an aircraft preliminary design under operational constraints. According to engineers' know-how, the aircraft preliminary design problem can be modelled as an uncertain optimization problem whose objective (the cost or the fuel consumption) is almost affine, and whose constraints are convex. It is shown that this uncertain optimization problem can be approximated in a conservative manner by an uncertain linear optimization program, which enables the use of the techniques of robust linear programming of Ben-Tal, El Ghaoui, and Nemirovski [Robust Optimization, Princeton University Press, 2009]. This methodology is then applied to two real cases of aircraft design and numerical results are presented.
Spectroscopic characterizations of organic/inorganic nanocomposites
NASA Astrophysics Data System (ADS)
Govani, Jayesh R.
2009-12-01
In the present study, pure and 0.3 wt%, 0.4 wt%, as well as 0.5 wt% L-arginine doped potassium dihydrogen phosphate (KDP) crystals were grown using solution growth techniques and further subjected to infrared (IR) absorption and Raman studies for confirmation of chemical group functionalization for investigating the incorporation mechanism of the L-arginine organic material into the KDP crystal structure. Infrared spectroscopic analysis suggests that structural changes are occurring for the L-arginine molecule as a result of its interaction with the KPD crystal. Infrared spectroscopic technique confirms the disturbance of the N-H, C-H and C-N bonds of the amino acid, suggesting successful incorporation of L-arginine into the KDP crystals. Raman analysis also reveals modification of the N-H, C-H and C-N bonds of the amino acid, implying successful inclusion of L-arginine into the KDP crystals. With the help of Gaussian software, a prediction of possible incorporation mechanisms of the organic material was obtained from comparison of the simulated infrared and Raman vibrational spectra with the experimental results. Furthermore, we also studied the effect of L-arginine doping on the thermal stability of the grown KDP crystal by employing Thermo gravimetric analysis (TGA). TGA suggests that increasing the level of L-arginine doping speeds the decomposition process and it weakens the KDP crystal, which indicates successful doping of the KDP crystals with L-arginine amino acid. Urinary stones are one of the oldest and most widely spread diseases in humans, animals and birds. Many remedies have been employed through the ages for the treatment of urinary stones. Recent medicinal measures reflect the modern advances, which are based on surgical removal, percutaneous techniques and extracorporeal shock wave lithotripsy (ESWL). Although these procedures are valuable, they are quite expensive for most people. Furthermore, recurrence of these diseases is awfully frequent with these procedures and the patients have to be subjected to careful follow up for several years. In contrast, in traditional therapeutic systems, most of the remedies were taken from plants and they proved to be helpful. However, the rationale behind their use is not thoroughly established through systematic pharmacological and clinical studies. In this regard, in the present investigation, with a view towards acquiring more insights, we have performed a detailed study of kidney stone formation and growth inhibition based on a traditional medicine approach with herbal extracts. The intricacy of calculi formation (i.e. nucleation, transformation, and aggregation) in a natural system such as urine is replicated to a certain extent in the present study by using a simplified single diffusion gel growth technique. Crystals were synthesized in a static gel environment without and with the presence of 1% and 2% concentration of Rotula Aquatica Lour (RAL) herbal extracts and further subjected to Raman, infrared absorption, X-ray photoelectron spectroscopy (XPS), and photoluminescence to analyze the effects of RAL on the growth of manganese-based calculi. Raman spectroscopy clearly provided an indication of the newberyite type of crystal as well as information on the chemical interaction between crystal and inhibitor. It also indicates the presence of organic components due to the RAL plant material. Infrared absorption spectroscopy indicates the presence of a strong reflecting component in the inhibitor as well as the newberyite type of crystal. XPS results indicated the presence of metallic zinc in the crystal with inhibitor. Furthermore, a considerable increase in the intensity of the magnesium and oxygen lines are noticed with the addition of the herbal extract, which suggest that the inhibitor chemical composition includes a substantial quantity of Mg and O. XPS analysis also demonstrates the presence of modified phosphorus oxidation states and suggest that they might make a contribution, too. The photoluminescence spectra of the crystal with inhibitor indicate the presence of chlorophyll, and hence, confirm the presence of Mg. This study provides evidence of Mg- and Zn-related inhibition of urinary calculi formation with the addition of RAL herbal extract, contributing, from the spectroscopic point of view, to an intricate subject. Our present investigation might serve as an important source of information on this tantalizing and multifaceted problem, which is not yet completely understood. (Abstract shortened by UMI.)
Buszka, Paul M.; Fitzpatrick, John A.; Watson, Lee R.; Kay, Robert T.
2007-01-01
Concentrations of boron greater than the U.S. Environmental Protection Agency (USEPA) 900 ?g/L removal action level (RAL) standard were detected in water sampled by the USEPA in 2004 from three domestic wells near Beverly Shores, Indiana. The RAL regulates only human-affected concentrations of a constituent. A lack of well logs and screened depth information precluded identification of whether water from sampled wells, and their boron sources, were from human-affected or natural sources in the surficial aquifer, or associated with a previously defined natural, confined aquifer source of boron from the subtill or basal sand aquifers. A geochemically-based classification of the source of boron in ground water could potentially determine the similarity of boron to known sources or mixtures between known sources, or classify whether the relative age of the ground water predated the potential sources of contamination. The U.S. Geological Survey (USGS), in cooperation with the USEPA, investigated the use of a geochemical method that applied boron stable isotopes, and concentrations of boron, tritium, and other constituents to distinguish between natural and human-affected sources of boron in ground water and thereby determine if the RAL was applicable to the situation. Boron stable-isotope ratios and concentrations of boron in 17 ground-water samples and tritium concentrations in 9 ground-water samples collected in 2004 were used to identify geochemical differences between potential sources of boron in ground water near Beverly Shores, Indiana. Boron and d11B analyses for this investigation were made on unacidified samples to assure consistency of the result with unacidified analyses of d11B values from other investigations. Potential sources of boron included surficial-aquifer water affected by coal-combustion products (CCP) or domestic-wastewater, upward discharge of ground water from confined aquifers, and unaffected water from the surficial aquifer that was distant from human-affected boron sources. Boron concentrations in potential ground-water sources of boron were largest (15,700 to 24,400 ?g/L) in samples of CCP-affected surficial aquifer water from four wells at a CCP landfill and smallest (27 to 63 ?g/L) in three wells in the surficial aquifer that were distant from human-affected boron sources. Boron concentrations in water from the basal sand aquifer ranged from 656 ?g/L to 1,800 ?g/L. Boron concentrations in water from three domestic-wastewater-affected surficial aquifer wells ranged from 84 to 387 ?g/L. Among the representative ground-water samples, boron concentrations from all four samples of CCP-affected surficial aquifer water and four of five samples of water from the basal sand aquifer had concentrations greater than the RAL. A comparison of boron concentrations in acid-preserved and unacidified samples indicated that boron concentrations reported for this investigation may be from about 11 to 16 percent less than would be reported in a standard analysis of an acidified sample. The stable isotope boron-11 was most enriched in comparison to boron-10 in ground water from a confined aquifer, the basal sand aquifer (d11B, 24.6 to 34.0 per mil, five samples); it was most depleted in CCP-affected water from the surficial aquifer (d11B, 0.1 to 6.6 per mil, four samples). Domestic-wastewater-affected water from the surficial aquifer (d11B, 8.7 to 11.7 per mil, four samples) was enriched in boron-11, in comparison to individual samples of a borax detergent additive and a detergent with perborate bleach; it was intermediate in composition between basal sand aquifer water and CCP-affected water from the surficial aquifer. The similarity between a ground-water sample from the surficial aquifer and a hypothetical mixture of unaffected surficial aquifer and basal sand aquifer waters indicates the potential for long-term upward discharge of ground water into the surficial aquifer from one or more confined aquifers. Est
NASA Astrophysics Data System (ADS)
Sutrisno; Widowati; Sunarsih; Kartono
2018-01-01
In this paper, a mathematical model in quadratic programming with fuzzy parameter is proposed to determine the optimal strategy for integrated inventory control and supplier selection problem with fuzzy demand. To solve the corresponding optimization problem, we use the expected value based fuzzy programming. Numerical examples are performed to evaluate the model. From the results, the optimal amount of each product that have to be purchased from each supplier for each time period and the optimal amount of each product that have to be stored in the inventory for each time period were determined with minimum total cost and the inventory level was sufficiently closed to the reference level.
Rocket ascent G-limited moment-balanced optimization program (RAGMOP)
NASA Technical Reports Server (NTRS)
Lyons, J. T.; Woltosz, W. S.; Abercrombie, G. E.; Gottlieb, R. G.
1972-01-01
This document describes the RAGMOP (Rocket Ascent G-limited Momentbalanced Optimization Program) computer program for parametric ascent trajectory optimization. RAGMOP computes optimum polynomial-form attitude control histories, launch azimuth, engine burn-time, and gross liftoff weight for space shuttle type vehicles using a search-accelerated, gradient projection parameter optimization technique. The trajectory model available in RAGMOP includes a rotating oblate earth model, the option of input wind tables, discrete and/or continuous throttling for the purposes of limiting the thrust acceleration and/or the maximum dynamic pressure, limitation of the structural load indicators (the product of dynamic pressure with angle-of-attack and sideslip angle), and a wide selection of intermediate and terminal equality constraints.
OPTIMIZATION OF COUNTERCURRENT STAGED PROCESSES.
CHEMICAL ENGINEERING , OPTIMIZATION), (*DISTILLATION, OPTIMIZATION), INDUSTRIAL PRODUCTION, INDUSTRIAL EQUIPMENT, MATHEMATICAL MODELS, DIFFERENCE EQUATIONS, NONLINEAR PROGRAMMING, BOUNDARY VALUE PROBLEMS, NUMERICAL INTEGRATION
CORSS: Cylinder Optimization of Rings, Skin, and Stringers
NASA Technical Reports Server (NTRS)
Finckenor, J.; Rogers, P.; Otte, N.
1994-01-01
Launch vehicle designs typically make extensive use of cylindrical skin stringer construction. Structural analysis methods are well developed for preliminary design of this type of construction. This report describes an automated, iterative method to obtain a minimum weight preliminary design. Structural optimization has been researched extensively, and various programs have been written for this purpose. Their complexity and ease of use depends on their generality, the failure modes considered, the methodology used, and the rigor of the analysis performed. This computer program employs closed-form solutions from a variety of well-known structural analysis references and joins them with a commercially available numerical optimizer called the 'Design Optimization Tool' (DOT). Any ring and stringer stiffened shell structure of isotropic materials that has beam type loading can be analyzed. Plasticity effects are not included. It performs a more limited analysis than programs such as PANDA, but it provides an easy and useful preliminary design tool for a large class of structures. This report briefly describes the optimization theory, outlines the development and use of the program, and describes the analysis techniques that are used. Examples of program input and output, as well as the listing of the analysis routines, are included.
Finding optimal vaccination strategies under parameter uncertainty using stochastic programming.
Tanner, Matthew W; Sattenspiel, Lisa; Ntaimo, Lewis
2008-10-01
We present a stochastic programming framework for finding the optimal vaccination policy for controlling infectious disease epidemics under parameter uncertainty. Stochastic programming is a popular framework for including the effects of parameter uncertainty in a mathematical optimization model. The problem is initially formulated to find the minimum cost vaccination policy under a chance-constraint. The chance-constraint requires that the probability that R(*)
Englesbe, Michael J; Grenda, Dane R; Sullivan, June A; Derstine, Brian A; Kenney, Brooke N; Sheetz, Kyle H; Palazzolo, William C; Wang, Nicholas C; Goulson, Rebecca L; Lee, Jay S; Wang, Stewart C
2017-06-01
The Michigan Surgical Home and Optimization Program is a structured, home-based, preoperative training program targeting physical, nutritional, and psychological guidance. The purpose of this study was to determine if participation in this program was associated with reduced hospital duration of stay and health care costs. We conducted a retrospective, single center, cohort study evaluating patients who participated in the Michigan Surgical Home and Optimization Program and subsequently underwent major elective general and thoracic operative care between June 2014 and December 2015. Propensity score matching was used to match program participants to a control group who underwent operative care prior to program implementation. Primary outcome measures were hospital duration of stay and payer costs. Multivariate regression was used to determine the covariate-adjusted effect of program participation. A total of 641 patients participated in the program; 82% were actively engaged in the program, recording physical activity at least 3 times per week for the majority of the program; 182 patients were propensity matched to patients who underwent operative care prior to program implementation. Multivariate analysis demonstrated that participation in the Michigan Surgical Home and Optimization Program was associated with a 31% reduction in hospital duration of stay (P < .001) and 28% lower total costs (P < .001) after adjusting for covariates. A home-based, preoperative training program decreased hospital duration of stay, lowered costs of care, and was well accepted by patients. Further efforts will focus on broader implementation and linking participation to postoperative complications and rigorous patient-reported outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.
Hybrid Nested Partitions and Math Programming Framework for Large-scale Combinatorial Optimization
2010-03-31
optimization problems: 1) exact algorithms and 2) metaheuristic algorithms . This project will integrate concepts from these two technologies to develop...optimal solutions within an acceptable amount of computation time, and 2) metaheuristic algorithms such as genetic algorithms , tabu search, and the...integer programming decomposition approaches, such as Dantzig Wolfe decomposition and Lagrangian relaxation, and metaheuristics such as the Nested
Dynamic programming for optimization of timber production and grazing in ponderosa pine
Kurt H. Riitters; J. Douglas Brodie; David W. Hann
1982-01-01
Dynamic programming procedures are presented for optimizing thinning and rotation of even-aged ponderosa pine by using the four descriptors: age, basal area, number of trees, and time since thinning. Because both timber yield and grazing yield are functions of stand density, the two outputs-forage and timber-can both be optimized. The soil expectation values for single...
SCI model structure determination program (OSR) user's guide. [optimal subset regression
NASA Technical Reports Server (NTRS)
1979-01-01
The computer program, OSR (Optimal Subset Regression) which estimates models for rotorcraft body and rotor force and moment coefficients is described. The technique used is based on the subset regression algorithm. Given time histories of aerodynamic coefficients, aerodynamic variables, and control inputs, the program computes correlation between various time histories. The model structure determination is based on these correlations. Inputs and outputs of the program are given.
A Kind of Nonlinear Programming Problem Based on Mixed Fuzzy Relation Equations Constraints
NASA Astrophysics Data System (ADS)
Li, Jinquan; Feng, Shuang; Mi, Honghai
In this work, a kind of nonlinear programming problem with non-differential objective function and under the constraints expressed by a system of mixed fuzzy relation equations is investigated. First, some properties of this kind of optimization problem are obtained. Then, a polynomial-time algorithm for this kind of optimization problem is proposed based on these properties. Furthermore, we show that this algorithm is optimal for the considered optimization problem in this paper. Finally, numerical examples are provided to illustrate our algorithms.
NASA Technical Reports Server (NTRS)
Sreekanta Murthy, T.
1992-01-01
Results of the investigation of formal nonlinear programming-based numerical optimization techniques of helicopter airframe vibration reduction are summarized. The objective and constraint function and the sensitivity expressions used in the formulation of airframe vibration optimization problems are presented and discussed. Implementation of a new computational procedure based on MSC/NASTRAN and CONMIN in a computer program system called DYNOPT for optimizing airframes subject to strength, frequency, dynamic response, and dynamic stress constraints is described. An optimization methodology is proposed which is thought to provide a new way of applying formal optimization techniques during the various phases of the airframe design process. Numerical results obtained from the application of the DYNOPT optimization code to a helicopter airframe are discussed.
JPL-ANTOPT antenna structure optimization program
NASA Technical Reports Server (NTRS)
Strain, D. M.
1994-01-01
New antenna path-length error and pointing-error structure optimization codes were recently added to the MSC/NASTRAN structural analysis computer program. Path-length and pointing errors are important measured of structure-related antenna performance. The path-length and pointing errors are treated as scalar displacements for statics loading cases. These scalar displacements can be subject to constraint during the optimization process. Path-length and pointing-error calculations supplement the other optimization and sensitivity capabilities of NASTRAN. The analysis and design functions were implemented as 'DMAP ALTERs' to the Design Optimization (SOL 200) Solution Sequence of MSC-NASTRAN, Version 67.5.
NASA Technical Reports Server (NTRS)
Aziz, Jonathan D.; Parker, Jeffrey S.; Scheeres, Daniel J.; Englander, Jacob A.
2017-01-01
Low-thrust trajectories about planetary bodies characteristically span a high count of orbital revolutions. Directing the thrust vector over many revolutions presents a challenging optimization problem for any conventional strategy. This paper demonstrates the tractability of low-thrust trajectory optimization about planetary bodies by applying a Sundman transformation to change the independent variable of the spacecraft equations of motion to the eccentric anomaly and performing the optimization with differential dynamic programming. Fuel-optimal geocentric transfers are shown in excess of 1000 revolutions while subject to Earths J2 perturbation and lunar gravity.
[The role of neurotrophic factors in regeneration of the nervous system].
Machaliński, Bogusław; Lażewski-Banaszak, Piotr; Dąbkowska, Elżbieta; Paczkowska, Edyta; Gołąb-Janowska, Monika; Nowacki, Przemysław
2012-01-01
Neurotrophic factors regulate survival, development, and function of nervous tissue. They act via two different classes of receptors and activation of various signaling pathways in the target cells. Illumination of their physiological role in the maintenance of central nervous system homeostasis as well as regeneration of damaged tissue have ignited expectations to heal neurodegenerative diseases, including amyotrophic late-ral sclerosis and Parkinson disease. Advances in pharmaco-therapy, gene therapy, and stem cell biology have enabled development of novel therapies with application of regenerating cell transplantation. In the foreseeable future, it may lead to the establishment of safe and effective ways of treatment of these severe and currently incurable diseases.
[Care and anthropology: a thinking process].
Rohrbach Viadas, Cécilia
2007-09-01
Caring for human beings, calls for relating unity and diversity in order to respect the equality of cultures and to recognize their cultural differences. Cultural difference is, however, privileged by recent publications within the culture caring domain, based on cultural relativism and disregarding the unity of humanity, transcultu-ral nursing theory is the case. For this reason, some historical elements related to the two original anthropological theories are included in this text to understand the philosophical and ethical implications of transcultural nursing theory. The objective of this article is to analyse six recent publications within the caring and anthropology field, through a reflexive method identifying two different caring traditions and demonstrating their philosophical and ethical reach for caring practice.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pirozhkov, A. S.; Mori, M.; Yogo, A.
High-power laser contrast is challenging to measure, especially in the real target irradiation conditions. We present a convenient and relatively simple contrast diagnostic technique based on the measurement of target specular reflectivity at full laser power. The reflectivity remains high even at intensities above 10{sup 19} W/cm{sup 2} in the case of a high-contrast prepulse-free laser. On the contrary, the specular reflectivity drops in the case of lower contrast, due to the beam break-up and increased absorption caused by the preformed plasma. The technique was demonstrated using three different laser systems with several contrast conditions: Astra (CLF, RAL), TiS lasermore » at APRI, GIST, and J-KAREN (APRC, JAEA).« less
He, Lu; Friedman, Alan M; Bailey-Kellogg, Chris
2012-03-01
In developing improved protein variants by site-directed mutagenesis or recombination, there are often competing objectives that must be considered in designing an experiment (selecting mutations or breakpoints): stability versus novelty, affinity versus specificity, activity versus immunogenicity, and so forth. Pareto optimal experimental designs make the best trade-offs between competing objectives. Such designs are not "dominated"; that is, no other design is better than a Pareto optimal design for one objective without being worse for another objective. Our goal is to produce all the Pareto optimal designs (the Pareto frontier), to characterize the trade-offs and suggest designs most worth considering, but to avoid explicitly considering the large number of dominated designs. To do so, we develop a divide-and-conquer algorithm, Protein Engineering Pareto FRontier (PEPFR), that hierarchically subdivides the objective space, using appropriate dynamic programming or integer programming methods to optimize designs in different regions. This divide-and-conquer approach is efficient in that the number of divisions (and thus calls to the optimizer) is directly proportional to the number of Pareto optimal designs. We demonstrate PEPFR with three protein engineering case studies: site-directed recombination for stability and diversity via dynamic programming, site-directed mutagenesis of interacting proteins for affinity and specificity via integer programming, and site-directed mutagenesis of a therapeutic protein for activity and immunogenicity via integer programming. We show that PEPFR is able to effectively produce all the Pareto optimal designs, discovering many more designs than previous methods. The characterization of the Pareto frontier provides additional insights into the local stability of design choices as well as global trends leading to trade-offs between competing criteria. Copyright © 2011 Wiley Periodicals, Inc.
Interplanetary Program to Optimize Simulated Trajectories (IPOST). Volume 3: Programmer's manual
NASA Technical Reports Server (NTRS)
Hong, P. E.; Kent, P. D.; Olson, D. W.; Vallado, C. A.
1992-01-01
The Interplanetary Program to Optimize Space Trajectories (IPOST) is intended to support many analysis phases, from early interplanetary feasibility studies through spacecraft development and operations. Here, information is given on the IPOST code.
Large-scale linear programs in planning and prediction.
DOT National Transportation Integrated Search
2017-06-01
Large-scale linear programs are at the core of many traffic-related optimization problems in both planning and prediction. Moreover, many of these involve significant uncertainty, and hence are modeled using either chance constraints, or robust optim...
Post optimization paradigm in maximum 3-satisfiability logic programming
NASA Astrophysics Data System (ADS)
Mansor, Mohd. Asyraf; Sathasivam, Saratha; Kasihmuddin, Mohd Shareduwan Mohd
2017-08-01
Maximum 3-Satisfiability (MAX-3SAT) is a counterpart of the Boolean satisfiability problem that can be treated as a constraint optimization problem. It deals with a conundrum of searching the maximum number of satisfied clauses in a particular 3-SAT formula. This paper presents the implementation of enhanced Hopfield network in hastening the Maximum 3-Satisfiability (MAX-3SAT) logic programming. Four post optimization techniques are investigated, including the Elliot symmetric activation function, Gaussian activation function, Wavelet activation function and Hyperbolic tangent activation function. The performances of these post optimization techniques in accelerating MAX-3SAT logic programming will be discussed in terms of the ratio of maximum satisfied clauses, Hamming distance and the computation time. Dev-C++ was used as the platform for training, testing and validating our proposed techniques. The results depict the Hyperbolic tangent activation function and Elliot symmetric activation function can be used in doing MAX-3SAT logic programming.
ERIC Educational Resources Information Center
Brusco, Michael J.; Stahl, Stephanie
2005-01-01
There are two well-known methods for obtaining a guaranteed globally optimal solution to the problem of least-squares unidimensional scaling of a symmetric dissimilarity matrix: (a) dynamic programming, and (b) branch-and-bound. Dynamic programming is generally more efficient than branch-and-bound, but the former is limited to matrices with…
Guevara, V R
2004-02-01
A nonlinear programming optimization model was developed to maximize margin over feed cost in broiler feed formulation and is described in this paper. The model identifies the optimal feed mix that maximizes profit margin. Optimum metabolizable energy level and performance were found by using Excel Solver nonlinear programming. Data from an energy density study with broilers were fitted to quadratic equations to express weight gain, feed consumption, and the objective function income over feed cost in terms of energy density. Nutrient:energy ratio constraints were transformed into equivalent linear constraints. National Research Council nutrient requirements and feeding program were used for examining changes in variables. The nonlinear programming feed formulation method was used to illustrate the effects of changes in different variables on the optimum energy density, performance, and profitability and was compared with conventional linear programming. To demonstrate the capabilities of the model, I determined the impact of variation in prices. Prices for broiler, corn, fish meal, and soybean meal were increased and decreased by 25%. Formulations were identical in all other respects. Energy density, margin, and diet cost changed compared with conventional linear programming formulation. This study suggests that nonlinear programming can be more useful than conventional linear programming to optimize performance response to energy density in broiler feed formulation because an energy level does not need to be set.
NASA Technical Reports Server (NTRS)
Sobieszczanski-Sobieski, J.; Bhat, R. B.
1979-01-01
A finite element program is linked with a general purpose optimization program in a 'programing system' which includes user supplied codes that contain problem dependent formulations of the design variables, objective function and constraints. The result is a system adaptable to a wide spectrum of structural optimization problems. In a sample of numerical examples, the design variables are the cross-sectional dimensions and the parameters of overall shape geometry, constraints are applied to stresses, displacements, buckling and vibration characteristics, and structural mass is the objective function. Thin-walled, built-up structures and frameworks are included in the sample. Details of the system organization and characteristics of the component programs are given.
A nonlinear bi-level programming approach for product portfolio management.
Ma, Shuang
2016-01-01
Product portfolio management (PPM) is a critical decision-making for companies across various industries in today's competitive environment. Traditional studies on PPM problem have been motivated toward engineering feasibilities and marketing which relatively pay less attention to other competitors' actions and the competitive relations, especially in mathematical optimization domain. The key challenge lies in that how to construct a mathematical optimization model to describe this Stackelberg game-based leader-follower PPM problem and the competitive relations between them. The primary work of this paper is the representation of a decision framework and the optimization model to leverage the PPM problem of leader and follower. A nonlinear, integer bi-level programming model is developed based on the decision framework. Furthermore, a bi-level nested genetic algorithm is put forward to solve this nonlinear bi-level programming model for leader-follower PPM problem. A case study of notebook computer product portfolio optimization is reported. Results and analyses reveal that the leader-follower bi-level optimization model is robust and can empower product portfolio optimization.
Integrated solar energy system optimization
NASA Astrophysics Data System (ADS)
Young, S. K.
1982-11-01
The computer program SYSOPT, intended as a tool for optimizing the subsystem sizing, performance, and economics of integrated wind and solar energy systems, is presented. The modular structure of the methodology additionally allows simulations when the solar subsystems are combined with conventional technologies, e.g., a utility grid. Hourly energy/mass flow balances are computed for interconnection points, yielding optimized sizing and time-dependent operation of various subsystems. The program requires meteorological data, such as insolation, diurnal and seasonal variations, and wind speed at the hub height of a wind turbine, all of which can be taken from simulations like the TRNSYS program. Examples are provided for optimization of a solar-powered (wind turbine and parabolic trough-Rankine generator) desalinization plant, and a design analysis for a solar powered greenhouse.
Mass Optimization of Battery/Supercapacitors Hybrid Systems Based on a Linear Programming Approach
NASA Astrophysics Data System (ADS)
Fleury, Benoit; Labbe, Julien
2014-08-01
The objective of this paper is to show that, on a specific launcher-type mission profile, a 40% gain of mass is expected using a battery/supercapacitors active hybridization instead of a single battery solution. This result is based on the use of a linear programming optimization approach to perform the mass optimization of the hybrid power supply solution.
Scalable Rapidly Deployable Convex Optimization for Data Analytics
SOCPs , SDPs, exponential cone programs, and power cone programs. CVXPY supports basic methods for distributed optimization, on...multiple heterogenous platforms. We have also done basic research in various application areas , using CVXPY , to demonstrate its usefulness. See attached report for publication information....Over the period of the contract we have developed the full stack for wide use of convex optimization, in machine learning and many other areas .
Chung M. Chen; Dietmar W. Rose; Rolfe A. Leary
1980-01-01
Describes how dynamic programming can be used to solve optimal stand density problems when yields are given by prior simulation or by a new stand growth equation that is a function of the decision variable. Formulations of the latter type allow use of a calculus-based search procedure; they determine exact optimal residual density at each stage.
Modeling and Analysis of Power Processing Systems (MAPPS). Volume 2: Appendices
NASA Technical Reports Server (NTRS)
Lee, F. C.; Radman, S.; Carter, R. A.; Wu, C. H.; Yu, Y.; Chang, R.
1980-01-01
The computer programs and derivations generated in support of the modeling and design optimization program are presented. Programs for the buck regulator, boost regulator, and buck-boost regulator are described. The computer program for the design optimization calculations is presented. Constraints for the boost and buck-boost converter were derived. Derivations of state-space equations and transfer functions are presented. Computer lists for the converters are presented, and the input parameters justified.
Ritchie, Marylyn D; White, Bill C; Parker, Joel S; Hahn, Lance W; Moore, Jason H
2003-01-01
Background Appropriate definition of neural network architecture prior to data analysis is crucial for successful data mining. This can be challenging when the underlying model of the data is unknown. The goal of this study was to determine whether optimizing neural network architecture using genetic programming as a machine learning strategy would improve the ability of neural networks to model and detect nonlinear interactions among genes in studies of common human diseases. Results Using simulated data, we show that a genetic programming optimized neural network approach is able to model gene-gene interactions as well as a traditional back propagation neural network. Furthermore, the genetic programming optimized neural network is better than the traditional back propagation neural network approach in terms of predictive ability and power to detect gene-gene interactions when non-functional polymorphisms are present. Conclusion This study suggests that a machine learning strategy for optimizing neural network architecture may be preferable to traditional trial-and-error approaches for the identification and characterization of gene-gene interactions in common, complex human diseases. PMID:12846935
Direct Method Transcription for a Human-Class Translunar Injection Trajectory Optimization
NASA Technical Reports Server (NTRS)
Witzberger, Kevin E.; Zeiler, Tom
2012-01-01
This paper presents a new trajectory optimization software package developed in the framework of a low-to-high fidelity 3 degrees-of-freedom (DOF)/6-DOF vehicle simulation program named Mission Analysis Simulation Tool in Fortran (MASTIF) and its application to a translunar trajectory optimization problem. The functionality of the developed optimization package is implemented as a new "mode" in generalized settings to make it applicable for a general trajectory optimization problem. In doing so, a direct optimization method using collocation is employed for solving the problem. Trajectory optimization problems in MASTIF are transcribed to a constrained nonlinear programming (NLP) problem and solved with SNOPT, a commercially available NLP solver. A detailed description of the optimization software developed is provided as well as the transcription specifics for the translunar injection (TLI) problem. The analysis includes a 3-DOF trajectory TLI optimization and a 3-DOF vehicle TLI simulation using closed-loop guidance.
A sequential linear optimization approach for controller design
NASA Technical Reports Server (NTRS)
Horta, L. G.; Juang, J.-N.; Junkins, J. L.
1985-01-01
A linear optimization approach with a simple real arithmetic algorithm is presented for reliable controller design and vibration suppression of flexible structures. Using first order sensitivity of the system eigenvalues with respect to the design parameters in conjunction with a continuation procedure, the method converts a nonlinear optimization problem into a maximization problem with linear inequality constraints. The method of linear programming is then applied to solve the converted linear optimization problem. The general efficiency of the linear programming approach allows the method to handle structural optimization problems with a large number of inequality constraints on the design vector. The method is demonstrated using a truss beam finite element model for the optimal sizing and placement of active/passive-structural members for damping augmentation. Results using both the sequential linear optimization approach and nonlinear optimization are presented and compared. The insensitivity to initial conditions of the linear optimization approach is also demonstrated.
Warid, Warid; Hizam, Hashim; Mariun, Norman; Abdul-Wahab, Noor Izzri
2016-01-01
This paper proposes a new formulation for the multi-objective optimal power flow (MOOPF) problem for meshed power networks considering distributed generation. An efficacious multi-objective fuzzy linear programming optimization (MFLP) algorithm is proposed to solve the aforementioned problem with and without considering the distributed generation (DG) effect. A variant combination of objectives is considered for simultaneous optimization, including power loss, voltage stability, and shunt capacitors MVAR reserve. Fuzzy membership functions for these objectives are designed with extreme targets, whereas the inequality constraints are treated as hard constraints. The multi-objective fuzzy optimal power flow (OPF) formulation was converted into a crisp OPF in a successive linear programming (SLP) framework and solved using an efficient interior point method (IPM). To test the efficacy of the proposed approach, simulations are performed on the IEEE 30-busand IEEE 118-bus test systems. The MFLP optimization is solved for several optimization cases. The obtained results are compared with those presented in the literature. A unique solution with a high satisfaction for the assigned targets is gained. Results demonstrate the effectiveness of the proposed MFLP technique in terms of solution optimality and rapid convergence. Moreover, the results indicate that using the optimal DG location with the MFLP algorithm provides the solution with the highest quality.
Warid, Warid; Hizam, Hashim; Mariun, Norman; Abdul-Wahab, Noor Izzri
2016-01-01
This paper proposes a new formulation for the multi-objective optimal power flow (MOOPF) problem for meshed power networks considering distributed generation. An efficacious multi-objective fuzzy linear programming optimization (MFLP) algorithm is proposed to solve the aforementioned problem with and without considering the distributed generation (DG) effect. A variant combination of objectives is considered for simultaneous optimization, including power loss, voltage stability, and shunt capacitors MVAR reserve. Fuzzy membership functions for these objectives are designed with extreme targets, whereas the inequality constraints are treated as hard constraints. The multi-objective fuzzy optimal power flow (OPF) formulation was converted into a crisp OPF in a successive linear programming (SLP) framework and solved using an efficient interior point method (IPM). To test the efficacy of the proposed approach, simulations are performed on the IEEE 30-busand IEEE 118-bus test systems. The MFLP optimization is solved for several optimization cases. The obtained results are compared with those presented in the literature. A unique solution with a high satisfaction for the assigned targets is gained. Results demonstrate the effectiveness of the proposed MFLP technique in terms of solution optimality and rapid convergence. Moreover, the results indicate that using the optimal DG location with the MFLP algorithm provides the solution with the highest quality. PMID:26954783
DOE Office of Scientific and Technical Information (OSTI.GOV)
Huang, Kuo -Ling; Mehrotra, Sanjay
We present a homogeneous algorithm equipped with a modified potential function for the monotone complementarity problem. We show that this potential function is reduced by at least a constant amount if a scaled Lipschitz condition (SLC) is satisfied. A practical algorithm based on this potential function is implemented in a software package named iOptimize. The implementation in iOptimize maintains global linear and polynomial time convergence properties, while achieving practical performance. It either successfully solves the problem, or concludes that the SLC is not satisfied. When compared with the mature software package MOSEK (barrier solver version 6.0.0.106), iOptimize solves convex quadraticmore » programming problems, convex quadratically constrained quadratic programming problems, and general convex programming problems in fewer iterations. Moreover, several problems for which MOSEK fails are solved to optimality. In addition, we also find that iOptimize detects infeasibility more reliably than the general nonlinear solvers Ipopt (version 3.9.2) and Knitro (version 8.0).« less
GLOBAL SOLUTIONS TO FOLDED CONCAVE PENALIZED NONCONVEX LEARNING
Liu, Hongcheng; Yao, Tao; Li, Runze
2015-01-01
This paper is concerned with solving nonconvex learning problems with folded concave penalty. Despite that their global solutions entail desirable statistical properties, there lack optimization techniques that guarantee global optimality in a general setting. In this paper, we show that a class of nonconvex learning problems are equivalent to general quadratic programs. This equivalence facilitates us in developing mixed integer linear programming reformulations, which admit finite algorithms that find a provably global optimal solution. We refer to this reformulation-based technique as the mixed integer programming-based global optimization (MIPGO). To our knowledge, this is the first global optimization scheme with a theoretical guarantee for folded concave penalized nonconvex learning with the SCAD penalty (Fan and Li, 2001) and the MCP penalty (Zhang, 2010). Numerical results indicate a significant outperformance of MIPGO over the state-of-the-art solution scheme, local linear approximation, and other alternative solution techniques in literature in terms of solution quality. PMID:27141126
Zhu, Yuanheng; Zhao, Dongbin; Yang, Xiong; Zhang, Qichao
2018-02-01
Sum of squares (SOS) polynomials have provided a computationally tractable way to deal with inequality constraints appearing in many control problems. It can also act as an approximator in the framework of adaptive dynamic programming. In this paper, an approximate solution to the optimal control of polynomial nonlinear systems is proposed. Under a given attenuation coefficient, the Hamilton-Jacobi-Isaacs equation is relaxed to an optimization problem with a set of inequalities. After applying the policy iteration technique and constraining inequalities to SOS, the optimization problem is divided into a sequence of feasible semidefinite programming problems. With the converged solution, the attenuation coefficient is further minimized to a lower value. After iterations, approximate solutions to the smallest -gain and the associated optimal controller are obtained. Four examples are employed to verify the effectiveness of the proposed algorithm.
Integrated Network Decompositions and Dynamic Programming for Graph Optimization (INDDGO)
DOE Office of Scientific and Technical Information (OSTI.GOV)
The INDDGO software package offers a set of tools for finding exact solutions to graph optimization problems via tree decompositions and dynamic programming algorithms. Currently the framework offers serial and parallel (distributed memory) algorithms for finding tree decompositions and solving the maximum weighted independent set problem. The parallel dynamic programming algorithm is implemented on top of the MADNESS task-based runtime.
ERIC Educational Resources Information Center
Sikora, Stephanie
2006-01-01
The Optimal Aging Program (OAP) at the University of Arizona, College of Medicine is a longitudinal mentoring program that pairs students with older adults who are considered to be aging "successfully." This credit-bearing elective was initially established in 2001 through a grant from the John A. Hartford Foundation, and aims to expand…
Software for Optimizing Plans Involving Interdependent Goals
NASA Technical Reports Server (NTRS)
Estlin, Tara; Gaines, Daniel; Rabideau, Gregg
2005-01-01
A computer program enables construction and optimization of plans for activities that are directed toward achievement of goals that are interdependent. Goal interdependence is defined as the achievement of one or more goals affecting the desirability or priority of achieving one or more other goals. This program is overlaid on the Automated Scheduling and Planning Environment (ASPEN) software system, aspects of which have been described in a number of prior NASA Tech Briefs articles. Unlike other known or related planning programs, this program considers interdependences among goals that can change between problems and provides a language for easily specifying such dependences. Specifications of the interdependences can be formulated dynamically and provided to the associated planning software as part of the goal input. Then an optimization algorithm provided by this program enables the planning software to reason about the interdependences and incorporate them into an overall objective function that it uses to rate the quality of a plan under construction and to direct its optimization search. In tests on a series of problems of planning geological experiments by a team of instrumented robotic vehicles (rovers) on new terrain, this program was found to enhance plan quality.
The Retrofit Puzzle Extended: Optimal Fleet Owner Behavior over Multiple Time Periods
DOT National Transportation Integrated Search
2009-08-04
In "The Retrofit Puzzle: Optimal Fleet Owner Behavior in the Context of Diesel Retrofit Incentive Programs" (1) an integer program was developed to model profit-maximizing diesel fleet owner behavior when selecting pollution reduction retrofits. Flee...
Synthesis of multi-loop automatic control systems by the nonlinear programming method
NASA Astrophysics Data System (ADS)
Voronin, A. V.; Emelyanova, T. A.
2017-01-01
The article deals with the problem of calculation of the multi-loop control systems optimal tuning parameters by numerical methods and nonlinear programming methods. For this purpose, in the paper the Optimization Toolbox of Matlab is used.
NASA Astrophysics Data System (ADS)
Pradanti, Paskalia; Hartono
2018-03-01
Determination of insulin injection dose in diabetes mellitus treatment can be considered as an optimal control problem. This article is aimed to simulate optimal blood glucose control for patient with diabetes mellitus. The blood glucose regulation of diabetic patient is represented by Ackerman’s Linear Model. This problem is then solved using dynamic programming method. The desired blood glucose level is obtained by minimizing the performance index in Lagrange form. The results show that dynamic programming based on Ackerman’s Linear Model is quite good to solve the problem.
Thermal/Structural Tailoring of Engine Blades (T/STAEBL) User's manual
NASA Technical Reports Server (NTRS)
Brown, K. W.
1994-01-01
The Thermal/Structural Tailoring of Engine Blades (T/STAEBL) system is a computer code that is able to perform numerical optimizations of cooled jet engine turbine blades and vanes. These optimizations seek an airfoil design of minimum operating cost that satisfies realistic design constraints. This report documents the organization of the T/STAEBL computer program, its design and analysis procedure, its optimization procedure, and provides an overview of the input required to run the program, as well as the computer resources required for its effective use. Additionally, usage of the program is demonstrated through a validation test case.
Thermal/Structural Tailoring of Engine Blades (T/STAEBL): User's manual
NASA Astrophysics Data System (ADS)
Brown, K. W.
1994-03-01
The Thermal/Structural Tailoring of Engine Blades (T/STAEBL) system is a computer code that is able to perform numerical optimizations of cooled jet engine turbine blades and vanes. These optimizations seek an airfoil design of minimum operating cost that satisfies realistic design constraints. This report documents the organization of the T/STAEBL computer program, its design and analysis procedure, its optimization procedure, and provides an overview of the input required to run the program, as well as the computer resources required for its effective use. Additionally, usage of the program is demonstrated through a validation test case.
NASA Technical Reports Server (NTRS)
1971-01-01
The optimal allocation of resources to the national space program over an extended time period requires the solution of a large combinatorial problem in which the program elements are interdependent. The computer model uses an accelerated search technique to solve this problem. The model contains a large number of options selectable by the user to provide flexible input and a broad range of output for use in sensitivity analyses of all entering elements. Examples of these options are budget smoothing under varied appropriation levels, entry of inflation and discount effects, and probabilistic output which provides quantified degrees of certainty that program costs will remain within planned budget. Criteria and related analytic procedures were established for identifying potential new space program directions. Used in combination with the optimal resource allocation model, new space applications can be analyzed in realistic perspective, including the advantage gain from existing space program plant and on-going programs such as the space transportation system.
Multiple Choice Knapsack Problem: example of planning choice in transportation.
Zhong, Tao; Young, Rhonda
2010-05-01
Transportation programming, a process of selecting projects for funding given budget and other constraints, is becoming more complex as a result of new federal laws, local planning regulations, and increased public involvement. This article describes the use of an integer programming tool, Multiple Choice Knapsack Problem (MCKP), to provide optimal solutions to transportation programming problems in cases where alternative versions of projects are under consideration. In this paper, optimization methods for use in the transportation programming process are compared and then the process of building and solving the optimization problems is discussed. The concepts about the use of MCKP are presented and a real-world transportation programming example at various budget levels is provided. This article illustrates how the use of MCKP addresses the modern complexities and provides timely solutions in transportation programming practice. While the article uses transportation programming as a case study, MCKP can be useful in other fields where a similar decision among a subset of the alternatives is required. Copyright 2009 Elsevier Ltd. All rights reserved.
Manual of phosphoric acid fuel cell power plant optimization model and computer program
NASA Technical Reports Server (NTRS)
Lu, C. Y.; Alkasab, K. A.
1984-01-01
An optimized cost and performance model for a phosphoric acid fuel cell power plant system was derived and developed into a modular FORTRAN computer code. Cost, energy, mass, and electrochemical analyses were combined to develop a mathematical model for optimizing the steam to methane ratio in the reformer, hydrogen utilization in the PAFC plates per stack. The nonlinear programming code, COMPUTE, was used to solve this model, in which the method of mixed penalty function combined with Hooke and Jeeves pattern search was chosen to evaluate this specific optimization problem.
DSP code optimization based on cache
NASA Astrophysics Data System (ADS)
Xu, Chengfa; Li, Chengcheng; Tang, Bin
2013-03-01
DSP program's running efficiency on board is often lower than which via the software simulation during the program development, which is mainly resulted from the user's improper use and incomplete understanding of the cache-based memory. This paper took the TI TMS320C6455 DSP as an example, analyzed its two-level internal cache, and summarized the methods of code optimization. Processor can achieve its best performance when using these code optimization methods. At last, a specific algorithm application in radar signal processing is proposed. Experiment result shows that these optimization are efficient.
An Optimized Combined Wave and Current Bottom Boundary Layer Model for Arbitrary Bed Roughness
2017-06-30
Engineer Research and Development Center (ERDC), Coastal and Hydraulics Laboratory (CHL), Flood and Storm Protection Division (HF), Coastal ...ER D C/ CH L TR -1 7- 11 Coastal Inlets Research Program An Optimized Combined Wave and Current Bottom Boundary Layer Model for...client/default. Coastal Inlets Research Program ERDC/CHL TR-17-11 June 2017 An Optimized Combined Wave and Current Bottom Boundary Layer Model
Optimization-Based Selection of Influential Agents in a Rural Afghan Social Network
2010-06-01
nonlethal targeting model, a nonlinear programming ( NLP ) optimization formulation that identifies the k US agent assignment strategy producing the greatest...leader social network, and 3) the nonlethal targeting model, a nonlinear programming ( NLP ) optimization formulation that identifies the k US agent...NATO Coalition in Afghanistan. 55 for Afghanistan ( [54], [31], [48], [55], [30]). While Arab tribes tend to be more hierarchical, Pashtun tribes are
Aero/structural tailoring of engine blades (AERO/STAEBL)
NASA Technical Reports Server (NTRS)
Brown, K. W.
1988-01-01
This report describes the Aero/Structural Tailoring of Engine Blades (AERO/STAEBL) program, which is a computer code used to perform engine fan and compressor blade aero/structural numerical optimizations. These optimizations seek a blade design of minimum operating cost that satisfies realistic blade design constraints. This report documents the overall program (i.e., input, optimization procedures, approximate analyses) and also provides a detailed description of the validation test cases.
Dunne, Philip D; Dasgupta, Sonali; Blayney, Jaine K; McArt, Darragh G; Redmond, Keara L; Weir, Jessica-Anne; Bradley, Conor A; Sasazuki, Takehiko; Shirasawa, Senji; Wang, Tingting; Srivastava, Supriya; Ong, Chee Wee; Arthur, Ken; Salto-Tellez, Manuel; Wilson, Richard H; Johnston, Patrick G; Van Schaeybroeck, Sandra
2016-01-01
EphA2, a member of the Eph receptor tyrosine kinases family, is an important regulator of tumor initiation, neovascularization, and metastasis in a wide range of epithelial and mesenchymal cancers; however, its role in colorectal cancer recurrence and progression is unclear. EphA2 expression was determined by immunohistochemistry in stage II/III colorectal tumors (N = 338), and findings correlated with clinical outcome. The correlation between EphA2 expression and stem cell markers CD44 and Lgr5 was examined. The role of EphA2 in migration/invasion was assessed using a panel of KRAS wild-type (WT) and mutant (MT) parental and invasive colorectal cancer cell line models. Colorectal tumors displayed significantly higher expression levels of EphA2 compared with matched normal tissue, which positively correlated with high CD44 and Lgr5 expression levels. Moreover, high EphA2 mRNA and protein expression were found to be associated with poor overall survival in stage II/III colorectal cancer tissues, in both univariate and multivariate analyses. Preclinically, we found that EphA2 was highly expressed in KRASMT colorectal cancer cells and that EphA2 levels are regulated by the KRAS-driven MAPK and RalGDS-RalA pathways. Moreover, EphA2 levels were elevated in several invasive daughter cell lines, and downregulation of EphA2 using RNAi or recombinant EFNA1 suppressed migration and invasion of KRASMT colorectal cancer cells. These data show that EpHA2 is a poor prognostic marker in stage II/III colorectal cancer, which may be due to its ability to promote cell migration and invasion, providing support for the further investigation of EphA2 as a novel prognostic biomarker and therapeutic target. ©2015 American Association for Cancer Research.
Blayney, Jaine K.; McArt, Darragh G.; Redmond, Keara L.; Weir, Jessica-Anne; Bradley, Conor A.; Sasazuki, Takehiko; Shirasawa, Senji; Wang, Tingting; Srivastava, Supriya; Ong, Chee Wee; Arthur, Ken; Salto-Tellez, Manuel; Wilson, Richard H.
2015-01-01
Purpose EphA2, a member of the Eph receptor tyrosine kinases family, is an important regulator of tumour initiation, neo-vascularization and metastasis in a wide range of epithelial and mesenchymal cancers, however its role in colorectal cancer (CRC) recurrence and progression is unclear. Experimental Design EphA2 expression was determined by immunohistochemistry in stage II/III colorectal tumours (N=338), and findings correlated with clinical outcome. The correlation between EphA2 expression and stem cell markers CD44 and Lgr5 was examined. The role of EphA2 in migration/invasion was assessed using a panel of KRAS wild-type (WT) and mutant (MT) parental and invasive CRC cell line models. Results Colorectal tumours displayed significantly higher expression levels of EphA2 compared with matched normal tissue, which positively correlated with high CD44 and Lgr5 expression levels. Moreover, high EphA2 mRNA and protein expression were found to be associated with poor overall survival in stage II/III CRC tissues, in both univariate and multivariate analyses. Pre-clinically, we found that EphA2 was highly expressed in KRASMT CRC cells and that EphA2 levels are regulated by the KRAS-driven MAPK and RalGDS-RalA pathways. Moreover, EphA2 levels were elevated in several invasive daughter cell lines and down-regulation of EphA2 using RNAi or recombinant EFNA1, suppressed migration and invasion of KRASMT CRC cells. Conclusions These data show that EpHA2 is a poor prognostic marker in stage II/III CRC, which may be due to its ability to promote cell migration and invasion, providing support for the further investigation of EphA2 as a novel prognostic biomarker and therapeutic target. PMID:26283684
Rouvrais, Céline; Bacqueville, Daniel; Bogdanowicz, Patrick; Haure, Marie-José; Duprat, Laure; Coutanceau, Christine; Castex-Rizzi, Nathalie; Duplan, Hélène; Mengeaud, Valérie; Bessou-Touya, Sandrine
2017-01-01
Introduction Natural aging of skin tissues, the addition of the cumulative action of the time and radiation exposure result in skin atrophy, wrinkles and degeneration of the extracellular matrix (ECM). The aim of the study was to investigate the beneficial effect of a combination containing retinaldehyde (RAL), delta-tocopherol glucoside (delta-TC) and glycylglycine ole-amide (GGO) and of a dermocosmetic containing the combination. Materials and methods The protective effect of the combination was assessed through in vitro gene expression of ultraviolet (UV)-irradiated fibroblasts. A skin aging assay using UV light on ex vivo skin samples and a clinical study conducted in 36 women aged from 35 to 55 years with a minimum of level 4 to a maximum of level 6 on the crow’s feet photoscale assessed the antiaging effect of the dermocosmetic. Results When added to UV-irradiated fibroblasts, the combination substantially improved the ECM in activating the elastin fiber production (fibrillin 2, fibulin 1 and 5 and lysyl oxidase-like 2) as well as that of proteins involved in the cellular ECM interactions (integrin b1, paxillin and actin a2). An ex vivo photodamaged human skin model showed that the dermocosmetic formulation containing the combination of the active ingredients protected the elastic network against UV-induced alterations including both elastin and fibrillin-rich fibers in the dermis. A daily application of the dermocosmetic for 2 months on naturally aged skin resulted in a statistically significant improvement (p<0.05) of visible signs of aging comprising crow’s feet, wrinkles and periocular fine lines. Finally, the formulation was well tolerated. Conclusion The dermocosmetic containing RAL, delta-TC and GGO provides a substantial benefit in the daily care of naturally aged skin in women aged 35–55 years. PMID:28203099
Rivero, Antonio; Pérez-Molina, José Antonio; Blasco, Antonio Javier; Arribas, José Ramón; Asensi, Víctor; Crespo, Manuel; Domingo, Pere; Iribarren, José Antonio; Lázaro, Pablo; López-Aldeguer, José; Lozano, Fernando; Martínez, Esteban; Moreno, Santiago; Palacios, Rosario; Pineda, Juan Antonio; Pulido, Federico; Rubio, Rafael; Santos, Jesús; de la Torre, Javier; Tuset, Montserrat; Gatell, Josep M
2018-05-01
GESIDA and the Spanish National AIDS Plan panel of experts have recommended preferred (PR), alternative (AR) and other regimens (OR) for antiretroviral therapy (ART) as initial therapy in HIV-infected patients for 2017. The objective of this study was to evaluate the costs and the efficiency of initiating treatment with PR and AR. Economic assessment of costs and efficiency (cost-efficacy) based on decision tree analyses. Efficacy was defined as the probability of reporting a viral load <50copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen and drug resistance studies) during the first 48 weeks. The payer perspective (National Health System) was applied considering only differential direct costs: ART (official prices), management of adverse effects, resistance studies and HLA B*5701 screening. The setting was Spain and the costs correspond to those of 2017. A deterministic sensitivity analysis was conducted, building three scenarios for each regimen: base case, most favourable and least favourable. In the base case scenario, the cost of initiating treatment ranged from 6882 euro for TFV/FTC/RPV (AR) to 10,904 euros for TFV/FTC+RAL (PR). The efficacy varied from 0.82 for TFV/FTC+DRV/p (AR) to 0.92 for TAF/FTC/EVG/COBI (PR). The efficiency, in terms of cost-efficacy, ranged from 7923 to 12,765 euros per responder at 48 weeks, for ABC/3TC/DTG (PR) and TFV/FTC+RAL (PR), respectively. Considering ART official prices, the most efficient regimen was ABC/3TC/DTG (PR), followed by TFV/FTC/RPV (AR) and TAF/FTC/EVG/COBI (PR). Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
Weinstein, Nathan; Mendoza, Luis
2013-01-01
The vulva of Caenorhabditis elegans has been long used as an experimental model of cell differentiation and organogenesis. While it is known that the signaling cascades of Wnt, Ras/MAPK, and NOTCH interact to form a molecular network, there is no consensus regarding its precise topology and dynamical properties. We inferred the molecular network, and developed a multivalued synchronous discrete dynamic model to study its behavior. The model reproduces the patterns of activation reported for the following types of cell: vulval precursor, first fate, second fate, second fate with reversed polarity, third fate, and fusion fate. We simulated the fusion of cells, the determination of the first, second, and third fates, as well as the transition from the second to the first fate. We also used the model to simulate all possible single loss- and gain-of-function mutants, as well as some relevant double and triple mutants. Importantly, we associated most of these simulated mutants to multivulva, vulvaless, egg-laying defective, or defective polarity phenotypes. The model shows that it is necessary for RAL-1 to activate NOTCH signaling, since the repression of LIN-45 by RAL-1 would not suffice for a proper second fate determination in an environment lacking DSL ligands. We also found that the model requires the complex formed by LAG-1, LIN-12, and SEL-8 to inhibit the transcription of eff-1 in second fate cells. Our model is the largest reconstruction to date of the molecular network controlling the specification of vulval precursor cells and cell fusion control in C. elegans. According to our model, the process of fate determination in the vulval precursor cells is reversible, at least until either the cells fuse with the ventral hypoderm or divide, and therefore the cell fates must be maintained by the presence of extracellular signals. PMID:23785384
Pérez-Molina, José Antonio; Martínez, Esteban; Blasco, Antonio Javier; Arribas, José Ramón; Domingo, Pere; Iribarren, José Antonio; Knobel, Hernando; Lázaro, Pablo; López-Aldeguer, José; Lozano, Fernando; Mariño, Ana; Miró, José M; Moreno, Santiago; Negredo, Eugenia; Pulido, Federico; Rubio, Rafael; Santos, Jesús; de la Torre, Javier; Tuset, Montserrat; von Wichmann, Miguel A; Gatell, Josep M
2018-06-05
The GESIDA/National AIDS Plan expert panel recommended preferred regimens (PR), alternative regimens (AR) and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for 2018. The objective of this study was to evaluate the costs and the efficiency of initiating treatment with PR and AR. Economic assessment of costs and efficiency (cost-effectiveness) based on decision tree analyses. Effectiveness was defined as the probability of reporting a viral load <50copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug-resistance studies) over the first 48 weeks. The payer perspective (National Health System) was applied considering only differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting was Spain and the costs correspond to those of 2018. A deterministic sensitivity analysis was conducted, building three scenarios for each regimen: base case, most favourable and least favourable. In the base-case scenario, the cost of initiating treatment ranges from 6788 euros for TAF/FTC/RPV (AR) to 10,649 euros for TAF/FTC+RAL (PR). The effectiveness varies from 0.82 for TAF/FTC+DRV/r (AR) to 0.91 for TAF/FTC+DTG (PR). The efficiency, in terms of cost-effectiveness, ranges from 7814 to 12,412 euros per responder at 48 weeks, for ABC/3TC/DTG (PR) and TAF/FTC+RAL (PR), respectively. Considering ART official prices, the most efficient regimen was ABC/3TC/DTG (PR), followed by TAF/FTC/RPV (AR) and TAF/FTC/EVG/COBI (AR). Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.
The Legionella pneumophila global regulatory protein LetA affects DotA and Mip.
Shi, Chunwei; Forsbach-Birk, Vera; Marre, Reinhard; McNealy, Tamara L
2006-02-01
Several genes have been identified in Legionella pneumophila which are necessary for its virulence properties. These genes include the dot/icm type IV secretion system (T4SS), mip and letA. Genes of the dot/icm system, in particular dotA, have been found to be essential for intracellular growth. The macrophage infectivity protein (Mip) is also necessary for full virulence of the bacteria. Although these genes are well characterized, the regulation of such virulence factors is not. The LetA transcriptional activator interacts with the global regulator CsrA in controlling the switch from the replicative, non-infectious to the transmissive, highly infectious form of L. pneumophila. Regulation by LetA of the dot/icm genes has also been previously postulated. Here we show that the letA mutation exerts effects not only on DotA but on a substrate of the secretion system, RalF as well. LetA was found to be necessary for full transcriptional expression of the dotA and ralF genes. Although at the transcriptional level dotA was reduced, this did not result in a decrease of DotA protein in whole cell lysates. The letA mutation, however, does result in decreased amounts of the DotA protein found in the membrane and increased amounts in the culture supernatant. Additionally, the letA mutation dramatically decreased the secretion of Mip. This work demonstrates the participation of the global regulatory protein LetA in the regulation of an essential part of the dot/icm T4SS. Also shown is the presence of secreted Mip and a decrease in this secretion in the letA(-) strain. Exactly how LetA is regulating these virulence factors remains to be elucidated but it obviously occurs at both transcriptional and post-transcriptional levels.
Element Specific Imaging Using Muonic X-rays
NASA Astrophysics Data System (ADS)
Hillier, Adrian; Ishida, Katsu; Seller, Paul; Veale, Matthew C.; Wilson, Matthew D.
The RIKEN-RAL facility provides a source of negative muons that can be used to non-destructively determine the elemental composition of bulk samples. A negative muon can replace an electron in an atom and subsequently transition to lower orbital positions. As with conventional X-ray fluorescence, an X-ray photon is emitted with a characteristic energy to enable the transition between orbitals of an atom. As the mass of a negative muon is much greater than that of an electron, a higher energy X-ray photon is emitted when the negative muon transitions between orbitals compared to conventional X-ray fluorescence. The higher energy muonic X-rays are able to escape large samples even when they are emitted from lower Z atoms, making muonic X-rays fluorescence a unique method to characterize the elemental content of a sample. In a typical experiment a section of a sample will be probed with negative muons with the muon momentum tuned to interact at a desired depth in the sample. A small number of single element high purity Ge detectors are positioned to capture up to one photon each from each of the forty muon pulses per second at the RIKEN-RAL facility. This can provide a high resolution and high dynamic range X-ray energy spectrum when collected for several hours but can only provide a spatial average or single point elemental distribution per collection. Here, an STFC developed CdTe detector with 80 × 80 energy resolving channels has been used to demonstrate the ability to image the elemental distribution of a test sample. A test sample of C, Al, and Fe2O3 was positioned close to the detector surface and each of the 250 µm pitch pixels recorded a muonic X-ray energy spectrum. Results are presented to show the principal of this new technique and potential improvements to provide higher resolution and larger area elemental imaging using muonic X-rays are discussed.
Near-Optimal Tracking Control of Mobile Robots Via Receding-Horizon Dual Heuristic Programming.
Lian, Chuanqiang; Xu, Xin; Chen, Hong; He, Haibo
2016-11-01
Trajectory tracking control of wheeled mobile robots (WMRs) has been an important research topic in control theory and robotics. Although various tracking control methods with stability have been developed for WMRs, it is still difficult to design optimal or near-optimal tracking controller under uncertainties and disturbances. In this paper, a near-optimal tracking control method is presented for WMRs based on receding-horizon dual heuristic programming (RHDHP). In the proposed method, a backstepping kinematic controller is designed to generate desired velocity profiles and the receding horizon strategy is used to decompose the infinite-horizon optimal control problem into a series of finite-horizon optimal control problems. In each horizon, a closed-loop tracking control policy is successively updated using a class of approximate dynamic programming algorithms called finite-horizon dual heuristic programming (DHP). The convergence property of the proposed method is analyzed and it is shown that the tracking control system based on RHDHP is asymptotically stable by using the Lyapunov approach. Simulation results on three tracking control problems demonstrate that the proposed method has improved control performance when compared with conventional model predictive control (MPC) and DHP. It is also illustrated that the proposed method has lower computational burden than conventional MPC, which is very beneficial for real-time tracking control.
Ant Lion Optimization algorithm for kidney exchanges.
Hamouda, Eslam; El-Metwally, Sara; Tarek, Mayada
2018-01-01
The kidney exchange programs bring new insights in the field of organ transplantation. They make the previously not allowed surgery of incompatible patient-donor pairs easier to be performed on a large scale. Mathematically, the kidney exchange is an optimization problem for the number of possible exchanges among the incompatible pairs in a given pool. Also, the optimization modeling should consider the expected quality-adjusted life of transplant candidates and the shortage of computational and operational hospital resources. In this article, we introduce a bio-inspired stochastic-based Ant Lion Optimization, ALO, algorithm to the kidney exchange space to maximize the number of feasible cycles and chains among the pool pairs. Ant Lion Optimizer-based program achieves comparable kidney exchange results to the deterministic-based approaches like integer programming. Also, ALO outperforms other stochastic-based methods such as Genetic Algorithm in terms of the efficient usage of computational resources and the quantity of resulting exchanges. Ant Lion Optimization algorithm can be adopted easily for on-line exchanges and the integration of weights for hard-to-match patients, which will improve the future decisions of kidney exchange programs. A reference implementation for ALO algorithm for kidney exchanges is written in MATLAB and is GPL licensed. It is available as free open-source software from: https://github.com/SaraEl-Metwally/ALO_algorithm_for_Kidney_Exchanges.
WINDOWAC (Wing Design Optimization With Aeroelastic Constraints): Program manual
NASA Technical Reports Server (NTRS)
Haftka, R. T.; Starnes, J. H., Jr.
1974-01-01
User and programer documentation for the WIDOWAC programs is given. WIDOWAC may be used for the design of minimum mass wing structures subjected to flutter, strength, and minimum gage constraints. The wing structure is modeled by finite elements, flutter conditions may be both subsonic and supersonic, and mathematical programing methods are used for the optimization procedure. The user documentation gives general directions on how the programs may be used and describes their limitations; in addition, program input and output are described, and example problems are presented. A discussion of computational algorithms and flow charts of the WIDOWAC programs and major subroutines is also given.
An overview of the Douglas Aircraft Company Aeroelastic Design Optimization Program (ADOP)
NASA Technical Reports Server (NTRS)
Dodd, Alan J.
1989-01-01
From a program manager's viewpoint, the history, scope and architecture of a major structural design program at Douglas Aircraft Company called Aeroelastic Design Optimization Program (ADOP) are described. ADOP was originally intended for the rapid, accurate, cost-effective evaluation of relatively small structural models at the advanced design level, resulting in improved proposal competitiveness and avoiding many costly changes later in the design cycle. Before release of the initial version in November 1987, however, the program was expanded to handle very large production-type analyses.
OPTRAN- OPTIMAL LOW THRUST ORBIT TRANSFERS
NASA Technical Reports Server (NTRS)
Breakwell, J. V.
1994-01-01
OPTRAN is a collection of programs that solve the problem of optimal low thrust orbit transfers between non-coplanar circular orbits for spacecraft with chemical propulsion systems. The programs are set up to find Hohmann-type solutions, with burns near the perigee and apogee of the transfer orbit. They will solve both fairly long burn-arc transfers and "divided-burn" transfers. Program modeling includes a spherical earth gravity model and propulsion system models for either constant thrust or constant acceleration. The solutions obtained are optimal with respect to fuel use: i.e., final mass of the spacecraft is maximized with respect to the controls. The controls are the direction of thrust and the thrust on/off times. Two basic types of programs are provided in OPTRAN. The first type is for "exact solution" which results in complete, exact tkme-histories. The exact spacecraft position, velocity, and optimal thrust direction are given throughout the maneuver, as are the optimal thrust switch points, the transfer time, and the fuel costs. Exact solution programs are provided in two versions for non-coplanar transfers and in a fast version for coplanar transfers. The second basic type is for "approximate solutions" which results in approximate information on the transfer time and fuel costs. The approximate solution is used to estimate initial conditions for the exact solution. It can be used in divided-burn transfers to find the best number of burns with respect to time. The approximate solution is useful by itself in relatively efficient, short burn-arc transfers. These programs are written in FORTRAN 77 for batch execution and have been implemented on a DEC VAX series computer with the largest program having a central memory requirement of approximately 54K of 8 bit bytes. The OPTRAN program were developed in 1983.
Robust Constrained Blackbox Optimization with Surrogates
2015-05-21
algorithms with OPAL . Mathematical Programming Computation, 6(3):233–254, 2014. 6. M.S. Ouali, H. Aoudjit, and C. Audet. Replacement scheduling of a fleet of...Orban. Optimization of Algorithms with OPAL . Mathematical Programming Computation, 6(3), 233-254, September 2014. DISTRIBUTION A: Distribution
The Application Programming Interface (API) for Uncertainty Analysis, Sensitivity Analysis, and Parameter Estimation (UA/SA/PE API) tool development, here fore referred to as the Calibration, Optimization, and Sensitivity and Uncertainty Algorithms API (COSU-API), was initially d...
McConnel, M B; Galligan, D T
2004-10-01
Optimization programs are currently used to aid in the selection of bulls to be used in herd breeding programs. While these programs offer a systematic approach to the problem of semen selection, they ignore the impact of volume discounts. Volume discounts are discounts that vary depending on the number of straws purchased. The dynamic nature of volume discounts means that, in order to be adequately accounted for, they must be considered in the optimization routine. Failing to do this creates a missed economic opportunity because the potential benefits of optimally selecting and combining breeding company discount opportunities are not captured. To address these issues, an integer program was created which used binary decision variables to incorporate the effects of quantity discounts into the optimization program. A consistent set of trait criteria was used to select a group of bulls from 3 sample breeding companies. Three different selection programs were used to select the bulls, 2 traditional methods and the integer method. After the discounts were applied using each method, the integer program resulted in the lowest cost portfolio of bulls. A sensitivity analysis showed that the integer program also resulted in a low cost portfolio when the genetic trait goals were changed to be more or less stringent. In the sample application, a net benefit of the new approach over the traditional approaches was a 12.3 to 20.0% savings in semen cost.
Remediation Optimization: Definition, Scope and Approach
This document provides a general definition, scope and approach for conducting optimization reviews within the Superfund Program and includes the fundamental principles and themes common to optimization.
Yoo, Do Guen; Lee, Ho Min; Sadollah, Ali; Kim, Joong Hoon
2015-01-01
Water supply systems are mainly classified into branched and looped network systems. The main difference between these two systems is that, in a branched network system, the flow within each pipe is a known value, whereas in a looped network system, the flow in each pipe is considered an unknown value. Therefore, an analysis of a looped network system is a more complex task. This study aims to develop a technique for estimating the optimal pipe diameter for a looped agricultural irrigation water supply system using a harmony search algorithm, which is an optimization technique. This study mainly serves two purposes. The first is to develop an algorithm and a program for estimating a cost-effective pipe diameter for agricultural irrigation water supply systems using optimization techniques. The second is to validate the developed program by applying the proposed optimized cost-effective pipe diameter to an actual study region (Saemangeum project area, zone 6). The results suggest that the optimal design program, which applies an optimization theory and enhances user convenience, can be effectively applied for the real systems of a looped agricultural irrigation water supply.
Lee, Ho Min; Sadollah, Ali
2015-01-01
Water supply systems are mainly classified into branched and looped network systems. The main difference between these two systems is that, in a branched network system, the flow within each pipe is a known value, whereas in a looped network system, the flow in each pipe is considered an unknown value. Therefore, an analysis of a looped network system is a more complex task. This study aims to develop a technique for estimating the optimal pipe diameter for a looped agricultural irrigation water supply system using a harmony search algorithm, which is an optimization technique. This study mainly serves two purposes. The first is to develop an algorithm and a program for estimating a cost-effective pipe diameter for agricultural irrigation water supply systems using optimization techniques. The second is to validate the developed program by applying the proposed optimized cost-effective pipe diameter to an actual study region (Saemangeum project area, zone 6). The results suggest that the optimal design program, which applies an optimization theory and enhances user convenience, can be effectively applied for the real systems of a looped agricultural irrigation water supply. PMID:25874252
NASA Astrophysics Data System (ADS)
Chen, Buxin; Zhang, Zheng; Sidky, Emil Y.; Xia, Dan; Pan, Xiaochuan
2017-11-01
Optimization-based algorithms for image reconstruction in multispectral (or photon-counting) computed tomography (MCT) remains a topic of active research. The challenge of optimization-based image reconstruction in MCT stems from the inherently non-linear data model that can lead to a non-convex optimization program for which no mathematically exact solver seems to exist for achieving globally optimal solutions. In this work, based upon a non-linear data model, we design a non-convex optimization program, derive its first-order-optimality conditions, and propose an algorithm to solve the program for image reconstruction in MCT. In addition to consideration of image reconstruction for the standard scan configuration, the emphasis is on investigating the algorithm’s potential for enabling non-standard scan configurations with no or minimum hardware modification to existing CT systems, which has potential practical implications for lowered hardware cost, enhanced scanning flexibility, and reduced imaging dose/time in MCT. Numerical studies are carried out for verification of the algorithm and its implementation, and for a preliminary demonstration and characterization of the algorithm in reconstructing images and in enabling non-standard configurations with varying scanning angular range and/or x-ray illumination coverage in MCT.
Optimization of fuel-cell tram operation based on two dimension dynamic programming
NASA Astrophysics Data System (ADS)
Zhang, Wenbin; Lu, Xuecheng; Zhao, Jingsong; Li, Jianqiu
2018-02-01
This paper proposes an optimal control strategy based on the two-dimension dynamic programming (2DDP) algorithm targeting at minimizing operation energy consumption for a fuel-cell tram. The energy consumption model with the tram dynamics is firstly deduced. Optimal control problem are analyzed and the 2DDP strategy is applied to solve the problem. The optimal tram speed profiles are obtained for each interstation which consist of three stages: accelerate to the set speed with the maximum traction power, dynamically adjust to maintain a uniform speed and decelerate to zero speed with the maximum braking power at a suitable timing. The optimal control curves of all the interstations are connected with the parking time to form the optimal control method of the whole line. The optimized speed profiles are also simplified for drivers to follow.
Large-scale structural optimization
NASA Technical Reports Server (NTRS)
Sobieszczanski-Sobieski, J.
1983-01-01
Problems encountered by aerospace designers in attempting to optimize whole aircraft are discussed, along with possible solutions. Large scale optimization, as opposed to component-by-component optimization, is hindered by computational costs, software inflexibility, concentration on a single, rather than trade-off, design methodology and the incompatibility of large-scale optimization with single program, single computer methods. The software problem can be approached by placing the full analysis outside of the optimization loop. Full analysis is then performed only periodically. Problem-dependent software can be removed from the generic code using a systems programming technique, and then embody the definitions of design variables, objective function and design constraints. Trade-off algorithms can be used at the design points to obtain quantitative answers. Finally, decomposing the large-scale problem into independent subproblems allows systematic optimization of the problems by an organization of people and machines.
NASA Astrophysics Data System (ADS)
Sutrisno; Widowati; Solikhin
2016-06-01
In this paper, we propose a mathematical model in stochastic dynamic optimization form to determine the optimal strategy for an integrated single product inventory control problem and supplier selection problem where the demand and purchasing cost parameters are random. For each time period, by using the proposed model, we decide the optimal supplier and calculate the optimal product volume purchased from the optimal supplier so that the inventory level will be located at some point as close as possible to the reference point with minimal cost. We use stochastic dynamic programming to solve this problem and give several numerical experiments to evaluate the model. From the results, for each time period, the proposed model was generated the optimal supplier and the inventory level was tracked the reference point well.
Visual gene developer: a fully programmable bioinformatics software for synthetic gene optimization.
Jung, Sang-Kyu; McDonald, Karen
2011-08-16
Direct gene synthesis is becoming more popular owing to decreases in gene synthesis pricing. Compared with using natural genes, gene synthesis provides a good opportunity to optimize gene sequence for specific applications. In order to facilitate gene optimization, we have developed a stand-alone software called Visual Gene Developer. The software not only provides general functions for gene analysis and optimization along with an interactive user-friendly interface, but also includes unique features such as programming capability, dedicated mRNA secondary structure prediction, artificial neural network modeling, network & multi-threaded computing, and user-accessible programming modules. The software allows a user to analyze and optimize a sequence using main menu functions or specialized module windows. Alternatively, gene optimization can be initiated by designing a gene construct and configuring an optimization strategy. A user can choose several predefined or user-defined algorithms to design a complicated strategy. The software provides expandable functionality as platform software supporting module development using popular script languages such as VBScript and JScript in the software programming environment. Visual Gene Developer is useful for both researchers who want to quickly analyze and optimize genes, and those who are interested in developing and testing new algorithms in bioinformatics. The software is available for free download at http://www.visualgenedeveloper.net.
Visual gene developer: a fully programmable bioinformatics software for synthetic gene optimization
2011-01-01
Background Direct gene synthesis is becoming more popular owing to decreases in gene synthesis pricing. Compared with using natural genes, gene synthesis provides a good opportunity to optimize gene sequence for specific applications. In order to facilitate gene optimization, we have developed a stand-alone software called Visual Gene Developer. Results The software not only provides general functions for gene analysis and optimization along with an interactive user-friendly interface, but also includes unique features such as programming capability, dedicated mRNA secondary structure prediction, artificial neural network modeling, network & multi-threaded computing, and user-accessible programming modules. The software allows a user to analyze and optimize a sequence using main menu functions or specialized module windows. Alternatively, gene optimization can be initiated by designing a gene construct and configuring an optimization strategy. A user can choose several predefined or user-defined algorithms to design a complicated strategy. The software provides expandable functionality as platform software supporting module development using popular script languages such as VBScript and JScript in the software programming environment. Conclusion Visual Gene Developer is useful for both researchers who want to quickly analyze and optimize genes, and those who are interested in developing and testing new algorithms in bioinformatics. The software is available for free download at http://www.visualgenedeveloper.net. PMID:21846353
A dynamic model of functioning of a bank
NASA Astrophysics Data System (ADS)
Malafeyev, Oleg; Awasthi, Achal; Zaitseva, Irina; Rezenkov, Denis; Bogdanova, Svetlana
2018-04-01
In this paper, we analyze dynamic programming as a novel approach to solve the problem of maximizing the profits of a bank. The mathematical model of the problem and the description of bank's work is described in this paper. The problem is then approached using the method of dynamic programming. Dynamic programming makes sure that the solutions obtained are globally optimal and numerically stable. The optimization process is set up as a discrete multi-stage decision process and solved with the help of dynamic programming.
Portfolio optimization in enhanced index tracking with goal programming approach
NASA Astrophysics Data System (ADS)
Siew, Lam Weng; Jaaman, Saiful Hafizah Hj.; Ismail, Hamizun bin
2014-09-01
Enhanced index tracking is a popular form of passive fund management in stock market. Enhanced index tracking aims to generate excess return over the return achieved by the market index without purchasing all of the stocks that make up the index. This can be done by establishing an optimal portfolio to maximize the mean return and minimize the risk. The objective of this paper is to determine the portfolio composition and performance using goal programming approach in enhanced index tracking and comparing it to the market index. Goal programming is a branch of multi-objective optimization which can handle decision problems that involve two different goals in enhanced index tracking, a trade-off between maximizing the mean return and minimizing the risk. The results of this study show that the optimal portfolio with goal programming approach is able to outperform the Malaysia market index which is FTSE Bursa Malaysia Kuala Lumpur Composite Index because of higher mean return and lower risk without purchasing all the stocks in the market index.
Chen, Zhi; Yuan, Yuan; Zhang, Shu-Shen; Chen, Yu; Yang, Feng-Lin
2013-01-01
Critical environmental and human health concerns are associated with the rapidly growing fields of nanotechnology and manufactured nanomaterials (MNMs). The main risk arises from occupational exposure via chronic inhalation of nanoparticles. This research presents a chance-constrained nonlinear programming (CCNLP) optimization approach, which is developed to maximize the nanaomaterial production and minimize the risks of workplace exposure to MNMs. The CCNLP method integrates nonlinear programming (NLP) and chance-constrained programming (CCP), and handles uncertainties associated with both the nanomaterial production and workplace exposure control. The CCNLP method was examined through a single-walled carbon nanotube (SWNT) manufacturing process. The study results provide optimal production strategies and alternatives. It reveal that a high control measure guarantees that environmental health and safety (EHS) standards regulations are met, while a lower control level leads to increased risk of violating EHS regulations. The CCNLP optimization approach is a decision support tool for the optimization of the increasing MNMS manufacturing with workplace safety constraints under uncertainties. PMID:23531490
Chen, Zhi; Yuan, Yuan; Zhang, Shu-Shen; Chen, Yu; Yang, Feng-Lin
2013-03-26
Critical environmental and human health concerns are associated with the rapidly growing fields of nanotechnology and manufactured nanomaterials (MNMs). The main risk arises from occupational exposure via chronic inhalation of nanoparticles. This research presents a chance-constrained nonlinear programming (CCNLP) optimization approach, which is developed to maximize the nanaomaterial production and minimize the risks of workplace exposure to MNMs. The CCNLP method integrates nonlinear programming (NLP) and chance-constrained programming (CCP), and handles uncertainties associated with both the nanomaterial production and workplace exposure control. The CCNLP method was examined through a single-walled carbon nanotube (SWNT) manufacturing process. The study results provide optimal production strategies and alternatives. It reveal that a high control measure guarantees that environmental health and safety (EHS) standards regulations are met, while a lower control level leads to increased risk of violating EHS regulations. The CCNLP optimization approach is a decision support tool for the optimization of the increasing MNMS manufacturing with workplace safety constraints under uncertainties.
Human operator identification model and related computer programs
NASA Technical Reports Server (NTRS)
Kessler, K. M.; Mohr, J. N.
1978-01-01
Four computer programs which provide computational assistance in the analysis of man/machine systems are reported. The programs are: (1) Modified Transfer Function Program (TF); (2) Time Varying Response Program (TVSR); (3) Optimal Simulation Program (TVOPT); and (4) Linear Identification Program (SCIDNT). The TV program converts the time domain state variable system representative to frequency domain transfer function system representation. The TVSR program computes time histories of the input/output responses of the human operator model. The TVOPT program is an optimal simulation program and is similar to TVSR in that it produces time histories of system states associated with an operator in the loop system. The differences between the two programs are presented. The SCIDNT program is an open loop identification code which operates on the simulated data from TVOPT (or TVSR) or real operator data from motion simulators.
Weight optimization of plane truss using genetic algorithm
NASA Astrophysics Data System (ADS)
Neeraja, D.; Kamireddy, Thejesh; Santosh Kumar, Potnuru; Simha Reddy, Vijay
2017-11-01
Optimization of structure on basis of weight has many practical benefits in every engineering field. The efficiency is proportionally related to its weight and hence weight optimization gains prime importance. Considering the field of civil engineering, weight optimized structural elements are economical and easier to transport to the site. In this study, genetic optimization algorithm for weight optimization of steel truss considering its shape, size and topology aspects has been developed in MATLAB. Material strength and Buckling stability have been adopted from IS 800-2007 code of construction steel. The constraints considered in the present study are fabrication, basic nodes, displacements, and compatibility. Genetic programming is a natural selection search technique intended to combine good solutions to a problem from many generations to improve the results. All solutions are generated randomly and represented individually by a binary string with similarities of natural chromosomes, and hence it is termed as genetic programming. The outcome of the study is a MATLAB program, which can optimise a steel truss and display the optimised topology along with element shapes, deflections, and stress results.
Optimal cure cycle design of a resin-fiber composite laminate
NASA Technical Reports Server (NTRS)
Hou, Jean W.; Sheen, Jeenson
1987-01-01
A unified computed aided design method was studied for the cure cycle design that incorporates an optimal design technique with the analytical model of a composite cure process. The preliminary results of using this proposed method for optimal cure cycle design are reported and discussed. The cure process of interest is the compression molding of a polyester which is described by a diffusion reaction system. The finite element method is employed to convert the initial boundary value problem into a set of first order differential equations which are solved simultaneously by the DE program. The equations for thermal design sensitivities are derived by using the direct differentiation method and are solved by the DE program. A recursive quadratic programming algorithm with an active set strategy called a linearization method is used to optimally design the cure cycle, subjected to the given design performance requirements. The difficulty of casting the cure cycle design process into a proper mathematical form is recognized. Various optimal design problems are formulated to address theses aspects. The optimal solutions of these formulations are compared and discussed.
An introduction to the COLIN optimization interface.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hart, William Eugene
2003-03-01
We describe COLIN, a Common Optimization Library INterface for C++. COLIN provides C++ template classes that define a generic interface for both optimization problems and optimization solvers. COLIN is specifically designed to facilitate the development of hybrid optimizers, for which one optimizer calls another to solve an optimization subproblem. We illustrate the capabilities of COLIN with an example of a memetic genetic programming solver.
Development Optimization and Uncertainty Analysis Methods for Oil and Gas Reservoirs
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ettehadtavakkol, Amin, E-mail: amin.ettehadtavakkol@ttu.edu; Jablonowski, Christopher; Lake, Larry
Uncertainty complicates the development optimization of oil and gas exploration and production projects, but methods have been devised to analyze uncertainty and its impact on optimal decision-making. This paper compares two methods for development optimization and uncertainty analysis: Monte Carlo (MC) simulation and stochastic programming. Two example problems for a gas field development and an oilfield development are solved and discussed to elaborate the advantages and disadvantages of each method. Development optimization involves decisions regarding the configuration of initial capital investment and subsequent operational decisions. Uncertainty analysis involves the quantification of the impact of uncertain parameters on the optimum designmore » concept. The gas field development problem is designed to highlight the differences in the implementation of the two methods and to show that both methods yield the exact same optimum design. The results show that both MC optimization and stochastic programming provide unique benefits, and that the choice of method depends on the goal of the analysis. While the MC method generates more useful information, along with the optimum design configuration, the stochastic programming method is more computationally efficient in determining the optimal solution. Reservoirs comprise multiple compartments and layers with multiphase flow of oil, water, and gas. We present a workflow for development optimization under uncertainty for these reservoirs, and solve an example on the design optimization of a multicompartment, multilayer oilfield development.« less
NASA Astrophysics Data System (ADS)
Aziz, Jonathan D.; Parker, Jeffrey S.; Scheeres, Daniel J.; Englander, Jacob A.
2018-01-01
Low-thrust trajectories about planetary bodies characteristically span a high count of orbital revolutions. Directing the thrust vector over many revolutions presents a challenging optimization problem for any conventional strategy. This paper demonstrates the tractability of low-thrust trajectory optimization about planetary bodies by applying a Sundman transformation to change the independent variable of the spacecraft equations of motion to an orbit angle and performing the optimization with differential dynamic programming. Fuel-optimal geocentric transfers are computed with the transfer duration extended up to 2000 revolutions. The flexibility of the approach to higher fidelity dynamics is shown with Earth's J 2 perturbation and lunar gravity included for a 500 revolution transfer.
Simulator for multilevel optimization research
NASA Technical Reports Server (NTRS)
Padula, S. L.; Young, K. C.
1986-01-01
A computer program designed to simulate and improve multilevel optimization techniques is described. By using simple analytic functions to represent complex engineering analyses, the simulator can generate and test a large variety of multilevel decomposition strategies in a relatively short time. This type of research is an essential step toward routine optimization of large aerospace systems. The paper discusses the types of optimization problems handled by the simulator and gives input and output listings and plots for a sample problem. It also describes multilevel implementation techniques which have value beyond the present computer program. Thus, this document serves as a user's manual for the simulator and as a guide for building future multilevel optimization applications.
NASA Astrophysics Data System (ADS)
Aziz, Jonathan D.; Parker, Jeffrey S.; Scheeres, Daniel J.; Englander, Jacob A.
2018-06-01
Low-thrust trajectories about planetary bodies characteristically span a high count of orbital revolutions. Directing the thrust vector over many revolutions presents a challenging optimization problem for any conventional strategy. This paper demonstrates the tractability of low-thrust trajectory optimization about planetary bodies by applying a Sundman transformation to change the independent variable of the spacecraft equations of motion to an orbit angle and performing the optimization with differential dynamic programming. Fuel-optimal geocentric transfers are computed with the transfer duration extended up to 2000 revolutions. The flexibility of the approach to higher fidelity dynamics is shown with Earth's J 2 perturbation and lunar gravity included for a 500 revolution transfer.
Supercomputer optimizations for stochastic optimal control applications
NASA Technical Reports Server (NTRS)
Chung, Siu-Leung; Hanson, Floyd B.; Xu, Huihuang
1991-01-01
Supercomputer optimizations for a computational method of solving stochastic, multibody, dynamic programming problems are presented. The computational method is valid for a general class of optimal control problems that are nonlinear, multibody dynamical systems, perturbed by general Markov noise in continuous time, i.e., nonsmooth Gaussian as well as jump Poisson random white noise. Optimization techniques for vector multiprocessors or vectorizing supercomputers include advanced data structures, loop restructuring, loop collapsing, blocking, and compiler directives. These advanced computing techniques and superconducting hardware help alleviate Bellman's curse of dimensionality in dynamic programming computations, by permitting the solution of large multibody problems. Possible applications include lumped flight dynamics models for uncertain environments, such as large scale and background random aerospace fluctuations.
Comparative Evaluation of Different Optimization Algorithms for Structural Design Applications
NASA Technical Reports Server (NTRS)
Patnaik, Surya N.; Coroneos, Rula M.; Guptill, James D.; Hopkins, Dale A.
1996-01-01
Non-linear programming algorithms play an important role in structural design optimization. Fortunately, several algorithms with computer codes are available. At NASA Lewis Research Centre, a project was initiated to assess the performance of eight different optimizers through the development of a computer code CometBoards. This paper summarizes the conclusions of that research. CometBoards was employed to solve sets of small, medium and large structural problems, using the eight different optimizers on a Cray-YMP8E/8128 computer. The reliability and efficiency of the optimizers were determined from the performance of these problems. For small problems, the performance of most of the optimizers could be considered adequate. For large problems, however, three optimizers (two sequential quadratic programming routines, DNCONG of IMSL and SQP of IDESIGN, along with Sequential Unconstrained Minimizations Technique SUMT) outperformed others. At optimum, most optimizers captured an identical number of active displacement and frequency constraints but the number of active stress constraints differed among the optimizers. This discrepancy can be attributed to singularity conditions in the optimization and the alleviation of this discrepancy can improve the efficiency of optimizers.
Performance Trend of Different Algorithms for Structural Design Optimization
NASA Technical Reports Server (NTRS)
Patnaik, Surya N.; Coroneos, Rula M.; Guptill, James D.; Hopkins, Dale A.
1996-01-01
Nonlinear programming algorithms play an important role in structural design optimization. Fortunately, several algorithms with computer codes are available. At NASA Lewis Research Center, a project was initiated to assess performance of different optimizers through the development of a computer code CometBoards. This paper summarizes the conclusions of that research. CometBoards was employed to solve sets of small, medium and large structural problems, using different optimizers on a Cray-YMP8E/8128 computer. The reliability and efficiency of the optimizers were determined from the performance of these problems. For small problems, the performance of most of the optimizers could be considered adequate. For large problems however, three optimizers (two sequential quadratic programming routines, DNCONG of IMSL and SQP of IDESIGN, along with the sequential unconstrained minimizations technique SUMT) outperformed others. At optimum, most optimizers captured an identical number of active displacement and frequency constraints but the number of active stress constraints differed among the optimizers. This discrepancy can be attributed to singularity conditions in the optimization and the alleviation of this discrepancy can improve the efficiency of optimizers.
Optimization technique of wavefront coding system based on ZEMAX externally compiled programs
NASA Astrophysics Data System (ADS)
Han, Libo; Dong, Liquan; Liu, Ming; Zhao, Yuejin; Liu, Xiaohua
2016-10-01
Wavefront coding technique as a means of athermalization applied to infrared imaging system, the design of phase plate is the key to system performance. This paper apply the externally compiled programs of ZEMAX to the optimization of phase mask in the normal optical design process, namely defining the evaluation function of wavefront coding system based on the consistency of modulation transfer function (MTF) and improving the speed of optimization by means of the introduction of the mathematical software. User write an external program which computes the evaluation function on account of the powerful computing feature of the mathematical software in order to find the optimal parameters of phase mask, and accelerate convergence through generic algorithm (GA), then use dynamic data exchange (DDE) interface between ZEMAX and mathematical software to realize high-speed data exchanging. The optimization of the rotational symmetric phase mask and the cubic phase mask have been completed by this method, the depth of focus increases nearly 3 times by inserting the rotational symmetric phase mask, while the other system with cubic phase mask can be increased to 10 times, the consistency of MTF decrease obviously, the maximum operating temperature of optimized system range between -40°-60°. Results show that this optimization method can be more convenient to define some unconventional optimization goals and fleetly to optimize optical system with special properties due to its externally compiled function and DDE, there will be greater significance for the optimization of unconventional optical system.
Nie, Xianghui; Huang, Guo H; Li, Yongping
2009-11-01
This study integrates the concepts of interval numbers and fuzzy sets into optimization analysis by dynamic programming as a means of accounting for system uncertainty. The developed interval fuzzy robust dynamic programming (IFRDP) model improves upon previous interval dynamic programming methods. It allows highly uncertain information to be effectively communicated into the optimization process through introducing the concept of fuzzy boundary interval and providing an interval-parameter fuzzy robust programming method for an embedded linear programming problem. Consequently, robustness of the optimization process and solution can be enhanced. The modeling approach is applied to a hypothetical problem for the planning of waste-flow allocation and treatment/disposal facility expansion within a municipal solid waste (MSW) management system. Interval solutions for capacity expansion of waste management facilities and relevant waste-flow allocation are generated and interpreted to provide useful decision alternatives. The results indicate that robust and useful solutions can be obtained, and the proposed IFRDP approach is applicable to practical problems that are associated with highly complex and uncertain information.
SOL - SIZING AND OPTIMIZATION LANGUAGE COMPILER
NASA Technical Reports Server (NTRS)
Scotti, S. J.
1994-01-01
SOL is a computer language which is geared to solving design problems. SOL includes the mathematical modeling and logical capabilities of a computer language like FORTRAN but also includes the additional power of non-linear mathematical programming methods (i.e. numerical optimization) at the language level (as opposed to the subroutine level). The language-level use of optimization has several advantages over the traditional, subroutine-calling method of using an optimizer: first, the optimization problem is described in a concise and clear manner which closely parallels the mathematical description of optimization; second, a seamless interface is automatically established between the optimizer subroutines and the mathematical model of the system being optimized; third, the results of an optimization (objective, design variables, constraints, termination criteria, and some or all of the optimization history) are output in a form directly related to the optimization description; and finally, automatic error checking and recovery from an ill-defined system model or optimization description is facilitated by the language-level specification of the optimization problem. Thus, SOL enables rapid generation of models and solutions for optimum design problems with greater confidence that the problem is posed correctly. The SOL compiler takes SOL-language statements and generates the equivalent FORTRAN code and system calls. Because of this approach, the modeling capabilities of SOL are extended by the ability to incorporate existing FORTRAN code into a SOL program. In addition, SOL has a powerful MACRO capability. The MACRO capability of the SOL compiler effectively gives the user the ability to extend the SOL language and can be used to develop easy-to-use shorthand methods of generating complex models and solution strategies. The SOL compiler provides syntactic and semantic error-checking, error recovery, and detailed reports containing cross-references to show where each variable was used. The listings summarize all optimizations, listing the objective functions, design variables, and constraints. The compiler offers error-checking specific to optimization problems, so that simple mistakes will not cost hours of debugging time. The optimization engine used by and included with the SOL compiler is a version of Vanderplatt's ADS system (Version 1.1) modified specifically to work with the SOL compiler. SOL allows the use of the over 100 ADS optimization choices such as Sequential Quadratic Programming, Modified Feasible Directions, interior and exterior penalty function and variable metric methods. Default choices of the many control parameters of ADS are made for the user, however, the user can override any of the ADS control parameters desired for each individual optimization. The SOL language and compiler were developed with an advanced compiler-generation system to ensure correctness and simplify program maintenance. Thus, SOL's syntax was defined precisely by a LALR(1) grammar and the SOL compiler's parser was generated automatically from the LALR(1) grammar with a parser-generator. Hence unlike ad hoc, manually coded interfaces, the SOL compiler's lexical analysis insures that the SOL compiler recognizes all legal SOL programs, can recover from and correct for many errors and report the location of errors to the user. This version of the SOL compiler has been implemented on VAX/VMS computer systems and requires 204 KB of virtual memory to execute. Since the SOL compiler produces FORTRAN code, it requires the VAX FORTRAN compiler to produce an executable program. The SOL compiler consists of 13,000 lines of Pascal code. It was developed in 1986 and last updated in 1988. The ADS and other utility subroutines amount to 14,000 lines of FORTRAN code and were also updated in 1988.
Optimal Implantable Cardioverter Defibrillator Programming.
Shah, Bindi K
Optimal programming of implantable cardioverter defibrillators (ICDs) is essential to appropriately treat ventricular tachyarrhythmias and to avoid unnecessary and inappropriate shocks. There have been a series of large clinical trials evaluating tailored programming of ICDs. We reviewed the clinical trials evaluating ICD therapies and detection, and the consensus statement on ICD programming. In doing so, we found that prolonged ICD detection times, higher rate cutoffs, and antitachycardia pacing (ATP) programming decreases inappropriate and painful therapies in a primary prevention population. The use of supraventricular tachyarrhythmia discriminators can also decrease inappropriate shocks. Tailored ICD programming using the knowledge gained from recent ICD trials can decrease inappropriate and unnecessary ICD therapies and decrease mortality.
Method of optimization onboard communication network
NASA Astrophysics Data System (ADS)
Platoshin, G. A.; Selvesuk, N. I.; Semenov, M. E.; Novikov, V. M.
2018-02-01
In this article the optimization levels of onboard communication network (OCN) are proposed. We defined the basic parameters, which are necessary for the evaluation and comparison of modern OCN, we identified also a set of initial data for possible modeling of the OCN. We also proposed a mathematical technique for implementing the OCN optimization procedure. This technique is based on the principles and ideas of binary programming. It is shown that the binary programming technique allows to obtain an inherently optimal solution for the avionics tasks. An example of the proposed approach implementation to the problem of devices assignment in OCN is considered.
SeGRAm - A practical and versatile tool for spacecraft trajectory optimization
NASA Technical Reports Server (NTRS)
Rishikof, Brian H.; Mccormick, Bernell R.; Pritchard, Robert E.; Sponaugle, Steven J.
1991-01-01
An implementation of the Sequential Gradient/Restoration Algorithm, SeGRAm, is presented along with selected examples. This spacecraft trajectory optimization and simulation program uses variational calculus to solve problems of spacecraft flying under the influence of one or more gravitational bodies. It produces a series of feasible solutions to problems involving a wide range of vehicles, environments and optimization functions, until an optimal solution is found. The examples included highlight the various capabilities of the program and emphasize in particular its versatility over a wide spectrum of applications from ascent to interplanetary trajectories.
Experiences in using the CYBER 203 for three-dimensional transonic flow calculations
NASA Technical Reports Server (NTRS)
Melson, N. D.; Keller, J. D.
1982-01-01
In this paper, the authors report on some of their experiences modifying two three-dimensional transonic flow programs (FLO22 and FLO27) for use on the NASA Langley Research Center CYBER 203. Both of the programs discussed were originally written for use on serial machines. Several methods were attempted to optimize the execution of the two programs on the vector machine, including: (1) leaving the program in a scalar form (i.e., serial computation) with compiler software used to optimize and vectorize the program, (2) vectorizing parts of the existing algorithm in the program, and (3) incorporating a new vectorizable algorithm (ZEBRA I or ZEBRA II) in the program.
Microstructure/Oxidation/Microhardness Correlations in Gamma-Based and Tau-Based Al-Ti-Cr Alloys
NASA Technical Reports Server (NTRS)
Brady, Michael P.; Smialek, J. L.; Humphrey, D. L.
1994-01-01
The relationships between alloy microstructure and air oxidation kinetics and alloy microstructure and microhardness in the Al-Ti-Cr system for exposures at 800 C and 1000 C were investigated. The relevant phases were identified as tau (Ll2), gamma (LIO), r-Al2Ti, TiCrAl (laves), and Cr2AI. Protective alumina formation was associated with tau, Al-rich TiCrAl, and gamma/TiCrAl mixtures. Brittleness was associated with the TiCrAl phase and tau decomposition to A12Ti + Cr2AI. It was concluded that two-phase gamma + TiCrAl alloys offer the greatest potential for oxidation resistance and room temperature ductility in the Al-Ti-Cr system.
Structural Health Monitoring 2007: Quantification, Validation, and Implementation
2008-07-01
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Neutron Production from In-situ Heavy Ice Coated Targets at Vulcan
NASA Astrophysics Data System (ADS)
Morrison, John; Krygier, A. G.; Kar, S.; Ahmed, H.; Alejo, A.; Clarke, R.; Fuchs, J.; Green, A.; Jung, D.; Kleinschmidt, A.; Najmudin, Z.; Nakamura, H.; Norreys, P.; Notley, M.; Oliver, M.; Roth, M.; Vassura, L.; Zepf, M.; Borghesi, M.; Freeman, R. R.
2015-05-01
Laser based neutron production experiments have been performed utilizing ultra-high intensity laser accelerated ions impinging upon a secondary target. The neutron yield from such experiments may be improved if the accelerated ions were primarily deuterons taking advantage of the d-d cross section. Recent experiments have demonstrated that selective deuteron acceleration from in-situ heavy ice coating of targets can produce ion spectra where deuterons comprise > 99 % of the measured ions. Results will be presented from integrated neutron production experiments from heavy ice targets coated in-situ recently performed on the Vulcan laser at Rutherford Appleton Laboratory. We are grateful for the Staff at RAL and acknowledge funding from the US DoE. AFOSR, European Social Fund, and the Czech Republic.
Localisation humérale d'une tumeur à cellules géantes récidivantes (à propos d'un cas)
Nader, Youssef; Serghini, Issam; Koulali, Idrissi Khalid; Salahi, Hicham; Galwia, Farid
2015-01-01
Les auteurs rapportent un cas de localisation rare d'une tumeur à cellules géantes au niveau de la palette humérale du coude droit chez un militaire de 36 ans de sexe masculin, la radio standard montrait une image kystique ne soufflant pas la corticale. L'examen anatomo-pathologique a permis d’ établir le diagnostic et le traitement a fait appel: au début a une Exérèse chirurgicale totale et une greffe osseuse par un greffon iliaque de la totalité de la palette huméral qui s'est compliquée à 6 mois de recule d une récidive locale. PMID:25995809
NASA Astrophysics Data System (ADS)
Wang, Dong; Ning, Jing; Zhang, Jincheng; Guo, Lixin; Hao, Yue
2017-10-01
Here we systemically discussed the influence of dielectric substrates on the surface morphology, electrical and optical performance of transferred graphene. The electrical properties were investigated using a microwave-probing technique without metal-graphene contact. We found that a complex mechanism governed the influence of the surface properties of the dielectric substrates, such as morphology, hydrophilicity, crystallinity, and polarization, on the performance of the graphene. We also found that graphene on r-Al2O3 was more effective for graphene-based devices with a high carrier mobility of ˜5000 cm2 V-1 s-1. This provides a new method to choose the most suitable substrate for fabricating graphene-based devices.
On program restructuring, scheduling, and communication for parallel processor systems
DOE Office of Scientific and Technical Information (OSTI.GOV)
Polychronopoulos, Constantine D.
1986-08-01
This dissertation discusses several software and hardware aspects of program execution on large-scale, high-performance parallel processor systems. The issues covered are program restructuring, partitioning, scheduling and interprocessor communication, synchronization, and hardware design issues of specialized units. All this work was performed focusing on a single goal: to maximize program speedup, or equivalently, to minimize parallel execution time. Parafrase, a Fortran restructuring compiler was used to transform programs in a parallel form and conduct experiments. Two new program restructuring techniques are presented, loop coalescing and subscript blocking. Compile-time and run-time scheduling schemes are covered extensively. Depending on the program construct, thesemore » algorithms generate optimal or near-optimal schedules. For the case of arbitrarily nested hybrid loops, two optimal scheduling algorithms for dynamic and static scheduling are presented. Simulation results are given for a new dynamic scheduling algorithm. The performance of this algorithm is compared to that of self-scheduling. Techniques for program partitioning and minimization of interprocessor communication for idealized program models and for real Fortran programs are also discussed. The close relationship between scheduling, interprocessor communication, and synchronization becomes apparent at several points in this work. Finally, the impact of various types of overhead on program speedup and experimental results are presented.« less
NASA Technical Reports Server (NTRS)
Holms, A. G.
1982-01-01
A previous report described a backward deletion procedure of model selection that was optimized for minimum prediction error and which used a multiparameter combination of the F - distribution and an order statistics distribution of Cochran's. A computer program is described that applies the previously optimized procedure to real data. The use of the program is illustrated by examples.
NASA Technical Reports Server (NTRS)
Rommel, Bruce A.
1989-01-01
An overview of the Aeroelastic Design Optimization Program (ADOP) at the Douglas Aircraft Company is given. A pilot test program involving the animation of mode shapes with solid rendering as well as wire frame displays, a complete aircraft model of a high-altitude hypersonic aircraft to test ADOP procedures, a flap model, and an aero-mesh modeler for doublet lattice aerodynamics are discussed.
Optimizing a mobile robot control system using GPU acceleration
NASA Astrophysics Data System (ADS)
Tuck, Nat; McGuinness, Michael; Martin, Fred
2012-01-01
This paper describes our attempt to optimize a robot control program for the Intelligent Ground Vehicle Competition (IGVC) by running computationally intensive portions of the system on a commodity graphics processing unit (GPU). The IGVC Autonomous Challenge requires a control program that performs a number of different computationally intensive tasks ranging from computer vision to path planning. For the 2011 competition our Robot Operating System (ROS) based control system would not run comfortably on the multicore CPU on our custom robot platform. The process of profiling the ROS control program and selecting appropriate modules for porting to run on a GPU is described. A GPU-targeting compiler, Bacon, is used to speed up development and help optimize the ported modules. The impact of the ported modules on overall performance is discussed. We conclude that GPU optimization can free a significant amount of CPU resources with minimal effort for expensive user-written code, but that replacing heavily-optimized library functions is more difficult, and a much less efficient use of time.
Power Grid Construction Project Portfolio Optimization Based on Bi-level programming model
NASA Astrophysics Data System (ADS)
Zhao, Erdong; Li, Shangqi
2017-08-01
As the main body of power grid operation, county-level power supply enterprises undertake an important emission to guarantee the security of power grid operation and safeguard social power using order. The optimization of grid construction projects has been a key issue of power supply capacity and service level of grid enterprises. According to the actual situation of power grid construction project optimization of county-level power enterprises, on the basis of qualitative analysis of the projects, this paper builds a Bi-level programming model based on quantitative analysis. The upper layer of the model is the target restriction of the optimal portfolio; the lower layer of the model is enterprises’ financial restrictions on the size of the enterprise project portfolio. Finally, using a real example to illustrate operation proceeding and the optimization result of the model. Through qualitative analysis and quantitative analysis, the bi-level programming model improves the accuracy and normative standardization of power grid enterprises projects.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Arnis Judzis
2003-07-01
This document details the progress to date on the ''OPTIMIZATION OF MUD HAMMER DRILLING PERFORMANCE--A PROGRAM TO BENCHMARK THE VIABILITY OF ADVANCED MUD HAMMER DRILLING'' contract for the quarter starting April 2003 through June 2003. The DOE and TerraTek continue to wait for Novatek on the optimization portion of the testing program (they are completely rebuilding their fluid hammer). Accomplishments included the following: (1) Hughes Christensen has recently expressed interest in the possibility of a program to examine cutter impact testing, which would be useful in a better understanding of the physics of rock impact. Their interest however is notmore » necessarily fluid hammers, but to use the information for drilling bit development. (2) Novatek (cost sharing supplier of tools) has informed the DOE project manager that their tool may not be ready for ''optimization'' testing late summer 2003 (August-September timeframe) as originally anticipated. During 3Q Novatek plans to meet with TerraTek to discuss progress with their tool for 4Q 2003 testing. (3) A task for an addendum to the hammer project related to cutter impact studies was written during 2Q 2003. (4) Smith International internally is upgrading their hammer for the optimization testing phase. One currently known area of improvement is their development program to significantly increase the hammer blow energy.« less
Optimal Physical Training During Military Basic Training Period.
Santtila, Matti; Pihlainen, Kai; Viskari, Jarmo; Kyröläinen, Heikki
2015-11-01
The goal for military basic training (BT) is to create a foundation for physical fitness and military skills of soldiers. Thereafter, more advanced military training can safely take place. Large differences in the initial physical performance of conscripts or recruits have led military units to develop more safe and effective training programs. The purpose of this review article was to describe the limiting factors of optimal physical training during the BT period. This review revealed that the high volume of low-intensity physical activity combined with endurance-type military training (like combat training, prolonged physical activity, and field shooting) during BT interferes with optimal development of maximal oxygen uptake and muscle strength of the soldiers. Therefore, more progressive, periodized, and individualized training programs are needed. In conclusion, optimal training programs lead to higher training responses and lower risks for injuries and overloading.
Use of CYBER 203 and CYBER 205 computers for three-dimensional transonic flow calculations
NASA Technical Reports Server (NTRS)
Melson, N. D.; Keller, J. D.
1983-01-01
Experiences are discussed for modifying two three-dimensional transonic flow computer programs (FLO 22 and FLO 27) for use on the CDC CYBER 203 computer system. Both programs were originally written for use on serial machines. Several methods were attempted to optimize the execution of the two programs on the vector machine: leaving the program in a scalar form (i.e., serial computation) with compiler software used to optimize and vectorize the program, vectorizing parts of the existing algorithm in the program, and incorporating a vectorizable algorithm (ZEBRA I or ZEBRA II) in the program. Comparison runs of the programs were made on CDC CYBER 175. CYBER 203, and two pipe CDC CYBER 205 computer systems.
Optimization by nonhierarchical asynchronous decomposition
NASA Technical Reports Server (NTRS)
Shankar, Jayashree; Ribbens, Calvin J.; Haftka, Raphael T.; Watson, Layne T.
1992-01-01
Large scale optimization problems are tractable only if they are somehow decomposed. Hierarchical decompositions are inappropriate for some types of problems and do not parallelize well. Sobieszczanski-Sobieski has proposed a nonhierarchical decomposition strategy for nonlinear constrained optimization that is naturally parallel. Despite some successes on engineering problems, the algorithm as originally proposed fails on simple two dimensional quadratic programs. The algorithm is carefully analyzed for quadratic programs, and a number of modifications are suggested to improve its robustness.
Translator for Optimizing Fluid-Handling Components
NASA Technical Reports Server (NTRS)
Landon, Mark; Perry, Ernest
2007-01-01
A software interface has been devised to facilitate optimization of the shapes of valves, elbows, fittings, and other components used to handle fluids under extreme conditions. This software interface translates data files generated by PLOT3D (a NASA grid-based plotting-and- data-display program) and by computational fluid dynamics (CFD) software into a format in which the files can be read by Sculptor, which is a shape-deformation- and-optimization program. Sculptor enables the user to interactively, smoothly, and arbitrarily deform the surfaces and volumes in two- and three-dimensional CFD models. Sculptor also includes design-optimization algorithms that can be used in conjunction with the arbitrary-shape-deformation components to perform automatic shape optimization. In the optimization process, the output of the CFD software is used as feedback while the optimizer strives to satisfy design criteria that could include, for example, improved values of pressure loss, velocity, flow quality, mass flow, etc.
Nonlinear Programming Models to Optimize Uneven-Aged Shortleaf Pine Management
Benedict J. Schulte; Joseph Buongiorno
2002-01-01
Nonlinear programming models of uneven-aged shortleaf pine (Pinus echinata Mill.) management were developed to identify sustainable management regimes that optimize soil expectation value (SEV) or annual sawtimber yields. The models recognize three species groups (shortleaf pine and other softwoods, soft hardwoods and hard hardwoods) and 13 2-inch...
Roadmap to Long-Term Monitoring Optimization
This roadmap focuses on optimization of established long-term monitoring programs for groundwater. Tools and techniques discussed concentrate on methods for optimizing the monitoring frequency and spatial (three-dimensional) distribution of wells ...
NASA Technical Reports Server (NTRS)
Murthy, T. Sreekanta; Kvaternik, Raymond G.
1991-01-01
A NASA/industry rotorcraft structural dynamics program known as Design Analysis Methods for VIBrationS (DAMVIBS) was initiated at Langley Research Center in 1984 with the objective of establishing the technology base needed by the industry for developing an advanced finite-element-based vibrations design analysis capability for airframe structures. As a part of the in-house activities contributing to that program, a study was undertaken to investigate the use of formal, nonlinear programming-based, numerical optimization techniques for airframe vibrations design work. Considerable progress has been made in connection with that study since its inception in 1985. This paper presents a unified summary of the experiences and results of that study. The formulation and solution of airframe optimization problems are discussed. Particular attention is given to describing the implementation of a new computational procedure based on MSC/NASTRAN and CONstrained function MINimization (CONMIN) in a computer program system called DYNOPT for the optimization of airframes subject to strength, frequency, dynamic response, and fatigue constraints. The results from the application of the DYNOPT program to the Bell AH-1G helicopter are presented and discussed.
Seyfried, Timo F; Gruber, Michael; Streithoff, Fabian; Mandle, Robert J; Pawlik, Michael T; Busse, Hendrik; Hansen, Ernil
2017-03-01
Cell salvage is an essential element in the concept of blood management. Modern devices provide different bowl sizes and sensor-directed programs to optimally adjust to varying clinical situations. In an experimental performance study, the discontinuous autotransfusion device XTRA (LivaNova/Sorin) was evaluated using fresh donor blood anticoagulated with heparin 5 U/mL and adjusted to a hematocrit of 10% or 25%, representing orthopedic or cardiac surgery. Test blood was processed with the autotransfusion device XTRA in four different bowls (55 mL, 125 mL, 175 mL, and 225 mL) and in three different program modes (a standard program, an optimized program, and an emergency program). Processing speed increased with bowl size and with the emergency program (range, 6.4-29.8 mL red blood cells [RBCs]/min). The RBC recovery rate exceeded 90% for all bowls and programs except the 55-mL bowl with the emergency program. Plasma elimination exceeded 95% for all bowls and programs except the 225-mL bowl with the emergency and standard programs. Maximal RBC recovery (range, 94.7%-97.6%) and plasma elimination (range, 98.7%-99.5%) were obtained with the medium-sized bowls (125 mL and 175 mL) and the optimized program. Elimination rates for potassium or plasma free hemoglobin were consistently lower than for protein or albumin and were highest for heparin. Increased hematocrit and RBC recovery rates are obtained with the optimized program Popt with the discontinuous autotransfusion device. The emergency program Pem speeds up the process but leads to RBC loss and reduced plasma elimination rates; therefore, it should be restricted to emergency situations. All four different sized bowls have high performance. Plasma elimination is represented best by protein or albumin elimination rates. © 2017 AABB.
A summary report on system effectiveness and optimization study
NASA Technical Reports Server (NTRS)
Williamson, O. L.; Rydberg, A. J.; Dorris, G.
1973-01-01
Report treats optimization and effectiveness separately. Report illustrates example of dynamic programming solution to system optimization. Computer algorithm has been developed to solve effectiveness problem and is included in report.
Thompkins, Amanda C; Chauveron, Lisa M; Harel, Ofer; Perkins, Daniel F
2014-07-01
While demand for youth violence prevention programs increases, the ability of the school-day schedule to accommodate their time requirements has diminished. Viable school-based prevention programs must strike a balance between brevity and effectiveness. This article reports results from an effectiveness trial of a 12-session curriculum-based universal violence prevention program that promotes healthy conflict resolution skills among urban adolescents. Using a review of program record data and a multisite quasi-experimental study design, we examined the effectiveness of a New York City-based violence prevention program entitled the Violence Prevention project (VPP) optimized to meet school needs. We analyzed survey data from 1112 9th- and 10th-grade students in 13 New York City public high schools across 4 consecutive school years. Both participants and nonparticipants were surveyed. Review of program record data indicated that the program was implemented with acceptable fidelity to the core component structure, and that participant responsiveness to the model was high. Multilevel modeling indicated that VPP participation was protective for academic self-concept and promoted conflict resolution skills. Findings indicate that semester-long violence prevention programs optimized to meet the needs of a typical high school can be effective at promoting healthy conflict resolution skills in urban adolescents. © 2014, American School Health Association.
Robotic-Assisted Minimally Invasive Surgery for Gynecologic and Urologic Oncology
2010-01-01
Executive Summary Objective An application was received to review the evidence on the ‘The Da Vinci Surgical System’ for the treatment of gynecologic malignancies (e.g. endometrial and cervical cancers). Limitations to the current standard of care include the lack of trained physicians on minimally invasive surgery and limited access to minimally invasive surgery for patients. The potential benefits of ‘The Da Vinci Surgical System’ include improved technical manipulation and physician uptake leading to increased surgeries, and treatment and management of these cancers. The demand for robotic surgery for the treatment and management of prostate cancer has been increasing due to its alleged benefits of recovery of erectile function and urinary continence, two important factors of men’s health. The potential technical benefits of robotic surgery leading to improved patient functional outcomes are surgical precision and vision. Clinical Need Uterine and cervical cancers represent 5.4% (4,400 of 81,700) and 1.6% (1,300 of 81,700), respectively, of incident cases of cancer among female cancers in Canada. Uterine cancer, otherwise referred to as endometrial cancer is cancer of the lining of the uterus. The most common treatment option for endometrial cancer is removing the cancer through surgery. A surgical option is the removal of the uterus and cervix through a small incision in the abdomen using a laparoscope which is referred to as total laparoscopic hysterectomy. Risk factors that increase the risk of endometrial cancer include taking estrogen replacement therapy after menopause, being obese, early age at menarche, late age at menopause, being nulliparous, having had high-dose radiation to the pelvis, and use of tamoxifen. Cervical cancer occurs at the lower narrow end of the uterus. There are more treatment options for cervical cancer compared to endometrial cancer, however total laparoscopic hysterectomy is also a treatment option. Risk factors that increase the risk for cervical cancer are multiple sexual partners, early sexual activity, infection with the human papillomavirus, and cigarette smoking, whereas barrier-type of contraception as a risk factor decreases the risk of cervical cancer. Prostate cancer is ranked first in men in Canada in terms of the number of new cases among all male cancers (25,500 of 89,300 or 28.6%). The impact on men who develop prostate cancer is substantial given the potential for erectile dysfunction and urinary incontinence. Prostate cancer arises within the prostate gland, which resides in the male reproductive system and near the bladder. Radical retropubic prostatectomy is the gold standard treatment for localized prostate cancer. Prostate cancer affects men above 60 years of age. Other risk factors include a family history of prostate cancer, being of African descent, being obese, consuming a diet high in fat, physical inactivity, and working with cadium. The Da Vinci Surgical System The Da Vinci Surgical System is a robotic device. There are four main components to the system: 1) the surgeon’s console, where the surgeon sits and views a magnified three-dimensional image of the surgical field; 2) patient side-cart, which sits beside the patient and consists of three instrument arms and one endoscope arm; 3) detachable instruments (endowrist instruments and intuitive masters), which simulate fine motor human movements. The hand movements of the surgeon’s hands at the surgeon’s console are translated into smaller ones by the robotic device and are acted out by the attached instruments; 4) three-dimensional vision system: the camera unit or endoscope arm. The main advantages of use of the robotic device are: 1) the precision of the instrument and improved dexterity due to the use of “wristed” instruments; 2) three-dimensional imaging, with improved ability to locate blood vessels, nerves and tissues; 3) the surgeon’s console, which reduces fatigue accompanied with conventional laparoscopy surgery and allows for tremor-free manipulation. The main disadvantages of use of the robotic device are the costs including instrument costs ($2.6 million in US dollars), cost per use ($200 per use), the costs associated with training surgeons and operating room personnel, and the lack of tactile feedback, with the trade-off being increased visual feedback. Research Questions For endometrial and cervical cancers, 1. What is the effectiveness of the Da Vinci Surgical System vs. laparoscopy and laparotomy for women undergoing any hysterectomy for the surgical treatment and management of their endometrial and cervical cancers? 2. What are the incremental costs of the Da Vinci Surgical System vs. laparoscopy and laparotomy for women undergoing any hysterectomy for the surgical treatment and management of their endometrial and cervical cancers? For prostate cancer, 3. What is the effectiveness of robotically-assisted radical prostatectomy using the Da Vinci Surgical System vs. laparoscopic radical prostatectomy and retropubic radical prostatectomy for the surgical treatment and management of prostate cancer? 4. What are the incremental costs of robotically-assisted radical prostatectomy using the Da Vinci Surgical System vs. laparoscopic radical prostatectomy and retropubic radical prostatectomy for the surgical treatment and management of prostate cancer? Research Methods Literature Search Search Strategy A literature search was performed on May 12, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, Wiley Cochrane, CINAHL, Centre for Reviews and Dissemination/International Agency for Health Technology Assessment for studies published from January 1, 2000 until May 12, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist, then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology. Inclusion Criteria English language articles (January 1, 2000-May 12, 2010) Journal articles that report on the effectiveness or cost-effectiveness for the comparisons of interest using a primary data source (e.g. obtained in a clinical setting) Journal articles that report on the effectiveness or cost-effectiveness for the comparisons of interest using a secondary data source (e.g. hospital- or population-based registries) Study design and methods must be clearly described Health technology assessments, systematic reviews, randomized controlled trials, non-randomized controlled trials and/or cohort studies, case-case studies, regardless of sample size, cost-effectiveness studies Exclusion Criteria Duplicate publications (with the more recent publication on the same study population included) Non-English papers Animal or in-vitro studies Case reports or case series without a referent or comparison group Studies on long-term survival which may be affected by treatment Studies that do not examine the cancers (e.g. advanced disease) or outcomes of interest Outcomes of Interest For endometrial and cervical cancers, Primary outcomes: Morbidity factors - Length of hospitalization - Number of complications* Peri-operative factors - Operation time - Amount of blood loss* - Number of conversions to laparotomy* Number of lymph nodes recovered For prostate cancer, Primary outcomes: Morbidity factors - Length of hospitalization - Amount of morphine use/pain* Peri-operative factors - Operation time - Amount of blood loss* - Number of transfusions* - Duration of catheterization - Number of complications* - Number of anastomotic strictures* Number of lymph nodes recovered Oncologic factors - Proportion of positive surgical margins Long-term outcomes - Urinary continence - Erectile function Summary of Findings Robotic use for gynecologic oncology compared to: Laparotomy: benefits of robotic surgery in terms of shorter length of hospitalization and less blood loss. These results indicate clinical effectiveness in terms of reduced morbidity and safety, respectively, in the context of study design limitations. The beneficial effect of robotic surgery was shown in pooled analysis for complications, owing to increased sample size. More work is needed to clarify the role of complications in terms of safety, including improved study designs, analysis and measurement. Laparoscopy: benefits of robotic surgery in terms of shorter length of hospitalization, less blood loss and fewer conversions to laparotomy likely owing to the technical difficulty of conventional laparoscopy, in the context of study design limitations. Clinical significance of significant findings for length of hospitalizations and blood loss is low. Fewer conversions to laparotomy indicate clinical effectiveness in terms of reduced morbidity. Robotic use for urologic oncology, specifically prostate cancer, compared to: Retropubic surgery: benefits of robotic surgery in terms of shorter length of hospitalization and less blood loss/fewer individuals requiring transfusions. These results indicate clinical effectiveness in terms of reduced morbidity and safety, respectively, in the context of study design limitations. There was a beneficial effect in terms of decreased positive surgical margins and erectile dysfunction. These results indicate clinical effectiveness in terms of improved cancer control and functional outcomes, respectively, in the context of study design limitations. Surgeon skill had an impact on cancer control and functional outcomes. The results for complications were inconsistent when measured as either total number of complications, pain management or anastomosis. There is some suggestion that robotic surgery is safe with respect to less post-operative pain management required compared to retropubic surgery, however improved study design and measurement of complications need to be further addressed. Clinical significance of significant findings for length of hospitalizations is low. Laparoscopy: benefits of robotic surgery in terms of less blood loss and fewer individuals requiring transfusions likely owing to the technical difficulty of conventional laparoscopy, in the context of study design limitations. Clinical significance of significant findings for blood loss is low. The potential link between less blood loss, improved visualization and improved functional outcomes is an important consideration for use of robotics. All studies included were observational in nature and therefore the results must be interpreted cautiously. Economic Analysis The objective of this project was to assess the economic impact of robotic-assisted laparoscopy (RAL) for endometrial, cervical, and prostate cancers in the province of Ontario. A budget impact analysis was undertaken to report direct costs associated with open surgery (OS), endoscopic laparoscopy (EL) and robotic-assisted laparoscopy (RAL) based on clinical literature review outcomes, to report a budget impact in the province based on volumes and costs from administrative data sets, and to project a future impact of RAL in Ontario. A cost-effectiveness analysis was not conducted because of the low quality evidence from the clinical literature review. Hospital costs were obtained from the Ontario Case Costing Initiative (OCCI) for the appropriate Canadian Classification of Health Intervention (CCI) codes restricted to selective ICD-10 diagnostic codes after consultation with experts in the field. Physician fees were obtained from the Ontario Schedule of Benefits (OSB) after consultation with experts in the field. Fees were costed based on operation times reported in the clinical literature for the procedures being investigated. Volumes of procedures were obtained from the Ministry of Health and Long-Term Care (MOHLTC) administrative databases. Direct costs associated with RAL, EL and OS included professional fees, hospital costs (including disposable instruments), radiotherapy costs associated with positive surgical margins in prostate cancer and conversion to OS in gynecological cancer. The total cost per case was higher for RAL than EL and OS for both gynecological and prostate cancers. There is also an acquisition cost associated with RAL. After conversation with the only supplier in Canada, hospitals are looking to spend an initial 3.6M to acquire the robotic surgical system Previous volumes of OS and EL procedures were used to project volumes into Years 1-3 using a linear mathematical expression. Burden of OS and EL hysterectomies and prostatectomies was calculated by multiplying the number of cases for that year by the cost/case of the procedure. The number of procedures is expected to increase in the next three years based on historical data. RAL is expected to capture this market by 65% after consultation with experts. If it’s assumed that RAL will capture the current market in Ontario by 65%, the net impact is expected to be by Year 3, 3.1M for hysterectomy and 6.7M for prostatectomy procedures respectively in the province. RAL has diffused in the province with four surgical systems in place in Ontario, two in Toronto and two in London. RAL is a more expensive technology on a per case basis due to more expensive robot specific instrumentation and physician labour reflected by increased OR time reported in the clinical literature. There is also an upfront cost to acquire the machine and maintenance contract. RAL is expected to capture the market at 65% with project net impacts by Year 3 of 3.1M and 6.7M for hysterectomy and prostatectomy respectively. PMID:23074405
2015-07-06
NUMBER 5b. GRANT NUMBER AFOSR FA9550-12-1-0154 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Shabbir Ahmed and Santanu S. Dey 5d. PROJECT NUMBER 5e. TASK...standard mixed-integer programming (MIP) formulations of selective optimization problems. While such formulations can be attacked by commercial...F33615-86-C-5169. 5b. GRANT NUMBER. Enter all grant numbers as they appear in the report, e.g. AFOSR-82-1234. 5c. PROGRAM ELEMENT NUMBER. Enter
Clinical implementation of stereotaxic brain implant optimization
DOE Office of Scientific and Technical Information (OSTI.GOV)
Rosenow, U.F.; Wojcicka, J.B.
1991-03-01
This optimization method for stereotaxic brain implants is based on seed/strand configurations of the basic type developed for the National Cancer Institute (NCI) atlas of regular brain implants. Irregular target volume shapes are determined from delineation in a stack of contrast enhanced computed tomography scans. The neurosurgeon may then select up to ten directions, or entry points, of surgical approach of which the program finds the optimal one under the criterion of smallest target volume diameter. Target volume cross sections are then reconstructed in 5-mm-spaced planes perpendicular to the implantation direction defined by the entry point and the target volumemore » center. This information is used to define a closed line in an implant cross section along which peripheral seed strands are positioned and which has now an irregular shape. Optimization points are defined opposite peripheral seeds on the target volume surface to which the treatment dose rate is prescribed. Three different optimization algorithms are available: linear least-squares programming, quadratic programming with constraints, and a simplex method. The optimization routine is implemented into a commercial treatment planning system. It generates coordinate and source strength information of the optimized seed configurations for further dose rate distribution calculation with the treatment planning system, and also the coordinate settings for the stereotaxic Brown-Roberts-Wells (BRW) implantation device.« less
Fuzzy multiobjective models for optimal operation of a hydropower system
NASA Astrophysics Data System (ADS)
Teegavarapu, Ramesh S. V.; Ferreira, André R.; Simonovic, Slobodan P.
2013-06-01
Optimal operation models for a hydropower system using new fuzzy multiobjective mathematical programming models are developed and evaluated in this study. The models use (i) mixed integer nonlinear programming (MINLP) with binary variables and (ii) integrate a new turbine unit commitment formulation along with water quality constraints used for evaluation of reservoir downstream impairment. Reardon method used in solution of genetic algorithm optimization problems forms the basis for development of a new fuzzy multiobjective hydropower system optimization model with creation of Reardon type fuzzy membership functions. The models are applied to a real-life hydropower reservoir system in Brazil. Genetic Algorithms (GAs) are used to (i) solve the optimization formulations to avoid computational intractability and combinatorial problems associated with binary variables in unit commitment, (ii) efficiently address Reardon method formulations, and (iii) deal with local optimal solutions obtained from the use of traditional gradient-based solvers. Decision maker's preferences are incorporated within fuzzy mathematical programming formulations to obtain compromise operating rules for a multiobjective reservoir operation problem dominated by conflicting goals of energy production, water quality and conservation releases. Results provide insight into compromise operation rules obtained using the new Reardon fuzzy multiobjective optimization framework and confirm its applicability to a variety of multiobjective water resources problems.
Optimization of Thermal Object Nonlinear Control Systems by Energy Efficiency Criterion.
NASA Astrophysics Data System (ADS)
Velichkin, Vladimir A.; Zavyalov, Vladimir A.
2018-03-01
This article presents the results of thermal object functioning control analysis (heat exchanger, dryer, heat treatment chamber, etc.). The results were used to determine a mathematical model of the generalized thermal control object. The appropriate optimality criterion was chosen to make the control more energy-efficient. The mathematical programming task was formulated based on the chosen optimality criterion, control object mathematical model and technological constraints. The “maximum energy efficiency” criterion helped avoid solving a system of nonlinear differential equations and solve the formulated problem of mathematical programming in an analytical way. It should be noted that in the case under review the search for optimal control and optimal trajectory reduces to solving an algebraic system of equations. In addition, it is shown that the optimal trajectory does not depend on the dynamic characteristics of the control object.
Nonlinear program based optimization of boost and buck-boost converter designs
NASA Astrophysics Data System (ADS)
Rahman, S.; Lee, F. C.
The facility of an Augmented Lagrangian (ALAG) multiplier based nonlinear programming technique is demonstrated for minimum-weight design optimizations of boost and buck-boost power converters. Certain important features of ALAG are presented in the framework of a comprehensive design example for buck-boost power converter design optimization. The study provides refreshing design insight of power converters and presents such information as weight and loss profiles of various semiconductor components and magnetics as a function of the switching frequency.
Optimal inventories for overhaul of repairable redundant systems - A Markov decision model
NASA Technical Reports Server (NTRS)
Schaefer, M. K.
1984-01-01
A Markovian decision model was developed to calculate the optimal inventory of repairable spare parts for an avionics control system for commercial aircraft. Total expected shortage costs, repair costs, and holding costs are minimized for a machine containing a single system of redundant parts. Transition probabilities are calculated for each repair state and repair rate, and optimal spare parts inventory and repair strategies are determined through linear programming. The linear programming solutions are given in a table.
The solution of the optimization problem of small energy complexes using linear programming methods
NASA Astrophysics Data System (ADS)
Ivanin, O. A.; Director, L. B.
2016-11-01
Linear programming methods were used for solving the optimization problem of schemes and operation modes of distributed generation energy complexes. Applicability conditions of simplex method, applied to energy complexes, including installations of renewable energy (solar, wind), diesel-generators and energy storage, considered. The analysis of decomposition algorithms for various schemes of energy complexes was made. The results of optimization calculations for energy complexes, operated autonomously and as a part of distribution grid, are presented.
Optimization of thermal protection systems for the space vehicle. Volume 2: User's manual
NASA Technical Reports Server (NTRS)
1972-01-01
The development of the computational techniques for the design optimization of thermal protection systems for the space shuttle vehicle are discussed. The resulting computer program was then used to perform initial optimization and sensitivity studies on a typical thermal protection system (TPS) to demonstrate its application to the space shuttle TPS design. The program was developed in FORTRAN IV for CDC 6400 computer, but it was subsequently converted to the FORTRAN V language to be used on the Univac 1108.
Optimal partitioning of random programs across two processors
NASA Technical Reports Server (NTRS)
Nicol, D. M.
1986-01-01
The optimal partitioning of random distributed programs is discussed. It is concluded that the optimal partitioning of a homogeneous random program over a homogeneous distributed system either assigns all modules to a single processor, or distributes the modules as evenly as possible among all processors. The analysis rests heavily on the approximation which equates the expected maximum of a set of independent random variables with the set's maximum expectation. The results are strengthened by providing an approximation-free proof of this result for two processors under general conditions on the module execution time distribution. It is also shown that use of this approximation causes two of the previous central results to be false.
Application of Modern Fortran to Spacecraft Trajectory Design and Optimization
NASA Technical Reports Server (NTRS)
Williams, Jacob; Falck, Robert D.; Beekman, Izaak B.
2018-01-01
In this paper, applications of the modern Fortran programming language to the field of spacecraft trajectory optimization and design are examined. Modern object-oriented Fortran has many advantages for scientific programming, although many legacy Fortran aerospace codes have not been upgraded to use the newer standards (or have been rewritten in other languages perceived to be more modern). NASA's Copernicus spacecraft trajectory optimization program, originally a combination of Fortran 77 and Fortran 95, has attempted to keep up with modern standards and makes significant use of the new language features. Various algorithms and methods are presented from trajectory tools such as Copernicus, as well as modern Fortran open source libraries and other projects.
NASA Technical Reports Server (NTRS)
Brauer, G. L.; Habeger, A. R.; Stevenson, R.
1974-01-01
The basic equations and models used in a computer program (6D POST) to optimize simulated trajectories with six degrees of freedom were documented. The 6D POST program was conceived as a direct extension of the program POST, which dealt with point masses, and considers the general motion of a rigid body with six degrees of freedom. It may be used to solve a wide variety of atmospheric flight mechanics and orbital transfer problems for powered or unpowered vehicles operating near a rotating oblate planet. Its principal features are: an easy to use NAMELIST type input procedure, an integrated set of Flight Control System (FCS) modules, and a general-purpose discrete parameter targeting and optimization capability. It was written in FORTRAN 4 for the CDC 6000 series computers.
DEGAS: Dynamic Exascale Global Address Space Programming Environments
DOE Office of Scientific and Technical Information (OSTI.GOV)
Demmel, James
The Dynamic, Exascale Global Address Space programming environment (DEGAS) project will develop the next generation of programming models and runtime systems to meet the challenges of Exascale computing. The Berkeley part of the project concentrated on communication-optimal code generation to optimize speed and energy efficiency by reducing data movement. Our work developed communication lower bounds, and/or communication avoiding algorithms (that either meet the lower bound, or do much less communication than their conventional counterparts) for a variety of algorithms, including linear algebra, machine learning and genomics. The Berkeley part of the project concentrated on communication-optimal code generation to optimize speedmore » and energy efficiency by reducing data movement. Our work developed communication lower bounds, and/or communication avoiding algorithms (that either meet the lower bound, or do much less communication than their conventional counterparts) for a variety of algorithms, including linear algebra, machine learning and genomics.« less
Enhanced index tracking modeling in portfolio optimization with mixed-integer programming z approach
NASA Astrophysics Data System (ADS)
Siew, Lam Weng; Jaaman, Saiful Hafizah Hj.; Ismail, Hamizun bin
2014-09-01
Enhanced index tracking is a popular form of portfolio management in stock market investment. Enhanced index tracking aims to construct an optimal portfolio to generate excess return over the return achieved by the stock market index without purchasing all of the stocks that make up the index. The objective of this paper is to construct an optimal portfolio using mixed-integer programming model which adopts regression approach in order to generate higher portfolio mean return than stock market index return. In this study, the data consists of 24 component stocks in Malaysia market index which is FTSE Bursa Malaysia Kuala Lumpur Composite Index from January 2010 until December 2012. The results of this study show that the optimal portfolio of mixed-integer programming model is able to generate higher mean return than FTSE Bursa Malaysia Kuala Lumpur Composite Index return with only selecting 30% out of the total stock market index components.
Accurate multiple sequence-structure alignment of RNA sequences using combinatorial optimization.
Bauer, Markus; Klau, Gunnar W; Reinert, Knut
2007-07-27
The discovery of functional non-coding RNA sequences has led to an increasing interest in algorithms related to RNA analysis. Traditional sequence alignment algorithms, however, fail at computing reliable alignments of low-homology RNA sequences. The spatial conformation of RNA sequences largely determines their function, and therefore RNA alignment algorithms have to take structural information into account. We present a graph-based representation for sequence-structure alignments, which we model as an integer linear program (ILP). We sketch how we compute an optimal or near-optimal solution to the ILP using methods from combinatorial optimization, and present results on a recently published benchmark set for RNA alignments. The implementation of our algorithm yields better alignments in terms of two published scores than the other programs that we tested: This is especially the case with an increasing number of input sequences. Our program LARA is freely available for academic purposes from http://www.planet-lisa.net.