KEEL for Mission Planning

DTIC Science & Technology

2016-10-06

Copyright 2016, Compsim, All Rights Reserved 1 KEEL® Technology in support of Mission Planning and Execution delivering Adaptive...Executing, and Auditing ) This paper focuses on the decision-making component (#2) with the use of Knowledge Enhanced Electronic logic (KEEL) Technology ...Copyright 2016, Compsim, All Rights Reserved 2 • Eliminate “coding errors” (auto-generated code) • 100% explainable and auditable

Quantitative Analysis of Global Proteome and Lysine Acetylome Reveal the Differential Impacts of VPA and SAHA on HL60 Cells.

PubMed

Zhu, Xiaoyu; Liu, Xin; Cheng, Zhongyi; Zhu, Jun; Xu, Lei; Wang, Fengsong; Qi, Wulin; Yan, Jiawei; Liu, Ning; Sun, Zimin; Liu, Huilan; Peng, Xiaojun; Hao, Yingchan; Zheng, Nan; Wu, Quan

2016-01-29

Valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) are both HDAC inhibitors (HDACi). Previous studies indicated that both inhibitors show therapeutic effects on acute myeloid leukaemia (AML), while the differential impacts of the two different HDACi on AML treatment still remains elusive. In this study, using 3-plex SILAC based quantitative proteomics technique, anti-acetyllysine antibody based affinity enrichment, high resolution LC-MS/MS and intensive bioinformatic analysis, the quantitative proteome and acetylome in SAHA and VPA treated AML HL60 cells were extensively studied. In total, 5,775 proteins and 1,124 lysine acetylation sites were successfully obtained in response to VAP and SAHA treatment. It is found that VPA and SAHA treatment differently induced proteome and acetylome profiling in AML HL60 cells. This study revealed the differential impacts of VPA and SAHA on proteome/acetylome in AML cells, deepening our understanding of HDAC inhibitor mediated AML therapeutics.

SAHA and S116836, a novel tyrosine kinase inhibitor, synergistically induce apoptosis in imatinib-resistant chronic myelogenous leukemia cells

PubMed Central

Bu, Qiangui; Cui, Lijing; Li, Juan; Du, Xin; Zou, Waiyi; Ding, Ke; Pan, Jingxuan

2014-01-01

Limited treatment options are available for chronic myelogenous leukemia (CML) patients who develop imatinib mesylate (IM) resistance. Here we proposed a novel combination regimen, a co-administration of S116836, a novel small molecule multi-targeted tyrosine kinase inhibitor that was synthesized by rational design, and histone deacetylases inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA), to overcome IM resistance in CML. S116836 at low concentrations used in the present study mildly downregulates auto-tyrosine phosphorylation of Bcr-Abl. SAHA, an FDA-approved HDACi drug, at 1 μM has modest anti-tumor activity in treating CML. However, we found a synergistic interaction between SAHA and S116836 in Bcr-Abl-positive CML cells that were sensitive or resistant to IM. Exposure of KBM5 and KBM5-T315I cells to minimal or non-toxic concentrations of SAHA and S116836 synergistically reduced cell viability and induced cell death. Co-treatment with SAHA and S116838 repressed the expressions of anti-apoptosis proteins, such as Mcl-1 and XIAP, but promoted Bim expression and mitochondrial damage. Of importance, treatment with both drugs significantly reduced cell viability of primary human CML cells, as compared with either agent alone. Taken together, our findings suggest that SAHA exerts synergistically with S116836 at a non-toxic concentration to promote apoptosis in the CML, including those resistant to imatinib or dasatinib. PMID:24759597

46 CFR 128.420 - Keel cooler installations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ENGINEERING: EQUIPMENT AND SYSTEMS Design Requirements for Specific Systems § 128.420 Keel cooler...-metallic hose-clamps may be used at machinery connections if— (1) The clamps are of a corrosion-resistant...

Design, Synthesis and Biological Evaluation of Histone Deacetylase (HDAC) Inhibitors: Saha (Vorinostat) Analogs and Biaryl Indolyl Benzamide Inhibitors Display Isoform Selectivity

NASA Astrophysics Data System (ADS)

Negmeldin, Ahmed Thabet

HDAC proteins have emerged as interesting targets for anti-cancer drugs due to their involvement in cancers, as well as several other diseases. Several HDAC inhibitors have been approved by the FDA as anti-cancer drugs, including SAHA (suberoylanilide hydroxamic acid, Vorinostat). Unfortunately, SAHA inhibits most HDAC isoforms, which limit its use as a pharmacological tool and may lead to side effects in the clinic. In this work we were interested in developing isoform selective HDAC inhibitors, which may decrease or eliminate the side effects associated with non-selective inhibitors treatment. In addition, isoform selective HDAC inhibitors can be used as biological tools to help understand the HDAC-related cancer biology. Our strategy was based on synthesis and screening of several derivatives of the non-selective FDA approved drug SAHA substituted at different positions of the linker region. Several SAHA analogs modified at the C4 and C5 positions of the linker were synthesized. The new C4- and C5-modified SAHA libraries, along with the previously synthesized C2-modified SAHA analogs were screened in vitro and in cellulo for HDAC isoform selectivity. Interestingly, several analogs exhibited dual HDAC6/HDAC8 selectivity. Enantioselective syntheses of the pure enantiomers of some of the interesting analogs were performed and the enantiomers were screened in vitro. Among the most interesting analogs, ( R)-C4-benzyl SAHA displayed 520- to 1300-fold selectivity for HDAC6 and HDAC8 over HDAC1, 2, and 3, with IC50 values of 48 and 27 nM with HDAC6 and 8, respectively. Docking studies were performed to provide structural rationale for the observed selectivity of the new analogs. In addition, rational design, synthesis, and screening of several other biaryl indolyl benzamide HDAC inhibitors is discussed, and some showed modest HDAC1 selectivity. The new biaryl indolyl benzamides can be useful to further develop HDAC1 selective inhibitors. The dual HDAC6/8 selective

Global cost and weight evaluation of fuselage keel design concepts

NASA Technical Reports Server (NTRS)

Flynn, B. W.; Morris, M. R.; Metschan, S. L.; Swanson, G. D.; Smith, P. J.; Griess, K. H.; Schramm, M. R.; Humphrey, R. J.

1993-01-01

The Boeing program entitled Advanced Technology Composite Aircraft Structure (ATCAS) is focused on the application of affordable composite technology to pressurized fuselage structure of future aircraft. As part of this effort, a design study was conducted on the keel section of the aft fuselage. A design build team (DBT) approach was used to identify and evaluate several design concepts which incorporated different material systems, fabrication processes, structural configurations, and subassembly details. The design concepts were developed in sufficient detail to accurately assess their potential for cost and weight savings as compared with a metal baseline representing current wide body technology. The cost and weight results, along with an appraisal of performance and producibility risks, are used to identify a globally optimized keel design; one which offers the most promising cost and weight advantages over metal construction. Lastly, an assessment is given of the potential for further cost and weight reductions of the selected keel design during local optimization.

Combinatorial Study of a Novel Poly (ADP-ribose) Polymerase Inhibitor and an HDAC Inhibitor, SAHA, in Leukemic Cell Lines.

PubMed

Hegde, Mahesh; Mantelingu, Kempegowda; Pandey, Monica; Pavankumar, Chottanahalli S; Rangappa, Kanchugarakoppal S; Raghavan, Sathees C

2016-10-01

Cancer is a multifactorial disease, which makes it difficult to cure. Since more than one defective cellular component is often involved during oncogenesis, combination therapy is gaining prominence in the field of cancer therapeutics. The purpose of this study was to investigate the combinatorial effects of a novel PARP inhibitor, P10, and HDAC inhibitor, SAHA, in leukemic cells. Combinatorial effects of P10 and SAHA were tested using propidium iodide staining in different leukemic cells. Further, flowcytometry-based assays such as calcein-AM/ethidium homodimer staining, annexin-FITC/PI staining, and JC-1 staining were carried out to elucidate the mechanism of cell death. In addition, cell-cycle analysis, immunocytochemistry studies, and western blotting analysis were conducted to check the combinatorial effect in Nalm6 cells. Propidium iodide staining showed that P10 in combination with SAHA induced cell death in Nalm6 cells, in which PARP expression and activity is high with a combination index of <0.2. Annexin-FITC/PI staining, JC-1 staining, and other biochemical assays revealed that P10 in combination with SAHA induced apoptosis by causing a change in mitochondrial membrane potential in >65 % cells. Importantly, combinatorial treatment induced S phase arrest in 40-45 % cells due to DNA damage and plausible replicative stress. Finally, we demonstrated that treatment with P10 led to DNA strand breaks, which were further potentiated by SAHA (p < 0.01), leading to activation of apoptosis and increased cell death in PARP-positive leukemic cells. Our study reveals that coadministration of PARP inhibitor with SAHA could be used as a combination therapy against leukemic cells that possess high levels of intrinsic PARP activity.

Behavioral Differences of Laying Hens with Fractured Keel Bones within Furnished Cages

PubMed Central

Casey-Trott, Teresa M.; Widowski, Tina M.

2016-01-01

High prevalence of keel bone fractures in laying hens is reported in all housing systems. Keel fractures have been associated with pain and restricted mobility in hens in loose housing. The objective was to determine whether keel fractures were associated with activity of hens in furnished cages. Thirty-six pairs of LSL-Lite hens (72 weeks) were enrolled in the study. One hen with a fractured keel and one hen without were identified by palpation in each of 36 groups of hens housed in either 30- or 60-bird cages stocked at 750 cm2/hen. Behavioral activity of each hen was recorded by four observers blind to keel status using focal animal sampling for 10 min within a 2-h period in the morning (08:00–10:00), afternoon (12:00–14:00), and evening (17:00–19:00). All hens were observed during each of the three sample periods for 3 days totaling 90 min, and individual hen data were summed for analysis. Hens were euthanized 48 h after final observations, dissected, and classified by keel status: F0 (no fracture, N = 24), F1 (single fracture, N = 17), and F2 (multiple fractures, N = 31). The percentages of time hens performed each behavior were analyzed using a mixed procedure in SAS with fracture severity, body weight, cage size, rearing environment, and tier in the model. Fracture severity affected the duration of perching (P = 0.04) and standing (P = 0.001), bout length of standing (P < 0.0001), and location (floor vs. perch) of resting behaviors (P = 0.01). F2 hens perched longer than F0 hens, 20.0 ± 2.9 and 11.6 ± 3.2%. F2 hens spent less time standing, 15.2 ± 1.5%, than F0 and F1 hens, 20.7 ± 1.6 and 21.6 ± 1.8%. F2 hens had shorter standing bouts (22.0 ± 4.2 s) than both F0 and F1 hens, 33.1 ± 4.3 and 27.4 ± 4.4 s. Non-fractured hens spent 80.0 ± 6.9% of total resting time on the floor, whereas F1 and F2 hens spent 56.9 ± 12.4 and 51.5 ± 7.7% resting on the floor

Effect of anesthesia, positioning, time, and feeding on the proventriculus: keel ratio of clinically healthy parrots.

PubMed

Dennison, Sophie E; Paul-Murphy, Joanne R; Yandell, Brian S; Adams, William M

2010-01-01

Healthy, adult Hispaniolan Amazon parrots (Amazona ventralis) were imaged on three occasions to determine the effects of anesthesia, patient rotation, feeding, and short/long-term temporal factors on the proventriculus:keel ratio. Increasing rotation up to 15 degrees from right lateral resulted in increased inability to measure the proventriculus in up to 44% of birds, meaning that the proventriculus:keel ratio could not be calculated from those radiographs. There was a significant difference between the proventriculus:keel ratio for individual parrots when quantified 3 weeks apart. Despite this difference, all ratios remained within normal limits. No significant effect was identified due to anesthesia, feeding, fasting, or repeated imaging through an 8-h period. Interobserver agreement for measurability and correlation for the proventriculus:keel ratio values was high. It is recommended that the proventriculus:keel ratio be calculated from anesthetized parrots to attain images in true lateral recumbency. Ratio fluctuations within the normal range between radiographs obtained on different dates may be observed in normal parrots.

Susceptibility to keel bone fractures in laying hens and the role of genetic variation.

PubMed

Candelotto, Laura; Stratmann, Ariane; Gebhardt-Henrich, Sabine G; Rufener, Christina; van de Braak, Teun; Toscano, Michael J

2017-10-01

Keel bone fractures are a well-known welfare problem in modern commercial laying hen systems. The present study sought to identify genetic variation in relation to keel bone fracture susceptibility of 4 distinct crossbred and one pure line, and by extension, possible breeding traits. Susceptibility to fractures were assessed using an ex vivo impact testing protocol in combination with a study design that minimized environmental variation to focus on genetic differences. The 5 crossbred/pure lines differed in their susceptibility to keel bone fractures with the greatest likelihood of fracture in one of the 3 commercial lines and the lowest susceptibility to fractures in one of the experimental lines. Egg production at the hen-level did not differ between the crossbred/pure lines (P > 0.05), though an increased susceptibility to keel bone fractures was associated with thinner eggshells and reduced egg breaking strength, a pattern consistent among all tested crossbred/pure lines. Our findings suggest an association between egg quality and bone strength which appeared to be independent of crossbred/pure line. The findings indicate the benefit of the impact methodology to identify potential breeding characteristics to reduce incidence of keel fracture as well as the potential relationship with eggshell quality. © 2017 Poultry Science Association Inc.

46 CFR 169.607 - Keel cooler installations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Machinery and Electrical Internal Combustion Engine Installations § 169.607 Keel cooler installations. (a... vessel. (d) Short lengths of approved nonmetallic flexible hose may be used at machinery connections... do not depend on spring tension for their holding power; and (3) Two clamps are used on each end of...

46 CFR 169.607 - Keel cooler installations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Machinery and Electrical Internal Combustion Engine Installations § 169.607 Keel cooler installations. (a... vessel. (d) Short lengths of approved nonmetallic flexible hose may be used at machinery connections... do not depend on spring tension for their holding power; and (3) Two clamps are used on each end of...

46 CFR 169.607 - Keel cooler installations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Machinery and Electrical Internal Combustion Engine Installations § 169.607 Keel cooler installations. (a... vessel. (d) Short lengths of approved nonmetallic flexible hose may be used at machinery connections... do not depend on spring tension for their holding power; and (3) Two clamps are used on each end of...

46 CFR 169.607 - Keel cooler installations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Machinery and Electrical Internal Combustion Engine Installations § 169.607 Keel cooler installations. (a... vessel. (d) Short lengths of approved nonmetallic flexible hose may be used at machinery connections... do not depend on spring tension for their holding power; and (3) Two clamps are used on each end of...

46 CFR 169.607 - Keel cooler installations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Machinery and Electrical Internal Combustion Engine Installations § 169.607 Keel cooler installations. (a... vessel. (d) Short lengths of approved nonmetallic flexible hose may be used at machinery connections... do not depend on spring tension for their holding power; and (3) Two clamps are used on each end of...

HDACi Valproic Acid (VPA) and Suberoylanilide Hydroxamic Acid (SAHA) Delay but Fail to Protect against Warm Hepatic Ischemia-Reperfusion Injury.

PubMed

Ruess, Dietrich A; Probst, Moriz; Marjanovic, Goran; Wittel, Uwe A; Hopt, Ulrich T; Keck, Tobias; Bausch, Dirk

2016-01-01

Histone deacetylases (HDAC) catalyze N-terminal deacetylation of lysine-residues on histones and multiple nuclear and cytoplasmic proteins. In various animal models, such as trauma/hemorrhagic shock, ischemic stroke or myocardial infarction, HDAC inhibitor (HDACi) application is cyto- and organoprotective and promotes survival. HDACi reduce stress signaling, cell death and inflammation. Hepatic ischemia-reperfusion (I/R) injury during major liver resection or transplantation increases morbidity and mortality. Assuming protective properties, the aim of this study was to investigate the effect of the HDACi VPA and SAHA on warm hepatic I/R. Male Wistar-Kyoto rats (age: 6-8 weeks) were randomized to VPA, SAHA, vehicle control (pre-) treatment or sham-groups and underwent partial no-flow liver ischemia for 90 minutes with subsequent reperfusion for 6, 12, 24 and 60 hours. Injury and regeneration was quantified by serum AST and ALT levels, by macroscopic aspect and (immuno-) histology. HDACi treatment efficiency, impact on MAPK/SAPK-activation and Hippo-YAP signaling was determined by Western blot. Treatment with HDACi significantly enhanced hyperacetylation of Histone H3-K9 during I/R, indicative of adequate treatment efficiency. Liver injury, as measured by macroscopic aspect, serum transaminases and histology, was delayed, but not alleviated in VPA and SAHA treated animals. Importantly, tissue destruction was significantly more pronounced with VPA. SAPK-activation (p38 and JNK) was reduced by VPA and SAHA in the early (6h) reperfusion phase, but augmented later on (JNK, 24h). Regeneration appeared enhanced in SAHA and VPA treated animals and was dependent on Hippo-YAP signaling. VPA and SAHA delay warm hepatic I/R injury at least in part through modulation of SAPK-activation. However, these HDACi fail to exert organoprotective effects, in this setting. For VPA, belated damage is even aggravated.

The HDAC inhibitor SAHA regulates CBX2 stability via a SUMO-triggered ubiquitin-mediated pathway in leukemia.

PubMed

Di Costanzo, Antonella; Del Gaudio, Nunzio; Conte, Lidio; Dell'Aversana, Carmela; Vermeulen, Michiel; de Thé, Hugues; Migliaccio, Antimo; Nebbioso, Angela; Altucci, Lucia

2018-05-01

Polycomb group (PcG) proteins regulate transcription, playing a key role in stemness and differentiation. Deregulation of PcG members is known to be involved in cancer pathogenesis. Emerging evidence suggests that CBX2, a member of the PcG protein family, is overexpressed in several human tumors, correlating with lower overall survival. Unraveling the mechanisms regulating CBX2 expression may thus provide a promising new target for anticancer strategies. Here we show that the HDAC inhibitor SAHA regulates CBX2 stability via a SUMO-triggered ubiquitin-mediated pathway in leukemia. We identify CBX4 and RNF4 as the E3 SUMO and E3 ubiquitin ligase, respectively, and describe the specific molecular mechanism regulating CBX2 protein stability. Finally, we show that CBX2-depleted leukemic cells display impaired proliferation, underscoring its critical role in regulating leukemia cell tumorogenicity. Our results show that SAHA affects CBX2 stability, revealing a potential SAHA-mediated anti-leukemic activity though SUMO2/3 pathway.

Limited Associations between Keel Bone Damage and Bone Properties Measured with Computer Tomography, Three-Point Bending Test, and Analysis of Minerals in Swiss Laying Hens

PubMed Central

Gebhardt-Henrich, Sabine G.; Pfulg, Andreas; Fröhlich, Ernst K. F.; Käppeli, Susanna; Guggisberg, Dominik; Liesegang, Annette; Stoffel, Michael H.

2017-01-01

Keel bone damage is a wide-spread welfare problem in laying hens. It is unclear so far whether bone quality relates to keel bone damage. The goal of the present study was to detect possible associations between keel bone damage and bone properties of intact and damaged keel bones and of tibias in end-of-lay hens raised in loose housing systems. Bones were palpated and examined by peripheral quantitative computer tomography (PQCT), a three-point bending test, and analyses of bone ash. Contrary to our expectations, PQCT revealed higher cortical and trabecular contents in fractured than in intact keel bones. This might be due to structural bone repair after fractures. Density measurements of cortical and trabecular tissues of keel bones did not differ between individuals with and without fractures. In the three-point bending test of the tibias, ultimate shear strength was significantly higher in birds with intact vs. fractured keel bones. Likewise, birds with intact or slightly deviated keel bones had higher mineral and calcium contents of the keel bone than birds with fractured keel bones. Calcium content in keel bones was correlated with calcium content in tibias. Although there were some associations between bone traits related to bone strength and keel bone damage, other factors such as stochastic events related to housing such as falls and collisions seem to be at least as important for the prevalence of keel bone damage. PMID:28848740

A modified technique to reduce tibial keel cutting errors during an Oxford unicompartmental knee arthroplasty.

PubMed

Inui, Hiroshi; Taketomi, Shuji; Tahara, Keitarou; Yamagami, Ryota; Sanada, Takaki; Tanaka, Sakae

2017-03-01

Bone cutting errors can cause malalignment of unicompartmental knee arthroplasties (UKA). Although the extent of tibial malalignment due to horizontal cutting errors has been well reported, there is a lack of studies evaluating malalignment as a consequence of keel cutting errors, particularly in the Oxford UKA. The purpose of this study was to examine keel cutting errors during Oxford UKA placement using a navigation system and to clarify whether two different tibial keel cutting techniques would have different error rates. The alignment of the tibial cut surface after a horizontal osteotomy and the surface of the tibial trial component was measured with a navigation system. Cutting error was defined as the angular difference between these measurements. The following two techniques were used: the standard "pushing" technique in 83 patients (group P) and a modified "dolphin" technique in 41 patients (group D). In all 123 patients studied, the mean absolute keel cutting error was 1.7° and 1.4° in the coronal and sagittal planes, respectively. In group P, there were 22 outlier patients (27 %) in the coronal plane and 13 (16 %) in the sagittal plane. Group D had three outlier patients (8 %) in the coronal plane and none (0 %) in the sagittal plane. Significant differences were observed in the outlier ratio of these techniques in both the sagittal (P = 0.014) and coronal (P = 0.008) planes. Our study demonstrated overall keel cutting errors of 1.7° in the coronal plane and 1.4° in the sagittal plane. The "dolphin" technique was found to significantly reduce keel cutting errors on the tibial side. This technique will be useful for accurate component positioning and therefore improve the longevity of Oxford UKAs. Retrospective comparative study, Level III.

Use of the Keele injector for sample introduction for gas chromatographic analysis of vinclozolin in lettuces.

PubMed

Shim, J H; Lee, Y S; Kim, M R; Lee, C J; Kim, I S

2003-10-10

We examined a Keele injector for sample introduction for gas chromatographic analysis of vinclozolin treated in lettuces. Samples in milligram quantity were introduced into a glass tube in a Keele injector at a gas chromatograph injection port. The glass tube was then crushed to allow the sample to carry onto a capillary column in a normal manner. The standard calibration curve for quantitative detection of vinclozolin was obtained by determining vinclozolin spiked in samples at variable concentrations. The calibration curve showed a linear response to vinclozolin ranging from 0.05 to 1.0 microg/g, giving a slope value of 174.8, the y-intercept value of -2.8146 and the mean r2-value of 0.9994. Limit of quantification for vinclozolin was 0.05 microg/g by this method, comparable to 0.01 microg/g by a normal injector. When samples treated previously with vinclozolin were determined by the Keele injector, vinclozolin was found to be about 30% lower as compared to a normal method, suggesting about 70% recovery of the spiked vinclozolin by the Keele injector. From these results, the Keele injector was suggested to be potential for sample introduction in gas chromatographic analysis of vinclozolin in lettuce samples.

Anisotropic tomography of the Indian continent and the geodynamic role of its keel

NASA Astrophysics Data System (ADS)

Montagner, J. P.; Maurya, S.; Sibrant, A.; Davaille, A.; Stutzmann, E.; Kumar, R.; Jean, B.

2017-12-01

The Indian moved at an exceptional high rate (18-20cm/year) after the birth of La Réunion hotspot, ≈65Ma ago and the Deccan volcanic province before the collision with the Asian continent. Other older plumes Marion, Kerguelen located in the Indian ocean are also associated with very fast plate motion. We present a high-resolution 3D anisotropic model of the Indian plate region down to 300 km depth, obtained by inverting a new massive database of surface-wave observations. The Rayleigh and Love wave dispersion measurements along 14,000 paths are made in a broad frequency range (16-250s). Our estimates of the depth to the Lithosphere-Asthenosphere Boundary (LAB) derived from seismic velocity Vsv variations at depth reveal large variations (120-250 km) beneath the different cratonic blocks. A low velocity layer associated with the Mid-lithospheric discontinuity is present when the root of the lithosphere is deep. This extensive anisotropic tomographic investigation of the Indian continent displays an almost north-south keel, 600km long and 300km wide, down to 250km depth. The keel is characterized by fast velocities, smaller than average radial and azimuthal anisotropies. The distribution of azimuthal anisotropy defines the flow lines around the keel, and, at the LAB, coincides with the APM direction of the Indian plate. The fast axis azimuths at 250 km depth are also in accordance with the results from SK(K)S splitting. Such a keel could probably perturb plume-induced flow in the asthenosphere. To determine the influence of such a keel on the interaction of India with several mantle plumes (Marion, Crozet, Kerguelen, La Réunion), we used laboratory experiments. Some preliminary results will be presented on the comparison between the laboratory flowlines and the direction of seismic anisotropy.

Design and analysis of a keel latch for use on the Hubble Space Telescope

NASA Technical Reports Server (NTRS)

Calvert, John; Stinson, Melanie

1986-01-01

The mechanical design of the keel latch is discussed, as well as the stress analysis of the keel latch. Background information; mechanical design requirements; some of the initial design considerations; the design considerations that led to the selection of the final design; the mechanics of the final design; testing that has been and will be accomplished to verify that design requirements have been met; and future tests are discussed.

Slow reception and under-citedness in climate change research: A case study of Charles David Keeling, discoverer of the risk of global warming.

PubMed

Marx, Werner; Haunschild, Robin; French, Bernie; Bornmann, Lutz

2017-01-01

The Keeling curve has become a chemical landmark, whereas the papers by Charles David Keeling about the underlying carbon dioxide measurements are not cited as often as can be expected against the backdrop of his final approval. In this bibliometric study, we analyze Keeling's papers as a case study for under-citedness of climate change publications. Three possible reasons for the under-citedness of Keeling's papers are discussed: (1) The discourse on global cooling at the starting time of Keeling's measurement program, (2) the underestimation of what is often seen as "routine science", and (3) the amount of implicit/informal citations at the expense of explicit/formal (reference-based) citations. Those reasons may have contributed more or less to the slow reception and the under-citedness of Keeling's seminal works.

Ovarian SAHA syndrome is associated with a more insulin-resistant profile and represents an independent risk factor for glucose abnormalities in women with polycystic ovary syndrome: a prospective controlled study.

PubMed

Dalamaga, Maria; Papadavid, Evangelia; Basios, Georgios; Vaggopoulos, Vassilios; Rigopoulos, Dimitrios; Kassanos, Dimitrios; Trakakis, Eftihios

2013-12-01

SAHA syndrome is characterized by the tetrad: seborrhea, acne, hirsutism, and androgenetic alopecia. No previous study has examined the prevalence of glucose abnormalities in ovarian SAHA and explored whether it may be an independent risk factor for glucose abnormalities. In a prospective controlled study, we investigated the spectrum of glucose abnormalities in ovarian SAHA and explored whether it is associated with a more insulin-resistant profile. In all, 316 patients with a diagnosis of polycystic ovary syndrome (PCOS) (56 with SAHA) and 102 age-matched healthy women were examined and underwent a 2-hour oral glucose tolerance test. Serum glucose homeostasis parameters, hormones, and adipokines were determined. SAHA prevalence was 17.7% in patients with PCOS and predominance of the severe PCOS phenotype. Ovarian SAHA was independently associated with a more insulin-resistant profile (higher homeostatic model assessment of insulin resistance score, lower quantitative insulin sensitivity check index [QUICKI] and MATSUDA indices, and relative hypoadiponectinemia), and represented an independent risk factor for glucose abnormalities regardless of anthropometric features, age, and PCOS phenotype. There was no performance of skin biopsies. The prompt recognition of SAHA syndrome in women with PCOS permits an earlier diagnosis and surveillance of metabolic abnormalities, especially in Mediterranean PCOS population exhibiting a lower prevalence of glucose abnormalities. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Web thickness determines the therapeutic effect of endoscopic keel placement on anterior glottic web.

PubMed

Chen, Jian; Shi, Fang; Chen, Min; Yang, Yue; Cheng, Lei; Wu, Haitao

2017-10-01

This work is a retrospective analysis to investigate the critical risk factor for the therapeutic effect of endoscopic keel placement on anterior glottic web. Altogether, 36 patients with anterior glottic web undergoing endoscopic lysis and silicone keel placement were enrolled. Their voice qualities were evaluated using the voice handicap index-10 (VHI-10) questionnaire, and improved significantly 3 months after surgery (21.53 ± 3.89 vs 9.81 ± 6.68, P < 0.0001). However, 10 (27.8%) cases had web recurrence during the at least 1-year follow-up. Therefore, patients were classified according to the Cohen classification or web thickness, and the recurrence rates were compared. The distribution of recurrence rates for Cohen type 1 ~ 4 were 28.6, 16.7, 33.3, and 40%, respectively. The difference was not statistically significant (P = 0.461). When classified by web thickness, only 2 of 27 (7.41%) thin type cases relapsed whereas 8 of 9 (88.9%) cases in the thick group reformed webs (P < 0.001). These results suggest that the therapeutic outcome of endoscopic keel placement mostly depends on the web thickness rather than the Cohen grades. Endoscopic lysis and keel placement is only effective for cases with thin glottic webs. Patients with thick webs should be treated by other means.

Iceberg and ice-keel ploughmarks on the Gdansk-Gotland Sill (south-eastern Baltic Sea)

NASA Astrophysics Data System (ADS)

Dorokhov, D. V.; Dorokhova, E. V.; Sivkov, V. V.

2018-02-01

New interpretation of the undulating moraine relief of the Gdansk-Gotland Sill, Baltic Sea is proposed. Relict iceberg and ice-keel ploughmarks were observed based on the integration of recently acquired side-scan sonar, multi-beam, single-beam and lithological data. The most likely time of their formation is the period of fast Scandinavian sheet retreat occurring from approximately 13.2 to 11.7 ka. Weak erosional-accumulative processes on the sill from 11.7 ka until the present favoured preservation of the iceberg ploughmarks. The predominant directions of the ploughmarks (north-south and northwest-southeast) coincide with the major iceberg (ice) drift direction from the Scandinavian ice sheet. Furrow width varies from 1 to 300 m with a main width of 20-60 m in a depth range of 1 to 10 m (mostly 2-4 m depth). The ploughmarks are flanked by side ridges 0.5-2 m high, and there is a push mound at the end of some furrows. Three types of cross-sectional furrow profiles have been distinguished: V-shaped cross-section profiles would have been formed by a peaked iceberg keel, U-shaped profiles by a flat keel, and W-shaped profiles by double-keel icebergs (ice ridges). The wide local depressions at the end of ploughmarks could have been formed during periods of fast falling of the Baltic Ice Lake water level, when the ice ridges (stamukhi) or icebergs could ground into the seafloor.

Effect of Suberoylanilide Hydroxamic Acid (SAHA) Administration on the Residual Virus Pool in a Model of Combination Antiretroviral Therapy-Mediated Suppression in SIVmac239-Infected Indian Rhesus Macaques

PubMed Central

Del Prete, Gregory Q.; Shoemaker, Rebecca; Oswald, Kelli; Lara, Abigail; Trubey, Charles M.; Fast, Randy; Schneider, Douglas K.; Kiser, Rebecca; Coalter, Vicky; Wiles, Adam; Wiles, Rodney; Freemire, Brandi; Keele, Brandon F.; Estes, Jacob D.; Quiñones, Octavio A.; Smedley, Jeremy; Macallister, Rhonda; Sanchez, Rosa I.; Wai, John S.; Tan, Christopher M.; Alvord, W. Gregory; Hazuda, Daria J.; Piatak, Michael

2014-01-01

Nonhuman primate models are needed for evaluations of proposed strategies targeting residual virus that persists in HIV-1-infected individuals receiving suppressive combination antiretroviral therapy (cART). However, relevant nonhuman primate (NHP) models of cART-mediated suppression have proven challenging to develop. We used a novel three-class, six-drug cART regimen to achieve durable 4.0- to 5.5-log reductions in plasma viremia levels and declines in cell-associated viral RNA and DNA in blood and tissues of simian immunodeficiency virus SIVmac239-infected Indian-origin rhesus macaques, then evaluated the impact of treatment with the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA; Vorinostat) on the residual virus pool. Ex vivo SAHA treatment of CD4+ T cells obtained from cART-suppressed animals increased histone acetylation and viral RNA levels in culture supernatants. cART-suppressed animals each received 84 total doses of oral SAHA. We observed SAHA dose-dependent increases in acetylated histones with evidence for sustained modulation as well as refractoriness following prolonged administration. In vivo virologic activity was demonstrated based on the ratio of viral RNA to viral DNA in peripheral blood mononuclear cells, a presumptive measure of viral transcription, which significantly increased in SAHA-treated animals. However, residual virus was readily detected at the end of treatment, suggesting that SAHA alone may be insufficient for viral eradication in the setting of suppressive cART. The effects observed were similar to emerging data for repeat-dose SAHA treatment of HIV-infected individuals on cART, demonstrating the feasibility, utility, and relevance of NHP models of cART-mediated suppression for in vivo assessments of AIDS virus functional cure/eradication approaches. PMID:25182644

Dual-keel electrodynamic maglev system

DOEpatents

He, Jianliang; Wang, Zian; Rote, Donald M.; Coffey, Howard T.; Hull, John R.; Mulcahy, Thomas M.; Cal, Yigang

1996-01-01

A propulsion and stabilization system with a plurality of superconducting magnetic devices affixed to the dual-keels of a vehicle, where the superconducting magnetic devices produce a magnetic field when energized. The system also includes a plurality of figure-eight shaped null-flux coils affixed to opposing vertical sides of slots in a guideway. The figure-eight shaped null-flux coils are vertically oriented, laterally cross-connected in parallel, longitudinally connected in series, and continue the length of the vertical slots providing levitation and guidance force. An external power source energizes the figure-eight shaped null-flux coils to create a magnetic traveling wave that interacts with the magnetic field produced by the superconducting magnets to impart motion to the vehicle.

Dual-keel electrodynamic maglev system

DOEpatents

He, J.L.; Wang, Z.; Rote, D.M.; Coffey, H.T.; Hull, J.R.; Mulcahy, T.M.; Cal, Y.

1996-12-24

A propulsion and stabilization system is disclosed with a plurality of superconducting magnetic devices affixed to the dual-keels of a vehicle, where the superconducting magnetic devices produce a magnetic field when energized. The system also includes a plurality of figure-eight shaped null-flux coils affixed to opposing vertical sides of slots in a guideway. The figure-eight shaped null-flux coils are vertically oriented, laterally cross-connected in parallel, longitudinally connected in series, and continue the length of the vertical slots providing levitation and guidance force. An external power source energizes the figure-eight shaped null-flux coils to create a magnetic traveling wave that interacts with the magnetic field produced by the superconducting magnets to impart motion to the vehicle. 6 figs.

Kinetic and Thermodynamic Rationale for SAHA Being a Preferential Human HDAC8 Inhibitor as Compared to the Structurally Similar Ligand, TSA

PubMed Central

Singh, Raushan K.; Lall, Naveena; Leedahl, Travis S.; McGillivray, Abigail; Mandal, Tanmay; Haldar, Manas; Mallik, Sanku; Cook, Gregory; Srivastava, D.K.

2013-01-01

Of the different hydroxamate-based histone deacetylase (HDAC) inhibitors, Suberoylanilide hydroxamic acid (SAHA) has been approved by the FDA for treatment of T-cell lymphoma. Interestingly, a structurally similar inhibitor, Trichostatin A (TSA), which has a higher in vitro inhibitory-potency against HDAC8, reportedly shows a poor efficacy in clinical settings. In order to gain the molecular insight into the above discriminatory feature, we performed transient kinetic and isothermal titration calorimetric studies for the interaction of SAHA and TSA to the recombinant form of human HDAC8. The transient kinetic data revealed that the binding of both the inhibitors to the enzyme showed the biphasic profiles, which represented an initial encounter of enzyme with the inhibitor followed by the isomerization of the transient enzyme-inhibitor complexes. The temperature-dependent transient kinetic studies with the above inhibitors revealed that the bimolecular process is primarily dominated by favorable enthalpic changes, as opposed to the isomerization step; which is solely contributed by entropic changes. The standard binding-enthalpy (ΔH0) of SAHA, deduced from the transient kinetic as well as the isothermal titration calorimetric experiments, was 2–3 kcal/mol higher as compared to TSA. The experimental data presented herein suggests that SAHA serves as a preferential (target-specific/selective) HDAC8 inhibitor as compared to TSA. Arguments are presented that the detailed kinetic and thermodynamic studies may guide in the rational design of HDAC inhibitors as therapeutic agents. PMID:24079912

Review of Knowledge Enhanced Electronic Logic (KEEL) Technology

DTIC Science & Technology

2016-09-01

compiled. Two KEEL Engine processing models are available for most languages : The “Normal Model” processes information as if it was processed on an... language also makes it easy to “see” the functional relationships and the dynamic (interactive) nature of the language , allows one to interact with...for the Accelerated Processing Model ( Patent number 7,512,581 (3/31/2009)). In June 2006, application US 11/446/801 was submitted to support

Synchrotron X-ray studies of the keel of the short-spined sea urchin Lytechinus variegatus: absorption microtomography (microCT) and small beam diffraction mapping.

PubMed

Stock, S R; Barss, J; Dahl, T; Veis, A; Almer, J D; Carlo, F

2003-05-01

In sea urchin teeth, the keel plays an important structural role, and this paper reports results of microstructural characterization of the keel of Lytechinus variegatus using two noninvasive synchrotron x-ray techniques: x-ray absorption microtomography (microCT) and x-ray diffraction mapping. MicroCT with 14 keV x-rays mapped the spatial distribution of mineral at the 1.3 microm level in a millimeter-sized fragment of a mature portion of the keel. Two rows of low absorption channels (i.e., primary channels) slightly less than 10 microm in diameter were found running linearly from the flange to the base of the keel and parallel to its sides. The primary channels paralleled the oral edge of the keel, and the microCT slices revealed a planar secondary channel leading from each primary channel to the side of the keel. The primary and secondary channels were more or less coplanar and may correspond to the soft tissue between plates of the carinar process. Transmission x-ray diffraction with 80.8 keV x-rays and a 0.1 mm beam mapped the distribution of calcite crystal orientations and the composition Ca(1-x)Mg(x)CO(3) of the calcite. Unlike the variable Mg concentration and highly curved prisms found in the keel of Paracentrotus lividus, a constant Mg content (x = 0.13) and relatively little prism curvature was found in the keel of Lytechinus variegatus.

28. Historic drawing, Marine Railway. Section showing bilge and keel ...

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

28. Historic drawing, Marine Railway. Section showing bilge and keel blocks, 1919. Photographic copy of original. Boston National Historical Park Archives, Charlestown Navy Yard. BOSTS 13439, #551-20 - Charlestown Navy Yard, Marine Railway, Between Piers 2 & 3, on Charlestown Waterfront at west end of Navy Yard, Boston, Suffolk County, MA

Implementing the Keele stratified care model for patients with low back pain: an observational impact study.

PubMed

Bamford, Adrian; Nation, Andy; Durrell, Susie; Andronis, Lazaros; Rule, Ellen; McLeod, Hugh

2017-02-03

The Keele stratified care model for management of low back pain comprises use of the prognostic STarT Back Screening Tool to allocate patients into one of three risk-defined categories leading to associated risk-specific treatment pathways, such that high-risk patients receive enhanced treatment and more sessions than medium- and low-risk patients. The Keele model is associated with economic benefits and is being widely implemented. The objective was to assess the use of the stratified model following its introduction in an acute hospital physiotherapy department setting in Gloucestershire, England. Physiotherapists recorded data on 201 patients treated using the Keele model in two audits in 2013 and 2014. To assess whether implementation of the stratified model was associated with the anticipated range of treatment sessions, regression analysis of the audit data was used to determine whether high- or medium-risk patients received significantly more treatment sessions than low-risk patients. The analysis controlled for patient characteristics, year, physiotherapists' seniority and physiotherapist. To assess the physiotherapists' views on the usefulness of the stratified model, audit data on this were analysed using framework methods. To assess the potential economic consequences of introducing the stratified care model in Gloucestershire, published economic evaluation findings on back-related National Health Service (NHS) costs, quality-adjusted life years (QALYs) and societal productivity losses were applied to audit data on the proportion of patients by risk classification and estimates of local incidence. When the Keele model was implemented, patients received significantly more treatment sessions as the risk-rating increased, in line with the anticipated impact of targeted treatment pathways. Physiotherapists were largely positive about using the model. The potential annual impact of rolling out the model across Gloucestershire is a gain in approximately 30

Evidence of marine ice-cliff instability in Pine Island Bay from iceberg-keel plough marks

NASA Astrophysics Data System (ADS)

Wise, Matthew G.; Dowdeswell, Julian A.; Jakobsson, Martin; Larter, Robert D.

2017-10-01

Marine ice-cliff instability (MICI) processes could accelerate future retreat of the Antarctic Ice Sheet if ice shelves that buttress grounding lines more than 800 metres below sea level are lost. The present-day grounding zones of the Pine Island and Thwaites glaciers in West Antarctica need to retreat only short distances before they reach extensive retrograde slopes. When grounding zones of glaciers retreat onto such slopes, theoretical considerations and modelling results indicate that the retreat becomes unstable (marine ice-sheet instability) and thus accelerates. It is thought that MICI is triggered when this retreat produces ice cliffs above the water line with heights approaching about 90 metres. However, observational evidence confirming the action of MICI has not previously been reported. Here we present observational evidence that rapid deglacial ice-sheet retreat into Pine Island Bay proceeded in a similar manner to that simulated in a recent modelling study, driven by MICI. Iceberg-keel plough marks on the sea-floor provide geological evidence of past and present iceberg morphology, keel depth and drift direction. From the planform shape and cross-sectional morphologies of iceberg-keel plough marks, we find that iceberg calving during the most recent deglaciation was not characterized by small numbers of large, tabular icebergs as is observed today, which would produce wide, flat-based plough marks or toothcomb-like multi-keeled plough marks. Instead, it was characterized by large numbers of smaller icebergs with V-shaped keels. Geological evidence of the form and water-depth distribution of the plough marks indicates calving-margin thicknesses equivalent to the threshold that is predicted to trigger ice-cliff structural collapse as a result of MICI. We infer rapid and sustained ice-sheet retreat driven by MICI, commencing around 12,300 years ago and terminating before about 11,200 years ago, which produced large numbers of icebergs smaller than the

Histone deacetylase inhibitor SAHA mediates mast cell death and epigenetic silencing of constitutively active D816V KIT in systemic mastocytosis.

PubMed

Lyberg, Katarina; Ali, Hani Abdulkadir; Grootens, Jennine; Kjellander, Matilda; Tirfing, Malin; Arock, Michel; Hägglund, Hans; Nilsson, Gunnar; Ungerstedt, Johanna

2017-02-07

Systemic mastocytosis (SM) is a clonal bone marrow disorder, where therapeutical options are limited. Over 90% of the patients carry the D816V point mutation in the KIT receptor that renders this receptor constitutively active. We assessed the sensitivity of primary mast cells (MC) and mast cell lines HMC1.2 (D816V mutated), ROSA (KIT WT) and ROSA (KIT D816V) cells to histone deacetylase inhibitor (HDACi) treatment. We found that of four HDACi, suberoyl anilide hydroxamic acid (SAHA) was the most effective in killing mutated MC. SAHA downregulated KIT, followed by major MC apoptosis. Primary SM patient MC cultured ex vivo were even more sensitive to SAHA than HMC1.2 cells, whereas primary MC from healthy subjects were less affected. There was a correlation between cell death and SM disease severity, where cell death was more pronounced in the case of aggressive SM, with almost 100% cell death among MC from the mast cell leukemia patient. Additionally, ROSA (KIT D816V) was more affected by HDACi than ROSA (KIT WT) cells. Using ChIP qPCR, we found that the level of active chromatin mark H3K18ac/H3 decreased significantly in the KIT region. This epigenetic silencing was seen only in the KIT region and not in control genes upstream and downstream of KIT, indicating that the downregulation of KIT is exerted by specific epigenetic silencing. In conclusion, KIT D816V mutation sensitized MC to HDACi mediated killing, and SAHA may be of value as specific treatment for SM, although the specific mechanism of action requires further investigation.

Histone deacetylase inhibitor SAHA mediates mast cell death and epigenetic silencing of constitutively active D816V KIT in systemic mastocytosis

PubMed Central

Lyberg, Katarina; Ali, Hani Abdulkadir; Grootens, Jennine; Kjellander, Matilda; Tirfing, Malin; Arock, Michel; Hägglund, Hans

2017-01-01

Systemic mastocytosis (SM) is a clonal bone marrow disorder, where therapeutical options are limited. Over 90% of the patients carry the D816V point mutation in the KIT receptor that renders this receptor constitutively active. We assessed the sensitivity of primary mast cells (MC) and mast cell lines HMC1.2 (D816V mutated), ROSA (KIT WT) and ROSA (KIT D816V) cells to histone deacetylase inhibitor (HDACi) treatment. We found that of four HDACi, suberoyl anilide hydroxamic acid (SAHA) was the most effective in killing mutated MC. SAHA downregulated KIT, followed by major MC apoptosis. Primary SM patient MC cultured ex vivo were even more sensitive to SAHA than HMC1.2 cells, whereas primary MC from healthy subjects were less affected. There was a correlation between cell death and SM disease severity, where cell death was more pronounced in the case of aggressive SM, with almost 100% cell death among MC from the mast cell leukemia patient. Additionally, ROSA (KIT D816V) was more affected by HDACi than ROSA (KIT WT) cells. Using ChIP qPCR, we found that the level of active chromatin mark H3K18ac/H3 decreased significantly in the KIT region. This epigenetic silencing was seen only in the KIT region and not in control genes upstream and downstream of KIT, indicating that the downregulation of KIT is exerted by specific epigenetic silencing. In conclusion, KIT D816V mutation sensitized MC to HDACi mediated killing, and SAHA may be of value as specific treatment for SM, although the specific mechanism of action requires further investigation. PMID:28038453

Iron complexation to histone deacetylase inhibitors SAHA and LAQ824 in PEGylated liposomes can considerably improve pharmacokinetics in rats.

PubMed

Wang, Yan; Tu, Sheng; Steffen, Dana; Xiong, May

2014-01-01

The formulation of histone deacetylase inhibitors (HDACi) is challenging due to poor water solubility and rapid elimination of drugs in vivo. This study investigated the effects of complexing iron (Fe3+) to the HDACi suberoylanilide hydroxamic acid (SAHA) and LAQ824 (LAQ) prior to their encapsulation into PEGylated liposomes, and investigated whether this technique could improve drug solubility, in vitro release and in vivo pharmacokinetic (PK) properties. METHODS. The reaction stoichiometry, binding constants and solubility were measured for Fe complexes of SAHA and LAQ. The complexes were passively encapsulated into PEGylated liposomes and characterized by size distribution, zeta-potential, encapsulation efficiency (EE), and in vitro drug release studies. PC-3 cells were used to verify the in vitro anticancer activity of the formulations. In vivo pharmacokinetic properties of liposomal LAQ-Fe (L-LAQ-Fe) was evaluated in rats. RESULTS. SAHA and LAQ form complexes with Fe at 1:1 stoichiometric ratio, with a binding constant on the order of 104 M-1. Fe complexation improved the aqueous solubility and the liposomal encapsulation efficiency of SAHA and LAQ (29-35% EE, final drug concentration > 1 mM). Liposomal encapsulated complexes (L-HDACi-Fe) exhibited sustained in vitro release properties compared to L-HDACi but cytotoxicity on PC-3 cells was comparable to free drugs. The PK of L-LAQ-Fe revealed 15-fold improvement in the plasma t1/2 (12.11 h)and 211-fold improvement in the AUC∞ (105.7 µg·h/ml) compared to free LAQ (0.79 h, 0.5 µg·h/ml). Similarly, the plasma t1/2 of Fe was determined to be 11.83 h in a separate experiment using radioactive Fe-59. The majority of Fe-59 activity was found in liver and spleen of rats and correlates with liposomal uptake by the mononuclear phagocyte system. CONCLUSIONS. We have demonstrated that encapsulation of Fe complexes of HDACi into PEGylated liposomes can improve overall drug aqueous solubility, in vitro release and in

Iron Complexation to Histone Deacetylase Inhibitors SAHA and LAQ824 in PEGylated Liposomes Can Considerably Improve Pharmacokinetics in Rats

PubMed Central

Wang, Yan; Tu, Sheng; Steffen, Dana; Xiong, May P.

2015-01-01

PURPOSE The formulation of histone deacetylase inhibitors (HDACi) is challenging due to poor water solubility and rapid elimination of drugs in vivo. This study investigated the effects of complexing iron (Fe3+) to the HDACi suberoylanilide hydroxamic acid (SAHA) and LAQ824 (LAQ) prior to their encapsulation into PEGylated liposomes, and investigated whether this technique could improve drug solubility, in vitro release and in vivo pharmacokinetic (PK) properties. METHODS The reaction stoichiometry, binding constants and solubility were measured for Fe complexes of SAHA and LAQ. The complexes were passively encapsulated into PEGylated liposomes and characterized by size distribution, zeta-potential, encapsulation efficiency (EE), and in vitro drug release studies. PC-3 cells were used to verify the in vitro anticancer activity of the formulations. In vivo pharmacokinetic properties of liposomal LAQ-Fe (L-LAQ-Fe) was evaluated in rats. RESULTS SAHA and LAQ form complexes with Fe at 1:1 stoichiometric ratio, with a binding constant on the order of 104 M−1. Fe complexation improved the aqueous solubility and the liposomal encapsulation efficiency of SAHA and LAQ (29–35% EE, final drug concentration > 1 mM). Liposomal encapsulated complexes (L-HDACi-Fe) exhibited sustained in vitro release properties compared to L-HDACi but cytotoxicity on PC-3 cells was comparable to free drugs. The PK of L-LAQ-Fe revealed 15-fold improvement in the plasma t1/2 (12.11 h) and 211-fold improvement in the AUC∞ (105.7 μg·h/ml) compared to free LAQ (0.79 h, 0.5 μg·h/ml). Similarly, the plasma t1/2 of Fe was determined to be 11.83 h in a separate experiment using radioactive Fe-59. The majority of Fe-59 activity was found in liver and spleen of rats and correlates with liposomal uptake by the mononuclear phagocyte system. CONCLUSIONS We have demonstrated that encapsulation of Fe complexes of HDACi into PEGylated liposomes can improve overall drug aqueous solubility, in vitro

Synergistic anticancer effects of cisplatin and histone deacetylase inhibitors (SAHA and TSA) on cholangiocarcinoma cell lines.

PubMed

Asgar, Md Ali; Senawong, Gulsiri; Sripa, Banchob; Senawong, Thanaset

2016-01-01

Clinical application of cisplatin against cholangiocarcinoma is often associated with resistance and toxicity posing urgent demand for combination therapy. In this study, we evaluated the combined anticancer effect of cisplatin and histone deacetylase inhibitors (HDACIs), suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA), on the cholangiocarcinoma KKU-100 and KKU-M214 cell lines. Antiproliferative activity was evaluated using MTT assay. Apoptosis induction and cell cycle arrest were analyzed by flow cytometry. Cell cycle and apoptosis regulating proteins were evaluated by western blot analysis. MTT assay showed that cisplatin, SAHA and TSA dose-dependently reduced the viability of KKU-100 and KKU-M214 cells. The combination of cisplatin and HDACIs exerted significantly more cytotoxicity than the single drugs. Combination indices below 1.0 reflect synergism between cisplatin and HDACIs, leading to positive dose reductions of cisplatin and HDACIs. Cisplatin and HDACIs alone induced G0/G1 phase arrest in KKU-100 cells, but the drug combinations increased sub-G1 percent more than either drug. However, cisplatin and HDACIs alone or in combination increased only the sub-G1 percent in KKU-M214 cells. Annexin V-FITC staining revealed that cisplatin and HDACIs combinations induced more apoptotic cell death of both KKU-100 and KKU-M214 cells than the single drug. In KKU-100 cells, growth inhibition was accompanied by upregulation of p53 and p21 and downregulation of CDK4 and Bcl-2 due to exposure to cisplatin, SAHA and TSA alone or in combination. Moreover, combination of agents exerted higher impacts on protein expression. Single agents or combination did not affect p53 expression, however, combination of cisplatin and HDACIs increased the expression of p21 in KKU-M214 cells. Taken together, cisplatin and HDACIs combination may improve the therapeutic outcome in cholangiocarcinoma patients.

Combined treatment with Ad-hTRAIL and DTIC or SAHA is associated with increased mitochondrial-mediated apoptosis in human melanoma cell lines.

PubMed

Lillehammer, Trine; Engesaeter, Birgit O; Prasmickaite, Lina; Maelandsmo, Gunhild M; Fodstad, Oystein; Engebraaten, Olav

2007-06-01

Currently, dacarbazine (DTIC) is the only approved systemic treatment for metastatic malignant melanoma. However, the modest treatment effect encourages studies on novel therapeutic molecules, delivery systems and combination therapies. Full-length TRAIL, delivered from an adenoviral vector (Ad-hTRAIL), was studied in combination with DTIC or the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in human melanoma cell lines. The cytotoxic potential of the combination treatments was assessed by cell viability measurements and CalcuSyn analysis. Involvement of apoptosis was analyzed by TUNEL staining, mitochondrial membrane potential measurements, and activation and expression levels of caspases and other mediators of apoptosis. Ad-hTRAIL in combination with DTIC or SAHA resulted in additive or synergistic growth inhibition compared to each treatment used as single agent. Both combinations augmented apoptosis, which was mediated through the death receptor (DR) pathway by enhanced activation of caspase-8, and through increased loss of mitochondrial integrity. Provoked cleavage of Bid, which bridges the extrinsic and intrinsic apoptosis pathways, and downregulation of the anti-apoptotic mediators Bcl-X(L), Mcl-1 and XIAP (but not Bcl-2) were critical contributing factors. Increased levels of DR4 and DR5 were not a common underlying mechanism as DTIC did not affect the levels of either of the receptors. However, SAHA-induced expression of DR4 may have reduced the TRAIL resistance in the SKMEL-28 cell line. Administration of Ad-hTRAIL in combination with DTIC or SAHA enhances apoptosis in human melanoma cell lines, and suggests that the therapeutic potential of such treatment strategies should be further evaluated for possible clinical use.

Genetic selection to increase bone strength affects prevalence of keel bone damage and egg parameters in commercially housed laying hens.

PubMed

Stratmann, A; Fröhlich, E K F; Gebhardt-Henrich, S G; Harlander-Matauschek, A; Würbel, H; Toscano, M J

2016-05-01

The prevalence of keel bone damage as well as external egg parameters of 2 pure lines divergently selected for high (H) and low (L) bone strength were investigated in 2 aviary systems under commercial conditions. A standard LSL hybrid was used as a reference group. Birds were kept mixed per genetic line (77 hens of the H and L line and 201 or 206 hens of the LSL line, respectively, per pen) in 8 pens of 2 aviary systems differing in design. Keel bone status and body mass of 20 focal hens per line and pen were assessed at 17, 18, 23, 30, 36, 43, 52, and 63 wk of age. External egg parameters (i.e., egg mass, eggshell breaking strength, thickness, and mass) were measured using 10 eggs per line at both 38 and 57 wk of age. Body parameters (i.e. tarsus and third primary wing feather length to calculate index of wing loading) were recorded at 38 wk of age and mortality per genetic line throughout the laying cycle. Bone mineral density (BMD) of 15 keel bones per genetic line was measured after slaughter to confirm assignment of the experimental lines. We found a greater BMD in the H compared with the L and LSL lines. Fewer keel bone fractures and deviations, a poorer external egg quality, as well as a lower index of wing loading were found in the H compared with the L line. Mortality was lower and production parameters (e.g., laying performance) were higher in the LSL line compared with the 2 experimental lines. Aviary design affected prevalence of keel bone damage, body mass, and mortality. We conclude that selection of specific bone traits associated with bone strength as well as the related differences in body morphology (i.e., lower index of wing loading) have potential to reduce keel bone damage in commercial settings. Also, the housing environment (i.e., aviary design) may have additive effects. © 2016 Poultry Science Association Inc.

Effects of treatment with suppressive combination antiretroviral drug therapy and the histone deacetylase inhibitor suberoylanilide hydroxamic acid; (SAHA) on SIV-infected Chinese rhesus macaques.

PubMed

Ling, Binhua; Piatak, Michael; Rogers, Linda; Johnson, Ann-Marie; Russell-Lodrigue, Kasi; Hazuda, Daria J; Lifson, Jeffrey D; Veazey, Ronald S

2014-01-01

Viral reservoirs-persistent residual virus despite combination antiretroviral therapy (cART)-remain an obstacle to cure of HIV-1 infection. Difficulty studying reservoirs in patients underscores the need for animal models that mimics HIV infected humans on cART. We studied SIV-infected Chinese-origin rhesus macaques (Ch-RM) treated with intensive combination antiretroviral therapy (cART) and 3 weeks of treatment with the histone deacetyalse inhibitor, suberoylanilide hydroxamic acid (SAHA). SIVmac251 infected Ch-RM received reverse transcriptase inhibitors PMPA and FTC and integrase inhibitor L-870812 beginning 7 weeks post infection. Integrase inhibitor L-900564 and boosted protease inhibitor treatment with Darunavir and Ritonavir were added later. cART was continued for 45 weeks, with daily SAHA administered for the last 3 weeks, followed by euthanasia/necropsy. Plasma viral RNA and cell/tissue-associated SIV gag RNA and DNA were quantified by qRT-PCR/qPCR, with flow cytometry monitoring changes in immune cell populations. Upon cART initiation, plasma viremia declined, remaining <30 SIV RNA copy Eq/ml during cART, with occasional blips. Decreased viral replication was associated with decreased immune activation and partial restoration of intestinal CD4+ T cells. SAHA was well tolerated but did not result in demonstrable treatment-associated changes in plasma or cell associated viral parameters. The ability to achieve and sustain virological suppression makes cART-suppressed, SIV-infected Ch-RM a potentially useful model to evaluate interventions targeting residual virus. However, despite intensive cART over one year, persistent viral DNA and RNA remained in tissues of all three animals. While well tolerated, three weeks of SAHA treatment did not demonstrably impact viral RNA levels in plasma or tissues; perhaps reflecting dosing, sampling and assay limitations.

Effect of Afterbody Length and Keel Angle on Minimum Depth of Step for Landing Stability and on Take-Off Stability of a Flying Boat

NASA Technical Reports Server (NTRS)

Olson, Roland E; Land, Norman S

1949-01-01

Tests were made to fill partly the need for information on the effect of afterbody dimensions on the hydrodynamic stability of a flying boat in smooth water. The dimensions investigated were depth of step, angle of afterbody keel, and length of afterbody. An analysis of the data showed that as either the afterbody length or keel angle was increased an accompanying increase in depth of step was required in order to maintain adequate landing stability. The landing-tests results have been reduced to an empirical formula giving the minimum depth of step in terms of afterbody length and keel angle. This formula is compared with results from other tank tests, and the correlation is fairly good. The formula thus becomes of use in preliminary design.

Parameterization of Keeling's network generation algorithm.

PubMed

Badham, Jennifer; Abbass, Hussein; Stocker, Rob

2008-09-01

Simulation is increasingly being used to examine epidemic behaviour and assess potential management options. The utility of the simulations rely on the ability to replicate those aspects of the social structure that are relevant to epidemic transmission. One approach is to generate networks with desired social properties. Recent research by Keeling and his colleagues has generated simulated networks with a range of properties, and examined the impact of these properties on epidemic processes occurring over the network. However, published work has included only limited analysis of the algorithm itself and the way in which the network properties are related to the algorithm parameters. This paper identifies some relationships between the algorithm parameters and selected network properties (mean degree, degree variation, clustering coefficient and assortativity). Our approach enables users of the algorithm to efficiently generate a network with given properties, thereby allowing realistic social networks to be used as the basis of epidemic simulations. Alternatively, the algorithm could be used to generate social networks with a range of property values, enabling analysis of the impact of these properties on epidemic behaviour.

Setup for potential bias experiments on the Saha Institute of Nuclear Physics tokamak

NASA Astrophysics Data System (ADS)

Ghosh, J.; Pal, R.; Chattopadhyay, P. K.

1999-12-01

An experimental setup for studying the influence of the radial electric field on very low qa plasma on the Saha Institute of Nuclear Physics tokamak is presented. A high current, high voltage pulsed power supply, using a semiconductor controlled rectifier (SCR) as a dc switch is developed and used to bias a tungsten electrode inserted inside the plasma. The electrode's exposed length and its position inside the plasma are controlled by a double bellows assembly to optimize the electrode-exposed length. We show that using the force commutation method to turn the SCR off to get the power pulse desired has good potential for carrying out similar kinds of studies, especially in a low budget small tokamak.

Isotopic Characterisation of Methane Emissions: use of Keeling-plot Methods to Identify Source Signatures in Boreal Wetlands and Other Settings

NASA Astrophysics Data System (ADS)

Fisher, R. E.; Lowry, D.; France, J.; Lanoiselle, M.; Zazzeri, G.; Nisbet, E. G.

2012-12-01

Different methane sources have different δ13CCH4 and δDCH4 signatures, which potentially provides a powerful constraint on models of methane emission budgets. However source signatures remain poorly known and need to be studied in more detail if isotopic measurements of ambient air are to be used to constrain regional and global emissions. The Keeling plot method (plotting δ13CCH4 or δDCH4 against 1/CH4 concentration in samples of ambient air in the close vicinity of known sources) directly assesses the source signature of the methane that is actually emitted to the air. This contrasts with chamber studies, measuring air within a chamber, where local micro-meteorological and microbiological processes are occurring. Keeling plot methods have been applied to a wide variety of settings in this study. The selection of appropriate background measurements for Keeling plot analysis is also considered. The method has been used on a local scale to identify the source signature of summer emissions from subarctic wetlands in Fennoscandia. Samples are collected from low height (0.3-3m) over the wetlands during 24-hour periods, to collect daily emissions maxima (warm late afternoons), inversion maxima (at the coldest time of the 24hr daylight: usually earliest morning), and ambient minima when mixing occurs (often mid afternoon). Some results are comparable to parallel chamber studies, but in other cases there are small but significant shifts between CH4 in chamber air and CH4 that is dispersing in the above-ground air. On a regional to continental scale the isotopic signature of bulk sources of emissions can be identified using Keeling plots. The methodology is very applicable for use in urban and urban-rural settings. For example, the winter SE monsoon sweeps from inland central Asia over China to Hong Kong. Application of back trajectory analysis and Keeling plot methods implied coal emissions may be a significant Chinese source of methane in January, although in other

The effects of two non-steroidal anti-inflammatory drugs on the mobility of laying hens with keel bone fractures.

PubMed

Nasr, Mohammed Af; Nicol, Christine J; Wilkins, Lindsay; Murrell, Joanna C

2015-03-01

Investigate the effects of administration of meloxicam and carprofen on the mobility of hens with and without keel fractures. Within each of two experiments a 'blinded' randomised cross over design whereby birds received either the test drug (carprofen or meloxicam) or saline. Two groups of Lohman Brown hens with and without keel bone fractures. The first group (n = 63) was treated with carprofen 25 mg kg(-1) and saline subcutaneously, twice. The second group (n = 40) was treated with meloxicam (5 mg kg(-1) ) and saline subcutaneously. The latency of birds to fly down from perches 50, 100 and 150 cm above the ground was measured after each treatment. Data from experiment 1 and 2 were analysed separately; the effects of drug treatment compared with saline on landing time for birds with and without keel bone fractures were evaluated using MLwiN. In both experiments latency to fly down from perches was longer in hens with keel fractures and there was a significant interaction between perch height and fracture status. For carprofen, at the 50 cm, 100 cm and 150 cm perch heights, birds with fractures took (mean ± SD) 2.5 ± 2.9, 6.8 ± 9.7 and 11.5 ± 13.2 seconds respectively to fly down compared with 1.3 ± 0.5, 2.3 ± 1.2 and 4.2 ± 3.1 seconds for birds without fractures. For meloxicam, at the 50 cm, 100 cm and 150 cm perch heights, birds with fractures took 2.9 ± 2.5, 49.8 ± 85.4 and 100.3 ± 123.6 seconds respectively compared with 0.7 ± 0.5, 2.5 ± 7.1 and 3.0 ± 4.6 seconds to fly down for birds without fractures. There was no significant effect of carprofen or meloxicam treatment. These data provide further confirmation that keel fractures reduce the willingness of birds to move from perches. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Adaptive momentum management for the dual keel Space Station

NASA Technical Reports Server (NTRS)

Hopkins, M.; Hahn, E.

1987-01-01

The report discusses momentum management for a large space structure with the structure selected configuration being the Initial Orbital Configuration of the dual-keel Space Station. The external torques considered were gravity gradient and aerodynamic torques. The goal of the momentum management scheme developed is to remove the bias components of the external torques and center the cyclic components of the stored angular momentum. The scheme investigated is adaptive to uncertainties of the inertia tensor and requires only approximate knowledge of principal moments of inertia. Computational requirements are minimal and should present no implementation problem in a flight-type computer. The method proposed is shown to be effective in the presence of attitude control bandwidths as low as 0.01 radian/sec.

Design, Fabrication, and Testing of Composite Energy-Absorbing Keel Beams for General Aviation Type Aircraft

NASA Technical Reports Server (NTRS)

Kellas, Sotiris; Knight, Norman F., Jr.

2002-01-01

A lightweight energy-absorbing keel-beam concept was developed and retrofitted in a general aviation type aircraft to improve crashworthiness performance. The energy-absorbing beam consisted of a foam-filled cellular structure with glass fiber and hybrid glass/kevlar cell walls. Design, analysis, fabrication and testing of the keel beams prior to installation and subsequent full-scale crash testing of the aircraft are described. Factors such as material and fabrication constraints, damage tolerance, crush stress/strain response, seat-rail loading, and post crush integrity, which influenced the course of the design process are also presented. A theory similar to the one often used for ductile metal box structures was employed with appropriate modifications to estimate the sustained crush loads for the beams. This, analytical tool, coupled with dynamic finite element simulation using MSC.Dytran were the prime design and analysis tools. The validity of the theory as a reliable design tool was examined against test data from static crush tests of beam sections while the overall performance of the energy-absorbing subfloor was assessed through dynamic testing of 24 in long subfloor assemblies.

Exploring alternative Zn-binding groups in the design of HDAC inhibitors: squaric acid, N-hydroxyurea, and oxazoline analogues of SAHA.

PubMed

Hanessian, Stephen; Vinci, Valerio; Auzzas, Luciana; Marzi, Mauro; Giannini, Giuseppe

2006-09-15

Analogues of suberoylanilide hydroxamic acid (SAHA) were prepared by replacing the Zn-binding group with squaric acid, N-hydroxyurea, and 4-hydroxymethyl oxazoline units, also varying the length of the aliphatic chain. No inhibitory activity on HDAC was observed below 1.0 microM and no cytotoxic activity on different tumor cell lines was seen below 20.0 microM.

New species of Nuuanu (Amphipoda: Nuuanuidae) from Norfolk Island, Torres Strait and the Cocos (Keeling) Islands.

PubMed

Hughes, L E; Bopiah, A

2013-01-01

Three new species of Nuuanu, N. quintalana sp. nov., N. stuckeyorun sp. nov. and N. titaseyi sp. nov. are described from Norfolk Island, Tasman Sea; Cocos (Keeling) Islands, Indian Ocean and the Torres Strait, Australia, respectively. There are currently 17 described species of Nuuanu with the genus distributed world-wide.

The Role of Water in the Stability of Cratonic Keels

NASA Technical Reports Server (NTRS)

Peslier, Anne H.; Woodland, Alan B.; Bell, David R.; Lazarov, Marina

2011-01-01

Cratons are typically underlain by large, deep, and old lithospheric keels (to greater than 200 km depth, greater than 2.5 Ga old) projecting into the asthenosphere (e.g., Jordan, 1978; Richardson et al., 1984). This has mystified Earth scientists as the dynamic and relatively hot asthenosphere should have eroded away these keels over time (e.g., Sleep, 2003; O'Neill et al., 2008; Karato, 2010). Three key factors have been invoked to explain cratonic root survival: 1) Low density makes the cratonic mantle buoyant (e.g., Poudjom Djomani et al., 2001). 2) Low temperatures (e.g., Pollack, 1986; Boyd, 1987), and 3) low water contents (e.g., Pollack, 1986), would make cratonic roots mechanically strong. Here we address the mechanism of the longevity of continental mantle lithosphere by focusing on the water parameter. Although nominally anhydrous , olivine, pyroxene and garnet can accommodate trace amounts of water in the form of H bonded to structural O in mineral defects (e.g., Bell and Rossman, 1992). Olivine softens by orders of magnitude if water (1-1000 ppm H2O) is added to its structure (e.g., Mackwell et al., 1985). Our recent work has placed constraints on the distribution of water measured in peridotite minerals in the cratonic root beneath the Kaapvaal in southern Africa (Peslier et al., 2010). At P greater than 5 GPa, the water contents of pyroxene remain relatively constant while those of olivine systematically decrease from 50 to less than 10 ppm H2O at 6.4 GPa. We hypothesized that at P greater than 6.4 GPa, i.e. at the bottom of the cratonic lithosphere, olivines are essentially dry (greater than 10 ppm H2O). As olivine likely controls the rheology of the mantle, we calculated that the dry olivines could be responsible for a contrast in viscosity between cratonic lithosphere and surrounding asthenosphere large enough to explain the resistance of cratonic root to asthenospheric delamination.

In silico modification of Zn2+ binding group of suberoylanilide hydroxamic acid (SAHA) by organoselenium compounds as Homo sapiens class II HDAC inhibitor of cervical cancer

NASA Astrophysics Data System (ADS)

Sumo Friend Tambunan, Usman; Bakri, Ridla; Aditya Parikesit, Arli; Ariyani, Titin; Dyah Puspitasari, Ratih; Kerami, Djati

2016-02-01

Cervical cancer is the most common cancer in women, and ranks seventh of all cancers worldwide, with 529000 cases in 2008 and more than 85% cases occur in developing countries. One way to treat this cancer is through the inhibition of HDAC enzymes which play a strategic role in the regulation of gene expression. Suberoyl Anilide Hydroxamic Acid (SAHA) or Vorinostat is a drug which commercially available to treat the cancer, but still has some side effects. This research present in silico SAHA modification in Zinc Binding Group (ZBG) by organoselenium compound to get ligands which less side effect. From molecular docking simulation, and interaction analysis, there are five best ligands, namely CC27, HA27, HB28, IB25, and KA7. These five ligands have better binding affinity than the standards, and also have interaction with Zn2+ cofactor of inhibited HDAC enzymes. This research is expected to produce more potent HDAC inhibitor as novel drug for cervical cancer treatment.

A dedicated undergraduate gynaecology teaching clinic: The Keele experience.

PubMed

Katali, Hamza Mahamadu; Parry-Smith, William Rhys; Eliot, Rees L; O'Mahony, Fidelma

2016-01-01

Much discussion in the literature centres on how best to teach medical students the intricacies of gynaecological assessment and the subsequent formulation of a management plan. At Keele University skills are initially developed in a simulated setting and then transferred to the workplace where students continue to develop their skills. A dedicated undergraduate gynaecology teaching clinic has been developed and comprises of 2-3 students and a tutor. All 38 students rotating through the department between January and June 2013 were invited to complete an anonymous questionnaire to evaluate this clinic and 36 (95%) of them responded. Respondents felt significantly more comfortable taking a gynaecology history, ensuring privacy during examination and formulating a management plan post-clinic (all p < 0.001), with female students feeling significantly more comfortable than their male counterparts (p = 0.04). The use of this clinic shows great promise to help students learn an unfamiliar and challenging skill.

Can We Monitor Ecosystem Function Using Keeling Plot Analyses of Nocturnal Cold-Air Drainage?

NASA Astrophysics Data System (ADS)

Bond, B. J.; Ocheltree, T.; Pypker, T.; Unsworth, M. H.; Mix, A. C.; William, R.

2003-12-01

The carbon isotope signature of ecosystem respiration, δ 13CR, as measured by the Keeling Plot approach, has been related to short-term variations in weather and ecosystem function in several recent studies. In order to obtain an adequate range of [CO2] and to sample a consistent vegetation type, investigators typically select sampling locations in relatively flat terrain and uniform canopy cover, but these are unusual conditions for many forested ecosystems. In a pilot study, we are collecting samples for Keeling Plot analyses in cold-air drainage systems in small (60-100 ha), deeply-incised watersheds, one covered with old-growth (ca 450-years-old) Douglas-fir/hemlock forest and one covered with young (ca 45-years-old) Douglas-fir forest. We found that the nightly range of [CO2] was typically 380-460 ppm, sufficient to develop good estimates of δ 13CR. At any point in time there was little variation in [CO2] with height through the canopy (0.5-30m), so the required range was obtained by sampling over several hours. There was no indication that samples taken from different heights or at different times of night represented sources with different isotopic signatures. The isotopic signature of respired CO2 in the older watershed averaged about 1 per mil greater than that of the young watershed, and δ 13CR of both locations correlated with modeled stomatal conductance 6 days prior to flask sampling.

Methods for assessment of keel bone damage in poultry.

PubMed

Casey-Trott, T; Heerkens, J L T; Petrik, M; Regmi, P; Schrader, L; Toscano, M J; Widowski, T

2015-10-01

Keel bone damage (KBD) is a critical issue facing the laying hen industry today as a result of the likely pain leading to compromised welfare and the potential for reduced productivity. Recent reports suggest that damage, while highly variable and likely dependent on a host of factors, extends to all systems (including battery cages, furnished cages, and non-cage systems), genetic lines, and management styles. Despite the extent of the problem, the research community remains uncertain as to the causes and influencing factors of KBD. Although progress has been made investigating these factors, the overall effort is hindered by several issues related to the assessment of KBD, including quality and variation in the methods used between research groups. These issues prevent effective comparison of studies, as well as difficulties in identifying the presence of damage leading to poor accuracy and reliability. The current manuscript seeks to resolve these issues by offering precise definitions for types of KBD, reviewing methods for assessment, and providing recommendations that can improve the accuracy and reliability of those assessments. © 2015 Poultry Science Association Inc.

The influence of David Keeling on oceanic CO2 measurements

NASA Astrophysics Data System (ADS)

Brewer, Peter G.

Dave Keeling—only Roger Revelle called him "Charles David" and always in a tone that could command Dave's attention—had a remarkable influence on the creation of modern understanding of the oceanic CO2 system. Although Dave resided at an oceanographic institution for almost his entire professional career, the great majority of his work concerned atmospheric measurements; his own account of his work [Keeling, 1998] makes scant reference to his ocean science papers. But those relatively few oceanic papers, and more importantly his intense personal interest and unimpeachable reputation for classic measurement, had enormous impact. It is possible to trace Dave's influence on oceanic measurement through the course of five decades, and over that time, our understanding has grown enormously. The following is a somewhat personal account, but Dave so influenced the careers of the small group of ocean CO2 scientists that have led the way that any one of them would write a similar account.

Thickened cranial vault and parasagittal keeling: correlated traits and autapomorphies of Homo erectus?

PubMed

Balzeau, Antoine

2013-06-01

Homo erectus sensu lato (s.l.) is a key species in the hominin fossil record for the study of human evolution, being one of the first species discovered and perhaps the most documented, but also because of its long temporal range and having dispersed out of Africa earlier than any other human species. Here I test two proposed autapomorphic traits of H. erectus, namely the increased thickness of the upper cranial vault and parasagittal keeling. The definition of these two anatomical features and their expression and variation among hominids are discussed. The results of this study indicate that the upper vault in Asian H. erectus is not absolutely thicker compared with fossil anatomically modern Homo sapiens, whereas Broken Hill and Petralona have values above the range of variation of H. erectus. Moreover, this anatomical region in Asian H. erectus is not significantly thicker compared with Pan paniscus. In addition, these results demonstrate that cranial vault thickness should not be used to make hypotheses regarding sexual attribution of fossil hominin specimens. I also show that the relation between relief on the external surface of the upper vault, parasagittal keeling and bregmatic eminence, and bone thickness is complex. In this context, the autapomorphic status of the two analysed traits in H. erectus may be rejected. Nevertheless, different patterns in the distribution of bone thickness on the upper vault were identified. Some individual variations are visible, but specificities are observable in samples of different species. The pattern of bone thickness distribution observed in Asian H. erectus, P. paniscus, possibly australopiths, and early Homo or Homo ergaster/erectus appears to be shared by these different species and would be a plesiomorphic trait among hominids. In contrast, two apomorphic states for this feature were identified for Neandertals and H. sapiens. Copyright © 2013 Elsevier Ltd. All rights reserved.

Seismic imaging of the lithosphere beneath Hudson Bay: Episodic growth of the Laurentian mantle keel

NASA Astrophysics Data System (ADS)

Darbyshire, Fiona A.; Eaton, David W.; Bastow, Ian D.

2013-07-01

The Hudson Bay basin in northern Canada conceals one of the major collisional zones of the Canadian Shield, the Trans-Hudson Orogen (THO), which marks the Paleoproterozoic collision between the Archean Superior and Western Churchill cratons at ˜1.9-1.8Ga. Improved knowledge of upper mantle structure beneath the region is essential to establish the nature of the THO, specifically whether Himalayan-style plate tectonics operated in Paleoproterozoic times. Detailed seismological constraints on lithospheric architecture are also required to advance our understanding of the mechanism and timing of keel formation. We use surface wave tomography to illuminate new details of the lithospheric architecture of the Hudson Bay region, resolving both seismic wavespeed and azimuthal anisotropy. Phase velocity maps are calculated from fundamental-mode Rayleigh wave dispersion curves, then used to construct a 3D model exploring upper mantle structure to depths of ˜300km. Fast shear wavespeeds suggest a lithospheric thickness varying from ˜180km to almost 280 km beneath the Hudson Bay region. The new study confirms previous inferences that there is no correlation between crustal ages and lithospheric thickness. Patterns of shear wavespeed and azimuthal anisotropy indicate a layered lithosphere. In the uppermost mantle, both the highest velocities and the anisotropic fast directions wrap around the Bay. This structure is likely related to the formation processes of the Paleozoic intracratonic basin. At greater depth (˜70-150km) we resolve two high-wavespeed cores separated by a relatively narrow near-vertical lower-velocity curtain. This internal architecture is suggested to result from the terminal phase of a modern-style plate-tectonic collision between the Archean Superior and Churchill cratons during the Trans-Hudson orogeny, entrapping juvenile Proterozoic material. The lower lithosphere (≥160km depth) has a relatively homogeneous wavespeed structure across the region

Strong Winds over the Keel

NASA Astrophysics Data System (ADS)

2009-02-01

The latest ESO image reveals amazing detail in the intricate structures of one of the largest and brightest nebulae in the sky, the Carina Nebula (NGC 3372), where strong winds and powerful radiation from an armada of massive stars are creating havoc in the large cloud of dust and gas from which the stars were born. ESO PR Photo 05a/09 The Carina Nebula ESO PR Video 05a/09 Pan over the Carina Nebula ESO PR Video 05b/09 Carina Nebula Zoom-in The large and beautiful image displays the full variety of this impressive skyscape, spattered with clusters of young stars, large nebulae of dust and gas, dust pillars, globules, and adorned by one of the Universe's most impressive binary stars. It was produced by combining exposures through six different filters from the Wide Field Imager (WFI), attached to the 2.2 m ESO/MPG telescope at ESO's La Silla Observatory, in Chile. The Carina Nebula is located about 7500 light-years away in the constellation of the same name (Carina; the Keel). Spanning about 100 light-years, it is four times larger than the famous Orion Nebula and far brighter. It is an intensive star-forming region with dark lanes of cool dust splitting up the glowing nebula gas that surrounds its many clusters of stars. The glow of the Carina Nebula comes mainly from hot hydrogen basking in the strong radiation of monster baby stars. The interaction between the hydrogen and the ultraviolet light results in its characteristic red and purple colour. The immense nebula contains over a dozen stars with at least 50 to 100 times the mass of our Sun. Such stars have a very short lifespan, a few million years at most, the blink of an eye compared with the Sun's expected lifetime of ten billion years. One of the Universe's most impressive stars, Eta Carinae, is found in the nebula. It is one of the most massive stars in our Milky Way, over 100 times the mass of the Sun and about four million times brighter, making it the most luminous star known. Eta Carinae is highly

Did clockwise rotation of Antarctica cause the break-up of Gondwanaland? An investigation in the 'deep-keeled cratons' frame for global dynamics

NASA Astrophysics Data System (ADS)

Osmaston, M. F.

2012-04-01

Introduction. The 'deep-keeled cratons' frame for global dynamics is the result of seeking Earth-behaviour answers to the following outside-the-box proposition:- "If cratons have tectospheric keels that reach or approach the 660 km discontinuity, AND the 660 level is an effective barrier to mantle circulation, then obviously (i) when two cratons separate, the upper mantle to put under the nascent ocean must arrive by a circuitous route and, conversely, (ii) if they approach one another, the mantle volume that was in between them must get extruded sideways." Surprisingly it has turned out [1 - 4] that Earth dynamical behaviour for at least the past 150 Ma provides persuasive affirmation of both these expectations and that there is a rational petrological explanation for the otherwise-unexpected immobility of subcratonic material to such depths [5 - 7]. Clockwise rotation of Antarctica? This contribution greatly amplifies my original plate dynamical arguments for suggesting [8] that such rotation is ongoing. Convection is unsuited to causing rotation about a pole within the plate so, as noted then, a gearwheel-like linkage to Africa at the SWIR would provide its clearly CCW (Biscay-Caucasus) relationship to the Mediterranean belt for the past 100 Ma, also seen in its separation from South America. Gearwheel-like linkage of motion requires the presence of some kind of E-W restraint further north. In that case it was the N Africa/Arabia involvement in the Alpide belt, but the earlier opening of the central Atlantic by the eastward motion of Africa, suggests its rigid Gondwanan attachment to Antarctica rotation at that time, with little constraint in the north. Further east, the seafloor data show that Australia-Antarctica separation involved no such opposite rotational linkage, so, with no E-W mechanical constraint in the north by Indonesia, they must have rotated together, as is recorded by Australia's eastward motion to generate the Mesozoic seafloor at its western

The MaPLE device of Saha Institute of Nuclear Physics: construction and its plasma aspects.

PubMed

Pal, Rabindranath; Biswas, Subir; Basu, Subhasis; Chattopadhyay, Monobir; Basu, Debjyoti; Chaudhuri, Manis; Chowdhuri, Manis

2010-07-01

The Magnetized Plasma Linear Experimental (MaPLE) device is a low cost laboratory plasma device at Saha Institute of Nuclear Physics fabricated in-house with the primary aim of studying basic plasma physics phenomena such as plasma instabilities, wave propagation, and their nonlinear behavior in magnetized plasma regime in a controlled manner. The machine is specially designed to be a versatile laboratory device that can provide a number of magnetic and electric scenario to facilitate such studies. A total of 36 number of 20-turn magnet coils, designed such as to allow easy handling, is capable of producing a uniform, dc magnetic field of about 0.35 T inside the plasma chamber of diameter 0.30 m. Support structure of the coils is planned in an innovative way facilitating straightforward fabrication and easy positioning of the coils. Further special feature lies in the arrangement of the spacers between the coils that can be maneuvered rather easily to create different magnetic configurations. Various methods of plasma production can be suitably utilized according to the experimental needs at either end of the vacuum vessel. In the present paper, characteristics of a steady state plasma generated by electron cyclotron resonance method using 2.45 GHz microwave power are presented. Scans using simple probe drives revealed that a uniform and long plasma column having electron density approximately 3-5x10(10) cm(-3) and temperature approximately 7-10 eV, is formed in the center of the plasma chamber which is suitable for wave launching experiments.

STS-110 Astronaut Morin Totes S0 Keel Pins During EVA

NASA Technical Reports Server (NTRS)

2002-01-01

Hovering in space some 240 miles above the blue and white Earth, STS-110 astronaut M.E. Morin participates in his first ever and second of four scheduled space walks for the STS-110 mission. He is seen toting one of the S0 (S-Zero) keel pins which were removed from their functional position on the truss and attached on the truss' exterior for long term stowage. The 43-foot-long, 27,000 pound S0 truss was the first of 9 segments that will make up the International Space Station's external framework that will eventually stretch 356 feet (109 meters), or approximately the length of a football field. This central truss segment also includes a flatcar called the Mobile Transporter and rails that will become the first 'space railroad,' which will allow the Station's robotic arm to travel up and down the finished truss for future assembly and maintenance. The completed truss structure will hold solar arrays and radiators to provide power and cooling for additional international research laboratories from Japan and Europe that will be attached to the Station. The mission completed the installations and preparations of the S0 truss and the Mobile Transporter within four space walks. STS-110 Extravehicular Activity (EVA) marked the first use of the Station's robotic arm to maneuver space walkers around the Station and was the first time all of a shuttle crew's space walks were based out of the Station's Quest Airlock. It was also the first Shuttle to use three Block II Main Engines. The Space Shuttle Orbiter Atlantis STS-110 mission was launched April 8, 2002 and returned to Earth April 19, 2002.

Upper mantle beneath foothills of the western Himalaya: subducted lithospheric slab or a keel of the Indian shield?

NASA Astrophysics Data System (ADS)

Vinnik, L.; Singh, A.; Kiselev, S.; Kumar, M. Ravi

2007-12-01

The fate of the mantle lithosphere of the Indian Plate in the India-Eurasia collision zone is not well understood. Tomographic studies reveal high P velocity in the uppermost mantle to the south of the western Himalaya, and these high velocities are sometimes interpreted as an image of subducting Indian lithosphere. We suggest that these high velocities are unrelated to the ongoing subduction but correspond to a near-horizontal mantle keel of the Indian shield. In the south of the Indian shield upper-mantle velocities are anomalously low, and relatively high velocities may signify a recovery of the normal shield structure in the north. Our analysis is based on the recordings of seismograph station NIL in the foothills of the western Himalaya. The T component of the P receiver functions is weak relative to the Q component, which is indicative of a subhorizontally layered structure. Joint inversion of the P and S receiver functions favours high uppermost mantle velocities, typical of the lithosphere of Archean cratons. The arrival of the Ps converted phase from 410 km discontinuity at NIL is 2.2 s earlier than in IASP91 global model. This can be an effect of remnants of Tethys subduction in the mantle transition zone and of high velocities in the keel of the Indian shield. Joint inversion of SKS particle motions and P receiver functions reveals a change in the fast direction of seismic azimuthal anisotropy from 60° at 80-160 km depths to 150° at 160-220 km. The fast direction in the lower layer is parallel to the trend of the Himalaya. The change of deformation regimes at a depth of 160 km suggests that this is the base of the lithosphere of the Indian shield. A similar boundary was found with similar techniques in central Europe and the Tien Shan region, but the base of the lithosphere in these regions is relatively shallow, in agreement with the higher upper-mantle temperatures. The ongoing continental collision is expressed in crustal structure: the crust

[The geometry of the keel determines the behaviour of the tibial tray against torsional forces in total knee replacement].

PubMed

García David, S; Cortijo Martínez, J A; Navarro Bermúdez, I; Maculé, F; Hinarejos, P; Puig-Verdié, L; Monllau, J C; Hernández Hermoso, J A

2014-01-01

The keel design of the tibial tray is essential for the transmission of the majority of the forces to the peripheral bone structures, which have better mechanical proprieties, thus reducing the risk of loosening. The aim of the present study was to compare the behaviour of different tibial tray designs submitted to torsional forces. Four different tibial components were modelled. The 3-D reconstruction was made using the Mimics software. The solid elements were generated by SolidWorks. The finite elements study was done by Unigraphics. A torsional force of 6 Nm. applied to the lateral aspects of each tibial tray was simulated. The GENUTECH® tibial tray, with peripheral trabecular bone support, showed a lower displacement and less transmitted tensions under torsional forces. The results suggest that a tibial tray with more peripheral support behaves mechanically better than the other studied designs. Copyright © 2013 SECOT. Published by Elsevier Espana. All rights reserved.

Optimization of papain hydrolysis conditions for release of glycosaminoglycans from the chicken keel cartilage

NASA Astrophysics Data System (ADS)

Le Vien, Nguyen Thi; Nguyen, Pham Bao; Cuong, Lam Duc; An, Trinh Thi Thua; Dao, Dong Thi Anh

2017-09-01

Glycosaminoglycans (GAGs) are natural biocompounds which join to construct cartilage tissuses, it can be extracted from cartilage of sharks, pigs, cows, chickens, etc. GAGs contain a Chondroitin sulfate (CS) content which is a supplement of functional food used for preventing and supporting treatment of arthritis and eye diseases. Therefore, the GAGs extraction from byproducts of the industry of cattle and poultry slaughter to identify the CS content by papain enzyme is necessary. In this study, the optimal hydrolysis conditions were obtained by response surface methodology (RSM). The independent variables were coded as: pH (x1), enzyme concentration (x2), incubation temperature (x3) and hydrolysis time (x4). The results of the analysis of variance (ANOVA) shown that the variables actively affected GAGs content. The optimal conditions of hydrolysis were derived at pH of 7.1, ratio of enzyme per substances of 0.62% w/wpo, temperature of 65°C and hydrolysis time of 230 minutes, GAGs content reached 14.3% of the dry matter of raw material. Analyzes by HPLC revealed that 56.17% of the dry preparations of GAGs were CS compound, were equivalent to 8.11% of the dry matter of chicken keel cartilage. Molecular weight of the dry preparations GAGs was 259.6 kDa. The dry preparations included the contents of moisture 12.2%, protein 8.42%, lipid 0%, ash 10.03% and extracted GAGs 69.35%.

Enhanced suppression of tumor growth by concomitant treatment of human lung cancer cells with suberoylanilide hydroxamic acid and arsenic trioxide

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

Chien, Chia-Wen; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan; Yao, Ju-Hsien

2011-11-15

The efficacy of arsenic trioxide (ATO) against acute promyelocytic leukemia (APL) and relapsed APL has been well documented. ATO may cause DNA damage by generating reactive oxygen intermediates. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, modulates gene and protein expression via histone-dependent or -independent pathways that may result in chromatin decondensation, cell cycle arrest, differentiation, and apoptosis. We investigated whether ATO and SAHA act synergistically to enhance the death of cancer cells. Our current findings showed that combined treatment with ATO and SAHA resulted in enhanced suppression of non-small-cell lung carcinoma in vitro in H1299 cells and in vivomore » in a xenograft mouse model. Flow cytometric analysis of annexin V+ cells showed that apoptotic cell death was significantly enhanced after combined treatment with ATO and SAHA. At the doses used, ATO did not interfere with cell cycle progression, but SAHA induced p21 expression and led to G1 arrest. A Comet assay demonstrated that ATO, but not SAHA, induced DNA strand breaks in H1299 cells; however, co-treatment with SAHA significantly increased ATO-induced DNA damage. Moreover, SAHA enhanced acetylation of histone H3 and sensitized genomic DNA to DNase I digestion. Our results suggest that SAHA may cause chromatin relaxation and increase cellular susceptibility to ATO-induced DNA damage. Combined administration of SAHA and ATO may be an effective approach to the treatment of lung cancer. -- Highlights: Black-Right-Pointing-Pointer ATO and SAHA are therapeutic agents with different action modes. Black-Right-Pointing-Pointer Combination of ATO and SAHA synergistically inhibits tumor cell growth. Black-Right-Pointing-Pointer SAHA loosens chromatin structure resulting in increased sensitivity to DNase I. Black-Right-Pointing-Pointer ATO-induced DNA damage and apoptosis are enhanced by co-treatment with SAHA.« less

Suberoylanilide hydroxamic acid increases anti-cancer effect of tumor necrosis factor-α through up-regulation of TNF receptor 1 in lung cancer cells.

PubMed

You, Bo Ra; Han, Bo Ram; Park, Woo Hyun

2017-03-14

Suberoylanilide hydroxamic acid (SAHA) as a histone deacetylase (HDAC) inhibitor has anti-cancer effect. Here, we evaluated the effect of SAHA on HDAC activity and cell growth in many normal lung and cancer cells. We observed that the HDAC activities of lung cancer cells were higher than that of normal lung cells. SAHA inhibited the growth of lung cancer cells regardless of the inhibitory effect on HDAC. This agent induced a G2/M phase arrest and apoptosis, which was accompanied by mitochondrial membrane potential (MMP: ΔΨm) loss in lung cancer cells. However, SAHA did not induce cell death in normal lung cells. All tested caspase inhibitors prevented apoptotic cell death in SAHA-treated A549 and Calu-6 lung cancer cells. Treatment with tumor necrosis factor-alpha (TNF-α) enhanced apoptosis in SAHA-treated lung cancer cells through caspase-8 and caspase-9 activations. Especially, SAHA increased the expression level of TNF-α receptor 1 (TNFR1), especially acetylation of the region of TNFR1 promoter -223/-29 in lung cancer cells. The down-regulation of TNFR1 suppressed apoptosis in TNF-α and SAHA-treated lung cancer cells. In conclusion, SAHA inhibited the growth of lung cancer cells via a G2/M phase arrest and caspase-dependent apoptosis. SAHA also enhanced apoptotic effect of TNF-α in human lung cancer cells through up-regulation of TNFR1. TNF-α may be a key to improve anti-cancer effect of HDAC inhibitors.

HDAC Inhibition Blunts Ischemia/Reperfusion Injury by Inducing Cardiomyocyte Autophagy

PubMed Central

Xie, Min; Kong, Yongli; Tan, Wei; May, Herman; Battiprolu, Pavan K.; Pedrozo, Zully; Wang, Zhao; Morales, Cyndi; Luo, Xiang; Cho, Geoffrey; Jiang, Nan; Jessen, Michael E.; Warner, John J.; Lavandero, Sergio; Gillette, Thomas G.; Turer, Aslan T.; Hill, Joseph A.

2014-01-01

Background Reperfusion accounts for a substantial fraction of the myocardial injury occurring with ischemic heart disease. Yet, no standard therapies are available targeting reperfusion injury. Here, we tested the hypothesis that SAHA, a histone deacetylase (HDAC) inhibitor FDA-approved for cancer treatment, will blunt reperfusion injury. Methods and Results Twenty-one rabbits were randomized into 3 groups: a) vehicle control, b) SAHA pretreatment (one day prior and at surgery), and c) SAHA treatment at the time of reperfusion only. Each arm was subjected to ischemia/reperfusion surgery (I/R, 30min coronary ligation, 24h reperfusion). Additionally cultured neonatal and adult rat ventricular cardiomyocytes were subjected to simulated I/R (sI/R) to probe mechanism. SAHA reduced infarct (those reduction inhibitor, SAHA, infarct size in a large animal model, even when delivered in the clinically relevant context of reperfusion. The cardioprotective effects of SAHA during I/R occur, at least in part, through induction of autophagic flux. assayed in both rabbit myocardium and in mice harboring an RFP-GFP-LC3 transgene. In cultured myocytes subjected to sI/R, SAHA pretreatment reduced cell death by 40%. This eduction in cell death correlated with increased autophagic activity in SAHA-treated cells. RNAi-mediated knockdown of ATG7 and ATG5, essential autophagy proteins, abolished SAHA's cardioprotective effects. Conclusions The FDS-approved anti-cancer HDAC inhibitor, SAHA, reduces myocardial infarct size in a large animal model, even when delivered in the clinically relevant context of reperfusion. The cardioprotective effects of SAHA during I/R occur, at least in part, through induction of autophagic flux. PMID:24396039

Histone deacetylase inhibition blunts ischemia/reperfusion injury by inducing cardiomyocyte autophagy.

PubMed

Xie, Min; Kong, Yongli; Tan, Wei; May, Herman; Battiprolu, Pavan K; Pedrozo, Zully; Wang, Zhao V; Morales, Cyndi; Luo, Xiang; Cho, Geoffrey; Jiang, Nan; Jessen, Michael E; Warner, John J; Lavandero, Sergio; Gillette, Thomas G; Turer, Aslan T; Hill, Joseph A

2014-03-11

Reperfusion accounts for a substantial fraction of the myocardial injury occurring with ischemic heart disease. Yet, no standard therapies are available targeting reperfusion injury. Here, we tested the hypothesis that suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor approved for cancer treatment by the US Food and Drug Administration, will blunt reperfusion injury. Twenty-one rabbits were randomly assigned to 3 groups: (1) vehicle control, (2) SAHA pretreatment (1 day before and at surgery), and (3) SAHA treatment at the time of reperfusion only. Each arm was subjected to ischemia/reperfusion surgery (30 minutes coronary ligation, 24 hours reperfusion). In addition, cultured neonatal and adult rat ventricular cardiomyocytes were subjected to simulated ischemia/reperfusion to probe mechanism. SAHA reduced infarct size and partially rescued systolic function when administered either before surgery (pretreatment) or solely at the time of reperfusion. SAHA plasma concentrations were similar to those achieved in patients with cancer. In the infarct border zone, SAHA increased autophagic flux, assayed in both rabbit myocardium and in mice harboring an RFP-GFP-LC3 transgene. In cultured myocytes subjected to simulated ischemia/reperfusion, SAHA pretreatment reduced cell death by 40%. This reduction in cell death correlated with increased autophagic activity in SAHA-treated cells. RNAi-mediated knockdown of ATG7 and ATG5, essential autophagy proteins, abolished SAHA's cardioprotective effects. The US Food and Drug Administration-approved anticancer histone deacetylase inhibitor, SAHA, reduces myocardial infarct size in a large animal model, even when delivered in the clinically relevant context of reperfusion. The cardioprotective effects of SAHA during ischemia/reperfusion occur, at least in part, through the induction of autophagic flux.

(7-Diethylaminocoumarin-4-yl)methyl ester of suberoylanilide hydroxamic acid as a caged inhibitor for photocontrol of histone deacetylase activity.

PubMed

Ieda, Naoya; Yamada, Sota; Kawaguchi, Mitsuyasu; Miyata, Naoki; Nakagawa, Hidehiko

2016-06-15

Histone deacetylases (HDACs) are involved in epigenetic control of the expression of various genes by catalyzing deacetylation of ε-acetylated lysine residues. Here, we report the design, synthesis and evaluation of the (7-diethylaminocoumarin-4-yl)methyl ester of suberoylanilide hydroxamic acid (AC-SAHA) as a caged HDAC inhibitor, which releases the known pan-HDAC inhibitor SAHA upon cleavage of the photolabile (7-diethylaminocoumarin-4-yl)methyl protecting group in response to photoirradiation. A key advantage of AC-SAHA is that the caged derivative itself shows essentially no HDAC-inhibitory activity. Upon photoirradiation, AC-SAHA decomposes to SAHA and a 7-diethylaminocoumarin derivative, together with some minor products. We confirmed that AC-SAHA inhibits HDAC in response to photoirradiation in vitro by means of chemiluminescence assay. AC-SAHA also showed photoinduced inhibition of proliferation of human colon cancer cell line HCT116, as determined by MTT assay. Thus, AC-SAHA should be a useful tool for spatiotemporally controlled inhibition of HDAC activity, as well as a candidate chemotherapeutic reagent for human colon cancer. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Suberoylanilide hydroxamic acid increases anti-cancer effect of tumor necrosis factor-α through up-regulation of TNF receptor 1 in lung cancer cells

PubMed Central

You, Bo Ra; Han, Bo Ram; Park, Woo Hyun

2017-01-01

Suberoylanilide hydroxamic acid (SAHA) as a histone deacetylase (HDAC) inhibitor has anti-cancer effect. Here, we evaluated the effect of SAHA on HDAC activity and cell growth in many normal lung and cancer cells. We observed that the HDAC activities of lung cancer cells were higher than that of normal lung cells. SAHA inhibited the growth of lung cancer cells regardless of the inhibitory effect on HDAC. This agent induced a G2/M phase arrest and apoptosis, which was accompanied by mitochondrial membrane potential (MMP: ΔΨm) loss in lung cancer cells. However, SAHA did not induce cell death in normal lung cells. All tested caspase inhibitors prevented apoptotic cell death in SAHA-treated A549 and Calu-6 lung cancer cells. Treatment with tumor necrosis factor-alpha (TNF-α) enhanced apoptosis in SAHA-treated lung cancer cells through caspase-8 and caspase-9 activations. Especially, SAHA increased the expression level of TNF-α receptor 1 (TNFR1), especially acetylation of the region of TNFR1 promoter −223/-29 in lung cancer cells. The down-regulation of TNFR1 suppressed apoptosis in TNF-α and SAHA-treated lung cancer cells. In conclusion, SAHA inhibited the growth of lung cancer cells via a G2/M phase arrest and caspase-dependent apoptosis. SAHA also enhanced apoptotic effect of TNF-α in human lung cancer cells through up-regulation of TNFR1. TNF-α may be a key to improve anti-cancer effect of HDAC inhibitors. PMID:28099148

The functional significance of the spinose keel structure of benthic foraminifera: inferences from Miliolina cristata Millett, 1898 (Miliolida) from northeast Romania

NASA Astrophysics Data System (ADS)

Dumitriţa Dumitriu, Simina; Dubicka, Zofia; Ionesi, Viorel

2018-01-01

The paper presents Miocene (lower Sarmatian) benthic foraminifera from the FH3P1 Rădăuţi Core section from the northwestern part of the Moldavian Platform, Romania. Based on foraminiferal assemblages we infer sediments were deposited in shallow-water, including marine-marginal environments, of varying salinities from brackish to normal marine with some short and rather small sea-level changes. Moreover, we describe for the first time in the Moldavian Platform a very rare species, Miliolina cristata Millett, which presents a characteristic spinose keel. Based on a detailed study of the test morphology and its variability, observed in picked material as well as in thin sections, we discuss some palaeoecological aspects of these foraminifera. M. cristata probably does not constitute a distinctive species, but it is more probable that some miliolid taxa developed such an exoskeletal feature in response to new environmental conditions, such as more turbulent water. Accordingly, our study would support the thesis that one of the functions of the benthic foraminiferal spines is to stabilize foraminiferal tests found in sandy substrates from high-energy environments.

The Keeling Curve and The Coral Reef Mosaic Project - Introducing the Realities of Climate Change to Educators and Scholars using Mosaic Arts.

NASA Astrophysics Data System (ADS)

Lueker, T.; Chinn, P. W. U.

2014-12-01

In May 2013, The, record of atmospheric CO2 at Mauna Loa, popularly known as "The Keeling Curve" reached 400 ppm for the first time in human history. Among the most sobering consequences of rising CO2 is Ocean Acidification, caused when the excess CO2 emitted from the burning of fossil fuels is absorbed by the surface oceans. The resulting reduction in pH harms stony corals (Scleractinia), and many other calcareous organisms. If civilization continues along the current trajectory of fossil fuel emissions, most coral reef ecosystems are expected to suffer extreme stress or mortality within the lifetime of the next generation. "If we do not reverse current trends in carbon dioxide emissions soon, we will cause the biggest and most rapid change in ocean chemistry since the extinction of the dinosaurs." (www.seaweb.org/getinvolved/oceanvoices/KenCaldeira.php). This looming tragedy is topical among marine scientists, but less appreciated or unknown to the general public, particularly among communities in the tropics where impacts to coral reef ecosystems will be severe. The Coral Reef Mosaic Project grew from my experiences leading education outreach in local schools. Making mosaics is an engaging way to enlighten educators and scholars on the pressing issues of climate change. When taking part in a mural project, students find mosaic art is a fun and rewarding experience that results in a beautiful depiction of a coral reef. Students explore the ecosystem diversity of coral reef inhabitants as they design the mural and piece together a representative environment. They work together as a team to learn the mosaic techniques and then build their own chosen creatures to inhabit the reef. The result is a beautiful and lasting mural for their school or community that provides an important message for the future. In a cooperative project with Dr. Pauline Chin at UH Manoa we traveled to Hawaii to train teachers on the Big Island in the art of mosaic and to convey the

Suberoylanilide hydroxamic acid treatment reveals crosstalks among proteome, ubiquitylome and acetylome in non-small cell lung cancer A549 cell line.

PubMed

Wu, Quan; Cheng, Zhongyi; Zhu, Jun; Xu, Weiqing; Peng, Xiaojun; Chen, Chuangbin; Li, Wenting; Wang, Fengsong; Cao, Lejie; Yi, Xingling; Wu, Zhiwei; Li, Jing; Fan, Pingsheng

2015-03-31

Suberoylanilide hydroxamic acid (SAHA) is a well-known histone deacetylase (HDAC) inhibitor and has been used as practical therapy for breast cancer and non-small cell lung cancer (NSCLC). It is previously demonstrated that SAHA treatment could extensively change the profile of acetylome and proteome in cancer cells. However, little is known about the impact of SAHA on other protein modifications and the crosstalks among different modifications and proteome, hindering the deep understanding of SAHA-mediated cancer therapy. In this work, by using SILAC technique, antibody-based affinity enrichment and high-resolution LC-MS/MS analysis, we investigated quantitative proteome, acetylome and ubiquitylome as well as crosstalks among the three datasets in A549 cells toward SAHA treatment. In total, 2968 proteins, 1099 acetylation sites and 1012 ubiquitination sites were quantified in response to SAHA treatment, respectively. With the aid of intensive bioinformatics, we revealed that the proteome and ubiquitylome were negatively related upon SAHA treatment. Moreover, the impact of SAHA on acetylome resulted in 258 up-regulated and 99 down-regulated acetylation sites at the threshold of 1.5 folds. Finally, we identified 55 common sites with both acetylation and ubiquitination, among which ubiquitination level in 43 sites (78.2%) was positive related to acetylation level.

Synergistic Effect of the Combination of Novel Suberoylanilide Hydroxamic Acid Derivatives with Cisplatin on Anti-proliferation of Human Cancer Cells.

PubMed

Xie, Rui; Shi, Jinghua; Cheng, Chunhui; Yun, Fan; Liu, Xia; Tang, Pingwah; Wu, Xinying; Yang, Ming; Yuan, Qipeng

2016-01-01

A novel, green, and atom-economical boric acid catalyzed direct amidation without the use of any coupling agents for the preparation of suberoylanilide hydroxamic acid (SAHA) and SAHA-based inhibitors targeting anti-proliferation of cancer cells is provided. The new SAHA-based inhibitor B123, when used alone, exhibited higher anti-proliferative activities than SAHA or Cisplatin against a number of human cancer cells. We have examined the effect of combination of these SAHA-based inhibitors with Cisplatin. We found synergistic effects of the combination of SAHA-based inhibitors with Cisplatin over a wide range of concentrations against human liver cancer cells HepG2 and two human lung cancer cell lines H1299 and H460. This synergism leads up to 8-fold of dose reduction for Cisplatin in the combination with our synthesized inhibitor B123 against H1299.

Suberoylanilide hydroxamic acid (vorinostat): its role on equine corneal fibrosis and matrix metalloproteinase activity.

PubMed

Donnelly, Kevin S; Giuliano, Elizabeth A; Sharm, Ajay; Mohan, Rajiv R

2014-07-01

To explore the effect of suberoylanilide hydroxamic acid (SAHA) (i) on corneal fibroblast differentiation, morphology, and viability; and (ii) on the expression levels of matrix metalloproteinases (MMPs) 2 and 9 using an in vitro model of equine corneal fibrosis. Healthy donor corneas were used to generate primary cultures of equine corneal fibroblasts. The fibroblasts were exposed to 5 ng/mL TGFβ1 to induce myofibroblast formation. The cultures were treated with either 5 μm or 10 μm SAHA for 72 h in the presence of TGFβ1. Real-time PCR and immunocytochemistry were used to determine the antifibrotic efficacy of SAHA by quantifying α-smooth muscle actin (αSMA), a marker of myofibroblast formation and fibrosis. Real-time PCR was used to determine the effects of SAHA on MMP2 and MMP9 expression. Cytotoxicity of SAHA was evaluated with phase contrast microscopy and trypan blue exclusion assays. Suberoylanilide hydroxamic acid (SAHA) significantly attenuated TGFβ1-induced differentiation of equine fibroblasts to myofibroblasts as indicated by 3- to 3.5-fold (P < 0.001) decrease in αSMA mRNA and 86-88% (P < 0.001) decrease in αSMA+ immunocytochemical staining. SAHA treatment also resulted in 4.5- to 5.5-fold (P < 0.01) decrease in MMP9 expression. A dose-dependent bimodal effect of SAHA on MMP2 expression was noted (3.5-fold increase with 5 μm dose; 0.5-fold decrease with 10 μm dose). No change in fibroblast viability was observed with a 5 μm SAHA dose, whereas a 10 μm dose resulted in a moderate 17% decrease in cell viability. Suberoylanilide hydroxamic acid (SAHA) can effectively inhibit TGFβ-induced differentiation of equine corneal fibroblasts to myofibroblasts and modulates MMP production in vitro. © 2013 American College of Veterinary Ophthalmologists.

Anti-tumor effects of suberoylanilide hydroxamic acid on Epstein–Barr virus-associated T cell and natural killer cell lymphoma

PubMed Central

Siddiquey, Mohammed NA; Nakagawa, Hikaru; Iwata, Seiko; Kanazawa, Tetsuhiro; Suzuki, Michio; Imadome, Ken-Ichi; Fujiwara, Shigeyoshi; Goshima, Fumi; Murata, Takayuki; Kimura, Hiroshi

2014-01-01

The ubiquitous Epstein–Barr virus (EBV) infects not only B cells but also T cells and natural killer (NK) cells and is associated with various lymphoid malignancies. Recent studies have reported that histone deacetylase (HDAC) inhibitors exert anticancer effects against various tumor cells. In the present study, we have evaluated both the in vitro and in vivo effects of suberoylanilide hydroxamic acid (SAHA), an HDAC inhibitor, on EBV-positive and EBV-negative T and NK lymphoma cells. Several EBV-positive and EBV-negative T and NK cell lines were treated with various concentrations of SAHA. SAHA suppressed the proliferation of T and NK cell lines, although no significant difference was observed between EBV-positive and EBV-negative cell lines. SAHA induced apoptosis and/or cell cycle arrest in several T and NK cell lines. In addition, SAHA increased the expression of EBV-lytic genes and decreased the expression of EBV-latent genes. Next, EBV-positive NK cell lymphoma cells were subcutaneously inoculated into severely immunodeficient NOD/Shi-scid/IL-2Rγnull mice, and then SAHA was administered intraperitoneally. SAHA inhibited tumor progression and metastasis in the murine xenograft model. SAHA displayed a marked suppressive effect against EBV-associated T and NK cell lymphomas through either induction of apoptosis or cell cycle arrest, and may represent an alternative treatment option. PMID:24712440

Efficacy and Safety Comparison Between Suberoylanilide Hydroxamic Acid and Mitomycin C in Reducing the Risk of Corneal Haze After PRK Treatment In Vivo.

PubMed

Anumanthan, Govindaraj; Sharma, Ajay; Waggoner, Michael; Hamm, Chuck W; Gupta, Suneel; Hesemann, Nathan P; Mohan, Rajiv R

2017-12-01

This study compared the efficacy and safety of suberoylanilide hydroxamic acid (SAHA) and mitomycin C (MMC) up to 4 months in the prevention of corneal haze induced by photorefractive keratectomy (PRK) in rabbits in vivo. Corneal haze in rabbits was produced with -9.00 diopter PRK. A single application of SAHA (25 μM) or MMC (0.02%) was applied topically immediately after PRK. Effects of the two drugs were analyzed by slit-lamp microscope, specular microscope, TUNEL assay, and immunofluorescence. Single topical adjunct use of SAHA (25 μM) or MMC (0.02%) after PRK attenuated more than 95% corneal haze and myofibroblast formation (P < .001). SAHA did not reduce keratocyte density, cause keratocyte apoptosis, or increase immune cell infiltration compared to MMC (P < .01 or .001). Furthermore, SAHA dosing did not compromise corneal endothelial phenotype, density, or function in rabbit eyes, whereas MMC application did (P < .01 or .001). SAHA and MMC significantly decreased corneal haze after PRK in rabbits in vivo. SAHA exhibited significantly reduced short- and long-term damage to the corneal endothelium compared to MMC in rabbits. SAHA is an effective and potentially safer alternative to MMC for the prevention of corneal haze after PRK. Clinical trials are warranted. [J Refract Surg. 2017;33(12):834-839.]. Copyright 2017, SLACK Incorporated.

Metabolic changes in rat serum after administration of suberoylanilide hydroxamic acid and discriminated by SVM.

PubMed

Yu, J; Wu, H; Lin, Z; Su, K; Zhang, J; Sun, F; Wang, X; Wen, C; Cao, H; Hu, L

2017-12-01

Suberoylanilide hydroxamic acid (SAHA) exerts marked anticancer effects via promotion of apoptosis, cell cycle arrest, and prevention of oncogene expression. In this study, serum metabolomics and artificial intelligence recognition were used to investigate SAHA toxicity. Forty rats (220 ± 20 g) were randomly divided into control and three SAHA groups (low, medium, and high); the experimental groups were treated with 12.3, 24.5, or 49.0 mg kg -1 SAHA once a day via intragastric administration. After 7 days, blood samples from the four groups were collected and analyzed by gas chromatography-mass spectrometry, and pathological changes in the liver were examined using microscopy. The results showed that increased levels of urea, oleic acid, and glutaconic acid were the most significant indicators of toxicity. Octadecanoic acid, pentadecanoic acid, glycerol, propanoic acid, and uric acid levels were lower in the high SAHA group. Microscopic observation revealed no obvious damage to the liver. Based on these data, a support vector machine (SVM) discrimination model was established that recognized the metabolic changes in the three SAHA groups and the control group with 100% accuracy. In conclusion, the main toxicity caused by SAHA was due to excessive metabolism of saturated fatty acids, which could be recognized by an SVM model.

Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses vasculogenic mimicry and proliferation of highly aggressive pancreatic cancer PaTu8988 cells

PubMed Central

2014-01-01

Background Pancreatic cancer is one of the most aggressive human malignancies with a extremely low 5-year survival rate. Hence, the search for more effective anti-pancreatic cancer agents is urgent. Methods PaTu8988 pancreatic cancer cells were treated with different concentrations of suberoylanilide hydroxamic acid (SAHA), cell survival, proliferation, migration and vasculogenic mimicry (VM) were analyzed. Associated signaling changes were also analyzed by RT-PCR and Western blots. Results Here, we reported that SAHA, a histone deacetylase inhibitor (HDACi), exerted significant inhibitory efficiency against pancreatic cancer cell survival, proliferation, migration and VM. SAHA dose-dependently inhibited PaTu8988 pancreatic cancer cell growth with the IC-50 of 3.4 ± 0. 7 μM. Meanwhile, SAHA suppressed PaTu8988 cell cycle progression through inducing G2/M arrest, which was associated with cyclin-dependent kinase 1 (CDK-1)/cyclin-B1 degradation and p21/p27 upregulation. Further, SAHA induced both apoptotic and non-apoptotic death of PaTu8988 cells. Significantly, SAHA suppressed PaTu8988 cell in vitro migration and cell-dominant tube formation or VM, which was accompanied by semaphorin-4D (Sema-4D) and integrin-β5 down-regulation. Our evidences showed that Akt activation might be important for Sema-4D expression in PaTu8988 cells, and SAHA-induced Sema-4D down-regulation might be associated with Akt inhibition. Conclusions This study is among the first to report the VM formation in cultured human pancreatic cancer cells. And we provided strong evidence to suggest that SAHA executes significant anti-VM efficiency in the progressive pancreatic cancer cells. Thus, SAHA could be further investigated as a promising anti-pancreatic cancer agent. PMID:24886166

PLGA-PEG Nanoparticles Coated with Anti-CD45RO and Loaded with HDAC Plus Protease Inhibitors Activate Latent HIV and Inhibit Viral Spread

NASA Astrophysics Data System (ADS)

Tang, Xiaolong; Liang, Yong; Liu, Xinkuang; Zhou, Shuping; Liu, Liang; Zhang, Fujina; Xie, Chunmei; Cai, Shuyu; Wei, Jia; Zhu, Yongqiang; Hou, Wei

2015-10-01

Activating HIV-1 proviruses in latent reservoirs combined with inhibiting viral spread might be an effective anti-HIV therapeutic strategy. Active specific delivery of therapeutic drugs into cells harboring latent HIV, without the use of viral vectors, is a critical challenge to this objective. In this study, nanoparticles of poly(lactic-co-glycolic acid)-polyethylene glycol diblock copolymers conjugated with anti-CD45RO antibody and loaded with the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) and/or protease inhibitor nelfinavir (Nel) were tested for activity against latent virus in vitro. Nanoparticles loaded with SAHA, Nel, and SAHA + Nel were characterized in terms of size, surface morphology, zeta potential, entrapment efficiency, drug release, and toxicity to ACH-2 cells. We show that SAHA- and SAHA + Nel-loaded nanoparticles can target latently infected CD4+ T-cells and stimulate virus production. Moreover, nanoparticles loaded with SAHA + NEL were capable of both activating latent virus and inhibiting viral spread. Taken together, these data demonstrate the potential of this novel reagent for targeting and eliminating latent HIV reservoirs.

Nanostructured delivery system for Suberoylanilide hydroxamic acid against lung cancer cells.

PubMed

Sankar, Renu; Karthik, Selvaraju; Subramanian, Natesan; Krishnaswami, Venkateshwaran; Sonnemann, Jürgen; Ravikumar, Vilwanathan

2015-06-01

With the objective to provide a potential approach for the treatment of lung cancer, nanotechnology based Suberoylanilide hydroxamic acid (SAHA)-loaded Poly-d, l-lactide-co glycolide (PLGA) nanoparticles have been formulated using the nanoprecipitation technique. The acquired nanoparticles were characterized by various throughput techniques and the analyses showed the presence of smooth and spherical shaped SAHA-loaded PLGA nanoparticles, with an encapsulation efficiency of 44.8% and a particle size of 208nm. The compatibility between polymer and drug in the formulation was tested using FT-IR, Micro-Raman spectrum and DSC thermogram analyses, revealing a major interaction between the drug and polymer. The in vitro drug release from the SAHA-loaded PLGA nanoparticles was found to be biphasic with an initial burst followed by a sustained release for up to 50h. In experiments using the lung cancer cell line A549, SAHA-loaded PLGA nanoparticles demonstrated a superior antineoplastic activity over free SAHA. In conclusion, SAHA-loaded PLGA nanoparticles may be a useful novel approach for the treatment of lung cancer. Copyright © 2015. Published by Elsevier B.V.

Synergistic effects of combined treatment with histone deacetylase inhibitor suberoylanilide hydroxamic acid and TRAIL on human breast cancer cells

PubMed Central

Zhou, Weiqiang; Feng, Xiuyan; Han Han; Guo, Shanchun; Wang, Guangdi

2016-01-01

Previous studies showed that either histone deacetylase (HDAC) inhibitors or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can induce apoptosis in tumor cells including breast cancer. However, the underling mechanisms of combining HDAC inhibitors with TRAIL in the treatment of breast cancer are poorly understood. In this study, we determined the ability of SAHA and TRAIL as single agents or in combination to inhibit the growth and survival of MCF-7 and MDA-MB-231 breast cancer cells. Our results demonstrate that the distinct effects of SAHA or TRAIL individually and in combination on the proliferation, cell viability, apoptosis, cell cycle distribution, and morphological changes of MDA-MB-231 and MCF-7 cells. We further determined the different effects of SAHA or TRAIL alone and combining SAHA with TRAIL on the expression of a number of apoptosis-related molecules, cell cycle, growth factors and their receptors in cancer cells. Our results demonstrated that the combinatorial treatment of SAHA and TRAIL may target multiple pathways and serve as an effective therapeutic strategy against breast cancer. An improved understanding of the molecular mechanisms may facilitate either SAHA or TRAIL targeted use and the selection of suitable combinations. PMID:27292433

Histone Deacetylase Inhibition Promotes Osteoblast Maturation by Altering the Histone H4 Epigenome and Reduces Akt Phosphorylation*

PubMed Central

Dudakovic, Amel; Evans, Jared M.; Li, Ying; Middha, Sumit; McGee-Lawrence, Meghan E.; van Wijnen, Andre J.; Westendorf, Jennifer J.

2013-01-01

Bone has remarkable regenerative capacity, but this ability diminishes during aging. Histone deacetylase inhibitors (HDIs) promote terminal osteoblast differentiation and extracellular matrix production in culture. The epigenetic events altered by HDIs in osteoblasts may hold clues for the development of new anabolic treatments for osteoporosis and other conditions of low bone mass. To assess how HDIs affect the epigenome of committed osteoblasts, MC3T3 cells were treated with suberoylanilide hydroxamic acid (SAHA) and subjected to microarray gene expression profiling and high-throughput ChIP-Seq analysis. As expected, SAHA induced differentiation and matrix calcification of osteoblasts in vitro. ChIP-Seq analysis revealed that SAHA increased histone H4 acetylation genome-wide and in differentially regulated genes, except for the 500 bp upstream of transcriptional start sites. Pathway analysis indicated that SAHA increased the expression of insulin signaling modulators, including Slc9a3r1. SAHA decreased phosphorylation of insulin receptor β, Akt, and the Akt substrate FoxO1, resulting in FoxO1 stabilization. Thus, SAHA induces genome-wide H4 acetylation and modulates the insulin/Akt/FoxO1 signaling axis, whereas it promotes terminal osteoblast differentiation in vitro. PMID:23940046

Combination of suberoylanilide hydroxamic acid with heavy ion therapy shows promising effects in infantile sarcoma cell lines

PubMed Central

2011-01-01

Introduction The pan-HDAC inhibitor (HDACI) suberoylanilide hydroxamic acid (SAHA) has previously shown to be a radio-sensitizer to conventional photon radiotherapy (XRT) in pediatric sarcoma cell lines. Here, we investigate its effect on the response of two sarcoma cell lines and a normal tissue cell line to heavy ion irradiation (HIT). Materials and methods Clonogenic assays after different doses of heavy ions were performed. DNA damage and repair were evaluated by measuring γH2AX via flow-cytometry. Apoptosis and cell cycle analysis were also measured via flow cytometry. Protein expression of repair proteins, p53 and p21 were measured using immunoblot analysis. Changes of nuclear architecture after treatment with SAHA and HIT were observed in one of the sarcoma cell lines via light microscopy after staining towards chromatin and γH2AX. Results Corresponding with previously reported photon data, SAHA lead to an increase of sensitivity to heavy ions along with an increase of DSB and apoptosis in the two sarcoma cell lines. In contrast, in the osteoblast cell line (hFOB 1.19), the combination of SAHA and HIT showed a significant radio-protective effect. Laser scanning microscopy revealed no significant morphologic changes after HIT compared to the combined treatment with SAHA. Immunoblot analysis revealed no significant up or down regulation of p53. However, p21 was significantly increased by SAHA and combination treatment as compared to HIT only in the two sarcoma cell lines - again in contrast to the osteoblast cell line. Changes in the repair kinetics of DSB p53-independent apoptosis with p21 involvement may be part of the underlying mechanisms for radio-sensitization by SAHA. Conclusion Our in vitro data suggest an increase of the therapeutic ratio by the combination of SAHA with HIT in infantile sarcoma cell lines. PMID:21933400

Tank tests to determine the effect of varying design parameters of planing-tail hulls II : effect of varying depth of step, angle of after- body keel, length of afterbody chine, and gross load

NASA Technical Reports Server (NTRS)

Dawson, John R; Mckann, Robert; Hay, Elizabeth S

1946-01-01

The second part of a series of tests made in Langley tank no. 2 to determine the effect of varying design parameters of planing-tail hulls is presented. Results are given to show the effects on resistance characteristics of varying angle of afterbody keel, depth of step, and length of afterbody chine. The effect of varying the gross load is shown for one configuration. The resistance characteristics of planing-tail hulls are compared with those of a conventional flying-boat hull. The forces on the forebody and afterbody of one configuration are compared with the forces on a conventional hull. Increasing the angle of afterbody keel had small effect on hump resistance and no effect on high-speed resistance but increased free-to-trim resistance at intermediate speeds. Increasing the depth of step increased hump resistance, had little effect on high-speed resistance, and increased free-to-trim resistance at intermediate speeds. Omitting the chines on the forward 25 percent of the afterbody had no appreciable effect on resistance. Omitting 70 percent of the chine length had almost no effect on maximum resistance but broadened the hump and increased spray around the afterbody. Load-resistance ratio at the hump decreased more rapidly with increasing load coefficient for the planing-tail hull than for the representative conventional hull, although the load-resistance ratio at the hump was greater for the planing-tail hull than for the conventional hull throughout the range of loads tested. At speeds higher than hump speed, load-resistance ratio for the planing-tail hull was a maximum at a particular gross load and was slightly less at heavier and lighter gross loads. The planing-tail hull was found to have lower resistance than the conventional hull at both the hump and at high speeds, but at intermediate speeds there was little difference. The lower hump resistance of the planing-tail hull was attributed to the ability of the afterbody to carry a greater percentage of the

Is subduction really in the plate tectonics driving seat, or do two other global mechanisms do the driving? A review in the 'deep-keeled cratons' frame for global dynamics

NASA Astrophysics Data System (ADS)

Osmaston, M. F.

2012-04-01

Introduction. The title poses a question very like that of my talk in 2003 [1], concluding then that, as a driver, subduction comes 'a doubtful third'. My purpose here is to show that subsequent developments now cause even that limited status to be denied it with great assurance, except in a rare situation, of which there is no current example. The key point is that studies of subduction have been importantly mistaken as to the nature of the plate arriving for subduction. Deep-keeled cratons? The 'deep-keeled cratons' frame for global dynamics [2 - 5] is the result of seeking Earth-behaviour guidance on the following outside-the-box proposition:- "If cratons have tectospheric keels that reach or approach the 660 km discontinuity, AND the 660 level is an effective barrier to mantle circulation, then obviously (i) when two cratons separate, the upper mantle to put under the nascent ocean must arrive by a circuitous route and, conversely, (ii) if they approach one another, the mantle volume that was in between them must get extruded sideways." Remarkably it has turned out [2 - 5] that Earth dynamical behaviour for at least the past 150 Ma provides persuasive affirmation of both these expectations and that the explanation for the otherwise-unexpected immobility of subcratonic material to such depths is a petrological one which is also applicable to the behaviour of LVZ mantle below MORs [6 - 8]. Straight away this result has major consequences for the character of the plate arriving for subduction. First, to construct them, we need a 'thick-plate' (>100km?) model of the MOR process which recognizes that this LVZ immobility renders invalid the existing concept of divergent mantle flow below MORs. I show that my now not-so-new model [1, 8 - 10], based on a deep, narrrow, wall-accreting sub-axis crack, possesses outstandingly relevant properties, even appropriately dependent on spreading rate. Second, the oceanic plate arriving for subduction is no longer just the cooled

Targeting MTA1/HIF-1alpha Signaling by Pterostilbene in Combination with Histone Deacetylase Inhibitor Attenuates Prostate Cancer Progression (Open Access)

DTIC Science & Technology

2017-08-30

stained cells in five randomly selected fields for each slide. ELISA Conditioned media from cell lines or mice sera diluted in carbonate coating buffer... ELISA . Our results showed that Pter/SAHA combination treat- ment was more effective in suppressing VEGF- c and IL- 1β circulating levels compared to...3) SAHA (50 mg/kg; n = 5), and (4) Pter + SAHA (10 mg/kg and 50 mg/kg; n = 7) by i.p. injections for 10 weeks were quantitatively analyzed by ELISA

The Therapeutic Potential of AN-7, a Novel Histone Deacetylase Inhibitor, for Treatment of Mycosis Fungoides/Sezary Syndrome Alone or with Doxorubicin.

PubMed

Moyal, Lilach; Feldbaum, Nataly; Goldfeiz, Neta; Rephaeli, Ada; Nudelman, Abraham; Weitman, Michal; Tarasenko, Nataly; Gorovitz, Batia; Maron, Leah; Yehezkel, Shiran; Amitay-Laish, Iris; Lubin, Ido; Hodak, Emmilia

2016-01-01

The 2 histone deacetylase inhibitors (HDACIs) approved for the treatment of cutaneous T-cell lymphoma (CTCL) including mycosis fungoides/sezary syndrome (MF/SS), suberoylanilide hydroxamic acid (SAHA) and romidepsin, are associated with low rates of overall response and high rates of adverse effects. Data regarding combination treatments with HDACIs is sparse. Butyroyloxymethyl diethylphosphate (AN-7) is a novel HDACI, which was found to have selective anticancer activity in several cell lines and animal models. The aim of this study was to compare the anticancer effects of AN-7 and SAHA, either alone or combined with doxorubicin, on MF/SS cell lines and peripheral blood lymphocytes (PBL) from patients with Sezary syndrome (SPBL). MyLa cells, Hut78 cells, SPBL, and PBL from healthy normal individuals (NPBL) were exposed to the test drugs, and the findings were analyzed by a viability assay, an apoptosis assay, and Western blot. AN-7 was more selectively toxic to MyLa cells, Hut78 cells, and SPBL (relative to NPBL) than SAHA and also acted more rapidly. Both drugs induced apoptosis in MF/SS cell lines, SAHA had a greater effect on MyLa cell line, while AN-7 induced greater apoptosis in SPBL; both caused an accumulation of acetylated histone H3, but AN-7 was associated with earlier kinetics; and both caused a downregulation of the HDAC1 protein in MF/SS cell lines. AN-7 acted synergistically with doxorubicin in both MF/SS cell lines and SPBL, and antagonistically with doxorubicin in NPBL. By contrast, SAHA acted antagonistically with doxorubicin on MF/SS cell lines, SPBL, and NPBL, leaving <50% viable cells. In conclusion, AN-7 holds promise as a therapeutic agent in MF/SS and has several advantages over SAHA. Our data provide a rationale for combining AN-7, but not SAHA, with doxorubicin to induce the cell death in MF/SS.

KENNEDY SPACE CENTER, FLA. - United Space Alliance employees Jeremy Schwarz (left) and Chris Keeling install new tiles on the heat shield of main engine 1 for the orbiter Discovery. A heat shield is a protective layer on a spacecraft designed to protect it from the high temperatures, usually those that result from aerobraking during reentry into the Earth’s atmosphere.

NASA Image and Video Library

2003-09-23

KENNEDY SPACE CENTER, FLA. - United Space Alliance employees Jeremy Schwarz (left) and Chris Keeling install new tiles on the heat shield of main engine 1 for the orbiter Discovery. A heat shield is a protective layer on a spacecraft designed to protect it from the high temperatures, usually those that result from aerobraking during reentry into the Earth’s atmosphere.

Altering histone acetylation status in donor cells with suberoylanilide hydroxamic acid does not affect dog cloning efficiency.

PubMed

Kim, Min Jung; Oh, Hyun Ju; Kim, Geon A; Suh, Han Na; Jo, Young Kwang; Choi, Yoo Bin; Kim, Dong Hoon; Han, Ho Jae; Lee, Byeong Chun

2015-10-15

Although dog cloning technology has been applied to conservation of endangered canids, propagation of elite dogs, and production of transgenic dogs, the efficiency of cloning is still very low. To help overcome this problem, we evaluated the effect of treating donor cells with suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, on dog cloning efficiency. Relative messenger RNA expressions of the bax1/bcl2 ratio and Dnmt1 in fibroblasts treated with different concentrations (0, 1, 10, 50 μM) of SAHA and durations (0, 20, 44 hours) were compared. Treatment with 1 μM for 20 hours showed significantly lower bax1/bcl2 and Dnmt1 transcript abundance. Acetylation of H3K9 was significantly increased after SAHA treatment, but H4K5, H4K8 and H4K16 were not changed. After SCNT using control or donor cells treated with SAHA, a total of 76 and 64 cloned embryos were transferred to seven and five recipients, respectively. Three fetuses were diagnosed in both control and SAHA-treated groups by ultrasonography 29 days after the embryo transfer, but there was no significant difference in the pregnancy rate (4.2% vs. 4.3%). In conclusion, although SAHA treatment as used in this study significantly decreased bax1/bcl2 and Dnmt1 transcripts of donor nuclei, as well as increased H3 acetylation, it was not enough to increase in vivo developmental competence of cloned dog embryos. Copyright © 2015 Elsevier Inc. All rights reserved.

The Therapeutic Potential of AN-7, a Novel Histone Deacetylase Inhibitor, for Treatment of Mycosis Fungoides/Sezary Syndrome Alone or with Doxorubicin

PubMed Central

Goldfeiz, Neta; Rephaeli, Ada; Nudelman, Abraham; Weitman, Michal; Tarasenko, Nataly; Gorovitz, Batia; Maron, Leah; Yehezkel, Shiran; Amitay-Laish, Iris; Lubin, Ido; Hodak, Emmilia

2016-01-01

The 2 histone deacetylase inhibitors (HDACIs) approved for the treatment of cutaneous T-cell lymphoma (CTCL) including mycosis fungoides/sezary syndrome (MF/SS), suberoylanilide hydroxamic acid (SAHA) and romidepsin, are associated with low rates of overall response and high rates of adverse effects. Data regarding combination treatments with HDACIs is sparse. Butyroyloxymethyl diethylphosphate (AN-7) is a novel HDACI, which was found to have selective anticancer activity in several cell lines and animal models. The aim of this study was to compare the anticancer effects of AN-7 and SAHA, either alone or combined with doxorubicin, on MF/SS cell lines and peripheral blood lymphocytes (PBL) from patients with Sezary syndrome (SPBL). MyLa cells, Hut78 cells, SPBL, and PBL from healthy normal individuals (NPBL) were exposed to the test drugs, and the findings were analyzed by a viability assay, an apoptosis assay, and Western blot. AN-7 was more selectively toxic to MyLa cells, Hut78 cells, and SPBL (relative to NPBL) than SAHA and also acted more rapidly. Both drugs induced apoptosis in MF/SS cell lines, SAHA had a greater effect on MyLa cell line, while AN-7 induced greater apoptosis in SPBL; both caused an accumulation of acetylated histone H3, but AN-7 was associated with earlier kinetics; and both caused a downregulation of the HDAC1 protein in MF/SS cell lines. AN-7 acted synergistically with doxorubicin in both MF/SS cell lines and SPBL, and antagonistically with doxorubicin in NPBL. By contrast, SAHA acted antagonistically with doxorubicin on MF/SS cell lines, SPBL, and NPBL, leaving <50% viable cells. In conclusion, AN-7 holds promise as a therapeutic agent in MF/SS and has several advantages over SAHA. Our data provide a rationale for combining AN-7, but not SAHA, with doxorubicin to induce the cell death in MF/SS. PMID:26752418

76 FR 27987 - Circular Welded Carbon Steel Pipes and Tubes From Thailand: Amended Final Results of Antidumping...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

... Pipes and Tubes From Thailand: Amended Final Results of Antidumping Duty Administrative Review Pursuant... tubes from Thailand, which covered Saha Thai Steel Pipe (Public) Co., Ltd. (Saha Thai) and the period March 1, 2006, through February 28, 2007. See Circular Welded Carbon Steel Pipes and Tubes from Thailand...

Alterations in histone acetylation following exposure to 60Co γ-rays and their relationship with chromosome damage in human lymphoblastoid cells.

PubMed

Tian, Xue-Lei; Lu, Xue; Feng, Jiang-Bin; Cai, Tian-Jing; Li, Shuang; Tian, Mei; Liu, Qing-Jie

2018-05-17

Chromosome damage is related to DNA damage and erroneous repair. It can cause cell dysfunction and ultimately induce carcinogenesis. Histone acetylation is crucial for regulating chromatin structure and DNA damage repair. Ionizing radiation (IR) can alter histone acetylation. However, variations in histone acetylation in response to IR exposure and the relationship between histone acetylation and IR-induced chromosome damage remains unclear. Hence, this study investigated the variation in the total acetylation levels of H3 and H4 in human lymphocytes exposed to 0-2 Gy 60 Co γ-rays. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, was added to modify the histone acetylation state of irradiated cells. Then, the total acetylation level, enzyme activity, dicentric plus centric rings (dic + r) frequencies, and micronucleus (MN) frequencies of the treated cells were analyzed. Results indicated that the acetylation levels of H3 and H4 significantly decreased at 1 and 24 h, respectively, after radiation exposure. The acetylation levels of H3 and H4 in irradiated groups treated with SAHA were significantly higher than those in irradiated groups that were not treated with SAHA. SAHA treatment inhibited HDAC activity in cells exposed to 0-1 Gy 60 Co γ-rays. SAHA treatment significantly decreased dic + r/cell and MN/cell in cells exposed to 0.5 or 1.0 Gy 60 Co γ-rays relative to that in cells that did not receive SAHA treatment. In conclusion, histone acetylation is significantly affected by IR and is involved in chromosome damage induced by 60 Co γ-radiation.

Effect of a Histone Deacetylases Inhibitor of IL-18 and TNF-Alpha Secretion in Vitro.

PubMed

Dobreva, Zlatka Georgieva; Grigorov, Boncho Grigorov; Stanilova, Spaska Angelova

2018-02-15

Interleukin-18 (IL-18) and Tumor Necrosis Factor-alpha (TNF-α) are proinflammatory cytokines that increased the development of Th1 immune response, but have a different type of regulation of the gene expression. Whereas TNF-α has an inducible expression, IL-18 is translated as an inactive protein and required proteolytic cleavage by Casp-1 in inflammasome complexes. To investigate the effect of the histone deacetylases inhibitor Suberoylanilide Hydroxamic Acid (SAHA) on the gene expression and secretion of both cytokines, IL-18 and TNF-α, according to their contribution to the cancer development and anticancer immunity. Isolated peripheral blood mononuclear cells (PBMC) were stimulated with LPS and C3bgp with or without SAHA. Cytokine production was assessed by ELISA at 6 and 24h. IL-18 and TNF-α secretion was significantly increased at 6h and 24h in response to stimulation. TNF-α production from stimulated PBMC was downregulated by SAHA at 6 and 24h. Treatment with SAHA does not inhibit the secretion of IL-18 significantly either at 6 or 24h of stimulation. The inhibition of histone deacetylases by SAHA does not influence the inflammasome-dependent production of immunologically active IL-18. In contrast, the production of proinflammatory TNF-α in cultures was mediated by the activity of HDAC class I and class II enzymes.

Evaluation of 4 years of continuous δ13C(CO2) data using a moving Keeling plot method

NASA Astrophysics Data System (ADS)

Vardag, Sanam Noreen; Hammer, Samuel; Levin, Ingeborg

2016-07-01

Different carbon dioxide (CO2) emitters can be distinguished by their carbon isotope ratios. Therefore measurements of atmospheric δ13C(CO2) and CO2 concentration contain information on the CO2 source mix in the catchment area of an atmospheric measurement site. This information may be illustratively presented as the mean isotopic source signature. Recently an increasing number of continuous measurements of δ13C(CO2) and CO2 have become available, opening the door to the quantification of CO2 shares from different sources at high temporal resolution. Here, we present a method to compute the CO2 source signature (δS) continuously and evaluate our result using model data from the Stochastic Time-Inverted Lagrangian Transport model. Only when we restrict the analysis to situations which fulfill the basic assumptions of the Keeling plot method does our approach provide correct results with minimal biases in δS. On average, this bias is 0.2 ‰ with an interquartile range of about 1.2 ‰ for hourly model data. As a consequence of applying the required strict filter criteria, 85 % of the data points - mainly daytime values - need to be discarded. Applying the method to a 4-year dataset of CO2 and δ13C(CO2) measured in Heidelberg, Germany, yields a distinct seasonal cycle of δS. Disentangling this seasonal source signature into shares of source components is, however, only possible if the isotopic end members of these sources - i.e., the biosphere, δbio, and the fuel mix, δF - are known. From the mean source signature record in 2012, δbio could be reliably estimated only for summer to (-25.0 ± 1.0) ‰ and δF only for winter to (-32.5 ± 2.5) ‰. As the isotopic end members δbio and δF were shown to change over the season, no year-round estimation of the fossil fuel or biosphere share is possible from the measured mean source signature record without additional information from emission inventories or other tracer measurements.

Enhancement of Radiation Response in Osteosarcoma and Rhabomyosarcoma Cell Lines by Histone Deacetylase Inhibition

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

Blattmann, Claudia, E-mail: claudia.blattmann@med.uni-heidelberg.d; Oertel, Susanne; Ehemann, Volker

2010-09-01

Purpose: Histone deacetylase inhibitors (HDACIs) can enhance the sensitivity of cells to photon radiation treatment (XRT) by altering numerous molecular pathways. We investigated the effect of pan-HDACIs such as suberoylanilide hydroxamic acid (SAHA) on radiation response in two osteosarcoma (OS) and two rhabdomyosarcoma (RMS) cell lines. Methods and Materials: Clonogenic survival, cell cycle analysis, and apoptosis were examined in OS (KHOS-24OS, SAOS2) and RMS (A-204, RD) cell lines treated with HDACI and HDACI plus XRT, respectively. Protein expression was investigated via immunoblot analysis, and cell cycle analysis and measurement of apoptosis were performed using flow cytometry. Results: SAHA induced anmore » inhibition of cell proliferation and clonogenic survival in OS and RMS cell lines and led to a significant radiosensitization of all tumor cell lines. Other HDACI such as M344 and valproate showed similar effects as investigated in one OS cell line. Furthermore, SAHA significantly increased radiation-induced apoptosis in the OS cell lines, whereas in the RMS cell lines radiation-induced apoptosis was insignificant with and without SAHA. In all investigated sarcoma cell lines, SAHA attenuated radiation-induced DNA repair protein expression (Rad51, Ku80). Conclusion: Our results show that HDACIs enhance radiation action in OS and RMS cell lines. Inhibition of DNA repair, as well as increased apoptosis induction after exposure to HDACIs, can be mechanisms of radiosensitization by HDACIs.« less

Toward a Molecular Understanding of Noise-Induced Hearing Loss

DTIC Science & Technology

2017-10-01

cell, SAHA, Heat shock, sex differences 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON...threshold shift, Temporary threshold shift, Noise induced hearing loss, Ribotag, RNA-seq, Hair cell, Supporting cell, SAHA, Heat shock, Sex ...also sex -specific. TTS-inducing noise exposure: crosses, calibration, validation cytocochleograms, noise exposure, tissue harvesting, polysome IP

Selective inhibition of histone deacetylase 6 (HDAC6) induces DNA damage and sensitizes transformed cells to anticancer agents.

PubMed

Namdar, Mandana; Perez, Gisela; Ngo, Lang; Marks, Paul A

2010-11-16

Histone deacetylase 6 (HDAC6) is structurally and functionally unique among the 11 human zinc-dependent histone deacetylases. Here we show that chemical inhibition with the HDAC6-selective inhibitor tubacin significantly enhances cell death induced by the topoisomerase II inhibitors etoposide and doxorubicin and the pan-HDAC inhibitor SAHA (vorinostat) in transformed cells (LNCaP, MCF-7), an effect not observed in normal cells (human foreskin fibroblast cells). The inactive analogue of tubacin, nil-tubacin, does not sensitize transformed cells to these anticancer agents. Further, we show that down-regulation of HDAC6 expression by shRNA in LNCaP cells enhances cell death induced by etoposide, doxorubicin, and SAHA. Tubacin in combination with SAHA or etoposide is more potent than either drug alone in activating the intrinsic apoptotic pathway in transformed cells, as evidenced by an increase in PARP cleavage and partial inhibition of this effect by the pan-caspase inhibitor Z-VAD-fmk. HDAC6 inhibition with tubacin induces the accumulation of γH2AX, an early marker of DNA double-strand breaks. Tubacin enhances DNA damage induced by etoposide or SAHA as indicated by increased accumulation of γH2AX and activation of the checkpoint kinase Chk2. Tubacin induces the expression of DDIT3 (CHOP/GADD153), a transcription factor up-regulated in response to cellular stress. DDIT3 induction is further increased when tubacin is combined with SAHA. These findings point to mechanisms by which HDAC6-selective inhibition can enhance the efficacy of certain anti-cancer agents in transformed cells.

SPARKy-Spring Ankle with Regenerative Kinematics

DTIC Science & Technology

2011-09-01

fiber keel. In our design considerations, we kept the passive carbon fiber keel to allow for walking in the event of battery failure. b. Test...used include a motor encoder, ankle encoder, and a heel switch. 7. Energy efficient carbon fiber keel is integrated into the device. Figure 6... Isometric and side views of SPARKy Phase 1 as modeled in SolidWorks. The Robotic Tendon actuator provides a dynamic moment about the ankle joint. Lever

Inhibition of Histone Deacetylases Attenuates Morphine Tolerance and Restores MOR Expression in the DRG of BCP Rats.

PubMed

He, Xiao-Tao; Zhou, Kai-Xiang; Zhao, Wen-Jun; Zhang, Chen; Deng, Jian-Ping; Chen, Fa-Ming; Gu, Ze-Xu; Li, Yun-Qing; Dong, Yu-Lin

2018-01-01

The easily developed morphine tolerance in bone cancer pain (BCP) significantly hindered its clinical use. Increasing evidence suggests that histone deacetylases (HDACs) regulate analgesic tolerance subsequent to continuous opioid exposure. However, whether HDACs contribute to morphine tolerance in the pathogenesis of BCP is still unknown. In the current study, we explored the possible engagement of HDACs in morphine tolerance during the pathogenesis of BCP. After intra-tibia tumor cell inoculation (TCI), we found that the increased expression of HDACs was negatively correlated with the decreased expression of MOR in the DRG following TCI. The paw withdrawal threshold (PWT) and percentage maximum possible effects (MPEs) decreased rapidly in TCI rats when morphine was used alone. In contrast, the concomitant use of SAHA and morphine significantly elevated the PWT and MPEs of TCI rats compared to morphine alone. Additionally, we found that SAHA administration significantly elevated MOR expression in the DRG of TCI rats with or without morphine treatment. Moreover, the TCI-induced increase in the co-expression of MOR and HDAC1 in neurons was significantly decreased after SAHA administration. These results suggest that HDACs are correlated with the downregulation of MOR in the DRG during the pathogenesis of BCP. Inhibition of HDACs using SAHA can be used to attenuate morphine tolerance in BCP.

An efficient synthesis of SK-658 and its analogs as potent histone deacetylase inhibitors.

PubMed

Shahidul Islam, Md; Nurul Islam, Md; Ashraful Hoque, Md; Nishino, Norikazu; Kato, Tamaki; Kim, Hyun-Jung; Ito, Akihiro; Yoshida, Minoru

2015-04-01

SK-658 is a potent histone deacetylase (HDAC) inhibitor that showed higher activity than SAHA due to the presence of extended hydrophobic group. We designed and synthesized thioester and SS-hybrid bearing SK-658 analogs as HDAC inhibitors. All the compounds were active in nano molar range and showed higher inhibitory activity than SAHA and SK-658. Among these, disulfide compounds showed the highest activity. Copyright © 2015 Elsevier Inc. All rights reserved.

Enhancement of Radiation Therapy in Prostate Cancer by DNA-PKcs Inhibitor

DTIC Science & Technology

2013-07-01

Dawen Zhao, Masaya Takahashi, Timothy Dobin, Leah Gandee, Timothy D. Solberg, Amyn A. Habib and Debabrata Saha; International Journal of Oncology, 42...5] Kong Z, Xie D, Boike T, Raghavan P, Burma S, Chen DJ, Habib AA, Chakraborty A, Hsieh JT, and Saha D (2010). Downregulation of human DAB2IP gene...study. Phys Med Biol 56: 1243-1258, 2011. 4. De Crevoisier R, Tucker SL , Dong L, et al: Increased risk of biochemical and local failure in patients

Histone Deacetylase Inhibitors Are Protective in Acute but Not in Chronic Models of Ototoxicity.

PubMed

Yang, Chao-Hui; Liu, Zhiqi; Dong, Deanna; Schacht, Jochen; Arya, Dev; Sha, Su-Hua

2017-01-01

Previous studies have reported that modification of histones alters aminoglycoside-induced hair cell death and hearing loss. In this study, we investigated three FDA-approved histone deacetylase (HDAC) inhibitors (vorinostat/SAHA, belinostat, and panobinostat) as protectants against aminoglycoside-induced ototoxicity in murine cochlear explants and in vivo in both guinea pigs and CBA/J mice. Individually, all three HDAC inhibitors reduced gentamicin (GM)-induced hair cell loss in a dose-dependent fashion in explants. In vivo , however, treatment with SAHA attenuated neither GM-induced hearing loss and hair cell loss in guinea pigs nor kanamycin (KM)-induced hearing loss and hair cell loss in mice under chronic models of ototoxicity. These findings suggest that treatment with the HDAC inhibitor SAHA attenuates aminoglycoside-induced ototoxicity in an acute model, but not in chronic models, cautioning that one cannot rely solely on in vitro experiments to test the efficacy of otoprotectant compounds.

Formula for the rms blur circle radius of Wolter telescope based on aberration theory

NASA Technical Reports Server (NTRS)

Shealy, David L.; Saha, Timo T.

1990-01-01

A formula for the rms blur circle for Wolter telescopes has been derived using the transverse ray aberration expressions of Saha (1985), Saha (1984), and Saha (1986). The resulting formula for the rms blur circle radius over an image plane and a formula for the surface of best focus based on third-, fifth-, and seventh-order aberration theory predict results in good agreement with exact ray tracing. It has also been shown that one of the two terms in the empirical formula of VanSpeybroeck and Chase (1972), for the rms blur circle radius of a Wolter I telescope can be justified by the aberration theory results. Numerical results are given comparing the rms blur radius and the surface of best focus vs the half-field angle computed by skew ray tracing and from analytical formulas for grazing incidence Wolter I-II telescopes and a normal incidence Cassegrain telescope.

Early Outcomes of Primary Total Hip Arthroplasty After Prior Lumbar Spinal Fusion.

PubMed

Barry, Jeffrey J; Sing, David C; Vail, Thomas P; Hansen, Erik N

2017-02-01

The coexistence of degenerative hip disease and spinal pathology is not uncommon with the number of surgical treatments performed for each condition increasing annually. The limited research available suggests spinal pathology portends less pain relief and worse outcomes after total hip arthroplasty (THA). We hypothesize that primary THA patients with preexisting lumbar spinal fusions (LSF) experience worse early postoperative outcomes. This study is a retrospective matched cohort study. Primary THA patients at 1 institution who had undergone prior LSF (spine arthrodesis-hip arthroplasty [SAHA]) were identified and matched to controls of primary THA without LSF. Early outcomes (<90 days) were compared. From 2012 to 2014, 35 SAHA patients were compared to 70 matched controls. Patients were similar in age, sex, American Society of Anesthesiologist score, body mass index, and Charlson Comorbidity Index. SAHA patients had higher rates of complications (31.4% vs 8.6%, P = .008), reoperation (14.3% vs 2.9%, P = .040), and general anesthesia (54.3% vs 5.7%, P = .0001). Bivariate analysis demonstrated SAHA to predict reoperation (odds ratio, 5.67; P = .045) and complications (odds ratio, 4.89; P = .005). With the numbers available, dislocations (0% vs 2.8%), infections (0% vs 8.6%), readmissions, postoperative walking distance, and disposition only trended to favor controls (P > .05). Comparing controls to SAHA patients with <3 or ≥3 levels fused, longer fusions had increased cumulative postoperative narcotic consumption (mean morphine equivalents, 44.3 vs 46.9 vs 169.4; P = .001). Patients with preexisting LSF experience worse early outcomes after primary THA including higher rates of complications and reoperation. Lower rates of neuraxial anesthesia and increased narcotic usage represent potential contributors. The complex interplay between the lumbar spine and hip warrants attention and further investigation. Copyright © 2016 Elsevier Inc. All rights reserved.

In Vitro Plasma Stability, Permeability and Solubility of Mercaptoacetamide Histone Deacetylase Inhibitors

PubMed Central

Konsoula, Roula; Jung, Mira

2008-01-01

Histone deacetylase inhibitors (HDACIs) are emerging as a new class of therapeutic agents with potent antitumor activities in a broad spectrum of human cancers. In this study, the in vitro plasma stability, permeability, solubility, and lipophilicity (logD) of two mercaptoacetamide-based HDACIs (coded as W2 and S2) were evaluated and compared to Vorinostat (SAHA). The results demonstrated that the compounds manifested high solubility in HCl (pH 1.2) but lower in PBS (pH 7.4) than SAHA. Moreover, mercaptoacetamide-based HDACIs exhibited higher lipophilicity values compared to SAHA. The permeability of these compounds was evaluated using the Caco-2 cell monolayer as a model of the intestinal mucosa. The Caco-2 studies revealed that the compounds S2 and W2 are highly permeable with apparent permeability coefficients (Papp) in the apical to basolateral direction of 7.33 × 10−6 and 15.0 × 10−6 cm/s, respectively. The in vitro stability was determined in human, mouse, porcine and rat plasma. Data showed that the compound W2 is more stable in human and rat plasma and the S2 is more stable in all plasma species than SAHA. Taken together, these results indicate that the mercaptoacetamide-based HDACIs possess favorable solubility, lipophilicity, permeability and plasma stability features. PMID:18562136

Synthesis and biochemical analysis of 2,2,3,3,4,4,5,5,6,6,7,7-dodecafluoro-N-hydroxy-octanediamides as inhibitors of human histone deacetylases.

PubMed

Henkes, Leonhard M; Haus, Patricia; Jäger, Felix; Ludwig, Joachim; Meyer-Almes, Franz-Josef

2012-01-15

Inhibition of human histone deacetylases (HDACs) has emerged as a novel concept in the chemotherapeutic treatment of cancer. Two chemical entities, SAHA (ZOLINZA, Merck) and romidepsin (Istodax, Celgene) have been recently approved by the FDA as first-in-class drugs against cutaneous T-cell lymphoma. Clinical use of these drugs revealed several side effects including gastro-intestinal symptoms, fatigue, thrombocytopenia, thrombosis. Romidepsin is associated with an yet unresolved cardiotoxicity issue. A general hypothesis for the diminishment of unwanted adverse effects and an improved therapeutical window suggests the development of more isotype selective inhibitors. In this study the first time HDAC inhibitors with perfluorinated spacers between the zinc chelating moiety and the aromatic capping group were synthesized and tested against representatives of HDAC classes I, IIa and IIb. Competitive binding assays and a combined approach by using blind docking and molecular dynamics support binding of the perfluorinated analogs of SAHA to the active site of the HDAC-like amidohydrolase from Bordetella/Alcaligenes and presumably also to human HDACs. In contrast to the alkyl spacer of SAHA and derivatives, the perfluorinated alkyl spacer seems to contribute to or facilitate the induction of selectivity for class II, particularly class IIa, HDACs even though the overall potency of the perfluorinated SAHA analogs in this study against human HDACs remained still rather moderate in the micromolar range. Copyright © 2011 Elsevier Ltd. All rights reserved.

Identification of a better Homo sapiens Class II HDAC inhibitor through binding energy calculations and descriptor analysis

PubMed Central

2010-01-01

Human papillomaviruses (HPVs) are the most common on sexually transmitted viruses in the world. HPVs are responsible for a large spectrum of deseases, both benign and malignant. The certain types of HPV are involved in the development of cervical cancer. In attemps to find additional drugs in the treatment of cervical cancer, inhibitors of the histone deacetylases (HDAC) have received much attention due to their low cytotoxic profiles and the E6/E7 oncogene function of human papilomavirus can be completely by passed by HDAC inhibition. The histone deacetylase inhibitors can induce growth arrest, differentiation and apoptosis of cancer cells. HDAC class I and class II are considered the main targets for cancer. Therefore, the six HDACs class II was modeled and about two inhibitors (SAHA and TSA) were docked using AutoDock4.2, to each of the inhibitor in order to identify the pharmacological properties. Based on the results of docking, SAHA and TSA were able to bind with zinc ion in HDACs models as a drug target. SAHA was satisfied almost all the properties i.e., binding affinity, the Drug-Likeness value and Drug Score with 70% oral bioavailability and the carbonyl group of these compound fits well into the active site of the target where the zinc is present. Hence, SAHA could be developed as potential inhibitors of class II HDACs and valuable cervical cancer drug candidate. PMID:21106123

Identification of a better Homo sapiens Class II HDAC inhibitor through binding energy calculations and descriptor analysis.

PubMed

Tambunan, Usman Sumo Friend; Wulandari, Evi Kristin

2010-10-15

Human papillomaviruses (HPVs) are the most common on sexually transmitted viruses in the world. HPVs are responsible for a large spectrum of deseases, both benign and malignant. The certain types of HPV are involved in the development of cervical cancer. In attemps to find additional drugs in the treatment of cervical cancer, inhibitors of the histone deacetylases (HDAC) have received much attention due to their low cytotoxic profiles and the E6/E7 oncogene function of human papilomavirus can be completely by passed by HDAC inhibition. The histone deacetylase inhibitors can induce growth arrest, differentiation and apoptosis of cancer cells. HDAC class I and class II are considered the main targets for cancer. Therefore, the six HDACs class II was modeled and about two inhibitors (SAHA and TSA) were docked using AutoDock4.2, to each of the inhibitor in order to identify the pharmacological properties. Based on the results of docking, SAHA and TSA were able to bind with zinc ion in HDACs models as a drug target. SAHA was satisfied almost all the properties i.e., binding affinity, the Drug-Likeness value and Drug Score with 70% oral bioavailability and the carbonyl group of these compound fits well into the active site of the target where the zinc is present. Hence, SAHA could be developed as potential inhibitors of class II HDACs and valuable cervical cancer drug candidate.

SKS Anisotropy Measurements in Mid-Plate South America: a Test of Subduction-Induced Upper Mantle Flow and the Effect of Cratonic Keels

NASA Astrophysics Data System (ADS)

Assumpcao, M.; Melo, B. C.

2017-12-01

Shear-wave splitting from core-refracted (SKS) waves indicates the amount and orientation of seismic anisotropy in the upper mantle, and is used to infer past and present mantle dynamics and continental evolution. Previous SKS studies in South America concentrated mainly in the Andes and in SE Brazil. Although effects of frozen anisotropy in the lithospheric mantle were suggested in some parts of SE Brazil, the main contribution to the orientation of the fast polarization directions have been attributed to asthenospheric flow around cratonic keels, especially around the São Francisco craton in eastern Brazil (Assumpção et al., 2006,2011). We added extra SKS splitting measurements in the area of the Pantanal and Paraná-Chaco basins (FAPESP-funded "3-Basins" Project). Results from 47 new stations will be presented, both from the temporary deployments and from the Brazilian permanent net. This data set partly fills the gap in SKS measurements between the Andes and SE Brazil, providing a more complete and robust anisotropy map of the S. American stable platform. On average, over most of the mid-continent, the fast polarization orientation tends to be close to the absolute plate motion given by the hotspot reference frame HS3-NUVEL-1A. Nevertheless, the new and previously published fast polarizations results suggest mantle flow around the Amazon and São Francisco cratons. A comparison with recent modeling of upper mantle flow induced by the Nazca plate subduction (Hu et al., 2017) shows good agreement with the predictions of mantle flow around the Amazon craton. Further south, however, especially in the Pantanal Basin, the observed SKS fast orientations are ENE-WSW, deviating from the general ESE-WNW predicted orientations. We propose that the observed ENE-WSW orientation may be due to flow around a possible cratonic nucleus beneath the northern part of the Paraná Basin ("Paranapanema block"). This cratonic block (inferred from geological observations) is also

Role of relativity in electron impact ionization

NASA Astrophysics Data System (ADS)

Saha, Bidhan C.; Basak, Arun K.; Alfaz Uddin, M.

2006-03-01

The recently modified MBELL parameters[1] are generalized in terms of nl quantum numbers and applied to few selective systems. We intend to describe the procedure and to report the excellent predictive role of this simple procedure[2]. [1] A. K. F. Haque, M. A. Uddin, A.K. Basak, K. R. Karim and B. C. Saha, Phys. Rev. A 76 (in press) [2] A. K. F. Haque, M. A. Uddin, A.K. Basak, K. R. Karim, B. C. Saha, and F. B. Malik, Phys. Rev. Lett (under consideration)

A cyclodextrin-capped histone deacetylase inhibitor.

PubMed

Amin, Jahangir; Puglisi, Antonino; Clarke, James; Milton, John; Wang, Minghua; Paranal, Ronald M; Bradner, James E; Spencer, John

2013-06-01

We have synthesized a β-cyclodextrin (βCD)-capped histone deacetylase (HDAC) inhibitor 3 containing an alkyl linker and a zinc-binding hydroxamic acid motif. Biological evaluation (HDAC inhibition studies) of 3 enabled us to establish the effect of replacing an aryl cap (in SAHA (vorinostat,)) 1 by a large saccharidic scaffold "cap". HDAC inhibition was observed for 3, to a lesser extent than SAHA, and rationalized by molecular docking into the active site of HDAC8. However, compound 3 displayed no cellular activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bias and uncertainty of δ13CO2 isotopic mixing models

Treesearch

Zachary E. Kayler; Lisa Ganio; Mark Hauck; Thomas G. Pypker; Elizabeth W. Sulzman; Alan C. Mix; Barbara J. Bond

2009-01-01

The goal of this study was to evaluate how factorial combinations of two mixing models and two regression approaches (Keeling-OLS, Miller—Tans-OLS, Keeling-GMR, Miller—Tans-GMR) compare in small [CO2] range versus large[CO2] range regimes, with different combinations of...

Epigenetic therapy potential of suberoylanilide hydroxamic acid on invasive human non-small cell lung cancer cells.

PubMed

Zhang, Shirong; Wu, Kan; Feng, Jianguo; Wu, Zhibing; Deng, Qinghua; Guo, Chao; Xia, Bing; Zhang, Jing; Huang, Haixiu; Zhu, Lucheng; Zhang, Ke; Shen, Binghui; Chen, Xufeng; Ma, Shenglin

2016-10-18

Metastasis is the reason for most cancer death, and a crucial primary step for cancer metastasis is invasion of the surrounding tissue, which may be initiated by some rare tumor cells that escape the heterogeneous primary tumor. In this study, we isolated invasive subpopulations of cancer cells from human non-small cell lung cancer (NSCLC) H460 and H1299 cell lines, and determined the gene expression profiles and the responses of these invasive cancer cells to treatments of ionizing radiation and chemotherapeutic agents. The subpopulation of highly invasive NSCLC cells showed epigenetic signatures of epithelial-mesenchymal transition, cancer cell stemness, increased DNA damage repair and cell survival signaling. We also investigated the epigenetic therapy potential of suberoylanilide hydroxamic acid (SAHA) on invasive cancer cells, and found that SAHA suppresses cancer cell invasiveness and sensitizes cancer cells to treatments of IR and chemotherapeutic agents. Our results provide guidelines for identification of metastatic predictors and for clinical management of NSCLC. This study also suggests a beneficial clinical potential of SAHA as a chemotherapeutic agent for NSCLC patients.

Monthly Atmospheric 13C/12C Isotopic Ratios for 11 SIO Stations (1977-2008)

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

Keeling, R. F.; Piper, S. C.; Bollenbacher, A. F.

Stable isotopic measurements for atmospheric 13C/12C and 18O/16O at global sampling sites were initiated by Dr. C.D. Keeling and co-workers at Scripps Institution of Oceanography (SIO) in 1977. These isotopic measurements complement the continuing global atmospheric and oceanic CO2 measurements initiated by Keeling in 1957. This work is currently being continued under the direction of R.F. Keeling, who also runs a parallel program at SIO to measure changes in atmospheric O2 and Ar abundances (Scripps O2 Program). A more complete set of 13CO2 data is found online at http://scrippsco2.ucsd.edu/data/atmospheric_co2.html

HDAC inhibitor-loaded bone cement for advanced local treatment of osteosarcoma and chondrosarcoma.

PubMed

Tonak, Marcus; Becker, Marc; Graf, Claudine; Eckhard, Lukas; Theobald, Matthias; Rommens, Pol-Maria; Wehler, Thomas C; Proschek, Dirk

2014-11-01

The treatment of osteosarcoma, especially wide resection, is challenging. An additional local drug therapy after resection using anti-neoplastic bone cement (Polymethylmethacrylate (PMMA)) could help improve the outcome of therapy. In this study, we evaluated the effects of PMMA loaded with valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) on the cell activity of a SaOs-2 cell culture, as well as the elution rate of the drugs out of the bone cement. In our experiments, we used the SaOs-2 osteosarcoma and the SW1353 chondrosarcoma cell line. Bone cement clots (5 g) were prepared and loaded with different drug concentrations of VPA (25 mg and 50 mg) and SAHA (1 mg, 2.5 mg and 5 mg). Two control groups were established, one with a native cement clot, the other with human mesenchymal stem cells, in order to evaluate toxicity on non tumor-cells. Cell activity was measured using an Alamar Blue assay on days 1, 2, 3, 4 and 7. The cement clots were additionally examined in a material testing unit for biomechanical and structural changes. Tumor cells showed a significant and complete reduction of activity under therapy with VPA and SAHA. Drug release of VPA was extensive between days 0 and 3 and decreased progressively to day 7. Cumulative drug concentration in the medium continuously increased. Biomechanical testing of the cement clots showed no differences in stability and architecture compared to the control group. SaOs-2 and SW1353 cells with medium from native cement clots without drug therapy presented a cell activity of 100% in all groups and during all measurements. Human mesenchymal stem cells were not significantly affected during therapy with VPA and low concentrations of SAHA. In contrast, cell activity of human mesenchymal stem cells was significantly reduced under therapy with higher concentrations of SAHA, with an approximately linear decrease between days 0-3 and a rapidly decreasing activity between days 4-7. A local cytotoxic therapy in the

New Method for Calculating The Electron Impact Ionization of Ions

NASA Astrophysics Data System (ADS)

Saha, Bidhan; Basak, Arun K.; Uddin, M. A.

2005-11-01

The electron impact single ionization of ionic targets ( 1 <= Z <= 92) is reported using a recently proposed method [1]. It is based on the simplified version of the improved-binary-encounter-dipole (siBED) model [2]. Including the both the ionic and the relativistic corrections (RQIBED model) [3] we have recently investigated the ionization of He-like[4] and Be-like systems [5] with considerable success. However, the presence of adjustable parameters make it dependent on available experimental results We have applied a new techniques to avoid this and show explicitly how to evaluate cross sections for filled as well as unfilled s-orbital targets. Details will be presented at the conference. [1] M. A. Uddin, A. K. F. Haque, a. K. Basak, K. R. Karim and B. C. Saha, Phys Rev A (2005) in press [2] W. M. Huo, Phys. Rev. A 64, 042719 (2001). [3]M. A. Uddin, M. A. K. F. Haque, A. K. Basak and B. C. Saha, Phys. Rev. A 70, 032706 (2004). [4] M. A. Uddin, A. K. F. Haque, M. S. Mahbub, K. R. Karim, A. K. Basak, B. C. Saha, Int. J. Mass Spect. 244, 76 (2005).

Inhibition of SRC-3 enhances sensitivity of human cancer cells to histone deacetylase inhibitors

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

Zou, Zhengzhi, E-mail: zouzhengzhi@m.scnu.edu.cn; Luo, Xiaoyong; Nie, Peipei

SRC-3 is widely expressed in multiple tumor types and involved in cancer cell proliferation and apoptosis. Histone deacetylase (HDAC) inhibitors are promising antitumor drugs. However, the poor efficacy of HDAC inhibitors in solid tumors has restricted its further clinical application. Here, we reported the novel finding that depletion of SRC-3 enhanced sensitivity of breast and lung cancer cells to HDAC inhibitors (SAHA and romidepsin). In contrast, overexpression of SRC-3 decreased SAHA-induced cancer cell apoptosis. Furthermore, we found that SRC-3 inhibitor bufalin increased cancer cell apoptosis induced by HDAC inhibitors. The combination of bufalin and SAHA was particular efficient in attenuatingmore » AKT activation and reducing Bcl-2 levels. Taken together, these accumulating data might guide development of new breast and lung cancer therapies. - Highlights: • Depletion of SRC-3 enhanced sensitivity of breast and lung cancer cells to HDAC inhibitors. • Overexpression of SRC-3 enhanced cancer cell resistance to HDAC inhibitors. • SRC-3 inhibitor bufalin increased cancer cell apoptosis induced by HDAC inhibitors. • Bufalin synergized with HDAC inhibitor attenuated AKT activation and reduced Bcl-2 levels in human cancer cell.« less

Bulldozing of Basal Continental Mantle Lithosphere During Flat-Slab Subduction

NASA Astrophysics Data System (ADS)

Axen, G. J.; van Wijk, J.; Currie, C. A.

2017-12-01

Flat-slab subduction occurs along 10% of subduction margins, forming magmatic gaps and causing inland migration of upper-plate deformation. We suggest that basal continental mantle lithosphere (CML) can be bulldozed ahead of the flat portion of horizontally-subducted oceanic lithosphere, forming a growing and advancing keel of thickened CML. This process fills the asthenospheric mantle wedge with CML, precluding melting. The bulldozed CML keel may transmit tectonic stresses ahead of the flat slab itself, causing upper-plate deformation ahead of the slab hinge. We designed 2-D numerical models after the North American Laramide orogeny, with subduction of a thick, buoyant oceanic plateau (conjugate Shatsky Rise) and with the continent advancing trenchward over the initial slab hinge. This results in slab-flattening, and removal of CML material. In our models, the thickness of the CML layer removed by this process depends on overriding plate rheology and is up to 25 km. The removed material is bulldozed ahead of the hinge and may fill up the asthenospheric wedge. Low-density (depleted) CML favors formation of bulldozed keels, which increase in width as CML strength decreases. Regular-density and/or stronger CML forms smaller bulldozed keels that are more likely to sink with the slab as eclogitization and densification proceed. When the flat slab rolls back, it leaves a step in the CML at the farthest extent of the slab. Relics of this step may remain below North America or may have dripped off. We interpret an upper-mantle fast-velocity anomaly below SE New Mexico and W Texas as a drip/keel, and the step in lithosphere thickness in southwestern Colorado as a fossil step, caused by the removal of the CML layer. Our model predicts that the Laramide bulldozed CML keel may have aided in stress transmission that caused basement uplifts as far as NE Wyoming and subsurface folds even farther N and E. Modern examples may exist in South American flat slab segments.

The effect of perch availability during pullet rearing and egg laying on musculoskeletal health of caged White Leghorn hens.

PubMed

Hester, P Y; Enneking, S A; Haley, B K; Cheng, H W; Einstein, M E; Rubin, D A

2013-08-01

A major skeletal problem of conventionally caged hens is increased susceptibility to osteoporosis mainly due to lack of exercise. Osteoporosis is characterized by a progressive decrease in mineralized structural bone. Whereas considerable attention has been given to enriching laying cages, little research has been conducted on providing caged pullets with furnishments, in particular perches. The objective of the current study was to determine if metal perches during all or part of the life cycle of White Leghorns affected hen musculoskeletal health, especially at end of lay. Treatments during the pullet phase (hatch to 16.9 wk) entailed cages with and without perches. Four treatments were used during the laying phase (17 to 71 wk of age). Treatment 1 chickens never had access to perches at any point during their life cycle, typical of egg industry practices in the United States for conventional cages. Treatment 2 chickens had access to perches only during the egg-laying phase, which was from 17 to 71 wk of age. Treatment 3 chickens had access to perches only during the pullet phase (0 to 16.9 wk of age). Treatment 4 chickens had perch access throughout their entire life cycle (0 to 71 wk of age). Musculoskeletal health was assessed by measuring muscle weights, bone mineralization, bone fracture incidence, and keel bone deviations. Muscle deposition of 71-wk-old hens increased when given access to perches as pullets. Bone mineralization of 71-wk-old hens also increased if given perch access as adults. However, the disadvantage of the adult perch was the higher incidence of keel deviations and keel fractures at end of lay. The increase in bone mineralization of the keel bone as a result of perch access during the pullet and laying phases was not great enough to prevent a higher incidence of keel bone fractures at end of lay. Perch redesign and placement of perches within the cage to minimize keel fractures and deviations are possible solutions.

Deployment loads data from a free-flight investigation of all flexible parawings having 371.612 sq meters (4000 sq feet) of wing area

NASA Technical Reports Server (NTRS)

Croom, D. R.

1971-01-01

A free-flight test program to determine the deployment characteristics of all-flexible parawings was conducted. Both single-keel and twin-keel parawings having a wing area of 4000 square feet with a five-stage reefing system were tested by use of a bomb-type instrumented test vehicle. Several twin-keel-parawing tests were also made by using an instrumented controllable sled-type test vehicle. The systems were launched from either a C-130 or a C-119 carrier airplane, and a programer parachute was used to bring the test vehicle to a proper dynamic pressure and near-vertical flight path prior to deployment of the parawing system. The free-flight deployment loads data are presented in the form of time histories of individual suspension-line loads and total loads.

Subduction beneath Laurentia modified the eastern North American cratonic edge: Evidence from P wave and S wave tomography

NASA Astrophysics Data System (ADS)

Boyce, A.; Bastow, I. D.; Darbyshire, F. A.; Ellwood, A. G.; Gilligan, A.; Levin, V.; Menke, W.

2016-07-01

The cratonic cores of the continents are remarkably stable and long-lived features. Their ability to resist destructive tectonic processes is associated with their thick (˜250 km), cold, chemically depleted, buoyant lithospheric keels that isolate the cratons from the convecting mantle. The formation mechanism and tectonic stability of cratonic keels remains under debate. To address this issue, we use P wave and S wave relative arrival-time tomography to constrain upper mantle structure beneath southeast Canada and the northeast USA, a region spanning three quarters of Earth's geological history. Our models show three distinct, broad zones: Seismic wave speeds increase systematically from the Phanerozoic coastal domains, through the Proterozoic Grenville Province, and to the Archean Superior craton in central Québec. We also recover the NW-SE trending track of the Great Meteor hot spot that crosscuts the major tectonic domains. The decrease in seismic wave speed from Archean to Proterozoic domains across the Grenville Front is consistent with predictions from models of two-stage keel formation, supporting the idea that keel growth may not have been restricted to Archean times. However, while crustal structure studies suggest that Archean Superior material underlies Grenvillian age rocks up to ˜300 km SE of the Grenville Front, our tomographic models show a near-vertical boundary in mantle wave speed directly beneath the Grenville Front. We interpret this as evidence for subduction-driven metasomatic enrichment of the Laurentian cratonic margin, prior to keel stabilization. Variable chemical depletion levels across Archean-Proterozoic boundaries worldwide may thus be better explained by metasomatic enrichment than inherently less depleted Proterozoic composition at formation.

Morphofunctional Traits and Pollination Mechanisms of Coronilla emerus L. Flowers (Fabaceae)

PubMed Central

Aronne, Giovanna; Giovanetti, Manuela; De Micco, Veronica

2012-01-01

It is accepted that the papilionaceous corolla of the Fabaceae evolved under the selective pressure of bee pollinators. Morphology and function of different parts of Coronilla emerus L. flowers were related to their role in the pollination mechanism. The corolla has a vexillum with red nectar lines, a keel hiding stamens and pistil, and two wing petals fasten to the keel with two notched folds. Pollinators land on the complex of keel and wings, trigger the protrusion of pollen and finally of the stigma from the keel tip. Data on pollen viability and stigma receptivity prove that flowers are proterandrous. The results of hand-pollination experiments confirmed that insects are fundamental to set seed. Interaction with pollinators allows not only the transport of pollen but also the rupture of the stigmatic cuticle, necessary to achieve both allogamy and autogamy. Field observations showed that Hymenoptera, Lepidoptera, and Diptera visited the flowers. Only some of the Hymenoptera landed on the flowers from the front and elicited pollination mechanisms. Most of the insects sucked the nectar from the back without any pollen transfer. Finally, morphological and functional characteristics of C. emerus flowers are discussed in terms of floral larceny and reduction in pollination efficiency. PMID:22666114

HDAC Inhibition Induces Increased Choline Uptake and Elevated Phosphocholine Levels in MCF7 Breast Cancer Cells

PubMed Central

Ward, Christopher S.; Eriksson, Pia; Izquierdo-Garcia, Jose L.; Brandes, Alissa H.; Ronen, Sabrina M.

2013-01-01

Histone deacetylase (HDAC) inhibitors have emerged as effective antineoplastic agents in the clinic. Studies from our lab and others have reported that magnetic resonance spectroscopy (MRS)-detectable phosphocholine (PC) is elevated following SAHA treatment, providing a potential noninvasive biomarker of response. Typically, elevated PC is associated with cancer while a decrease in PC accompanies response to antineoplastic treatment. The goal of this study was therefore to elucidate the underlying biochemical mechanism by which HDAC inhibition leads to elevated PC. We investigated the effect of SAHA on MCF-7 breast cancer cells using 13C MRS to monitor [1,2-13C] choline uptake and phosphorylation to PC. We found that PC synthesis was significantly higher in treated cells, representing 154±19% of control. This was within standard deviation of the increase in total PC levels detected by 31P MRS (129±7% of control). Furthermore, cellular choline kinase activity was elevated (177±31%), while cytidylyltransferase activity was unchanged. Expression of the intermediate-affinity choline transporter SLC44A1 and choline kinase α increased (144% and 161%, respectively) relative to control, as determined by mRNA microarray analysis with protein-level confirmation by Western blotting. Taken together, our findings indicate that the increase in PC levels following SAHA treatment results from its elevated synthesis. Additionally, the concentration of glycerophosphocholine (GPC) increased significantly with treatment to 210±45%. This is likely due to the upregulated expression of several phospholipase A2 (PLA2) isoforms, resulting in increased PLA2 activity (162±18%) in SAHA-treated cells. Importantly, the levels of total choline (tCho)-containing metabolites, comprised of choline, PC and GPC, are readily detectable clinically using 1H MRS. Our findings thus provide an important step in validating clinically translatable non-invasive imaging methods for follow-up diagnostics

HDAC Inhibitors Target Replication Forks to Take a Stab at Cancer | Center for Cancer Research

Cancer.gov

The stability and function of many proteins within the cell can be altered with the addition or removal of certain chemical groups, including acetyl groups. Therefore, the enzymes that regulate these modifications have an important impact on the cell. One class of such enzymes—histone deacetylases, or HDACs—has been implicated in cancer and has become a target for cancer therapy. One HDAC inhibitor, called SAHA, has been approved for use against cutaneous T-cell lymphoma, and more than 60 ongoing clinical trials are continuing to test this class of drugs in various forms of cancer. However, the mechanisms by which SAHA and other HDAC inhibitors undermine the viability of tumor cells are not completely understood.

Improvements to the RADIOM non-LTE model

NASA Astrophysics Data System (ADS)

Busquet, M.; Colombant, D.; Klapisch, M.; Fyfe, D.; Gardner, J.

2009-12-01

In 1993, we proposed the RADIOM model [M. Busquet, Phys. Fluids 85 (1993) 4191] where an ionization temperature T z is used to derive non-LTE properties from LTE data. T z is obtained from an "extended Saha equation" where unbalanced transitions, like radiative decay, give the non-LTE behavior. Since then, major improvements have been made. T z has been shown to be more than a heuristic value, but describes the actual distribution of excited and ionized states and can be understood as an "effective temperature". Therefore we complement the extended Saha equation by introducing explicitly the auto-ionization/dielectronic capture. Also we use the SCROLL model to benchmark the computed values of T z.

Development of programmable small DNA-binding molecules with epigenetic activity for induction of core pluripotency genes.

PubMed

Pandian, Ganesh N; Ohtsuki, Akimichi; Bando, Toshikazu; Sato, Shinsuke; Hashiya, Kaori; Sugiyama, Hiroshi

2012-04-15

Epigenetic modifications that govern the gene expression are often overlooked with the design of artificial genetic switches. N-Methylpyrrole-N-methylimidazole (PI) hairpin polyamides are programmable small DNA binding molecules that have been studied in the context of gene regulation. Recently, we synthesized a library of compounds by conjugating PI polyamides with SAHA, a chromatin-modifier. Among these novel compounds, PI polyamide-SAHA conjugate 1 was shown to epigenetically activate pluripotency genes in mouse embryonic fibroblasts. Here, we report the synthesis of the derivatives of conjugate 1 and demonstrate that these epigenetically active molecules could be developed to improve the induction of pluripotency factors. Copyright © 2012 Elsevier Ltd. All rights reserved.

Discovery of aliphatic-chain hydroxamates containing indole derivatives with potent class I histone deacetylase inhibitory activities.

PubMed

Chao, Shi-Wei; Chen, Liang-Chieh; Yu, Chia-Chun; Liu, Chang-Yi; Lin, Tony Eight; Guh, Jih-Hwa; Wang, Chen-Yu; Chen, Chun-Yung; Hsu, Kai-Cheng; Huang, Wei-Jan

2018-01-01

Histone deacetylase (HDAC) is a validated drug target for various diseases. This study combined indole recognition cap with SAHA, an FDA-approved HDAC inhibitor used to treat cutaneous T-cell lymphoma (CTCL). The structure activity relationship of the resulting compounds that inhibited HDAC was disclosed as well. Some compounds exhibited much stronger inhibitory activities than SAHA. We identified two meta-series compounds 6j and 6k with a two-carbon linker had IC 50 values of 3.9 and 4.5 nM for HDAC1, respectively. In contrast, the same oriented compounds with longer carbon chain linkers showed weaker inhibition. The result suggests that the linker chain length greatly contributed to enzyme inhibitory potency. In addition, comparison of enzyme-inhibiting activity between the compounds and SAHA showed that compounds 6j and 6k displayed higher inhibiting activity for class I (HDAC1, -2, -3 and -8). The molecular docking and structure analysis revealed structural differences with the inhibitor cap and metal-binding regions between the HDAC isozymes that affect interactions with the inhibitors and play a key role for selectivity. Further biological evaluation showed multiple cellular effects associated with compounds 6j- and 6k-induced HDAC inhibitory activity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

The epigenetic agents suberoylanilide hydroxamic acid and 5‑AZA‑2' deoxycytidine decrease cell proliferation, induce cell death and delay the growth of MiaPaCa2 pancreatic cancer cells in vivo.

PubMed

Susanto, Johana M; Colvin, Emily K; Pinese, Mark; Chang, David K; Pajic, Marina; Mawson, Amanda; Caldon, C Elizabeth; Musgrove, Elizabeth A; Henshall, Susan M; Sutherland, Robert L; Biankin, Andrew V; Scarlett, Christopher J

2015-05-01

Despite incremental advances in the diagnosis and treatment for pancreatic cancer (PC), the 5‑year survival rate remains <5%. Novel therapies to increase survival and quality of life for PC patients are desperately needed. Epigenetic thera-peutic agents such as histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) have demonstrated therapeutic benefits in human cancer. We assessed the efficacy of these epigenetic therapeutic agents as potential therapies for PC using in vitro and in vivo models. Treatment with HDACi [suberoylanilide hydroxamic acid (SAHA)] and DNMTi [5‑AZA‑2' deoxycytidine (5‑AZA‑dc)] decreased cell proliferation in MiaPaCa2 cells, and SAHA treatment, with or without 5‑AZA‑dc, resulted in higher cell death and lower DNA synthesis compared to 5‑AZA‑dc alone and controls (DMSO). Further, combination treatment with SAHA and 5‑AZA‑dc significantly increased expression of p21WAF1, leading to G1 arrest. Treatment with epigenetic agents delayed tumour growth in vivo, but did not decrease growth of established pancreatic tumours. In conclusion, these data demonstrate a potential role for epigenetic modifier drugs for the management of PC, specifically in the chemoprevention of PC, in combination with other chemotherapeutic agents.

Saha equation, single and two particle states

NASA Technical Reports Server (NTRS)

Kraeft, W. D.; Girardeau, M. D.; Strege, B.

1990-01-01

Single- and two-particle properties in a dense plasma are discussed in connection with their role in the mass action law for a partially ionized plasma. The two-particle-bound states are nearly density independent, while the continuum is essentially shifted. The single-particle states are damped, and their energy has a negative shift and a parabolic behavior for small momenta.

Characterization of Seismic Noise at Selected Non-Urban Sites

DTIC Science & Technology

2010-03-01

Field sites for seismic recordings: Scottish moor (upper left), Enfield, NH (upper right), and vicinity of Keele, England (bottom). ERDC...three sites. The sites are: a wind farm on a remote moor in Scotland, a ~13 acre field bounded by woods in a rural Enfield, NH neigh- borhood, and a site...in a rural Enfield, NH, neighborhood, and a site transitional from developed land to farmland within 1 km of the six-lane M6 motorway near Keele

Synthesis and structure-activity relationship of histone deacetylase (HDAC) inhibitors with triazole-linked cap group.

PubMed

Chen, Po C; Patil, Vishal; Guerrant, William; Green, Patience; Oyelere, Adegboyega K

2008-05-01

Histone deacetylase (HDAC) inhibition is a recent, clinically validated therapeutic strategy for cancer treatment. Small molecule HDAC inhibitors identified so far fall in to three distinct structural motifs: the zinc-binding group (ZBG), a hydrophobic linker, and a recognition cap group. Here we report the suitability of a 1,2,3-triazole ring as a surface recognition cap group-linking moiety in suberoylanilide hydroxamic acid-like (SAHA-like) HDAC inhibitors. Using "click" chemistry (Huisgen cycloaddition reaction), several triazole-linked SAHA-like hydroxamates were synthesized. Structure-activity relationship revealed that the position of the triazole moiety as well as the identity of the cap group markedly affected the in vitro HDAC inhibition and cell growth inhibitory activities of this class of compounds.

The Evolution of Armed Forces Enlisted Personnel Management Policies: Executive Summary.

DTIC Science & Technology

1982-07-01

Navy were equally severe with such added cruelties as keel-hauling, by which a man was dragged from one side of the ship to the other under the keel...cheeked sons of New England and the West, who are subjected to degradation and cruelty , compared with which the servitude of the South is freedom, and...the Algerine cruelty is Christian kindness. Another senator cited the case of the training ship Pennsylvania: As a receiving ship it was tied up at a

Comparative fixation methods of cervical disc arthroplasty versus conventional methods of anterior cervical arthrodesis: serration, teeth, keels, or screws?

PubMed

Cunningham, Bryan W; Hu, Nianbin; Zorn, Candace M; McAfee, Paul C

2010-02-01

higher pullout loads than all other treatments except the anterior plate (p < 0.05). The PCM VTeeth and Prestige and Kineflex/C implants exhibited higher pullout loads than the PCM Low Profile and tricortical iliac crest (p < 0.05). Tricortical iliac crest exhibited the lowest pullout strength, which was different from all other treatments (p < 0.05). The surface area of endplate contact, measuring 300 mm(2) (PCM treatments), 275 mm(2) (Prestige LP), 250 mm(2) (Kineflex/C disc), 180 mm(2) (plate + cage), and 235 mm(2) (tricortical iliac crest), did not correlate with pullout strength (p > 0.05). The PCM, Prestige, and Kineflex constructs, which did not use screw fixation, all failed by direct pullout. Screw fixation devices, including anterior plates, led to test block fracture, and tricortical iliac crest failed by direct pullout. These results demonstrate a continuum of fixation strength based on prosthetic endplate design. Disc arthroplasty constructs implanted using vertebral body screw fixation exhibited the highest pullout strength. Prosthetic endplates containing toothed ridges (>or= 1 mm) or keels placed second in fixation strength, whereas endplates containing serrated edges exhibited the lowest fixation strength. All treatments exhibited greater fixation strength than conventional tricortical iliac crest. The current study offers insights into the benefits of various prosthetic endplate designs, which may potentially improve acute fixation following cervical disc arthroplasty.

Analysis and modification of theory for impact of seaplanes on water

NASA Technical Reports Server (NTRS)

Mayo, Wilbur L

1945-01-01

An analysis of available theory on seaplane impact and a proposed modification thereto are presented. In previous methods the overall momentum of the float and virtual mass has been assumed to remain constant during the impact but the present analysis shows that this assumption is rigorously correct only when the resultant velocity of the float is normal to the keel. The proposed modification chiefly involves consideration of the fact that forward velocity of the seaplane float causes momentum to be passed into the hydrodynamic downwash (an action that is the entire consideration in the case of the planing float) and consideration of the fact that, for an impact with trim, the rate of penetration is determined not only by the velocity component normal to the keel but also by the velocity component parallel to the keel, which tends to reduce the penetration. Experimental data for planing, oblique impact, and vertical drop are used to show that the accuracy of the proposed theory is good.

Description and phylogenetic relationships of a new genus and two new species of lizards from Brazilian Amazonia, with nomenclatural comments on the taxonomy of Gymnophthalmidae (Reptilia: Squamata).

PubMed

Colli, Guarino R; Hoogmoed, Marinus S; Cannatella, David C; Cassimiro, José; Gomes, Jerriane Oliveira; Ghellere, José Mário; Gomes, Jerriane Oliveira; Ghellere, José Mário; Nunes, Pedro M Sales; Pellegrino, Kátia C M; Salerno, Patricia; Souza, Sergio Marques De; Rodrigues, Miguel Trefaut

2015-08-18

We describe a new genus and two new species of gymnophthalmid lizards based on specimens collected from Brazilian Amazonia, mostly in the "arc of deforestation". The new genus is easily distinguished from other Gymnophthalmidae by having very wide, smooth, and imbricate nuchals, arranged in two longitudinal and 6-10 transverse rows from nape to brachium level, followed by much narrower, strongly keeled, lanceolate, and mucronate scales. It also differs from all other Gymnophthalmidae, except Iphisa, by the presence of two longitudinal rows of ventrals. The new genus differs from Iphisa by having two pairs of enlarged chinshields (one in Iphisa); posterior dorsal scales lanceolate, strongly keeled and not arranged in longitudinal rows (dorsals broad, smooth and forming two longitudinal rows), and lateral scales keeled (smooth). Maximum parsimony, maximum likelihood, and Bayesian phylogenetic analyses based on morphological and molecular data indicate the new species form a clade that is most closely related to Iphisa. We also address several nomenclatural issues and present a revised classification of Gymnophthalmidae.

HDAC Inhibition Improves the Sarcoendoplasmic Reticulum Ca2+-ATPase Activity in Cardiac Myocytes

PubMed Central

Meraviglia, Viviana; Sacchetto, Roberta; Motta, Benedetta M.; Corti, Corrado; D’Elia, Yuri; Rosato-Siri, Marcelo D.; Suffredini, Silvia; Pompilio, Giulio; Pramstaller, Peter P.; Stilli, Donatella

2018-01-01

SERCA2a is the Ca2+ ATPase playing the major contribution in cardiomyocyte (CM) calcium removal. Its activity can be regulated by both modulatory proteins and several post-translational modifications. The aim of the present work was to investigate whether the function of SERCA2 can be modulated by treating CMs with the histone deacetylase (HDAC) inhibitor suberanilohydroxamic acid (SAHA). The incubation with SAHA (2.5 µM, 90 min) of CMs isolated from rat adult hearts resulted in an increase of SERCA2 acetylation level and improved ATPase activity. This was associated with a significant improvement of calcium transient recovery time and cell contractility. Previous reports have identified K464 as an acetylation site in human SERCA2. Mutants were generated where K464 was substituted with glutamine (Q) or arginine (R), mimicking constitutive acetylation or deacetylation, respectively. The K464Q mutation ameliorated ATPase activity and calcium transient recovery time, thus indicating that constitutive K464 acetylation has a positive impact on human SERCA2a (hSERCA2a) function. In conclusion, SAHA induced deacetylation inhibition had a positive impact on CM calcium handling, that, at least in part, was due to improved SERCA2 activity. This observation can provide the basis for the development of novel pharmacological approaches to ameliorate SERCA2 efficiency. PMID:29385061

HDAC Inhibition Improves the Sarcoendoplasmic Reticulum Ca2+-ATPase Activity in Cardiac Myocytes.

PubMed

Meraviglia, Viviana; Bocchi, Leonardo; Sacchetto, Roberta; Florio, Maria Cristina; Motta, Benedetta M; Corti, Corrado; Weichenberger, Christian X; Savi, Monia; D'Elia, Yuri; Rosato-Siri, Marcelo D; Suffredini, Silvia; Piubelli, Chiara; Pompilio, Giulio; Pramstaller, Peter P; Domingues, Francisco S; Stilli, Donatella; Rossini, Alessandra

2018-01-31

SERCA2a is the Ca 2+ ATPase playing the major contribution in cardiomyocyte (CM) calcium removal. Its activity can be regulated by both modulatory proteins and several post-translational modifications. The aim of the present work was to investigate whether the function of SERCA2 can be modulated by treating CMs with the histone deacetylase (HDAC) inhibitor suberanilohydroxamic acid (SAHA). The incubation with SAHA (2.5 µM, 90 min) of CMs isolated from rat adult hearts resulted in an increase of SERCA2 acetylation level and improved ATPase activity. This was associated with a significant improvement of calcium transient recovery time and cell contractility. Previous reports have identified K464 as an acetylation site in human SERCA2. Mutants were generated where K464 was substituted with glutamine (Q) or arginine (R), mimicking constitutive acetylation or deacetylation, respectively. The K464Q mutation ameliorated ATPase activity and calcium transient recovery time, thus indicating that constitutive K464 acetylation has a positive impact on human SERCA2a (hSERCA2a) function. In conclusion, SAHA induced deacetylation inhibition had a positive impact on CM calcium handling, that, at least in part, was due to improved SERCA2 activity. This observation can provide the basis for the development of novel pharmacological approaches to ameliorate SERCA2 efficiency.

Endosymbiont hunting in the metagenome of Asian citrus psyllid (Diaphorina citri) (7th Annual SFAF Meeting, 2012)

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

Saha, Surya

Surya Saha on "Endosymbiont hunting in the metagenome of Asian citrus psyllid (Diaphorina citri)" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

Endosymbiont hunting in the metagenome of Asian citrus psyllid (Diaphorina citri) (7th Annual SFAF Meeting, 2012)

ScienceCinema

Saha, Surya [Cornell University

2017-12-09

Surya Saha on "Endosymbiont hunting in the metagenome of Asian citrus psyllid (Diaphorina citri)" at the 2012 Sequencing, Finishing, Analysis in the Future Meeting held June 5-7, 2012 in Santa Fe, New Mexico.

Determination of the Stresses Produced by the Landing Impact in the Bulkheads of a Seaplane Bottom

NASA Technical Reports Server (NTRS)

Darevsky, V. M.

1944-01-01

The present report deals with the determination of the impact stresses in the bulkhead floors of a seaplane bottom. The dynamic problem is solved on the assumption of a certain elastic system, the floor being assumed as a weightless elastic beam with concentrated masses at the ends (due to the mass of the float) and with a spring which replaces the elastic action of the keel in the center. The distributed load on the floor is that due to the hydrodynamic force acting over a certain portion of the bottom. The pressure distribution over the width of the float is assumed to follow the Wagner law. The formulas given for the maximum bending moment are derived on the assumption that the keel is relatively elastic, in which case it can be shown that at each instant of time the maximum bending moment is at the point of juncture of the floor with the keel. The bending moment at this point is a function of the half width of the wetted surface c and reaches its maximum value when c is approximately equal to b/2 where b is the half width of the float. In general, however, for computing the bending moment the values of the bending moment at the keel for certain values of c are determined and a curve is drawn. The illustrative sample computation gave for the stresses a result approximately equal to that obtained by the conventional factory computation.

Recompression Chamber Communication Systems Test and Evaluation.

DTIC Science & Technology

1984-04-01

consisted of a selector switch and two banana jacks in order to use the same connecting cable on all of the systems tested. This modification would be...thin 6. din dic din dill 31. bark mark lark park 7. dun dud dung dug 32. gale pale bale male 8. f fig fin fizz fib 33. peel feel eel keel 9. leave...tale male bale S. fin fig fib fizz fill 33. heel keel feel peel eel 9. leash lead leave leach liege 34. till hill bill kill will 10. taj tog tong toss

Pectus carinatum.

PubMed

Robicsek, Francis; Watts, Larry T

2010-11-01

Pectus carinatum or keel chest is a spectrum of progressive inborn anomalies of the anterior chest wall, named after the keel (carina) of ancient Roman ships. It defines a wide spectrum of inborn protrusion anomalies of the sternum and/or the adjacent costal cartilages. Pectus carinatum is often associated with various conditions, notably Marfan disease, homocystinuria, prune belly, Morquio syndrome, osteogenesis imperfecta, Noonan syndrome, and mitral valve prolapse. Treatment of pectus carinatum by nonsurgical methods such as exercise and casting has not been worthwhile, whereas surgical management is simple and successful.

PREFACE: Continuum Models and Discrete Systems Symposia (CMDS-12)

NASA Astrophysics Data System (ADS)

Chakrabarti, Bikas K.

2011-09-01

The 12th International Symposium on Continuum Models and Discrete Systems (CMDS-12) (http://www.saha.ac.in/cmp/cmds.12/) took place at the Saha Institute of Nuclear Physics in Kolkata from 21-25 February 2011. Previous CMDS symposia were held in Kielce (Poland, 1975), Mont Gabriel (Canada, 1977), Freudenstadt (Federal Republic of Germany, 1979), Stockholm (Sweden, 1981), Nottingham (United Kingdom, 1985), Dijon (France, 1989), Paderborn (Germany, 1992), Varna (Bulgaria, 1995), Istanbul (Turkey, 1998), Shoresh (Israel, 2003) and Paris (France, 2007). The broad interdisciplinary character, limited number of participants (not exceeding 100) and informal and friendly atmosphere of these meetings has made them a well-acknowledged place to make highly fruitful contacts and exchange ideas, methods and results. The purpose of CMDS is to bring together scientists with different backgrounds who work on continuum theories of discrete mechanical and thermodynamical systems in the fields of mathematics, theoretical and applied mechanics, physics, material science, and engineering. The spirit of the CMDS meetings is to stimulate extensive and active interdisciplinary research. The International Scientific Committee members of this conference were: David J Bergman (Chairman CMDS 10), Tel Aviv University, Israel; Bikas K Chakrabarti (Chairman CMDS 12), Saha Institute of Nuclear Physics, India; Alex Hansen, Norwegian University of Science and Technology, Norway; Hans Jürgen Herrmann, Institute for Building Materials, ETH, Switzerland; Esin Inan (Chairman CMDS 9), Istanbul Technical University, Turkey; Dominique Jeulin (Chairman CMDS 11), Ecole des Mines de Paris, France; Frank Juelicher, Max-Planck-Institute for the Physics of Complex Systems, Germany; Hikaru Kawamura, University of Osaka, Japan; Graeme Milton, University of Utah, USA; Natalia Movchan, University of Liverpool, UK; and Ping Sheng, The Hong Kong University of Science and Technology, Hong Kong. At CMDS-12 the topics

Body-induced vortical flows: a common mechanism for self-corrective trimming control in boxfishes.

PubMed

Bartol, Ian K; Gharib, Morteza; Webb, Paul W; Weihs, Daniel; Gordon, Malcolm S

2005-01-01

Boxfishes (Teleostei: Ostraciidae) are marine fishes having rigid carapaces that vary significantly among taxa in their shapes and structural ornamentation. We showed previously that the keels of the carapace of one species of tropical boxfish, the smooth trunkfish, produce leading edge vortices (LEVs) capable of generating self-correcting trimming forces during swimming. In this paper we show that other tropical boxfishes with different carapace shapes have similar capabilities. We conducted a quantitative study of flows around the carapaces of three morphologically distinct boxfishes (spotted boxfish, scrawled cowfish and buffalo trunkfish) using stereolithographic models and three separate but interrelated analytical approaches: digital particle image velocimetry (DPIV), pressure distribution measurements, and force balance measurements. The ventral keels of all three forms produced LEVs that grew in circulation along the bodies, resembling the LEVs produced around delta-winged aircraft. These spiral vortices formed above the keels and increased in circulation as pitch angle became more positive, and formed below the keels and increased in circulation as pitch angle became more negative. Vortices also formed along the eye ridges of all boxfishes. In the spotted boxfish, which is largely trapezoidal in cross section, consistent dorsal vortex growth posterior to the eye ridge was also present. When all three boxfishes were positioned at various yaw angles, regions of strongest concentrated vorticity formed in far-field locations of the carapace compared with near-field areas, and vortex circulation was greatest posterior to the center of mass. In general, regions of localized low pressure correlated well with regions of attached, concentrated vorticity, especially around the ventral keels. Although other features of the carapace also affect flow patterns and pressure distributions in different ways, the integrated effects of the flows were consistent for all forms

The hydrodynamic model testing for closed loop DP assisted mooring

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

Aalbers, A.B.; Merchant, A.A.

1996-12-31

Far East Levingston Shipbuilding (FELS) is presently completing the construction of the Smedvig Production Unit SPU 380, which will be operated as FPSO for Esso Balder Field Offshore Norway. In good cooperation with FELS and ND and A Inc. of Houston an extensive model test program was carried out for approval and optimization of the DP assisted mooring system. The main aspects were: investigate the performance of the mooring in two water depths, i.e. 250 m and 70 m; optimization of DP control for the three azimuthing thrusters; measurement of motions and wave induced loads at e.g., the bilge keels,more » keel and deckhouse front; and determination of limit sea state for turning the vessel around against the weather. The tests were carried out in the Wave and Current Basin of MARIN, using a closed loop DP control system to steer the thrusters. The paper presents the findings with respect to the effect of DP control strategy on mooring loads and presents selected results of wave induced loads on bilge keels and deck house.« less

Trilysinoyl oleylamide-based cationic liposomes for systemic co-delivery of siRNA and an anticancer drug.

PubMed

Shim, Gayong; Han, Su-Eun; Yu, Yong-Hee; Lee, Sangbin; Lee, Han Young; Kim, Kwangmeyung; Kwon, Ick Chan; Park, Tae Gwan; Kim, Young Bong; Choi, Yong Seok; Kim, Chan-Wha; Oh, Yu-Kyoung

2011-10-10

Oligolysine-based cationic lipid derivatives were synthesized for delivery of siRNA, and formulated into cationic liposomes. Among various oligolysine-based lipid derivatives differing in lysine residue number and lipid moiety, trilysinoyl oleylamide (TLO)-based liposomes (TLOL) showed the highest delivery efficiency combined with minimal cytotoxicity. Delivery of siRNA using TLOL silenced target genes both in vitro and in vivo. In green fluorescent protein (GFP)-expressing tumor tissue, a significant reduction of fluorescence was observed after intratumoral administration of siGFP using TLOL compared with control siGL2. Intravenous administration of siMcl1 employing pegylated TLOL (pTLOL) reduced the expression of human Mcl1 protein in KB-xenografted tumor tissue. Despite the reduction in target protein Mcl1 expression following such systemic delivery, tumor growth was only slightly reduced compared to a siGL2-treated control group. To potentiate the anticancer activity of siMcl1, the anticancer drug suberoylanilide hydroxamic acid (SAHA) was additionally encapsulated in pTLOL. After intravenous administration of siMcl1 using SAHA-loaded pTLOL (pSTLOL), a significant reduction in tumor growth was observed compared to that seen in animals treated with free SAHA or siGL2 complexed with pSTLOL. The results indicate that pTLOL could be further developed as a systemic delivery system for synergistic anticancer siRNA and a drug. Copyright © 2010 Elsevier B.V. All rights reserved.

BCL11B-Mediated Epigenetic Repression Is a Crucial Target for Histone Deacetylase Inhibitors in Cutaneous T-Cell Lymphoma.

PubMed

Fu, Wenjing; Yi, Shengguo; Qiu, Lei; Sun, Jingru; Tu, Ping; Wang, Yang

2017-07-01

The treatment options for advanced cutaneous T-cell lymphoma (CTCL) are limited because of its unclear pathogenesis. Histone deacetylase (HDAC) inhibitors (HDACis) are recently developed therapeutics approved for refractory CTCL. However, the response rate is relatively low and unpredictable. Previously, we discovered that BCL11B, a key T-cell development regulator, was aberrantly overexpressed in mycosis fungoides, the most common CTCL, as compared with benign inflammatory skin. In this study, we identified a positive correlation between BCL11B expression and sensitivity to HDACi in CTCL lines. BCL11B suppression in BCL11B-high cells induced cell apoptosis by de-repressing apoptotic pathways and showed synergistic effects with suberoylanilide hydroxamic acid (SAHA), a pan-HDACi. Next, we identified the physical interaction and shared downstream genes between BCL11B and HDAC1/2 in CTCL lines. This interaction was essential in the anti-apoptosis effect of BCL11B, and the synergism between BCL11B suppression and HDACi treatment. Further, in clinical samples from 46 mycosis fungoides patients, BCL11B showed increased but varied expression in advanced tumor stage. Analysis of four patients receiving SAHA treatment suggested a positive correlation between BCL11B expression and favorable response to SAHA treatment. In conclusion, BCL11B may serve as a therapeutic target and a useful marker for improving HDACi efficacy in advanced CTCL. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Characterization of the Regulation and Function of Zinc-Dependent Histone Deacetylases During Mouse Liver Regeneration

PubMed Central

Huang, Jiansheng; Barr, Emily; Rudnick, David A.

2013-01-01

The studies reported here were undertaken to define the regulation and functional importance of zinc-dependent histone deacetylase (Zn-HDAC) activity during liver regeneration using the mouse partial hepatectomy (PH) model. The results showed that hepatic HDAC activity was significantly increased in nuclear and cytoplasmic fractions following PH. Further analyses showed isoform-specific effects of PH on HDAC mRNA and protein expression, with increased expression of the class I HDACs, 1 and 8, and class II HDAC4 in regenerating liver. Hepatic expression of (class II) HDAC5 was unchanged after PH; however HDAC5 exhibited transient nuclear accumulation in regenerating liver. These changes in hepatic HDAC expression, subcellular localization, and activity coincided with diminished histone acetylation in regenerating liver. The significance of these events was investigated by determining the effects of suberoylanilide hydroxyamic acid (SAHA, a specific inhibitor of Zn-HDAC activity) on hepatic regeneration. The results showed that SAHA-treatment suppressed the effects of PH on histone deacetylation and hepatocellular BrdU incorporation. Further examination showed that SAHA blunted hepatic expression and activation of cell cycle signals downstream of induction of cyclin D1 expression in mice subjected to PH. Conclusion The data reported here demonstrate isoform-specific regulation of Zn-HDAC expression, subcellular localization, and activity in regenerating liver. These studies also indicate that HDAC activity promotes liver regeneration by regulating hepatocellular cell cycle progression at a step downstream of cyclin D1 induction. PMID:23258575

In situ generation of sodium alginate/hydroxyapatite nanocomposite beads as drug-controlled release matrices.

PubMed

Zhang, J; Wang, Q; Wang, A

2010-02-01

In order to find a new way to slow down the release of drugs and to solve the burst release problem of drugs from traditionally used hydrogel matrices, a series of novel pH-sensitive sodium alginate/hydroxyapatite (SA/HA) nanocomposite beads was prepared by the in situ generation of HA micro-particles in the beads during the sol-gel transition process of SA. The SA/HA nanocomposites were characterized by Fourier transform IR spectroscopy, X-ray fluorescence spectrometry, scanning electron microscopy and field emission SEM in order to reveal their composition and surface morphology as well as the role that the in situ generated HA micro-particles play. The factors influencing the swelling behavior, drug loading and controlled release behavior of the SA/HA nanocomposite beads were also investigated using diclofenac sodium (DS) as the model drug. The HA micro-particles act as inorganic crosslinkers in the nanocomposites, which could contract and restrict the movability of the SA polymer chains, and then change the surface morphology and decrease the swell ratio. Meanwhile, the entrapment efficiency of DS was improved, and the burst release of DS was overcome. The factors (including concentration of Ca(2+), reaction time and temperature) affecting the growth of HA micro-particles have a clear influence on the entrapment efficiency and release rate of DS. In this work, the nanocomposite beads prepared under optimum condition could prolong the release of DS for 8h more compared with the pristine SA hydrogel beads.

Electron impact ionization of atomic targets at relativistic energies

NASA Astrophysics Data System (ADS)

Uddin, M. A.; Basak, A. K.; Saha, B. C.

2009-05-01

The huge demand and scarcity of electron impact ionization cross sections (EIICS) that are essential not only in modeling but also in basic researches can be best filled in by simple to use analytical models [1] that are sufficiently accurate and provide fast generation of EIICS data over wide domain. We report few such models and compare their productive powers in terms of few adjustable parameters. Details of our results will be presented in the conference. [1] A. K. F. Haque, M. A. Uddin, A. K. Basak, K. R. Karim, B. C. Saha, and F. B. Malik, Phys. Scr. 74, 377 (2006); Phys. Rev A 73, 052703; M. A. R. Patoary, M. A. Uddin, A. K. F. Haque, M. Shahjahan, A. K. Basak, M. R. Talukdar and B. C. Saha, Int. J. Quan. Chem (in press). Supported by NSF CREST.

KSC-02pp1759

NASA Image and Video Library

2002-11-10

KENNEDY SPACE CENTER, FLA. -- During an administrator's briefing at the IMAX 2 theatre, Lt. Gov. Jefferson Keel of the Chickasaw Nation (far left) presents a blanket with the seal of the Chickasaw Nation to NASA Administrator Sean O'Keefe (second from right). Next to O'Keefe is Chickasaw Gov. Bill Anoatubby. Next to Gov. Keel is Mrs. Laura O'Keefe. STS-113 Mission Specialist John Herrington is a tribally enrolled Chickasaw and the world's first Native American astronaut. Kennedy Space Center hosted more than 350 Native Americans in STS-113 prelaunch events surrounding the historic mission assignment of Herrington.

76 FR 29770 - National Cancer Institute; Notice of Closed Meetings

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-23

... K. Saha, PhD, Scientific Review Officer, Program Coordination and Referral Branch, Division of..., PhD, Scientific Review Officer, Scientific Review and Logistic Branch, Division of Extramural....395, Cancer Treatment Research; 93.396, Cancer Biology Research; 93.397, Cancer Centers Support; 93...

Concepts for diamond exploration in "on/off craton" areas—British Columbia, Canada

NASA Astrophysics Data System (ADS)

Simandl, George J.

2004-09-01

The tectonic setting of British Columbia (BC) differs from classic diamond-bearing intracratonic regions such as the Northwest Territories and South Africa. Nevertheless, several diamond occurrences have been reported in BC. It is also known that parts of the province are underlain by Proterozoic and possibly Archean basement. Because the continents of today are composites of fragments of ancient continents, it is possible that some of the regions underlain by old crystalline basement in eastern British Columbia were associated with a deep crustal keel. The keel may have predated the break-up of the early Neoproterozoic supercontinent called Rodinia and was preserved possibly until the Triassic. Some of these old continental fragments may have been displaced relative to their position of origin and dissociated from their keel, or the keel may have since been destroyed. Such fragments represent favourable exploration grounds in terms of the "Diamondiferous Mantle Root" model (DMR model) if they were intersected by kimberlites or lamproites prior to displacement or destruction of their underlying deep keel. Therefore, extrapolation of fragments of the diamond-bearing Precambrian basement from the Northwest Territories or Alberta to BC provides a sufficient reason for initiating reconnaissance indicator mineral surveys. The "Eclogite Subduction Zone" model (ES model) predicts formation of diamonds at lower pressure (i.e., depth) than required by the DMR model in convergent tectonic settings. Although not proven, this model is supported by thermal modeling of cold subduction zones and recent discoveries of diamonds in areas characterized by convergent tectonic settings. If the ES model is correct, then the parts of BC with a geological history similar to today's "cold" subduction zones, such as Honshu (Japan), or to continental collision zones, such as Kokchetav massif (Kazakhstan) and the Dabie-Sulu Terrane (east central China), may be diamondiferous. The terranes

What Drives Carbon Isotope Fractionation by the Terrestrial Biosphere?

NASA Astrophysics Data System (ADS)

Still, Christopher; Rastogi, Bharat

2017-11-01

During photosynthesis, terrestrial plants preferentially assimilate the lighter and much more abundant form of carbon, 12C, which accounts for roughly 99% of naturally occurring forms of this element. This photosynthetic preference for lighter carbon is driven principally by differences in molecular diffusion of carbon dioxide with differing 13C/12C across stomatal pores on leaves, followed by differences in carboxylation rates by the Rubisco enzyme that is central to the process of photosynthesis. As a result of these slight preferences, which work out to about a 2% difference in the fixation rates of 12CO2 versus 13CO2 by C3 vegetation, plant tissues are depleted in the heavier form of carbon (13C) relative to atmospheric CO2. This difference has been exploited in a wide range of scientific applications, as the photosynthetic isotope signature is passed to ecosystem carbon pools and through ecological food webs. What is less appreciated is the signature that terrestrial carbon exchanges leave on atmospheric CO2, as the net uptake of carbon by land plants during their growing season not only draws down the local CO2 concentration, it also leaves behind relatively more CO2 molecules containing 13C. The converse happens outside the growing season, when autotrophic and heterotrophic respiration predominate. During these periods, atmospheric CO2 concentration increases and its corresponding carbon isotope composition becomes relatively depleted in 13C as the products of photosynthesis are respired, along with some small isotope fractionation that happen downstream of the initial photosynthetic assimilation. Similar phenomena were first observed at shorter time scales by the eminent carbon cycle scientist, Charles (Dave) Keeling. Keeling collected samples of air in glass flasks from sites along the Big Sur coast that he later measured for CO2 concentration and carbon isotope composition (δ13C) in his lab (Keeling, 1998). From these samples, Keeling observed increasing

Increased risk of aseptic loosening for 43,525 rotating-platform vs. fixed-bearing total knee replacements

PubMed Central

Gothesen, Oystein; Lygre, Stein Hakon L; Lorimer, Michelle; Graves, Stephen; Furnes, Ove

2017-01-01

Background and purpose — Given similar functional outcomes with mobile and fixed bearings, a difference in survivorship may favor either. This study investigated the risk of aseptic loosening for the most used subtypes of mobile-bearing rotating-platform knees, in Norway and Australia. Patients and methods — Primary TKRs reported to the Norwegian and Australian joint registries, between 2003 and 2014, were analyzed with aseptic loosening as primary end-point and all revisions as secondary end-point. We hypothesized that no difference would be found in the rate of revision between rotating-platform and the most used fixed-bearing TKRs, or between keeled and non-keeled tibia. Kaplan–Meier estimates and curves, and Cox regression relative risk estimates adjusted for age, sex, and diagnosis were used for comparison. Results — The rotating-platform TKRs had an increased risk of revision for aseptic loosening compared with the most used fixed-bearing knees, in Norway (RR =6, 95% CI 4–8) and Australia (RR =2.1, 95% CI 1.8–2.5). The risk of aseptic loosening as a reason for revision was highest in Norway compared with Australia (RR =1.7, 95% CI 1.4–2.0). The keeled tibial component had the same risk of aseptic loosening as the non-keeled tibia (Australia). Fixation method and subtypes of the tibial components had no impact on the risk of aseptic loosening in these mobile-bearing knees. Interpretation — The rotating-platform TKRs in this study appeared to have a higher risk of revision for aseptic loosening than the most used fixed-bearing TKRs. PMID:28929828

Three-dimensional microarchitecture of the plates (primary, secondary, and carinar process) in the developing tooth of Lytechinus variegatus revealed by synchrotron X-ray absorption microtomography (microCT).

PubMed

Stock, S R; Ignatiev, K I; Dahl, T; Veis, A; De Carlo, F

2003-12-01

This paper reports the first noninvasive, volumetric study of entire cross-sections of a sea urchin tooth in which the individual calcite structural elements could be resolved. Two cross-sectionally intact fragments of a Lytechinus variegatus tooth were studied with synchrotron microCT (microcomputed tomography) with 1.66 microm voxels (volume elements). These fragments were from the plumula, that is the tooth zone with rapidly increasing levels of mineral; one fragment was from a position aboral of where the keel developed and the second was from the zone where the keel was developing. The primary plates, secondary plates, carinar process plates, prisms, and elements of the lamellar-needle complex were resolved. Comparison of the microCT data with optical micrographs of stained thin sections confirmed the identifications and measured dimensions of the characteristic microarchitectural features. The interplay of reinforcing structures (plates and prisms) was more clearly revealed in the volumetric numerical data sets than in single or sequential slices. While it is well known that the primary plates and prisms in camarodont teeth are situated to improve resistance to bending (which can be termed primary bending), the data presented provide a new understanding of the mechanical role of the carinar process plates, that is, a geometry consistent with that required in the keel to resist lateral or transverse bending of the tooth about a second axis. The increase in robustness of teeth incorporating lateral keel reinforcement suggests that the relative development of carinar processes (toward a geometry similar to that of L. variegatus) is a character which can be used to infer which sea urchins among the stirodonts are most primitive and among the camarodonts which are more primitive.

Epigenetic regulation of opioid-induced hyperalgesia, dependence, and tolerance in mice.

PubMed

Liang, De-Yong; Li, XiangQi; Clark, J David

2013-01-01

Repeated administration of opioids such as morphine induces persistent behavioral changes including opioid-induced hyperalgesia (OIH), tolerance, and physical dependence. In the current work we explored how the balance of histone acetyltransferase (HAT) versus histone deacetylase (HDAC) might regulate these morphine-induced changes. Nociceptive thresholds, analgesia, and physical dependence were assessed during and for a period of several weeks after morphine exposure. To probe the roles of histone acetylation, the HAT inhibitor curcumin or a selective HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) was administered daily to groups of animals. Histone acetylation in spinal cord was assessed by Western blot and immunohistochemistry. Concurrent administration of curcumin with morphine for 4 days significantly reduced development of opioid-induced mechanical allodynia, thermal hyperalgesia, tolerance, and physical dependence. Conversely, the HDAC inhibitor SAHA enhanced these responses. Interestingly, SAHA treatment after the termination of opioid administration sustained these behavioral changes for at least 4 weeks. Histone H3 acetylation in the dorsal horn of the spinal cord was increased after chronic morphine treatment, but H4 acetylation was unchanged. Moreover, we observed a decrease in HDAC activity in the spinal cords of morphine-treated mice while overall HAT activity was unchanged, suggesting a shift toward a state of enhanced histone acetylation. The current study indicates that epigenetic mechanisms play a crucial role in opioid-induced long-lasting neuroplasticity. These results provide new sight into understanding the mechanisms of opioid-induced neuroplasticity and suggest new strategies to limit opioid abuse potential and increase the value of these drugs as analgesics. Copyright © 2013 American Pain Society. All rights reserved.

Studies Using an in Vitro Model Show Evidence of Involvement of Epithelial-Mesenchymal Transition of Human Endometrial Epithelial Cells in Human Embryo Implantation*

PubMed Central

Uchida, Hiroshi; Maruyama, Tetsuo; Nishikawa-Uchida, Sayaka; Oda, Hideyuki; Miyazaki, Kaoru; Yamasaki, Akiko; Yoshimura, Yasunori

2012-01-01

Human embryo implantation is a critical multistep process consisting of embryo apposition/adhesion, followed by penetration and invasion. Through embryo penetration, the endometrial epithelial cell barrier is disrupted and remodeled by an unknown mechanism. We have previously developed an in vitro model for human embryo implantation employing the human choriocarcinoma cell line JAR and the human endometrial adenocarcinoma cell line Ishikawa. Using this model we have shown that stimulation with ovarian steroid hormones (17β-estradiol and progesterone, E2P4) and suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, enhances the attachment and adhesion of JAR spheroids to Ishikawa. In the present study we showed that the attachment and adhesion of JAR spheroids and treatment with E2P4 or SAHA individually induce the epithelial-mesenchymal transition (EMT) in Ishikawa cells. This was evident by up-regulation of N-cadherin and vimentin, a mesenchymal cell marker, and concomitant down-regulation of E-cadherin in Ishikawa cells. Stimulation with E2P4 or SAHA accelerated Ishikawa cell motility, increased JAR spheroid outgrowth, and enhanced the unique redistribution of N-cadherin, which was most prominent in proximity to the adhered spheroids. Moreover, an N-cadherin functional blocking antibody attenuated all events but not JAR spheroid adhesion. These results collectively provide evidence suggesting that E2P4- and implanting embryo-induced EMT of endometrial epithelial cells may play a pivotal role in the subsequent processes of human embryo implantation with functional control of N-cadherin. PMID:22174415

Reactivation of latent HIV-1 by new semi-synthetic ingenol esters

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

Pandeló José, Diego; Bartholomeeusen, Koen; Delveccio da Cunha, Rodrigo

The ability of HIV to establish long-lived latent infection is mainly due to transcriptional silencing of viral genome in resting memory T lymphocytes. Here, we show that new semi-synthetic ingenol esters reactivate latent HIV reservoirs. Amongst the tested compounds, 3-caproyl-ingenol (ING B) was more potent in reactivating latent HIV than known activators such as SAHA, ingenol 3,20-dibenzoate, TNF-α, PMA and HMBA. ING B activated PKC isoforms followed by NF-κB nuclear translocation. As virus reactivation is dependent on intact NF-κB binding sites in the LTR promoter region ING B, we have shown that. ING B was able to reactivate virus transcriptionmore » in primary HIV-infected resting cells up to 12 fold and up to 25 fold in combination with SAHA. Additionally, ING B promoted up-regulation of P-TEFb subunits CDK9/Cyclin T1. The role of ING B on promoting both transcription initiation and elongation makes this compound a strong candidate for an anti-HIV latency drug combined with suppressive HAART. - Highlights: • 3-caproyl-ingenol (ING B) reactivates latent HIV better than SAHA, ingenol 3,20-dibenzoate, TNF-α, PMA and HMBA. • ING B promotes PKC activation and NF-kB translocation to the nucleus. • ING B activates virus transcription of B and non-B subtypes of HIV-1. • ING B activates HIV transcription in infected primary resting CD4+ T cells. • ING B induces higher levels of P-TEFb components in human primary cells.« less

Characterization of the regulation and function of zinc-dependent histone deacetylases during rodent liver regeneration.

PubMed

Huang, Jiansheng; Barr, Emily; Rudnick, David A

2013-05-01

The studies reported here were undertaken to define the regulation and functional importance of zinc-dependent histone deacetylase (Zn-HDAC) activity during liver regeneration using the mouse partial hepatectomy (PH) model. The results showed that hepatic HDAC activity was significantly increased in nuclear and cytoplasmic fractions following PH. Further analyses showed isoform-specific effects of PH on HDAC messenger RNA (mRNA) and protein expression, with increased expression of the class I HDACs, 1 and 8, and class II HDAC4 in regenerating liver. Hepatic expression of (class II) HDAC5 was unchanged after PH; however, HDAC5 exhibited transient nuclear accumulation in regenerating liver. These changes in hepatic HDAC expression, subcellular localization, and activity coincided with diminished histone acetylation in regenerating liver. The significance of these events was investigated by determining the effects of suberoylanilide hydroxyamic acid (SAHA, a specific inhibitor of Zn-HDAC activity) on hepatic regeneration. The results showed that SAHA treatment suppressed the effects of PH on histone deacetylation and hepatocellular bromodeoxyuridine (BrdU) incorporation. Further examination showed that SAHA blunted hepatic expression and activation of cell cycle signals downstream of induction of cyclin D1 expression in mice subjected to PH. The data reported here demonstrate isoform-specific regulation of Zn-HDAC expression, subcellular localization, and activity in regenerating liver. These studies also indicate that HDAC activity promotes liver regeneration by regulating hepatocellular cell cycle progression at a step downstream of cyclin D1 induction. Copyright © 2012 American Association for the Study of Liver Diseases.

Comment on ‘On the realisation of quantum Fisher information’

NASA Astrophysics Data System (ADS)

Olendski, O.

2017-05-01

It is shown that calculation of the momentum Fisher information of the quasi-one-dimensional hydrogen atom recently presented by Saha et al (2017 Eur. J. Phys. 38 025103) is wrong. A correct derivation is provided and its didactical advantages and scientific significances are highlighted.

Diagnostic approaches for Rift Valley Fever

USDA-ARS?s Scientific Manuscript database

Disease outbreaks caused by arthropod-borne animal viruses (arboviruses) resulting in significant livestock and economic losses world-wide appear to be increasing. Rift Valley fever (RVF) virus (RVFV) is an important arbovirus that causes lethal disease in cattle, camels, sheep and goats in Sub-Saha...

Membrane Reflector Vertical Cavity Lasers at Near- and Midwave-Infrared

DTIC Science & Technology

2014-05-30

independent broadband reflectors based on cross-stacked gratings, Optics Express, (04 2011): 9050. doi: 10.1364/OE.19.009050 Tapas Kumar Saha, Mingyu Lu... Mingyu Lu, Huiqing Zhai, Deyin Zhao, Weidong Zhou. Design of a compact grating coupler with controllable linewidths via transverse resonance and

46 CFR 128.420 - Keel cooler installations.

Code of Federal Regulations, 2013 CFR

2013-10-01

...-metallic hose-clamps may be used at machinery connections if— (1) The clamps are of a corrosion-resistant material; (2) The clamps do not depend on spring tension for their holding power; and (3) Two of the clamps...

Utilization of Boron Compounds for the Modification of Suberoyl Anilide Hydroxamic Acid as Inhibitor of Histone Deacetylase Class II Homo sapiens

PubMed Central

Bakri, Ridla; Parikesit, Arli Aditya; Satriyanto, Cipta Prio; Kerami, Djati; Tambunan, Usman Sumo Friend

2014-01-01

Histone deacetylase (HDAC) has a critical function in regulating gene expression. The inhibition of HDAC has developed as an interesting anticancer research area that targets biological processes such as cell cycle, apoptosis, and cell differentiation. In this study, an HDAC inhibitor that is available commercially, suberoyl anilide hydroxamic acid (SAHA), has been modified to improve its efficacy and reduce the side effects of the compound. Hydrophobic cap and zinc-binding group of these compounds were substituted with boron-based compounds, whereas the linker region was substituted with p-aminobenzoic acid. The molecular docking analysis resulted in 8 ligands with ΔG binding value more negative than the standards, SAHA and trichostatin A (TSA). That ligands were analyzed based on the nature of QSAR, pharmacological properties, and ADME-Tox. It is conducted to obtain a potent inhibitor of HDAC class II Homo sapiens. The screening process result gave one best ligand, Nova2 (513246-99-6), which was then further studied by molecular dynamics simulations. PMID:25214833

Reptilia: Testudines: Emydidae Graptemys gibbonsi - Pascagoula Map Turtle

USGS Publications Warehouse

Lovich, Jeffrey E.; Ennen, Joshua R.

2014-01-01

The Pascagoula Map Turtle, Graptemys gibbonsi, is a large riverine species that exhibits pronounced sexual dimorphism, where females attain a maximum carapace length (CL) of 295 mm and males a maximum of 141 mm (Lovich et al. 2009). Mean adult female CL (248 mm) can be well over twice the mean CL of adult males (104 mm; Gibbons and Lovich 1990, Lovich et al. 2009). In addition, females have conspicuously enlarged heads (37.9 mm, SD = 14.0 mm) with broad alveolar surfaces (12.1 mm, SD = 4.9) compared to males (head width – 16.4 mm, SD = 1.1 mm; alveolar width – 4.3 mm, SD = 0.40 mm; Lindeman, unpublished data). Males have longer tails with the vent posterior to the edge of the carapace. Both sexes have relatively flat plastrons. Similar to other species within the pulchra clade, Graptemys gibbonsi possess a high-domed shell with a median keel. The median carapace keel is composed of prominent spines on the posterior portions of the second and third vertebrals. A broken black stripe, most pronounced anteriorly, marks the median keel of the vertebrals, and pleural scutes 1– 3 have a network of intersecting yellow lines or circular yellow markings on the distal parts. The plastron is pale yellow with dark pigment on some seams. Ground color of the head and limbs is brown to olive with light yellow or yellowish-green stripes and blotches. The yellow pigment on the upper marginal scutes is wide in comparison to other members of the pulchra clade.Hatchling pigmentation patterns resemble those of adults, but with more conspicuous patterns on the pleural scutes. Similarly, the plastron of hatchlings commonly has more dark pigmentation along the seams than adults. The shell is highly serrated along the edge of the carapace and the vertebral keel is more pronounced than in adults.

Truncorotalia crassaformis from its type locality: Comparison with Caribbean plankton and Pliocene relatives

USGS Publications Warehouse

Scott, George H.; Ingle, James C.; McCane, Brendan; Powell, Charles L.; Thunell, Robert C.

2015-01-01

Truncorotalia crassaformis has been identified in Pliocene-Holocene assemblages globally but there has been little analysis of specimens from its type locality at Lomita Quarry, California. This has led to confusion about some diagnostic criteria, particularly the presence of a peripheral keel. To better understand variation specimens are studied from the type locality (Pleistocene, c. 400–600 ka), supplemented by material from a plankton trap in Cariaco Basin and from ODP 925, Ceara Rise (Pliocene, c. 4.3 Ma). The damaged holotype has a weak topographic ridge (keel) at the periphery of early chambers of the outer whorl. Several well-preserved specimens have a keel on all chambers of the whorl. Encrustation obscures the periphery on some and masks shell shape. Several outliers in a morphometric analysis of axial shape have distinctive discoidal outlines but ventroconical (cone-like) forms are common. Lomita Marl was deposited on a sheltered, shallow shelf in Chron 1. Foraminifera reworked from the unconformably underlying Repetto Siltstone are present. Specimens resembling the holotype are very rare and often damaged. Morphological disparity is high. It is unlikely that an autochthonous population was sampled. The weak peripheral keel present on some living specimens from Cariaco Basin is built incrementally by a thin featureless calcitic veneer deposited between the morphogenesis of each chamber. The process progressively obscures pores in the primary wall. Its earliest stages have been misidentified as a poreless zone. Ventroconical form is weak in the Ceara Rise Pliocene specimens and is distinguishable from the Cariaco sample. There is only a veneer at the periphery. Although the study does not provide a population-based diagnosis of T. crassaformis it indicates that the name should not be applied to early Pliocene forms.

Adolescents in Transition: School and Family Characteristics in the Development of Violent Behaviors Entering High School

ERIC Educational Resources Information Center

Frey, Ariel; Ruchkin, Vladislav; Martin, Andres; Schwab-Stone; Mary

2009-01-01

Adolescents are vulnerable to becoming involved in problematic behaviors, disengaging academically, and dropping out of school. This study was designed to evaluate the protective role of self-perceived school attachment and family involvement on the development of these negative behaviors during adolescence. The Social and Health Assessment (SAHA)…

Ionizing Shocks in Argon. Part 1: Collisional-Radiative Model and Steady-State Structure (Preprint)

DTIC Science & Technology

2010-09-09

absorption oscillator strength is given by fabsij = gj gi Aji 3γ . (43) Contributions to the parameter γ have been assumed to result from a combination of...discretization, the Saha temperatures of the higher states (green, red and blue solid curves) overshoot Te and relaxes with Th, indicating over

Effect of humic acids with different characteristics on fermentative short-chain fatty acids production from waste activated sludge.

PubMed

Liu, Kun; Chen, Yinguang; Xiao, Naidong; Zheng, Xiong; Li, Mu

2015-04-21

Recently, the use of waste activated sludge to bioproduce short-chain fatty acids (SCFA) has attracted much attention as the sludge-derived SCFA can be used as a preferred carbon source to drive biological nutrient removal or biopolymer (polyhydroxyalkanoates) synthesis. Although large number of humic acid (HA) has been reported in sludge, the influence of HA on SCFA production has never been documented. This study investigated the effects on sludge-derived SCFA production of two commercially available humic acids (referred to as SHHA and SAHA purchased respectively from Shanghai Reagent Company and Sigma-Aldrich) that differ in chemical structure, hydrophobicity, surfactant properties, and degree of aromaticity. It was found that SHHA remarkably enhanced SCFA production (1.7-3.5 folds), while SAHA had no obvious effect. Mechanisms study revealed that all four steps (solubilization, hydrolysis, acidification, and methanogenesis) involved in sludge fermentation were unaffected by SAHA. However, SHHA remarkably improved the solubilization of sludge protein and carbohydrate and the activity of hydrolysis enzymes (protease and α-glucosidase) owing to its greater hydrophobicity and protection of enzyme activity. SHHA also enhanced the acidification step by accelerating the bioreactions of glyceradehyde-3P → d-glycerate 1,3-diphosphate, and pyruvate → acetyl-CoA due to its abundant quinone groups which served as electron acceptor. Further investigation showed that SHHA negatively influenced the activity of acetoclastic methanogens for its competition for electrons and inhibition on the reaction of acetyl-CoA → 5-methyl-THMPT, which caused less SCFA being consumed. All these observations were in correspondence with SHHA significantly enhancing the production of sludge derived SCFA.

Lost Talent? The Occupational Ambitions and Attainments of Young Australians

ERIC Educational Resources Information Center

Sikora, Joanna; Saha, Lawrence J.

2011-01-01

Given ongoing interest in increasing productivity and participation in the workforce, understanding when talent is lost is a useful exercise. The term "lost talent" describes the underutilisation or wastage of human potential. Focusing on young people, Sikora and Saha define lost talent as occurring when students in the top 50% of…

Mechanism for neurotropic action of vorinostat, a pan histone deacetylase inhibitor

USDA-ARS?s Scientific Manuscript database

In this study we investigated the effect of vorinostat (suberanilohydroxamic acid, SAHA), a class I and class II HDAC inhibitor, on the differentiation of Neuroscreen-1 (NS-1) cells. NS-1 cell is a subclone of the rat pheochromocytoma cell line (PC 12). PC12 cells on treatment with nerve growth fac...

Mitigation Strategies to Reduce Truck Crash Rates on Wyoming Highways

DOT National Transportation Integrated Search

2017-05-04

M Mahdi Rezapour Mashhadi (ORCID iD: 0000-0003-0774-737X); Promothes Saha, Ph.D., P.E. (ORCID iD: 0000-0003-3298-8327); Trenna Terrill (ORCID iD: 0000-0002-5239-6380); Khaled Ksaibati, Ph.D., P.E. (ORCID iD: 0000-0003-3532-6839) Wyoming has one of th...

Generalized theory for seaplane impact

NASA Technical Reports Server (NTRS)

Milwitzky, Benjamin

1952-01-01

The motions, hydrodynamic loads, and pitching moments experienced by v-bottom seaplanes during step-landing impacts are analyzed and the theoretical results are compared with experimental data. In the analysis, the primary flow about the immersed portion of a keeled hull or float is considered to occur in transverse flow planes and the concept of virtual mass is applied to determined the reaction of the water to the motions of the seaplane. The entire immersion process is analyzed from the instant of initial contact until the seaplane rebounds from the water surfaces. The analysis is applicable to the complete range of initial contact conditions between the case of impacts where the resultant velocity is normal to the keel and the limiting condition of planing.

Transformation products formation of ciprofloxacin in UVA/LED and UVA/LED/TiO2 systems: Impact of natural organic matter characteristics.

PubMed

Li, Si; Hu, Jiangyong

2018-04-01

The role of natural organic matter (NOM) in contaminants removal by photolysis and photocatalysis has aroused increasing interest. However, evaluation of the influence of NOM characteristics on the transformation products (TPs) formation and transformation pathways of contaminants has rarely been performed. This study investigated the decomposition kinetics, mineralization, TPs formation and transformation pathways of antibiotic ciprofloxacin (CIP) during photolysis and photocatalysis in the presence of three commercial NOM isolates (Sigma-Aldrich humic acid (SAHA), Suwannee River humic acid (SRHA) and Suwannee River NOM (SRNOM)) by using UVA light emitting diode (UVA/LED) as an alternative light source. NOM isolates insignificantly affected CIP photolysis but strongly inhibited CIP photocatalysis due to competitive radical quenching. The inhibitory effect followed the order of SAHA (49.6%) > SRHA (29.9%) > SRNOM (21.2%), consistent with their •OH quenching abilities, SUVA 254 values and orders of aromaticity. Mineralization rates as revealed by F - release were negatively affected by NOM during CIP photocatalysis. TPs arising from hydroxylation and defluorination were generally suppressed by NOM isolates in UVA/LED and UVA/LED/TiO 2 systems. In contrast, dealkylation and oxidation of piperazine ring were promoted by NOM. The enhancement in the apparent formation kinetics (k app ) of TP245, TP291, TP334a, TP334b and TP362 followed the order of SRNOM > SRHA > SAHA. k app values were positively correlated with O/C ratio, carboxyl content, E2/E3 and fluorescence index (FI) of NOM and negatively related with SUVA 254 values. The observed correlations indicate that NOM properties are important in determining the fate and transformation of organic contaminants during photolysis and photocatalysis. Copyright © 2018 Elsevier Ltd. All rights reserved.

SETI from the moon: an invitation to COSPAR

NASA Astrophysics Data System (ADS)

Heidmann, J.

After presenting arguments for SETI (Search for ExtraTerrestrial Intelligence) work to be done well into the 21st century, and in view of the dramatic increase of blinding human-made radiofrequency interference, this author proposed that a well defined locale on the farside of the Moon - crater Saha - be preserved for the next 20-30 years not only for SETI but also for future high-sensitivity radioastronomy. The long-term programmatic issues were presented at the Lunar Exploration Symposium of the Jerusalem 1994 International Astronautical Federation Congress. The legal questions raised were delineated at the International Institute of Space Law (IISL) Colloquium of the same Jerusalem Congress. Numerous suggestions were given for an action strategy, in particular to present a proposal at a COSPAR venue. In the words of IISL Director A.A. Cocca: ``This reservation of a lunar zone for scientific activities, and its further utilization aiming at the common good of humanity, must be recognized, and constitutes a precedent.'' At the Hamburg 1995 European Geophysical Society XXth GA, we pointed out that this Saha project could offer interesting possibilities for a symbiosis with the `Science on the Moon Exobiology' teams. We also presented it at the Berlin 1996 European Space Agency/Deutsche Forschungsanstalt für Luft und Raumfahrt `International Moon Workshop' to geologists and to bioastrononomers at the Capri 1996 Bioastronomy International Astronomical Union Colloquium #161. At the 1995 IAF Congress in Oslo, the SETI Committee of the International Academy of Astronautics took action for the future benefit of humankind by setting-up a Sub-committee for `A SETI Lunar Study', chaired by the author. We hope that, in view of these initial endeavors, COSPAR may become interested in this Saha proposal and supports it.

Propofol exposure during early gestation impairs learning and memory in rat offspring by inhibiting the acetylation of histone.

PubMed

Lin, Jiamei; Wang, Shengqiang; Feng, Yunlin; Zhao, Weihong; Zhao, Weilu; Luo, Foquan; Feng, Namin

2018-05-01

Propofol is widely used in clinical practice, including non-obstetric surgery in pregnant women. Previously, we found that propofol anaesthesia in maternal rats during the third trimester (E18) caused learning and memory impairment to the offspring rats, but how about the exposure during early pregnancy and the underlying mechanisms? Histone acetylation plays an important role in synaptic plasticity. In this study, propofol was administered to the pregnant rats in the early pregnancy (E7). The learning and memory function of the offspring were tested by Morris water maze (MWM) test on post-natal day 30. Two hours before each MWM trial, histone deacetylase 2 (HDAC2) inhibitor, suberoylanilide hydroxamic acid (SAHA), Senegenin (SEN, traditional Chinese medicine), hippyragranin (HGN) antisense oligonucleotide (HGNA) or vehicle were given to the offspring. The protein levels of HDAC2, acetylated histone 3 (H3) and 4 (H4), cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB), N-methyl-D-aspartate receptor (NMDAR) 2 subunit B (NR2B), HGN and synaptophysin in offspring's hippocampus were determined by Western blot or immunofluorescence test. It was discovered that infusion with propofol in maternal rats on E7 leads to impairment of learning and memory in offspring, increased the protein levels of HDAC2 and HGN, decreased the levels of acetylated H3 and H4 and phosphorylated CREB, NR2B and synaptophysin. HDAC2 inhibitor SAHA, Senegenin or HGN antisense oligonucleotide reversed all the changes. Thus, present results indicate exposure to propofol during the early gestation impairs offspring's learning and memory via inhibiting histone acetylation. SAHA, Senegenin and HGN antisense oligonucleotide might have therapeutic value for the adverse effect of propofol. © 2018 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Combined treatment of adenosine nucleoside inhibitor NITD008 and histone deacetylase inhibitor vorinostat represents an immunotherapy strategy to ameliorate West Nile virus infection.

PubMed

Nelson, Jacob; Roe, Kelsey; Orillo, Beverly; Shi, Pei-Yong; Verma, Saguna

2015-10-01

West Nile virus (WNV), a member of the Flaviviridae family, is the leading cause of viral encephalitis in the United States. Despite efforts to control the spread of WNV, there has been an increase in the number of outbreaks and clinical cases with neurological problems. There are no antiviral compounds currently in trials for WNV. NITD008 is an adenosine analogue inhibitor that interrupts the RNA-dependent RNA polymerase of flaviviruses. Previous studies demonstrated NITD008 as a potent antiviral for dengue virus, however this drug was associated with preclinical toxicity. The ability of NITD008 to block WNV replication is only shown in Vero cells. Neuroinflammation is also a major cause of the WNV-associated pathology, therefore we evaluated the effect of NITD008 and a newly characterized anti-inflammatory drug vorinostat (SAHA), a histone deacetylase inhibitor, on WNV replication and disease progression in a mouse model. When administered at 10 and 25mg/kg at days 1-6 after WNV infection in C57BL/6 mice, NITD008 conferred complete protection from clinical symptoms and death, which correlated with reduced viral load in the serum and restriction of virus-CNS entry. Delay of NITD008 treatment to days 3-6 and days 5-9 after infection, when WNV replication was high in the periphery and brain, resulted in the gradual loss of protection against WNV infection. However, co-treatment with SAHA and NITD008 during the CNS phase of disease improved disease outcome significantly by reducing inflammation and neuronal death. Our results support potential synergistic effect of combination therapy of NITD008 with SAHA for the treatment of WNV encephalitis. Copyright © 2015 Elsevier B.V. All rights reserved.

Improving the organic and biological fouling resistance and removal of pharmaceutical and personal care products through nanofiltration by using in situ radical graft polymerization.

PubMed

Lin, Yi-Li; Tsai, Chia-Cheng; Zheng, Nai-Yun

2018-09-01

In this study, an insitu radical graft polarization technique using monomers of 3-sulfopropyl methacrylate potassium salt (SPM) and 2-hydroxyethyl methacrylate (HEMA) was applied to a commercial nanofiltration membrane (NF90) to improve its removal of six commonly detected pharmaceutical and personal care products (PPCPs) and mitigate organic and biological fouling by humic acid (HA) and sodium alginate (SA). Compared with the virgin membrane, the modified NF90 membrane exhibited considerably improved fouling resistance and an increased reversible fouling percentage, especially for SA+HA composite fouling Moreover, the PPCP removal of the modified NF90 membrane was higher than that of the virgin membrane after SA and SA+HA fouling, respectively. Triclosan and carbamazepine, which are poorly rejected, could be effectively removed by modified membrane after SA or SA+HA fouling. Both monomers modified the membrane surface by increasing the hydrophilicity and decreasing the contact angle. The degree of grafting was quantified using attenuated total reflection Fourier-transform infrared spectroscopy. The mitigation in the fouling was evident from the low quantity of deposit formed on the modified membrane, as observed using scanning electron microscopy. A considerable amount of highly hydrophobic triclosan was adsorbed on the SA-fouled virgin membrane and penetrated through it. By contrast, the adsorption of triclosan was substantially lower in the SPM-modified membrane. After membrane modification, the fouling mechanism changed from solely intermediate blocking to both intermediate blocking and complete blocking after membrane modification. Thus, the in situ radical graft polymerization method effectively reduces organic and biological fouling and provides high PPCP removal, which is beneficial for fouling control and produces permeate of satisfactory quality for application in the field of membrane technology. Copyright © 2018 Elsevier B.V. All rights reserved.

Antisocial Behavior in Adolescence: Typology and Relation to Family Context

ERIC Educational Resources Information Center

Sobotková, Veronika; Blatný, Marek; Jelínek, Martin; Hrdlicka, Michal

2013-01-01

The study deals with the relationship between antisocial behavior in early adolescence and family environment. Sample consisted of 2,856 adolescents (53% girls, mean age 13.5 years, SD = 1.1) from urban areas in the Czech Republic. The Social and Health Assessment (SAHA), a school survey, was used to measure sociodemographic characteristics of the…

Concurrent Enrollment: Comparing How Educators and Students Categorize Students' Motivations

ERIC Educational Resources Information Center

Dare, Alec; Dare, Lynn; Nowicki, Elizabeth

2017-01-01

High-ability students have special education needs that are often overlooked or misunderstood (Blaas in "Aust J Guid Couns" 24(2):243-255, 2014) which may result in talent loss (Saha and Sikora in "Int J Contemp Sociol Discuss J Contemp Ideas Res" 48(1):9-34, 2011). Educational acceleration can help avoid these circumstances…

Climate Forecast System

Science.gov Websites

Weather Service NWS logo - Click to go to the NWS home page Climate Forecast System Home News Organization Web portal to all Federal, state and local government Web resources and services. The NCEP Climate when using the CFS Reanalysis (CFSR) data. Saha, Suranjana, and Coauthors, 2010: The NCEP Climate

Combined inhibition of BET family proteins and histone deacetylases as a potential epigenetics-based therapy for pancreatic ductal adenocarcinoma

PubMed Central

Mazur, Pawel K; Herner, Alexander; Mello, Stephano S; Wirth, Matthias; Hausmann, Simone; Sánchez-Rivera, Francisco J; Lofgren, Shane M; Kuschma, Timo; Hahn, Stephan A; Vangala, Deepak; Trajkovic-Arsic, Marija; Gupta, Aayush; Heid, Irina; Noël, Peter B; Braren, Rickmer; Erkan, Mert; Kleeff, Jörg; Sipos, Bence; Sayles, Leanne C; Heikenwalder, Mathias; Heßmann, Elisabeth; Ellenrieder, Volker; Esposito, Irene; Jacks, Tyler; Bradner, James E; Khatri, Purvesh; Sweet-Cordero, E Alejandro; Attardi, Laura D; Schmid, Roland M; Schneider, Guenter; Sage, Julien; Siveke, Jens T

2016-01-01

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers and shows resistance to any therapeutic strategy used. Here we tested small-molecule inhibitors targeting chromatin regulators as possible therapeutic agents in PDAC. We show that JQ1, an inhibitor of the bromodomain and extraterminal (BET) family of proteins, suppresses PDAC development in mice by inhibiting both MYC activity and inflammatory signals. The histone deacetylase (HDAC) inhibitor SAHA synergizes with JQ1 to augment cell death and more potently suppress advanced PDAC. Finally, using a CRISPR-Cas9–based method for gene editing directly in the mouse adult pancreas, we show that de-repression of p57 (also known as KIP2 or CDKN1C) upon combined BET and HDAC inhibition is required for the induction of combination therapy–induced cell death in PDAC. SAHA is approved for human use, and molecules similar to JQ1 are being tested in clinical trials. Thus, these studies identify a promising epigenetic-based therapeutic strategy that may be rapidly implemented in fatal human tumors. PMID:26390243

Role of Relativistic Effects in the Ionization of Heavy Ions by Electron Impact

NASA Astrophysics Data System (ADS)

Saha, Bidhan C.; Basak, Arun K.

2005-05-01

Electron impact single ionization cross sections of few heavy ions are evaluated using the recently proposed modifications [1] of the widely used simplified version of the improved binary-encounter (siBED) dipole model [2]. This model consists of two adjustable parameters and it is found that they are related to the nature of the charge distribution in the bonding region of the target. For its effective uses for ionic target the siBED model is further modified [3] in terms of the ionic and relativistic effects. This study focuses on the relativistic energy domain and the findings suggest the fate of those parameters. Details of our findings will be presented at the conference. [1] W. M. Huo, Phys. Rev. A 64, 042719 (2001). [2] M. A. Uddin, M. A. K. F. Haque, A. K. Basak and B. C. Saha, Phys. Rev A70, 0322706(2004). [3] M. a. Uddin, M. A. K. F. Haque, M. S. Mahbub, K. R. Karim, A.K. Basak and B. C. Saha, Phys. Rev. A (in press) 2005.

Electron Impact K-shell Ionization of Atomic Targets

NASA Astrophysics Data System (ADS)

Saha, Bidhan; Basak, Arun K.; Alfaz Uddin, M.; Patoary, A. A. R.

2008-05-01

In spite of considerable progress -both theoretically and experimentally- recently in evaluating accurate K-shell ionization cross sections that play a decisive role for quantitative analyses using (i) electron probe microanalysis, (ii) Auger electron spectroscopy and (iii) electron energy loss spectra, attempts are still continuing to search for a model that can easily generate reliable cross sections for a wide range of energies and for various targets needed for plasma modeling code We report few modifications of the widely used binary encounter approximation (BEA) [1,2] and have tested by evaluating the electron impact K-shell ionization of few neutral targets at various projectile energies. Details will be presented at the meeting. [1] M. Gryziniski, Phys. Rev. A 138, 336 (1965); [2] L. Vriens, Proc. Phys. Soc. (London) 89, 13, (1966). [3M. A. Uddin , A. K. F. Haque, M. M. Billah, A. K. Basak, K, R, Karim and B. C. Saha, ,Phys. Rev. A 71,032715 (2005); [4] M. A. Uddin, A. K. Basak, and B. C. Saha, Int. J. Quan. Chem 100, 184 (2004).

Oxime amides as a novel zinc binding group in histone deacetylase inhibitors: synthesis, biological activity, and computational evaluation.

PubMed

Botta, Cinzia B; Cabri, Walter; Cini, Elena; De Cesare, Lucia; Fattorusso, Caterina; Giannini, Giuseppe; Persico, Marco; Petrella, Antonello; Rondinelli, Francesca; Rodriquez, Manuela; Russo, Adele; Taddei, Maurizio

2011-04-14

Several oxime containing molecules, characterized by a SAHA-like structure, were explored to select a potentially new biasing binding element for the zinc in HDAC catalytic site. All compounds were evaluated for their in vitro inhibitory activity against the 11 human HDACs isoforms. After identification of a "hit" molecule, a programmed variation at the cap group and at the linker was carried out in order to increase HDAC inhibition and/or paralogue selectivity. Some of the new derivatives showed increased activity against a number of HDAC isoforms, even if their overall activity range is still far from the inhibition values reported for SAHA. Moreover, different from what was reported for their hydroxamic acid analogues the new α-oxime amide derivatives do not select between class I and class II HDACs; rather they target specific isoforms in each class. These somehow contradictory results were finally rationalized by a computational assisted SAR, which gave us the chance to understand how the oxime derivatives interact with the catalytic site and justify the observed activity profile.

Histone deacetylase inhibitors protect against cisplatin-induced acute kidney injury by activating autophagy in proximal tubular cells.

PubMed

Liu, Jing; Livingston, Man J; Dong, Guie; Tang, Chengyuan; Su, Yunchao; Wu, Guangyu; Yin, Xiao-Ming; Dong, Zheng

2018-02-23

Histone deacetylase inhibitors (HDACi) have therapeutic effects in models of various renal diseases including acute kidney injury (AKI); however, the underlying mechanism remains unclear. Here we demonstrate that two widely tested HDACi (suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA)) protect the kidneys in cisplatin-induced AKI by enhancing autophagy. In cultured renal proximal tubular cells, SAHA and TSA enhanced autophagy during cisplatin treatment. We further verified the protective effect of TSA against cisplatin-induced apoptosis in these cells. Notably, inhibition of autophagy by chloroquine or by autophagy gene 7 (Atg7) ablation diminished the protective effect of TSA. In mice, TSA increased autophagy in renal proximal tubules and protected against cisplatin-induced AKI. The in vivo effect of TSA was also abolished by chloroquine and by Atg7 knockout specifically from renal proximal tubules. Mechanistically, TSA stimulated AMPK and inactivated mTOR during cisplatin treatment of proximal tubule cells and kidneys in mice. Together, these results suggest that HDACi may protect kidneys by activating autophagy in proximal tubular cells.

Human factors evaluation of the HL-20 full-scale model

NASA Astrophysics Data System (ADS)

Willshire, Kelli F.; Simonsen, Lisa C.; Willshire, William L., Jr.

1993-09-01

The human factors testing of the HL-20 personnel launch system full-scale model was conducted in both the vertical and horizontal positions at NASA Langley Research Center. Three main areas of testing were considered: an anthropometric fit evaluation, the ingress and egress of a 10-person crew, and pilot viewing. The subjects, ranging from the 5th to 95th percentile size, had sufficient clearance in the model, with the exception of the last two rows of seats and the cockpit area. Adjustable seat heights and/or placement of the seats farther forward would provide more headroom. In the horizontal position, the model's seat placement and aisle width allowed a quick and orderly 10-person egress for the no-keel (a structural support running the length on the aisle), 6-in.-high keel, and 12-in.-high keel conditions. Egress times were less than 20 s. For the vertical position, the model's long cylindrical shape with the ladder in the ceiling allowed a quick and orderly egress with average times less than 30 s. Ingress and egress procedures were demonstrated using shuttle partial-pressure suits. The reduced mobility experienced while wearing the suits did increase egress times, although they still remained acceptable. The window arrangement for pilot viewing was found to be reasonably acceptable, although slight modifications, such as an increased downward view, is desirable.

On the importance of continental lithospheric roots in plume-continent interaction: implication for India motions over the last 130 Ma

NASA Astrophysics Data System (ADS)

Sibrant, A.; Davaille, A.

2015-12-01

Over the last 130 Ma, the India plate migration varied in velocity and direction. The oceanic magnetic anomalies indicates that the India-Asia convergence rate increase at ~ 90 Ma and at ~ 67 Ma. These episodes of acceleration correspond to the emplacement of Morondava and Deccan large igneous provinces, respectively. They therefore may be generated by the arrival of a mantle plume in the vicinity of India. We carried out laboratory experiments to examine and quantify the possible links between plume head impact and the acceleration of a continental plate. The latter is modelled by a buoyant raft, floating on the surface of a plexiglas tank containing Sugar Syrup, a temperature-dependent viscosity fluid. Plumes are generated by heating from below. The initial distance between the plume impact and the raft, as well as the raft size and density were systematically varied. The latter allows to evaluate the influence of a cratonic keel on the plate migration. Experimental results suggest that: (1) a continent can migrate under the influence of a plume head only if the thickness ratio between the keel and the plume head impact is greater than a critical value; (2) the maximum velocity achieved by the raft depends on the distance between the raft and the plume centre and (3) the direction taken by the raft is directly related to the position of the plume impact compared to the keel's. Given the Deccan Traps plume characteristics, the scaling laws derived from the experiments suggest that India could migrate after the plume impact with a velocity ranging between 61 and 125 mm/yr. This estimated range is fully coherent with the India plate velocity calculated from the oceanic magnetic anomalies, but it put strong constraints on the existence and position of cratonic keels under India. Moreover, India migration during the last 130 Ma can be quantitavely related to the successive impacts of three mantle plumes.

Iceberg Ploughmarks Indicate Past Rapid Iceberg Calving and Retreat of Pine Island-Thwaites Ice Stream due to Marine Ice-Cliff Instability Processes

NASA Astrophysics Data System (ADS)

Wise, M.; Dowdeswell, J. A.; Larter, R. D.; Jakobsson, M.

2016-12-01

Seafloor ploughmarks provide evidence of past and present iceberg dimensions and drift direction. Today, Pine Island and Thwaites glaciers, which account for 35% of mass loss from the West Antarctic Ice Sheet (WAIS), calve mainly large, tabular icebergs, which, when grounded, produce `toothcomb-like' multi-keeled ploughmarks. High-resolution multi-beam swath bathymetry of the mid-shelf Pine Island Trough and adjacent banks, reveals many linear-curvilinear depressions interpreted as iceberg-keel ploughmarks, the majority of which are single-keeled in form. From measurements of ploughmark planform and cross-sections, we find iceberg calving from the palaeo-Pine Island-Thwaites Ice Stream was not characterised by small numbers of large, tabular icebergs, but instead, by a large number of `smaller' icebergs with v-shaped keels. Geological evidence of ploughmark form and water-depth distribution indicates calving-margin thicknesses ( 950 m) and subaerial ice-cliff elevations ( 100 m) equivalent to the theoretical threshold recently predicted to trigger ice-cliff structural collapse through Marine Ice Cliff Instability (MICI) processes. Significantly, our proposed period of iceberg ploughing predates the early Holocene climate optimum, and likely occurred in an absence of widespread surface melt. We therefore provide the first observational evidence of rapid retreat of the Palaeo-Pine Island-Thwaites ice stream from the crest of a large, mid-shelf sedimentary depocentre or grounding-zone wedge, to a restabilising position 112 km offshore of the December 2013 calving line, driven by MICI processes commencing 12.3 cal. ka BP. We emphasise the effective operation of MICI processes without extensive surface melt and induced hydrofracture, and conclude that such processes are unlikely to be confined to the past, given the steep, retrograde bed-slope which the modern grounding lines of Pine Island and Thwaites Glaciers are approaching, and the absence of any discernible

How Principals Use Research

ERIC Educational Resources Information Center

Biddle, Bruce J.; Saha, Lawrence J.

2006-01-01

Claims that education research is flawed and that it has little or no impact on school practices have been circulating for at least 75 years, and this chorus of criticism has intensified in the past three decades. Yet the validity of such claims has not been investigated, write Biddle and Saha. The authors interviewed 120 school principals (81 in…

National Centers for Environmental Prediction

Science.gov Websites

: Influence of convective parameterization on the systematic errors of Climate Forecast System (CFS) model ; Climate Dynamics, 41, 45-61, 2013. Saha, S., S. Pokhrel and H. S. Chaudhari : Influence of Eurasian snow Organization Search Enter text Search Navigation Bar End Cap Search EMC Go Branches Global Climate and Weather

33 CFR 173.57 - Contents of report.

Code of Federal Regulations, 2012 CFR

2012-07-01

...”, “manual”, “propeller”, “sail”, “water jet”, or “other”; (ix) Fuel: authorized terms are “electric... transom to keel, horsepower, propulsion (outboard, inboard, inboard outdrive, sail, or other), fuel (gas...

33 CFR 173.57 - Contents of report.

Code of Federal Regulations, 2013 CFR

2013-07-01

...”, “manual”, “propeller”, “sail”, “water jet”, or “other”; (ix) Fuel: authorized terms are “electric... transom to keel, horsepower, propulsion (outboard, inboard, inboard outdrive, sail, or other), fuel (gas...

33 CFR 173.57 - Contents of report.

Code of Federal Regulations, 2014 CFR

2014-07-01

...”, “manual”, “propeller”, “sail”, “water jet”, or “other”; (ix) Fuel: authorized terms are “electric... transom to keel, horsepower, propulsion (outboard, inboard, inboard outdrive, sail, or other), fuel (gas...

Viral Evolution Core | FNLCR Staging

Cancer.gov

Brandon F. Keele, Ph.D. PI/Senior Principal Investigator, Retroviral Evolution Section Head, Viral Evolution Core Leidos Biomedical Research, Inc. Frederick National Laboratory for Cancer Research Frederick, MD 21702-1201 Tel: 301-846-173

Find an Audiologist

MedlinePlus

... Verde Cayman Islands Central African Republic Chad Chile China Christmas Island Cocos (Keeling) Islands Colombia Comoros Congo ... Sweden Switzerland Syrian Arab Republic Taiwan, Republic of China Tajikistan Tanzania, United Republic of Thailand Togo Tokelau ...

33 CFR 149.540 - What are the requirements for obstruction lights on a single point mooring?

Code of Federal Regulations, 2010 CFR

2010-07-01

... located at least 10 feet (3 meters) above mean high water. (b) A submerged turret loading (STL) deepwater... five-foot (1.5 meters) clearance beneath the net under keel clearance at the mean low water condition...

33 CFR 183.320 - Preconditioning for tests.

Code of Federal Regulations, 2010 CFR

2010-07-01

... percent of the result of the following calculation, but not less than zero: the maximum weight capacity... be sealed. (f) The boat must be keel down in the water. (g) The boat must be swamped, allowing water...

33 CFR 183.320 - Preconditioning for tests.

Code of Federal Regulations, 2013 CFR

2013-07-01

... percent of the result of the following calculation, but not less than zero: the maximum weight capacity... be sealed. (f) The boat must be keel down in the water. (g) The boat must be swamped, allowing water...

33 CFR 183.320 - Preconditioning for tests.

Code of Federal Regulations, 2014 CFR

2014-07-01

... percent of the result of the following calculation, but not less than zero: the maximum weight capacity... be sealed. (f) The boat must be keel down in the water. (g) The boat must be swamped, allowing water...

33 CFR 183.320 - Preconditioning for tests.

Code of Federal Regulations, 2011 CFR

2011-07-01

... percent of the result of the following calculation, but not less than zero: the maximum weight capacity... be sealed. (f) The boat must be keel down in the water. (g) The boat must be swamped, allowing water...

33 CFR 183.320 - Preconditioning for tests.

Code of Federal Regulations, 2012 CFR

2012-07-01

... percent of the result of the following calculation, but not less than zero: the maximum weight capacity... be sealed. (f) The boat must be keel down in the water. (g) The boat must be swamped, allowing water...

Two sympatric new species of woodlizards (Hoplocercinae, Enyalioides) from Cordillera Azul National Park in northeastern Peru

PubMed Central

Venegas, Pablo J.; Torres-Carvajal, Omar; Duran, Vilma; de Queiroz, Kevin

2013-01-01

Abstract We report the discovery of two sympatric new species of Enyalioides from a montane rainforest of the Río Huallaga basin in northeastern Peru. Among other characters, the first new species is distinguishable from other Enyalioides by the combination of the following characters: strongly keeled ventral scales, more than 37 longitudinal rows of dorsals in a transverse line between the dorsolateral crests at midbody, low vertebral crest on the neck with vertebrals on neck similar in size to those between hind limbs, projecting scales on body or limbs absent, 96 mm maximum SVL in both sexes, and caudals increasing in size posteriorly within each autotomic segment. The second new species differs from other species of Enyalioides in having strongly keeled ventral scales, scales posterior to the superciliaries forming a longitudinal row of strongly projecting scales across the lateral edge of the skull roof in adults of both sexes, 31 or fewer longitudinal rows of strongly keeled dorsals in a transverse line between the dorsolateral crests at midbody, vertebrals on neck more than five times the size of vertebrals between hind limbs in adult males, projecting scales on body or limbs absent, and caudals increasing in size posteriorly within each autotomic segment. We also present an updated molecular phylogenetic tree of hoplocercines including new samples of Enyalioides rudolfarndti, Enyalioides rubrigularis, both species described in this paper, as well as an updated identification key for species of Hoplocercinae. PMID:23794824

Rough-water Landings of a 0.1-Size Powered Dynamic Model of the XP5Y-1 Flying Boat with Two Types of Afterbody - Langley Tank Model 228 (TED No. NACA DE309)

NASA Technical Reports Server (NTRS)

Garrison, Charlie C.

1949-01-01

A 0.1-size powered dynamic model of a large, high-speed flying boat was landed in Langley tank no. 1 into oncoming waves 4 feet high (full size). The model was tested with two afterbodies of differing lengths (4.12 and 6.63 beams). The short afterbody had a constant angle of dead rise of 22.5deg and a keel angle of 6.5deg. The long afterbody had warped dead rise and a keel angle of 8.5deg. The vertical accelerations were slightly greater and the maximum angular accelerations and maxim= trims were slightly less for the model with the long afterbody than for the model with -the short afterbody. A wave length of 210 feet (full size) imposed the highest accelerations on the model with either the long or the short afterbody.

46 CFR 34.20-25 - Foam monitor capacity-T/ALL.

Code of Federal Regulations, 2014 CFR

2014-10-01

... keel laying date on or after January 1, 1975, must be at least 3 liters per minute per square meter (.073 gallons per minute per square foot) of cargo area protected by that monitor. [CGD 74-127, 41 FR...

46 CFR 34.20-25 - Foam monitor capacity-T/ALL.

Code of Federal Regulations, 2012 CFR

2012-10-01

... keel laying date on or after January 1, 1975, must be at least 3 liters per minute per square meter (.073 gallons per minute per square foot) of cargo area protected by that monitor. [CGD 74-127, 41 FR...

46 CFR 34.20-25 - Foam monitor capacity-T/ALL.

Code of Federal Regulations, 2013 CFR

2013-10-01

... keel laying date on or after January 1, 1975, must be at least 3 liters per minute per square meter (.073 gallons per minute per square foot) of cargo area protected by that monitor. [CGD 74-127, 41 FR...

46 CFR 34.20-25 - Foam monitor capacity-T/ALL.

Code of Federal Regulations, 2010 CFR

2010-10-01

... keel laying date on or after January 1, 1975, must be at least 3 liters per minute per square meter (.073 gallons per minute per square foot) of cargo area protected by that monitor. [CGD 74-127, 41 FR...

46 CFR 34.20-25 - Foam monitor capacity-T/ALL.

Code of Federal Regulations, 2011 CFR

2011-10-01

... keel laying date on or after January 1, 1975, must be at least 3 liters per minute per square meter (.073 gallons per minute per square foot) of cargo area protected by that monitor. [CGD 74-127, 41 FR...

Effect of Dietary-Resistant Starch on Inhibition of Colonic Preneoplasia and Wnt Signaling in Azoxymethane-Induced Rodent Models.

PubMed

Nelson, Bridget; Cray, Nicole; Ai, Yongfeng; Fang, Yinan; Liu, Peng; Whitley, Elizabeth M; Birt, Diane

2016-01-01

Dietary fiber has been reported to prevent preneoplastic colon lesions. The aim of this study was to determine the effect of resistant starches, novel dietary fibers, on the development of colonic preneoplasia and Wnt signaling in azoxymethane (AOM)-treated rats and mice fed resistant starches at 55% of the diet after AOM treatment. Another objective was to determine the effect of resistant starches on the development of preneoplasia in rats treated with antibiotics (Ab), administered between AOM treatment and resistant starch feeding. Diets containing resistant starches, high-amylose (HA7), high-amylose-octenyl succinic anhydride (OS-HA7), or high-amylose-stearic acid (SA-HA7) were compared with control cornstarch (CS). The resistant starch content of the diets did not alter the yield of colonic lesions but animals treated with AOM and fed the diet with the highest resistant starch content, SA-HA7 developed the highest average aberrant crypt foci (ACF) per animal. Mice fed the OS-HA7 diet had decreased expression of some upstream Wnt genes in the colonic crypts. This study suggests that further research is needed to determine if resistant starch impacts colon carcinogenesis in rodents.

Repurposing Pan-HDAC Inhibitors for ARID1A-Mutated Ovarian Cancer.

PubMed

Fukumoto, Takeshi; Park, Pyoung Hwa; Wu, Shuai; Fatkhutdinov, Nail; Karakashev, Sergey; Nacarelli, Timothy; Kossenkov, Andrew V; Speicher, David W; Jean, Stephanie; Zhang, Lin; Wang, Tian-Li; Shih, Ie-Ming; Conejo-Garcia, Jose R; Bitler, Benjamin G; Zhang, Rugang

2018-03-27

ARID1A, a subunit of the SWI/SNF complex, is among the most frequently mutated genes across cancer types. ARID1A is mutated in more than 50% of ovarian clear cell carcinomas (OCCCs), diseases that have no effective therapy. Here, we show that ARID1A mutation confers sensitivity to pan-HDAC inhibitors such as SAHA in ovarian cancers. This correlated with enhanced growth suppression induced by the inhibition of HDAC2 activity in ARID1A-mutated cells. HDAC2 interacts with EZH2 in an ARID1A status-dependent manner. HDAC2 functions as a co-repressor of EZH2 to suppress the expression of EZH2/ARID1A target tumor suppressor genes such as PIK3IP1 to inhibit proliferation and promote apoptosis. SAHA reduced the growth and ascites of the ARID1A-inactivated OCCCs in both orthotopic and genetic mouse models. This correlated with a significant improvement of survival of mice bearing ARID1A-mutated OCCCs. These findings provided preclinical rationales for repurposing FDA-approved pan-HDAC inhibitors for treating ARID1A-mutated cancers. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Suberoylanilide hydroxamic acid increases progranulin production in iPSC-derived cortical neurons of frontotemporal dementia patients.

PubMed

Almeida, Sandra; Gao, Fuying; Coppola, Giovanni; Gao, Fen-Biao

2016-06-01

Mutations in the granulin (GRN) gene cause frontotemporal dementia (FTD) due to progranulin haploinsufficiency. Compounds that can increase progranulin production and secretion may be considered as potential therapeutic drugs; however, very few of them have been directly tested on human cortical neurons. To this end, we differentiated 9 induced pluripotent stem cell lines derived from a control subject, a sporadic FTD case and an FTD patient with progranulin S116X mutation. Treatment with 1 μM suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, increased the production of progranulin in cortical neurons of all subjects at both the mRNA and protein levels without affecting their viability. Microarray analysis revealed that SAHA treatment not only reversed some gene expression changes caused by progranulin haploinsufficiency but also caused massive alterations in the overall transcriptome. Thus, histone deacetylase inhibitors may be considered as therapeutic drugs for GRN mutation carriers. However, this class of drugs also causes drastic changes in overall gene expression in human cortical neurons and their side effects and potential impacts on other pathways should be carefully evaluated. Copyright © 2016 Elsevier Inc. All rights reserved.

78 FR 51058 - Airworthiness Directives; Airbus Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-20

... below the center wing box between frame (FR) 40 and FR 42, and in part of the area of the upper... NDT inspections for cracks in the affected areas of the keel beam side panel below the center wing box...

Quadrature-Quadrature Phase Shift Keying.

DTIC Science & Technology

1986-09-01

SECURITY CLASSIFICATION OF -IS PAfr All other editions are obsolete ’r- Ac P..N -N- %.. .. V . .. b . h S Debabrata Saha 1986 All Rights Reserved...1.2/T T~,pe of AISA Q -PSK AMSK 0 Y(IitIo ?6 orthogonal Four -level F, J." 𔃻 1i 1/ 2 H13.4 a H P6 E 44 3.5 Modulator Demodulator and Synchronization

The Formation of Laurentia: Evidence from Shear Wave Splitting and Seismic Tomography

NASA Astrophysics Data System (ADS)

Liddell, M. V.; Bastow, I. D.; Gilligan, A.; Darbyshire, F. A.; Pugh, S.

2016-12-01

Earth conditions during the Precambrian, and their effect on plate tectonic processes during that era, are not fully understood; how the fast wave-speed cratonic roots, or keels, often found beneath these regions were formed is also debated. The geological record of northern Hudson Bay includes the 1.8Ga TransHudson Orogen (THO) terrane, a remnant of the Paleoproterozoic collision of the Archean Rae and Churchill domains that overlies one of Earth's largest cratonic keels. This region is thus an ideal natural laboratory for the study of Precambrian processes. We use broadband seismological data recorded at 65 stations in northern Hudson Bay to address questions regarding the manner and scale of plate deformation during Precambrian assembly of the region. To explore these questions, we conduct a study of mantle seismic anisotropy using SKS splitting. Our study constitutes the most complete shear wave splitting analysis of northern Canada to date utilising up to 11 years of data for some stations. Anisotropic fast directions (φ) and delay times (δt) are determined using a modified Silver and Chan (1991) method. In the Hudson Strait, φ directions parallel the THO, while the islands in northern Hudson Bay show changes in φ over length scales short enough to indicate lithospheric origin. Complex anisotropy patterns are observed in the central Rae craton and southern Baffin Island, suggesting multiple sources. Several possible sources of anisotropy are explored, including basal drag of the North American plate, mantle flow deflected by the Laurentian keel, and discontinuities associated with possible two-stage keel development P and S-wave relative arrival-time tomographic velocity models are also presented. Waveforms are aligned using the adaptive stacking routine of Rawlinson et al. (2004), and models are produced using the Fast Marching Tomography inversion code of Rawlinson et al. (2006). The THO is modeled as a low velocity feature relative to the neighbouring

Cardiomyogenic Differentiation of Human Dental Follicle-derived Stem Cells by Suberoylanilide Hydroxamic Acid and Their In Vivo Homing Property.

PubMed

Sung, Iel-Yong; Son, Han-Na; Ullah, Imran; Bharti, Dinesh; Park, Ju-Mi; Cho, Yeong-Cheol; Byun, June-Ho; Kang, Young-Hoon; Sung, Su-Jin; Kim, Jong-Woo; Rho, Gyu-Jin; Park, Bong-Wook

2016-01-01

The purpose of the present study was to investigate the in vitro cardiomyogenic differentiation potential of human dental follicle-derived stem cells (DFCs) under the influence of suberoylanilide hydroxamic acid (SAHA), a member of the histone deacetylase inhibitor family, and analyze the in vivo homing capacity of induced cardiomyocytes (iCMs) when transplanted systemically. DFCs from extracted wisdom teeth showed mesenchymal stem cell (MSC) characteristics such as plate adherent growing, expression of MSC markers (CD44, CD90, and CD105), and mesenchymal lineage-specific differentiation potential. Adding SAHA to the culture medium induced the successful in vitro differentiation of DFCs into cardiomyocytes. These iCMs expressed cardiomyogenic markers, including alpha-smooth muscle actin (α-SMA), cardiac muscle troponin T (TNNT2), Desmin, and cardiac muscle alpha actin (ACTC1) , at both the mRNA and protein level. For the assessment of homing capacity, PKH26 labeled iCMs were intraperitoneally injected (1×10 6 cells in 100 µL of PBS) into the experimental mice, and the ratios of PKH26 positive cells to the total number of injected cells, in multiple organs were determined. The calculated homing ratios, 14 days after systemic cell transplantation, were 5.6 ± 1.0%, 3.6 ± 1.1%, and 11.6 ± 2.7% in heart, liver, and kidney respectively. There was no difference in the serum levels of interleukin-2 and interleukin-10 at 14 days after transplantation, between the experimental (iCM injected) and control (no injection or PBS injection) groups. These results demonstrate that DFCs can be an excellent source for cardiomyocyte differentiation and regeneration. Moreover, the iCMs can be delivered into heart muscle via systemic administration without eliciting inflammatory or immune response. This can serve as the pilot study for further investigations into the in vitro cardiomyogenic differentiation potential of DFCs under the influence of SAHA and the in vivo homing

Sensitivity of osteosarcoma cells to HDAC inhibitor AR-42 mediated apoptosis.

PubMed

Murahari, Sridhar; Jalkanen, Aimee L; Kulp, Samuel K; Chen, Ching-Shih; Modiano, Jaime F; London, Cheryl A; Kisseberth, William C

2017-01-21

Osteosarcoma (OS) is the most common primary bone tumor in both humans and dogs and is the second leading cause of cancer related deaths in children and young adults. Limb sparing surgery along with chemotherapy has been the mainstay of treatment for OS. Many patients are not cured with current therapies, presenting a real need for developing new treatments. Histone deacetylase (HDAC) inhibitors are a promising new class of anticancer agents. In this study, we investigated the activity of the novel HDAC inhibitor AR-42 in a panel of human and canine OS cell lines. The effect of AR-42 and suberoylanilide hydroxamic acid (SAHA) alone or in combination with doxorubicin on OS cell viability was assessed. Induction of histone acetylation after HDAC inhibitor treatment was confirmed by Western blotting. Drug-induced apoptosis was analyzed by FACS. Apoptosis was assessed further by measuring caspase 3/7 enzymatic activity, nucleosome fragmentation, and caspase cleavage. Effects on Akt signaling were demonstrated by assessing phosphorylation of Akt and downstream signaling molecules. AR-42 was a potent inhibitor of cell viability and induced a greater apoptotic response compared to SAHA when used at the same concentrations. Normal osteoblasts were much less sensitive. The combination of AR-42 with doxorubicin resulted in a potent inhibition of cell viability and apparent synergistic effect. Furthermore, we showed that AR-42 and SAHA induced cell death via the activation of the intrinsic mitochondrial pathway through activation of caspase 3/7. This potent apoptotic activity was associated with the greater ability of AR-42 to downregulate survival signaling through Akt. These results confirm that AR-42 is a potent inhibitor of HDAC activity and demonstrates its ability to significantly inhibit cell survival through its pleiotropic effects in both canine and human OS cells and suggests that spontaneous OS in pet dogs may be a useful large animal model for preclinical

Cervical dermatome overlap: frequently forgotten in search of a clear answer.

PubMed

Bible, Jesse E

2016-01-01

Rainville J, Laxer E, Keel J, Pena E, Kim D, Milam RA, et al. Exploration of sensory impairments associated with C6 and C7 radiculopathies. Spine J 2016:16:49-54 (in this issue). Copyright © 2015 Elsevier Inc. All rights reserved.

Global Water Clarity: Continuing a Century-Long Monitoring

EPA Science Inventory

Aquatic systems worldwide are changing due to increasing climate variability and human activities, yet it is difficult to capture such temporal changes without standardized long-term observations [Boyce et al. 2015, Barton et al. 2016]. Unlike the well-established Keeling curve t...

A new species of Rock Gecko of the genus Cnemaspis Strauch, 1887 (Squamata: Gekkonidae) from Belitung Island, Indonesia.

PubMed

Riyanto, Awal; Hamidy, Amir; Sidik, Irvan; Gunalen, Danny

2017-11-30

A new species of rock gecko of the genus Cnemaspis Strauch is described from Belitung Island, Indonesia. The new species is differentiated from all other species in the Southern Sunda clade (sensu Grismer et al. 2014a) by having a unique combination of characters including: (1) a maximum SVL of 54.1 mm, (2) five or six postmental scales, (3) enlarged submetacarpal scales on the first finger, (4) enlarged submetatarsal scales on the first toe, (5) keeled ventral scales, (6) absence of precloacal pores, (7) absence of enlarged femoral scales, (8) absence of shield-like subtibial scales, (9) caudal tubercles encircling the tail, (10) an interrupted median row of enlarged keeled subcaudals, (11) presence of a distinct furrow on the lateral surface of the tail (12) 22-24 lamellae beneath fourth toe, and (13) two postcloacal tubercles on each side of the tail base.

Characterization of E. CHLOROTICUS Sea Urchin Tooth Using Nanoindentation and SEM

NASA Astrophysics Data System (ADS)

Laxminarayana, Radhika; Rodrigues, Samantha; Dickinson, Michelle

The teeth of Evenchinus chloroticus are not only vital tools for their survival but also have fascinating structures in the world of science and engineering. Despite being compositionally similar to rocks, these teeth are still able to scrape along the hard surfaces of rocks for food, while having the unique ability to self-sharpen. Yet these abilities arise from the properties of the teeth, which are in turn dependent on their design and composition. Nanoindentation was used in this study to characterise the hardness across the sea urchin tooth in detail. It focuses on the chewing tip since the main grinding function is performed by this region. In addition, SEM and EDS were used to explore any correlations between the mechanical properties of the tooth and its composition. It was found that there were two main relatively hard regions (stone part in the centre of the top flange part and another similar region in the centre of the bottom keel zone). These regions are similar in structure, consisting of thin needles and matrix and have a higher magnesium content compared to other areas of the tooth, which is attributed to the greater proportion of matrix present. Furthermore, the regions below the stone part and at the start of the keel zone appear to be weaker, which might be due to the significant amount of pores in these areas. The sharp tip is maintained by shedding of the primary plates surrounding the stone part and the keel fibres, leaving only the stone part at the chewing tip.

Towards a Molecular Understanding of Noise-Induced Hearing Loss

DTIC Science & Technology

2016-10-01

gene expression following different types of noise exposure and their treatments, in the inner ear. To this end, we have (a) Established the hair ...in hair cells, support cells and whole inner ears, 6 and 24 hours after noise exposure; (c) Collected and processed most of the tissue for TTS...SUBJECT TERMS Permanent threshold shift, Temporary threshold shift, Noise induced hearing loss, Ribotag, RNA-seq, hair cell, supporting cell, SAHA

A Distributed Approach to System-Level Prognostics

DTIC Science & Technology

2012-09-01

the end of (useful) life ( EOL ) and/or the remaining useful life (RUL) of components, subsystems, or systems. The prognostics problem itself can be...system state estimate, computes EOL and/or RUL. In this paper, we focus on a model-based prognostics approach (Orchard & Vachtse- vanos, 2009; Daigle...been focused on individual components, and determining their EOL and RUL, e.g., (Orchard & Vachtsevanos, 2009; Saha & Goebel, 2009; Daigle & Goebel

Educational and Nonprofit Institutions Receiving Prime Contract Awards for RDT&E (Research, Development, Test and Evaluation), Fiscal Year 1981.

DTIC Science & Technology

1981-01-01

SCIENCE & TECH 162 - UNITED KINGDOM MINISTRY OF DEFENCE 2,670 - UN KINGDOM 162 UN KINGDOM 2,670 INSTITUT FUER ATMOSPHAERISCHE 25 - UNIVERSITE RENE ... DESCARTES 10 - GERMANY 25 FRANCE 10 INVERESK RESEARCH INTERNATIONAL 106 - 8,602 UN KINGDOM 106 ISRAEL INSTITUTE OF TECHNOLOGY 55 - ISRAEL 55 KEELE UNIVERSITY

46 CFR 28.375 - Emergency source of electrical power.

Code of Federal Regulations, 2011 CFR

2011-10-01

... COMMERCIAL FISHING INDUSTRY VESSELS Requirements for Vessels Which Have Their Keel Laid or Are at a Similar... systems; (3) Bilge pumps; (4) Fire protection and detection systems, including fire pumps; (5... (11.0 meters) in length need only supply communication equipment by an emergency source of electrical...

46 CFR 28.375 - Emergency source of electrical power.

Code of Federal Regulations, 2014 CFR

2014-10-01

... COMMERCIAL FISHING INDUSTRY VESSELS Requirements for Vessels Which Have Their Keel Laid or Are at a Similar... systems; (3) Bilge pumps; (4) Fire protection and detection systems, including fire pumps; (5... (11.0 meters) in length need only supply communication equipment by an emergency source of electrical...

46 CFR 28.375 - Emergency source of electrical power.

Code of Federal Regulations, 2012 CFR

2012-10-01

... COMMERCIAL FISHING INDUSTRY VESSELS Requirements for Vessels Which Have Their Keel Laid or Are at a Similar... systems; (3) Bilge pumps; (4) Fire protection and detection systems, including fire pumps; (5... (11.0 meters) in length need only supply communication equipment by an emergency source of electrical...

46 CFR 28.375 - Emergency source of electrical power.

Code of Federal Regulations, 2013 CFR

2013-10-01

... COMMERCIAL FISHING INDUSTRY VESSELS Requirements for Vessels Which Have Their Keel Laid or Are at a Similar... systems; (3) Bilge pumps; (4) Fire protection and detection systems, including fire pumps; (5... (11.0 meters) in length need only supply communication equipment by an emergency source of electrical...

46 CFR 28.375 - Emergency source of electrical power.

Code of Federal Regulations, 2010 CFR

2010-10-01

... COMMERCIAL FISHING INDUSTRY VESSELS Requirements for Vessels Which Have Their Keel Laid or Are at a Similar... systems; (3) Bilge pumps; (4) Fire protection and detection systems, including fire pumps; (5... (11.0 meters) in length need only supply communication equipment by an emergency source of electrical...

Epistemic lenses and virtues, beyond evidence-based medicine.

PubMed

Murphy, Mark E

2018-06-01

This editorial is based on the keynote by Dr Mark Murphy, Department of General Practice, Royal College of Surgeons, Ireland, at the Health Libraries Group conference, Keele University on 13-15 June 2018. https://bit.ly/2rubsIR#HLG2018. © 2018 Health Libraries Group.

Seismic azimuthal anisotropy beneath the eastern United States and its geodynamic implications

NASA Astrophysics Data System (ADS)

Yang, Bin B.; Liu, Yunhua; Dahm, Haider; Liu, Kelly H.; Gao, Stephen S.

2017-03-01

Systematic spatial variations of anisotropic characteristics are revealed beneath the eastern U.S. using seismic data recorded between 1988 and 2016 by 785 stations. The resulting fast polarization orientations of the 5613 measurements are generally subparallel to the absolute plate motion (APM) and are inconsistent with the strike of major tectonic features. This inconsistency, together with the results of depth estimation using the spatial coherency of the splitting parameters, suggests a mostly asthenospheric origin of the observed azimuthal anisotropy. The observations can be explained by a combined effect of APM-induced mantle fabric and a flow system deflected horizontally around the edges of the keel of the North American continent. Beneath the southern and northeastern portions of the study area, the E-W keel-deflected flow enhances APM-induced fabric and produces mostly E-W fast orientations with large splitting times, while beneath the southeastern U.S., anisotropy from the N-S oriented flow is weakened by the APM.

Kinetic method for the large-scale analysis of the binding mechanism of histone deacetylase inhibitors.

PubMed

Meyners, Christian; Baud, Matthias G J; Fuchter, Matthew J; Meyer-Almes, Franz-Josef

2014-09-01

Performing kinetic studies on protein ligand interactions provides important information on complex formation and dissociation. Beside kinetic parameters such as association rates and residence times, kinetic experiments also reveal insights into reaction mechanisms. Exploiting intrinsic tryptophan fluorescence a parallelized high-throughput Förster resonance energy transfer (FRET)-based reporter displacement assay with very low protein consumption was developed to enable the large-scale kinetic characterization of the binding of ligands to recombinant human histone deacetylases (HDACs) and a bacterial histone deacetylase-like amidohydrolase (HDAH) from Bordetella/Alcaligenes. For the binding of trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), and two other SAHA derivatives to HDAH, two different modes of action, simple one-step binding and a two-step mechanism comprising initial binding and induced fit, were verified. In contrast to HDAH, all compounds bound to human HDAC1, HDAC6, and HDAC8 through a two-step mechanism. A quantitative view on the inhibitor-HDAC systems revealed two types of interaction, fast binding and slow dissociation. We provide arguments for the thesis that the relationship between quantitative kinetic and mechanistic information and chemical structures of compounds will serve as a valuable tool for drug optimization. Copyright © 2014 Elsevier Inc. All rights reserved.

Lactose Intolerance and Symptom Pattern of Lactose Intolerance among Healthy Volunteers.

PubMed

Saha, Madhusudan; Parveen, Irin; Shil, Bimal Chandra; Saha, Shasanka Kumar; Banik, Ranjit Kumar; Majumder, Monojit; Salam, Mahjuba Umme; Islam, Asm Nazmul

2016-01-01

To see the prevalence of lactose intolerance (LI) and related symptoms following oral lactose challenge in healthy volunteers. Symptoms of abdominal pain, nausea, borborygmi, flatulence, and diarrhea were noted for 24 hours and blood glucose was estimated at 0 hour and 30 minutes after 25 gm oral lactose load to healthy volunteers. Failure to rise blood glucose level ≥ 1.1 mmol/l at 30 minutes after lactose intake from fasting level was taken as lactose malabsorption (LM), i.e., LI. A total of 166 volunteers (123 males, 43 females) with a mean age 34.78 ± 11.45 years participated in this study. Lactose intolerance was found among 85.54% (n = 142, M = 104, F = 38). The main symptoms of LI were diarrhea (n = 83, 58.4.0%), borborygmi (n = 81, 57.04%), abdominal pain (n = 35, 24.65%), and flatulence (n = 27, 19.0%). Lactose intolerance among healthy adults may be common in Bangladesh. Diarrhea and borborygmi were mostly associated symptoms of LI. Saha M, Parveen I, Shil BC, Saha SK, Banik RK, Majumder M, Salam MU, Nazmul Islam ASM. Lactose Intolerance and Symptom Pattern of Lactose Intolerance among Healthy Volunteers. Euroasian J Hepato-Gastroenterol 2016;6(1):5-7.

[Lentivirus-mediated shRNA silencing of LAMP2A inhibits the proliferation of multiple myeloma cells].

PubMed

Li, Lixuan; Li, Jia

2015-05-01

To study the effects of lentivirus-mediated short hairpin RNA (shRNA) silencing of lysosome-associated membrane protein type 2A (LAMP2A) expression on the proliferation of multiple myeloma cells. The constructed shRNA lentiviral vector was applied to infect human multiple myeloma cell line MM.1S, and stable expression cell line was obtained by puromycin screening. Western blotting was used to verify the inhibitory effect on LAMP2A protein expression. MTT assay was conducted to detect the effect of knocked-down LAMP2A on MM.1S cell proliferation, and the anti-tumor potency of suberoylanilide hydroxamic acid (SAHA) against the obtained MM.1S LAMP2A(shRNA) stable cell line. Lactate assay was performed to observe the impact of low LAMP2A expression on cell glycolysis. The stable cell line with low LAMP2A expression were obtained with the constructed human LAMP2A-shRNA lentiviral vector. Down-regulation of LAMP2A expression significantly inhibited MM.1S cell proliferation and enhanced the anti-tumor activity of SAHA. Interestingly, decreased LAMP2A expression also inhibited MM.1S cell lactic acid secretion. Down-regulation of LAMP2A expression could inhibit cell proliferation in multiple myeloma cells.

PRL-3, a Metastasis Associated Tyrosine Phosphatase, Is Involved in FLT3-ITD Signaling and Implicated in Anti-AML Therapy

PubMed Central

Zhou, Jianbiao; Bi, Chonglei; Chng, Wee-Joo; Cheong, Lip-Lee; Liu, Shaw-Cheng; Mahara, Sylvia; Tay, Kian-Ghee; Zeng, Qi; Li, Jie; Guo, Ke; Tan, Cheng Peow Bobby; Yu, Hanry; Albert, Daniel H.; Chen, Chien-Shing

2011-01-01

Combination with other small molecule drugs represents a promising strategy to improve therapeutic efficacy of FLT3 inhibitors in the clinic. We demonstrated that combining ABT-869, a FLT3 inhibitor, with SAHA, a HDAC inhibitor, led to synergistic killing of the AML cells with FLT3 mutations and suppression of colony formation. We identified a core gene signature that is uniquely induced by the combination treatment in 2 different leukemia cell lines. Among these, we showed that downregulation of PTP4A3 (PRL-3) played a role in this synergism. PRL-3 is downstream of FLT3 signaling and ectopic expression of PRL-3 conferred therapeutic resistance through upregulation of STAT (signal transducers and activators of transcription) pathway activity and anti-apoptotic Mcl-1 protein. PRL-3 interacts with HDAC4 and SAHA downregulates PRL-3 via a proteasome dependent pathway. In addition, PRL-3 protein was identified in 47% of AML cases, but was absent in myeloid cells in normal bone marrows. Our results suggest such combination therapies may significantly improve the therapeutic efficacy of FLT3 inhibitors. PRL-3 plays a potential pathological role in AML and it might be a useful therapeutic target in AML, and warrant clinical investigation. PMID:21589872

SCL/TAL1-mediated transcriptional network enhances megakaryocytic specification of human embryonic stem cells.

PubMed

Toscano, Miguel G; Navarro-Montero, Oscar; Ayllon, Veronica; Ramos-Mejia, Veronica; Guerrero-Carreno, Xiomara; Bueno, Clara; Romero, Tamara; Lamolda, Mar; Cobo, Marien; Martin, Francisco; Menendez, Pablo; Real, Pedro J

2015-01-01

Human embryonic stem cells (hESCs) are a unique in vitro model for studying human developmental biology and represent a potential source for cell replacement strategies. Platelets can be generated from cord blood progenitors and hESCs; however, the molecular mechanisms and determinants controlling the in vitro megakaryocytic specification of hESCs remain elusive. We have recently shown that stem cell leukemia (SCL) overexpression accelerates the emergence of hemato-endothelial progenitors from hESCs and promotes their subsequent differentiation into blood cells with higher clonogenic potential. Given that SCL participates in megakaryocytic commitment, we hypothesized that it may potentiate megakaryopoiesis from hESCs. We show that ectopic SCL expression enhances the emergence of megakaryocytic precursors, mature megakaryocytes (MKs), and platelets in vitro. SCL-overexpressing MKs and platelets respond to different activating stimuli similar to their control counterparts. Gene expression profiling of megakaryocytic precursors shows that SCL overexpression renders a megakaryopoietic molecular signature. Connectivity Map analysis reveals that trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA), both histone deacetylase (HDAC) inhibitors, functionally mimic SCL-induced effects. Finally, we confirm that both TSA and SAHA treatment promote the emergence of CD34(+) progenitors, whereas valproic acid, another HDAC inhibitor, potentiates MK and platelet production. We demonstrate that SCL and HDAC inhibitors are megakaryopoiesis regulators in hESCs.

Suberoylanilide hydroxamic acid sensitizes neuroblastoma to paclitaxel by inhibiting thioredoxin-related protein 14-mediated autophagy.

PubMed

Zhen, Zijun; Yang, Kaibin; Ye, Litong; You, Zhiyao; Chen, Rirong; Liu, Ying; He, Youjian

2017-07-01

Paclitaxel is not as effective for neuroblastoma as most of the front-line chemotherapeutics due to drug resistance. This study explored the regulatory mechanism of paclitaxel-associated autophagy and potential solutions to paclitaxel resistance in neuroblastoma. The formation of autophagic vesicles was detected by scanning transmission electron microscopy and flow cytometry. The autophagy-associated proteins were assessed by western blot. Autophagy was induced and the autophagy-associated proteins LC3-I, LC3-II, Beclin 1, and thioredoxin-related protein 14 (TRP14), were found to be upregulated in neuroblastoma cells that were exposed to paclitaxel. The inhibition of Beclin 1 or TRP14 by siRNA increased the sensitivity of the tumor cells to paclitaxel. In addition, Beclin 1-mediated autophagy was regulated by TRP14. Furthermore, the TRP14 inhibitor suberoylanilide hydroxamic acid (SAHA) downregulated paclitaxel-induced autophagy and enhanced the anticancer effects of paclitaxel in normal control cancer cells but not in cells with upregulated Beclin 1 and TRP14 expression. Our findings showed that paclitaxel-induced autophagy in neuroblastoma cells was regulated by TRP14 and that SAHA could sensitize neuroblastoma cells to paclitaxel by specifically inhibiting TRP14. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Sphingomyelin-induced inhibition of the plasma membrane calcium ATPase causes neurodegeneration in type A Niemann-Pick disease.

PubMed

Pérez-Cañamás, A; Benvegnù, S; Rueda, C B; Rábano, A; Satrústegui, J; Ledesma, M D

2017-05-01

Niemann-Pick disease type A (NPA) is a rare lysosomal storage disorder characterized by severe neurological alterations that leads to death in childhood. Loss-of-function mutations in the acid sphingomyelinase (ASM) gene cause NPA, and result in the accumulation of sphingomyelin (SM) in lysosomes and plasma membrane of neurons. Using ASM knockout (ASMko) mice as a NPA disease model, we investigated how high SM levels contribute to neural pathology in NPA. We found high levels of oxidative stress both in neurons from these mice and a NPA patient. Impaired activity of the plasma membrane calcium ATPase (PMCA) increases intracellular calcium. SM induces PMCA decreased activity, which causes oxidative stress. Incubating ASMko-cultured neurons in the histone deacetylase inhibitor, SAHA, restores PMCA activity and calcium homeostasis and, consequently, reduces the increased levels of oxidative stress. No recovery occurs when PMCA activity is pharmacologically impaired or genetically inhibited in vitro. Oral administration of SAHA prevents oxidative stress and neurodegeneration, and improves behavioral performance in ASMko mice. These results demonstrate a critical role for plasma membrane SM in neuronal calcium regulation. Thus, we identify changes in PMCA-triggered calcium homeostasis as an upstream mediator for NPA pathology. These findings can stimulate new approaches for pharmacological remediation in a disease with no current clinical treatments.

Ionization of elements in medium power capacitively coupled argon plasma torch with single and double ring electrodes.

PubMed

Ponta, Michaela; Frentiu, Maria; Frentiu, Tiberiu

2012-06-01

A medium power, low Ar consumption capacitively coupled plasma torch (275 W, 0.4 L min-1) with molybdenum tubular electrode and single or two ring electrodes in non-local thermodynamic equilibrium (LTE) was characterized with respect to its ability to achieve element ionization. Ionization degrees of Ca, Mg, Mn and Cd were determined from ionic-to-atomic emission ratio and ionization equilibrium according to Saha's equation. The ionization degrees resulted from the Saha equation were higher by 9-32% than those obtained from spectral lines intensity in LTE regime and closer to reality. A linear decrease of ionization with increase of ionization energy of elements was observed. Plasma torch with two ring electrodes provided higher ionization degrees (85 ± 7% Ca, 79 ± 7% Mn, 80 ± 7% Mg and 73 ± 8% Cd) than those in single ring arrangement (70 ± 6% Ca, 57 ± 7% Mn, 57 ± 8% Mg and 42 ± 9% Cd). The Ca ionization decreased linearly by up to 79 ± 4% and 53 ± 6% in plasma with two ring electrodes and single ring respectively in the presence of up to 400 µg mL-1 Na as interferent. The studied plasma was effective in element ionization and could be a potential ion source in mass spectrometry.

A Thoroughly Validated Virtual Screening Strategy for Discovery of Novel HDAC3 Inhibitors.

PubMed

Hu, Huabin; Xia, Jie; Wang, Dongmei; Wang, Xiang Simon; Wu, Song

2017-01-18

Histone deacetylase 3 (HDAC3) has been recently identified as a potential target for the treatment of cancer and other diseases, such as chronic inflammation, neurodegenerative diseases, and diabetes. Virtual screening (VS) is currently a routine technique for hit identification, but its success depends on rational development of VS strategies. To facilitate this process, we applied our previously released benchmarking dataset, i.e., MUBD-HDAC3 to the evaluation of structure-based VS (SBVS) and ligand-based VS (LBVS) combinatorial approaches. We have identified FRED (Chemgauss4) docking against a structural model of HDAC3, i.e., SAHA-3 generated by a computationally inexpensive "flexible docking", as the best SBVS approach and a common feature pharmacophore model, i.e., Hypo1 generated by Catalyst/HipHop as the optimal model for LBVS. We then developed a pipeline that was composed of Hypo1, FRED (Chemgauss4), and SAHA-3 sequentially, and demonstrated that it was superior to other combinations in terms of ligand enrichment. In summary, we present the first highly-validated, rationally-designed VS strategy specific to HDAC3 inhibitor discovery. The constructed pipeline is publicly accessible for the scientific community to identify novel HDAC3 inhibitors in a time-efficient and cost-effective way.

A Thoroughly Validated Virtual Screening Strategy for Discovery of Novel HDAC3 Inhibitors

PubMed Central

Hu, Huabin; Xia, Jie; Wang, Dongmei; Wang, Xiang Simon; Wu, Song

2017-01-01

Histone deacetylase 3 (HDAC3) has been recently identified as a potential target for the treatment of cancer and other diseases, such as chronic inflammation, neurodegenerative diseases, and diabetes. Virtual screening (VS) is currently a routine technique for hit identification, but its success depends on rational development of VS strategies. To facilitate this process, we applied our previously released benchmarking dataset, i.e., MUBD-HDAC3 to the evaluation of structure-based VS (SBVS) and ligand-based VS (LBVS) combinatorial approaches. We have identified FRED (Chemgauss4) docking against a structural model of HDAC3, i.e., SAHA-3 generated by a computationally inexpensive “flexible docking”, as the best SBVS approach and a common feature pharmacophore model, i.e., Hypo1 generated by Catalyst/HipHop as the optimal model for LBVS. We then developed a pipeline that was composed of Hypo1, FRED (Chemgauss4), and SAHA-3 sequentially, and demonstrated that it was superior to other combinations in terms of ligand enrichment. In summary, we present the first highly-validated, rationally-designed VS strategy specific to HDAC3 inhibitor discovery. The constructed pipeline is publicly accessible for the scientific community to identify novel HDAC3 inhibitors in a time-efficient and cost-effective way. PMID:28106794

Comparing soil carbon of short rotation poplar plantations with agricultural crops and woodlots in north central United States

Treesearch

Mark D. Coleman; J.G. Isebrands; David N. Tolsted; Virginia R. Tolbert

2004-01-01

Atmospheric carbon dioxide (CO2) has increased dramatically since the beginning of the Industrial Revolution as a result of human activities (Keeling and others 1995, Houghton and others 2001). The primary cause of CO2 increases are worldwide fossil fuel burning, biomass burning, and cement manufacturing. These activities...

Causal Mediation in Educational Research: An Illustration Using International Assessment Data

ERIC Educational Resources Information Center

Caro, Daniel H.

2015-01-01

This paper applies the causal mediation framework proposed by Kosuke Imai and colleagues (Imai, Keele, & Tingley, 2010) to educational research by examining the causal mediating role of early literacy activities in parental education influences on reading performance. The paper argues that the study of causal mediation is particularly relevant…

Evaluation of RPM™ oak seedlings in afforesting floodplain crop fields along the Missouri River

Treesearch

Daniel C. Dey; John M. Kabrick; Michael A. Gold

2005-01-01

Regenerating oaks in agricultural floodplains is problematic because of their slow juvenile shoot growth, intense plant competition, seasonal flooding, and browsing by wildlife. Planting large nursery stock has been recommended to increase the competitiveness of oak seedlings. The Forrest Keeling Nursery in Missouri developed the Root Production Method (RPM™)...

Ecological speciation in an island snail: evidence for the parallel evolution of a novel ecotype and maintenance by ecologically dependent postzygotic isolation.

PubMed

Stankowski, Sean

2013-05-01

Speciation is the process by which reproductive isolation evolves between populations. Two general models of speciation have been proposed: ecological speciation, where reproductive barriers evolve due to ecologically based divergent selection, and mutation-order speciation, where populations fix different mutations as they adapt to similar selection pressures. I evaluate these alternative models and determine the progress of speciation in a diverse group of land snails, genus Rhagada, inhabiting Rosemary Island. A recently derived keeled-flat morphotype occupies two isolated rocky hills, while globose-shelled snails inhabit the surrounding plains. The study of one hill reveals that they are separated by a narrow hybrid zone. As predicted by ecological speciation theory, there are local and landscape level associations between shell shape and habitat, and the morphological transition coincides with a narrow ecotone between the two distinct environments. Microsatellite DNA revealed a cline of hybrid index scores much wider than the morphological cline, further supporting the ecological maintenance of the morphotypes. The hybrid zone does not run through an area of low population density, as is expected for mutation-order hybrid zones, and there is a unimodal distribution of phenotypes at the centre, suggesting that there is little or no prezygotic isolation. Instead, these data suggest that the ecotypes are maintained by ecologically dependent postzygotic isolation (i.e. ecological selection against hybrids). Mitochondrial and Microsatellite DNA indicate that the keeled-flat form evolved recently, and without major historical disruptions to gene flow. The data also suggest that the two keeled-flat populations, inhabiting similar rocky hills, have evolved in parallel. These snails provide a complex example of ecological speciation in its early stages. © 2013 Blackwell Publishing Ltd.

China’s Grand Strategy: From Confucius to Contemporary

DTIC Science & Technology

2010-02-02

DISTRIBUTION STATEMENT A: Approved for Public Release. Distribution is Unlimited. Only a work of the United States Government is not subject to...copyright. Based upon the nature of a particular student-author’s employment, a paper may not be a work of the United States Government and may, in fact...Brigadier Subrata Saha 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER Dr Janeen M. Klinger 7. PERFORMING

Synthesis, biological evaluation, and molecular docking of Ugi products containing a zinc-chelating moiety as novel inhibitors of histone deacetylases.

PubMed

Grolla, Ambra A; Podestà, Valeria; Chini, Maria Giovanna; Di Micco, Simone; Vallario, Antonella; Genazzani, Armando A; Canonico, Pier Luigi; Bifulco, Giuseppe; Tron, Gian Cesare; Sorba, Giovanni; Pirali, Tracey

2009-05-14

HDAC inhibitors show great promise for the treatment of cancer. As part of a broader effort to explore the SAR of HDAC inhibitors, synthesis, biological evaluation, and molecular docking of novel Ugi products containing a zinc-chelating moiety are presented. One compound shows improved inhibitory potencies compared to SAHA, demonstrating that hindered lipophilic residues grafted on the peptide scaffold of the alpha-aminoacylamides can be favorable in the interaction with the enzyme.

On the relations between cratonic lithosphere thickness, plate motions, and basal drag

USGS Publications Warehouse

Artemieva, I.M.; Mooney, W.D.

2002-01-01

An overview of seismic, thermal, and petrological evidence on the structure of Precambrian lithosphere suggests that its local maximum thickness is highly variable (140-350 km), with a bimodal distribution for Archean cratons (200-220 km and 300-350 km). We discuss the origin of such large differences in lithospheric thickness, and propose that the lithospheric base can have large depth variations over short distances. The topography of Bryce Canyon (western USA) is proposed as an inverted analog of the base of the lithosphere. The horizontal and vertical dimensions of Archean cratons are strongly correlated: larger cratons have thicker lithosphere. Analysis of the bimodal distribution of lithospheric thickness in Archean cratons shows that the "critical" surface area for cratons to have thick (>300 km) keels is >6-8 ?? 106 km2 . Extrapolation of the linear trend between Archean lithospheric thickness and cratonic area to zero area yields a thickness of 180 km. This implies that the reworking of Archean crust should be accompanied by thinning and reworking of the entire lithospheric column to a thickness of 180 km in accord with thickness estimates for Proterozoic lithosphere. Likewise, extrapolation of the same trend to the size equal to the total area of all Archean cratons implies that the lithospheric thickness of a hypothesized early Archean supercontinent could have been 350-450 km decreasing to 280-400 km for Gondwanaland. We evaluate the basal drag model as a possible mechanism that may thin the cratonic lithosphere. Inverse correlations are found between lithospheric thickness and (a) fractional subduction length and (b) the effective ridge length. In agreement with theoretical predictions, lithospheric thickness of Archean keels is proportional to the square root of the ratio of the craton length (along the direction of plate motion) to the plate velocity. Large cratons with thick keels and low plate velocities are less eroded by basal drag than small

14 CFR 23.529 - Hull and main float landing conditions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Hull and main float landing conditions. 23... Water Loads § 23.529 Hull and main float landing conditions. (a) Symmetrical step, bow, and stern... directed perpendicularly to the keel line. (b) Unsymmetrical landing for hull and single float seaplanes...

46 CFR 160.035-2 - General requirements for lifeboats.

Code of Federal Regulations, 2011 CFR

2011-10-01

... lever, from the keel to the side bench, shall be painted or otherwise colored white, to provide a contrasting background for the lever. This band of white should be approximately 12 inches wide depending on the internal arrangements of the lifeboat. (d) For the purpose of calculations and conducting tests...

46 CFR 160.035-2 - General requirements for lifeboats.

Code of Federal Regulations, 2010 CFR

2010-10-01

... lever, from the keel to the side bench, shall be painted or otherwise colored white, to provide a contrasting background for the lever. This band of white should be approximately 12 inches wide depending on the internal arrangements of the lifeboat. (d) For the purpose of calculations and conducting tests...

46 CFR 50.10-35 - Constructed.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Constructed. 50.10-35 Section 50.10-35 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING GENERAL PROVISIONS Definition of Terms Used in This Subchapter § 50.10-35 Constructed. The term constructed means the keel has been laid...

Lycopene Supplementation in the Complementary Management of PSA Failure: A Randomized Placebo-Controlled Trial for Prostate Cancer Survivors

DTIC Science & Technology

2007-01-01

Morris JC, Hulette C, Schmechel D, Reiman EM, Rogers J, Stephan DA. (2005). Gene expression correlates of neurofibrillary tangles in Alzheimer’s...Walker DG, Lafleur BJ, Coon KD, Brown KM, Caselli R, Kukull W, Higdon R, McKeel D, Morris JC, Hulette C, Schmechel D, Reiman EM, Rogers J, Stephan

A Response to Hartley

ERIC Educational Resources Information Center

Knapper, Christopher

2012-01-01

In his article, "Reflections on 50 years of teaching psychology", James Hartley concludes that the teaching of psychology has changed relatively little over the past several decades. Hartley begins his paper on a personal note with recollections of his first university teaching experience at Keele University. In his paper Hartley…

Soil-Profile Organic Carbon and Nitrogen during 12 Years of Pasture Management

USDA-ARS?s Scientific Manuscript database

Carbon dioxide (CO2) in the atmosphere has been increasing steadily during the past century. This is well documented by measurements in Hawaii since 1958 (initiated by Dr. Charles Keeling). Increasing CO2 in the atmosphere is a concern, because of its potential to warm the planet. CO2 and other g...

Graptemys gibbonsi Lovich and McCoy -- Pascagoula Map Turtle

USGS Publications Warehouse

Lovich, Jeffrey E.; Ennen, Joshua R.

2014-01-01

Hatchling pigmentation patterns resemble those of adults, but with more conspicuous patterns on the pleural scutes. Similarly, the plastron of hatchlings commonly has more dark pigmentation along the seams than adults. The shell is highly serrated along the edge of the carapace and the vertebral keel is more pronounced than in adults.

76 FR 18684 - Endangered and Threatened Wildlife and Plants; 12-Month Finding on a Petition To List the...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-05

... shell spire, degree of carination (i.e., presence and size of a keel or ridge around the outside whorl of the shell), width of umbilicus (i.e., the ventral opening formed in the center of the whorls), and color (Pilsbry 1939, p. 415). Shell morphology is plastic (variable in response to environmental...

Review of External Examining Arrangements in Universities and Colleges in the UK: Final Report and Recommendations

ERIC Educational Resources Information Center

Universities UK, 2011

2011-01-01

This report outlines the final recommendations of the review of external examining arrangements undertaken by UUK and GuildHE and chaired by Professor Dame Janet Finch, former Vice-Chancellor of Keele University. The review found that, on the whole, external examining arrangements in the UK are working well, but the report offers recommendations…

46 CFR 69.105 - Application for measurement services.

Code of Federal Regulations, 2013 CFR

2013-10-01

...) Type of vessel. (b) Vessel's name and official number (if assigned). (c) Builder's name and the vessel hull number assigned by the builder. (d) Place and year built. (e) Date keel was laid. (f) Overall length, breadth, and depth of vessel. (g) Lines plan. (h) Booklet of offsets. (i) Capacity plans for...

46 CFR 69.105 - Application for measurement services.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Type of vessel. (b) Vessel's name and official number (if assigned). (c) Builder's name and the vessel hull number assigned by the builder. (d) Place and year built. (e) Date keel was laid. (f) Overall length, breadth, and depth of vessel. (g) Lines plan. (h) Booklet of offsets. (i) Capacity plans for...

46 CFR 69.105 - Application for measurement services.

Code of Federal Regulations, 2012 CFR

2012-10-01

...) Type of vessel. (b) Vessel's name and official number (if assigned). (c) Builder's name and the vessel hull number assigned by the builder. (d) Place and year built. (e) Date keel was laid. (f) Overall length, breadth, and depth of vessel. (g) Lines plan. (h) Booklet of offsets. (i) Capacity plans for...

46 CFR 69.105 - Application for measurement services.

Code of Federal Regulations, 2014 CFR

2014-10-01

...) Type of vessel. (b) Vessel's name and official number (if assigned). (c) Builder's name and the vessel hull number assigned by the builder. (d) Place and year built. (e) Date keel was laid. (f) Overall length, breadth, and depth of vessel. (g) Lines plan. (h) Booklet of offsets. (i) Capacity plans for...

46 CFR 69.105 - Application for measurement services.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) Type of vessel. (b) Vessel's name and official number (if assigned). (c) Builder's name and the vessel hull number assigned by the builder. (d) Place and year built. (e) Date keel was laid. (f) Overall length, breadth, and depth of vessel. (g) Lines plan. (h) Booklet of offsets. (i) Capacity plans for...

Genetic implications for forest trees of increasing levels of greenhouse gases and UV-B radiation

Treesearch

David F. Karnosky; Kevin E. Percy; Blanka Mankovska

2000-01-01

Globally, the environment is changing and deteriorating as greenhouse gases such as carbon dioxide (CO2) and tropospheric ozone (03) continue to increase at a rate of about 1% per year (Keeling et al. 1995, Chameides et al. 1995). The increase in these gases is directly related to anthropogenic activities (Chameides et al...

46 CFR 169.739 - Lifeboats.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., Miscellaneous Systems, and Equipment Markings § 169.739 Lifeboats. (a) The name and port of the vessel marked on... thwarts, side benches and footings of lifeboats must be painted or otherwise colored international orange. The area in way of the red mechanical disengaging gear control lever, from the keel to the side bench...

Azimuthal Anisotropy beneath the Contiguous United States Revealed by Shear Wave Splitting

NASA Astrophysics Data System (ADS)

Liu, K. H.; Yang, B.; Liu, Y.; Dahm, H. H.; Refayee, H. A.; Gao, S. S.

2017-12-01

We have produced a uniformly-measured XKS (including SKS, SKKS, and PKS) splitting database for the contiguous United States and adjacent areas. The database consists of about 30,000 pairs of splitting parameters from 3185 stations. Both the fast orientations and splitting times show systematic spatial variations. The vast majority of the fast orientations are in agreement with the absolute plate motion (APM) direction computed under a fixed hot-spot reference frame. Spatial coherency analysis of the splitting parameters indicates that for the majority of the study area, where a single layer of anisotropy with a horizontal axis of symmetry is inferred, the source of anisotropy is located in the rheologically transitional zone between the lithosphere and asthenosphere. Beneath the western U.S., the previously recognized semi-circular feature of the fast orientations has a much greater spatial coverage, extending to northern Mexico and the Rio Grande Rift. The fast orientations are parallel to the western, southern, and southeastern edges of the North American Craton and can be interpreted by simple shear strain associated with mantle flow around the cratonic keel. The combination of anisotropy induced by this around keel flow and the APM can effectively explain the E-W fast orientations beneath the southern margin of the North American Craton and NE U.S., as well as the nearly N-S fast orientations and small splitting times observed in the SE U.S. The splitting times show a systematic decrease from both the western and eastern U.S. toward the central U.S., where the thickness of the lithosphere is the largest in the study area. This trend can be explained by the reduced efficiency of anisotropy development at greater depth, as well as by the lack of around keel flow in the continental interior.

46 CFR 32.56-1 - Application-T/ALL.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 1 2011-10-01 2011-10-01 false Application-T/ALL. 32.56-1 Section 32.56-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS SPECIAL EQUIPMENT, MACHINERY, AND HULL....56-1 Application—T/ALL. (a)This subpart applies to all tankships that have a keel laying date on or...

46 CFR 32.56-1 - Application-T/ALL.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 1 2010-10-01 2010-10-01 false Application-T/ALL. 32.56-1 Section 32.56-1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY TANK VESSELS SPECIAL EQUIPMENT, MACHINERY, AND HULL....56-1 Application—T/ALL. (a)This subpart applies to all tankships that have a keel laying date on or...

75 FR 77945 - Qualification of Drivers; Exemption Applications; Vision

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-14

... Randall S. Grauer Wesley A. Roberson Charles J. Dawber Darrell A. Harmon David M. Taylor Richard C. Dickinson Thomas W. Keel, Jr. David M. Wcisel Harold L. Elders Jay Rider The following 7 applicants had no... George Edward Mulherrin Alan D. Strain III John P. Chuda Mark Paugh Ronald R. Sumpter David L. Ellis...

33 CFR 183.220 - Preconditioning for tests.

Code of Federal Regulations, 2012 CFR

2012-07-01

... result of the following calculation, but not less than zero: The maximum weight capacity marked on the... be keel down in the water. (g) The boat must be swamped, allowing water to flow between the inside... flooded portion of the boat must be eliminated. (h) Water must flood the two largest air chambers and all...

33 CFR 183.220 - Preconditioning for tests.

Code of Federal Regulations, 2014 CFR

2014-07-01

... result of the following calculation, but not less than zero: The maximum weight capacity marked on the... be keel down in the water. (g) The boat must be swamped, allowing water to flow between the inside... flooded portion of the boat must be eliminated. (h) Water must flood the two largest air chambers and all...

33 CFR 183.220 - Preconditioning for tests.

Code of Federal Regulations, 2013 CFR

2013-07-01

... result of the following calculation, but not less than zero: The maximum weight capacity marked on the... be keel down in the water. (g) The boat must be swamped, allowing water to flow between the inside... flooded portion of the boat must be eliminated. (h) Water must flood the two largest air chambers and all...

46 CFR 170.055 - Definitions concerning a vessel.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) Barge means a vessel not equipped with a means of self-propulsion. (d) Beam or B means the maximum width... vessel's keel was laid; or (2) Construction identifiable with the vessel began and assembly of that... a vessel propelled only by sails. (q) Ship means a self-propelled vessel. (r) Tank vessel means a...

47 CFR 80.853 - Radiotelephone station.

Code of Federal Regulations, 2012 CFR

2012-10-01

... deck above the ship's main deck. (d) The principal operating position of the radiotelephone station must be in the room from which the ship is normally steered while at sea. In installations on cargo ships of 300 gross tons and upwards but less than 500 gross tons on which the keel was laid prior to...

47 CFR 80.853 - Radiotelephone station.

Code of Federal Regulations, 2013 CFR

2013-10-01

... deck above the ship's main deck. (d) The principal operating position of the radiotelephone station must be in the room from which the ship is normally steered while at sea. In installations on cargo ships of 300 gross tons and upwards but less than 500 gross tons on which the keel was laid prior to...

47 CFR 80.853 - Radiotelephone station.

Code of Federal Regulations, 2014 CFR

2014-10-01

... deck above the ship's main deck. (d) The principal operating position of the radiotelephone station must be in the room from which the ship is normally steered while at sea. In installations on cargo ships of 300 gross tons and upwards but less than 500 gross tons on which the keel was laid prior to...

47 CFR 80.853 - Radiotelephone station.

Code of Federal Regulations, 2011 CFR

2011-10-01

... deck above the ship's main deck. (d) The principal operating position of the radiotelephone station must be in the room from which the ship is normally steered while at sea. In installations on cargo ships of 300 gross tons and upwards but less than 500 gross tons on which the keel was laid prior to...

47 CFR 80.853 - Radiotelephone station.

Code of Federal Regulations, 2010 CFR

2010-10-01

... deck above the ship's main deck. (d) The principal operating position of the radiotelephone station must be in the room from which the ship is normally steered while at sea. In installations on cargo ships of 300 gross tons and upwards but less than 500 gross tons on which the keel was laid prior to...

Taking a Broader View: Using Institutional Research's Natural Qualities for Transformation

ERIC Educational Resources Information Center

Leimer, Christina

2009-01-01

Many authors (Kezar, 2005; Duke, 2002; Keeling, Underhile, and Wall, 2007; Matier, Sidle, and Hurst, 1994) propose a new model of higher education organizations or a style of decision making whose central component is collaboration. This key characteristic helps make full use of all of the institution's resources to increase the likelihood that it…

Damage-Tolerance Characteristics of Composite Fuselage Sandwich Structures with Thick Facesheets

NASA Technical Reports Server (NTRS)

McGowan, David M.; Ambur, Damodar R.

1997-01-01

Damage tolerance characteristics and results from experimental and analytical studies of a composite fuselage keel sandwich structure subjected to low-speed impact damage and discrete-source damage are presented. The test specimens are constructed from graphite-epoxy skins borided to a honeycomb core, and they are representative of a highly loaded fuselage keel structure. Results of compression-after-impact (CAI) and notch-length sensitivity studies of 5-in.-wide by 10-in.long specimens are presented. A correlation between low-speed-impact dent depth, the associated damage area, and residual strength for different impact-energy levels is described; and a comparison of the strength for undamaged and damaged specimens with different notch-length-to-specimen-width ratios is presented. Surface strains in the facesheets of the undamaged specimens as well as surface strains that illustrate the load redistribution around the notch sites in the notched specimens are presented and compared with results from finite element analyses. Reductions in strength of as much as 53.1 percent for the impacted specimens and 64.7 percent for the notched specimens are observed.

Kinome expression profiling of human neuroblastoma tumors identifies potential drug targets for ultra high-risk patients.

PubMed

Russo, Roberta; Cimmino, Flora; Pezone, Lucia; Manna, Francesco; Avitabile, Marianna; Langella, Concetta; Koster, Jan; Casale, Fiorina; Raia, Maddalena; Viola, Giampietro; Fischer, Matthias; Iolascon, Achille; Capasso, Mario

2017-10-01

Neuroblastoma (NBL) accounts for >7% of malignancies in patients younger than 15 years. Low- and intermediate-risk patients exhibit excellent or good prognosis after treatment, whereas for high-risk (HR) patients, the estimated 5-year survival rates is still <40%. The ability to stratify HR patients that will not respond to standard treatment strategies is critical for informed treatment decisions. In this study, we have generated a specific kinome gene signature, named Kinome-27, which is able to identify a subset of HR-NBL tumors, named ultra-HR NBL, with highly aggressive clinical behavior that not adequately respond to standard treatments. We have demonstrated that NBL cell lines expressing the same kinome signature of ultra-HR tumors (ultra-HR-like cell lines) may be selectively targeted by the use of two drugs [suberoylanilide hydroxamic acid (SAHA) and Radicicol], and that the synergic combination of these drugs is able to block the ultra-HR-like cells in G2/M phase of cell cycle. The use of our signature in clinical practice will allow identifying patients with negative outcome, which would benefit from new and more personalized treatments. Preclinical in vivo studies are needed to consolidate the SAHA and Radicicol treatment in ultra-HR NBL patients. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Alternative Fuels Data Center: Idle Reduction Programs at Tennessee Schools

Science.gov Websites

quality and reduce oil consumption," Keel said. But the impact is being felt inside the classroom too program is drawing interest, in part because the area has air quality challenges. "We're in a valley Jake Tisinger said that Knoxville has made great strides in improving its air quality, and the Idle

The Fate of Ineffective Teachers; Will It Be Different in Indiana?

ERIC Educational Resources Information Center

Olin, Harlod E.

2013-01-01

It has been widely publicized that approximately 98% of the teachers in the United States are rated as satisfactory (Weisberg, Sexton, Mulhern, & Keeling, 2009). This has led many Americans to think that there are very few ineffective teachers in the United States. But is this true? This study indicated that a majority of the principals in the…

Maritime Standards for Compliance Safety and Health Officers (Instructor Manual). Volume 3

DTIC Science & Technology

1981-03-01

and striking tools "o Hamers "o Sledge hsmers "o Riveting hamners. 7. Hazards and health effects associated with the use of hand tools o Loss of eyes...lettered starting at the keel, A-B-C, etc. Strakes are classified inner skin, outer or cover, clinker or in and out, forefoot , shoe, boss, sheer, and

Principle of the Boerner airship

NASA Technical Reports Server (NTRS)

Kapteyn, A

1922-01-01

The Boerner airship is built on entirely different principles from ordinary airships, of which the Zeppelin is the best known type. Mr. Boerner has abandoned the rigid body of the Zeppelin and has adopted a body with a double keel forming a rigid platform for attaching the gas ballonets, which must support the whole in the air.

46 CFR 45.3 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Definitions. 45.3 Section 45.3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES GREAT LAKES LOAD LINES General § 45.3 Definitions. As... the least moulded depth measured from the top of the keel or the length from the foreside of the stem...

46 CFR 45.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Definitions. 45.3 Section 45.3 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) LOAD LINES GREAT LAKES LOAD LINES General § 45.3 Definitions. As... the least moulded depth measured from the top of the keel or the length from the foreside of the stem...

46 CFR 28.315 - Fire pumps, fire mains, fire hydrants, and fire hoses.

Code of Federal Regulations, 2011 CFR

2011-10-01

... REQUIREMENTS FOR COMMERCIAL FISHING INDUSTRY VESSELS Requirements for Vessels Which Have Their Keel Laid or Are... siamese fitting, at a pitot tube pressure of at least 50 psi (0.345 Newtons per square millimeter) and a... material capable of providing a solid stream and a spray pattern. (4) A fire hose on a vessel 79 feet (24...

46 CFR 28.315 - Fire pumps, fire mains, fire hydrants, and fire hoses.

Code of Federal Regulations, 2012 CFR

2012-10-01

... REQUIREMENTS FOR COMMERCIAL FISHING INDUSTRY VESSELS Requirements for Vessels Which Have Their Keel Laid or Are... siamese fitting, at a pitot tube pressure of at least 50 psi (0.345 Newtons per square millimeter) and a... material capable of providing a solid stream and a spray pattern. (4) A fire hose on a vessel 79 feet (24...

Earth Science: It's All about the Processes

ERIC Educational Resources Information Center

King, Chris

2013-01-01

Readers of the draft new English primary science curriculum (DfE, 2012) might be concerned to see that there is much more detail on the Earth science content than previously in the United Kingdom. In this article, Chris King, a professor of Earth Science Education at Keele University and Director of the Earth Science Education Unit (ESEU),…

46 CFR 32.53-1 - Application-T/ALL.

Code of Federal Regulations, 2011 CFR

2011-10-01

... system that uses crude oil washing. (4) An existing product carrier of 20,000 deadweight tons (metric) or... REQUIREMENTS Inert Gas System § 32.53-1 Application—T/ALL. (a) Except as provided in paragraphs (b) and (c) of... tons (metric) or more or combination carrier of 50,000 DWT tons (metric) or more, that has a keel...

46 CFR 32.53-1 - Application-T/ALL.

Code of Federal Regulations, 2014 CFR

2014-10-01

... system that uses crude oil washing. (4) An existing product carrier of 20,000 deadweight tons (metric) or... REQUIREMENTS Inert Gas System § 32.53-1 Application—T/ALL. (a) Except as provided in paragraphs (b) and (c) of... tons (metric) or more or combination carrier of 50,000 DWT tons (metric) or more, that has a keel...

46 CFR 32.53-1 - Application-T/ALL.

Code of Federal Regulations, 2010 CFR

2010-10-01

... system that uses crude oil washing. (4) An existing product carrier of 20,000 deadweight tons (metric) or... REQUIREMENTS Inert Gas System § 32.53-1 Application—T/ALL. (a) Except as provided in paragraphs (b) and (c) of... tons (metric) or more or combination carrier of 50,000 DWT tons (metric) or more, that has a keel...

46 CFR 32.53-1 - Application-T/ALL.

Code of Federal Regulations, 2013 CFR

2013-10-01

... system that uses crude oil washing. (4) An existing product carrier of 20,000 deadweight tons (metric) or... REQUIREMENTS Inert Gas System § 32.53-1 Application—T/ALL. (a) Except as provided in paragraphs (b) and (c) of... tons (metric) or more or combination carrier of 50,000 DWT tons (metric) or more, that has a keel...

46 CFR 32.53-1 - Application-T/ALL.

Code of Federal Regulations, 2012 CFR

2012-10-01

... system that uses crude oil washing. (4) An existing product carrier of 20,000 deadweight tons (metric) or... REQUIREMENTS Inert Gas System § 32.53-1 Application—T/ALL. (a) Except as provided in paragraphs (b) and (c) of... tons (metric) or more or combination carrier of 50,000 DWT tons (metric) or more, that has a keel...

46 CFR 69.109 - Under-deck tonnage.

Code of Federal Regulations, 2012 CFR

2012-10-01

...” means the tonnage of the space below the line of the tonnage deck, as that volume is calculated under... deck from the keel. Only decks without openings that permit space below to be exempt from inclusion in....) Spaces between the line of the tonnage deck and the higher portions of that deck are not included in...

46 CFR 69.109 - Under-deck tonnage.

Code of Federal Regulations, 2014 CFR

2014-10-01

...” means the tonnage of the space below the line of the tonnage deck, as that volume is calculated under... deck from the keel. Only decks without openings that permit space below to be exempt from inclusion in....) Spaces between the line of the tonnage deck and the higher portions of that deck are not included in...

46 CFR 69.109 - Under-deck tonnage.

Code of Federal Regulations, 2013 CFR

2013-10-01

...” means the tonnage of the space below the line of the tonnage deck, as that volume is calculated under... deck from the keel. Only decks without openings that permit space below to be exempt from inclusion in....) Spaces between the line of the tonnage deck and the higher portions of that deck are not included in...

46 CFR 69.109 - Under-deck tonnage.

Code of Federal Regulations, 2011 CFR

2011-10-01

...” means the tonnage of the space below the line of the tonnage deck, as that volume is calculated under... deck from the keel. Only decks without openings that permit space below to be exempt from inclusion in....) Spaces between the line of the tonnage deck and the higher portions of that deck are not included in...

46 CFR 42.20-75 - Minimum freeboards.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Freeboards § 42.20-75 Minimum freeboards. (a) Summer freeboard. (1) The minimum freeboard in summer must be... the summer freeboard of one forty-eighth of the summer draft measured from the top of the keel to the... freeboard obtained by an addition to the summer freeboard of one forty-eighth of summer draft, measured from...

46 CFR 42.20-75 - Minimum freeboards.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Freeboards § 42.20-75 Minimum freeboards. (a) Summer freeboard. (1) The minimum freeboard in summer must be... the summer freeboard of one forty-eighth of the summer draft measured from the top of the keel to the... freeboard obtained by an addition to the summer freeboard of one forty-eighth of summer draft, measured from...

46 CFR 42.20-75 - Minimum freeboards.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Freeboards § 42.20-75 Minimum freeboards. (a) Summer freeboard. (1) The minimum freeboard in summer must be... the summer freeboard of one forty-eighth of the summer draft measured from the top of the keel to the... freeboard obtained by an addition to the summer freeboard of one forty-eighth of summer draft, measured from...

46 CFR 42.20-75 - Minimum freeboards.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Freeboards § 42.20-75 Minimum freeboards. (a) Summer freeboard. (1) The minimum freeboard in summer must be... the summer freeboard of one forty-eighth of the summer draft measured from the top of the keel to the... freeboard obtained by an addition to the summer freeboard of one forty-eighth of summer draft, measured from...

46 CFR 42.20-75 - Minimum freeboards.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Freeboards § 42.20-75 Minimum freeboards. (a) Summer freeboard. (1) The minimum freeboard in summer must be... the summer freeboard of one forty-eighth of the summer draft measured from the top of the keel to the... freeboard obtained by an addition to the summer freeboard of one forty-eighth of summer draft, measured from...

33 CFR 183.205 - Passenger carrying area.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Flotation Requirements for Outboard Boats Rated for Engines... section a boat is level when it is supported on its keel at the two points shown in Figure 2. (b) As used in this subpart, the term “passenger carrying area” means each area in a boat in which persons can...

33 CFR 183.205 - Passenger carrying area.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Flotation Requirements for Outboard Boats Rated for Engines... section a boat is level when it is supported on its keel at the two points shown in Figure 2. (b) As used in this subpart, the term “passenger carrying area” means each area in a boat in which persons can...

Formation and Evolution of the Continental Lithospheric Mantle: Perspectives From Radiogenic Isotopes of Silicate and Sulfide Inclusions in Macrodiamonds

NASA Astrophysics Data System (ADS)

Shirey, S. B.; Richardson, S. H.

2007-12-01

Silicate and sulfide inclusions that occur in diamonds comprise the oldest (>3 Ga), deepest (>140 km) samples of mantle-derived minerals available for study. Their relevance to the evolution of the continental lithosphere is clear because terrestrial macrodiamonds are confined to regions of the Earth with continental lithospheric mantle keels. The goals of analytical work on inclusions in diamond are to obtain paragenesis constraints, radiogenic ages, and initial isotopic compositions. The purpose is to place diamond formation episodes into the broader framework of the geological processes that create and modify the continental lithosphere and to relate the source of the C and N in diamond-forming fluids to understanding the Earth's C and N cycles in the Archean. Although sulfide and silicate inclusions rarely occur in the same diamond, they both can be grouped according to their geochemical similarity with the chief rock types that comprise the mantle keel: peridotite and eclogite. Silicate inclusions are classified as harzburgitic (depleted; olivine > Fo91, garnet Cr2O3 > 3 wt% and CaO from 0 to 5 wt%), lherzolitic (fertile), or eclogitic (basaltic; garnet Cr2O3 < 2 wt% and CaO from 3 to 15 wt%, clinopyroxene with higher Na2O, Al2O3, and FeO); they are amenable for trace element study by SIMS and for Sm-Nd and Rb-Sr analysis by conventional P-TIMS after grouping by mineralogical similarity. Sulfide inclusions (chiefly FeS with lesser Ni, Cu, and Co) are classified as peridotitic (Ni > 14 wt%; Os > 2 ppm) versus eclogitic (Ni < 10 wt%; Os < 200 ppb); single sulfides are amenable for S isotopic study by SIMS or TIMS, and Re-Os analysis by N-TIMS. Work on inclusions in diamonds depends on the distribution of mined, diamond-bearing kimberlites, and the generosity of mining companies because of the extreme rarity of inclusions in suites of mostly gem-quality diamonds. Most isotopic work has been on the Kaapvaal-Zimbabwe craton with lesser work on the Slave, Siberian

Calculation of thermodynamic functions of aluminum plasma for high-energy-density systems

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

Shumaev, V. V., E-mail: shumaev@student.bmstu.ru

The results of calculating the degree of ionization, the pressure, and the specific internal energy of aluminum plasma in a wide temperature range are presented. The TERMAG computational code based on the Thomas–Fermi model was used at temperatures T > 105 K, and the ionization equilibrium model (Saha model) was applied at lower temperatures. Quantitatively similar results were obtained in the temperature range where both models are applicable. This suggests that the obtained data may be joined to produce a wide-range equation of state.

Radio-sensitizing Effects of Novel Histone De-Acetylase Inhibitors in Prostate Cancer

DTIC Science & Technology

2007-03-01

were investigated in PC-3, LN -3 and DU-145 cells. (S)-HDAC-42 and SAHA could sensitize PC-3 and DU-145 cells to radiation. Aim 2: Effects of VAD- 18 ...combined effects of HDAC inhibitors and ionizing radiation on prostate cancer cell lines (PC-3, LN -3, LnCAP, DU-145 and 22Rv1). Aim 2. To understand the...cancer cell lines. Aim 3. To determine the combined effects of HDAC inhibitors plus ionizing radiation on the regression of (i) prostate cancer xenografts

Trithiocarbonates: exploration of a new head group for HDAC inhibitors.

PubMed

Dehmel, Florian; Ciossek, Thomas; Maier, Thomas; Weinbrenner, Steffen; Schmidt, Beate; Zoche, Martin; Beckers, Thomas

2007-09-01

Inhibition of histone deacetylases class I/II enzymes is a new, promising approach for cancer therapy. In the present study, we disclose a new structural class of HDAC inhibitors with the trithiocarbonate motif. A clear structure-activity-relationship was obtained for the cap-linker motif and the putative Zn(2+) complexing head group. Selected analogs display potent inhibition of HDAC enzymatic activity and a cellular potency comparable to that of suberoylanilide hydroxamic acid (SAHA), recently approved for treatment of patients with advanced cutaneous T-cell lymphoma.

The TRACE Model of Speech Perception.

DTIC Science & Technology

1984-11-01

One approach is to try to find relatively invariant -- generally relational -- features (e.g., Stevens and Blumstein, 1981). Another approach has...t Dr. Anders Ericsson I Dr. Steven W. Keele Department oi Psychology Dept. of Psychology University of Colorado University of Oregon Boulder, CO...Parallel distributed processing: Explorations in the microstructue of cogni- tion. Vol. 1: Foundations. Cambridge, MA: Bradford Books. Stevens , K

46 CFR 42.13-15 - Definitions of terms.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Definitions of terms. 42.13-15 Section 42.13-15 Shipping... General Rules for Determining Load Lines § 42.13-15 Definitions of terms. (a) Length. The length (L) shall... measured from the top of the keel, or as the length from the foreside of the stem to the axis of the rudder...

78 FR 33208 - Certifications and Exemptions Under the International Regulations for Preventing Collisions at...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-04

... 32 CFR Part 706 Marine Safety, Navigation (Water), and Vessels. For the reasons set forth in the... dk masthead ship's keel in flight dk Rule in meters; Rule in meters; light in sides in meters; in meters; 30(a)(i) Rule 21(e), 30(a)(ii) Sec. 2 meters; meters; Rule 21(a) Sec. Rule (g), Annex Sec. Sec. 2...

Assessing cellular efficacy of bromodomain inhibitors using fluorescence recovery after photobleaching

PubMed Central

2014-01-01

Background Acetylation of lysine residues in histone tails plays an important role in the regulation of gene transcription. Bromdomains are the readers of acetylated histone marks, and, consequently, bromodomain-containing proteins have a variety of chromatin-related functions. Moreover, they are increasingly being recognised as important mediators of a wide range of diseases. The first potent and selective bromodomain inhibitors are beginning to be described, but the diverse or unknown functions of bromodomain-containing proteins present challenges to systematically demonstrating cellular efficacy and selectivity for these inhibitors. Here we assess the viability of fluorescence recovery after photobleaching (FRAP) assays as a target agnostic method for the direct visualisation of an on-target effect of bromodomain inhibitors in living cells. Results Mutation of a conserved asparagine crucial for binding to acetylated lysines in the bromodomains of BRD3, BRD4 and TRIM24 all resulted in reduction of FRAP recovery times, indicating loss of or significantly reduced binding to acetylated chromatin, as did the addition of known inhibitors. Significant differences between wild type and bromodomain mutants for ATAD2, BAZ2A, BRD1, BRD7, GCN5L2, SMARCA2 and ZMYND11 required the addition of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) to amplify the binding contribution of the bromodomain. Under these conditions, known inhibitors decreased FRAP recovery times back to mutant control levels. Mutation of the bromodomain did not alter FRAP recovery times for full-length CREBBP, even in the presence of SAHA, indicating that other domains are primarily responsible for anchoring CREBBP to chromatin. However, FRAP assays with multimerised CREBBP bromodomains resulted in a good assay to assess the efficacy of bromodomain inhibitors to this target. The bromodomain and extraterminal protein inhibitor PFI-1 was inactive against other bromodomain targets

Complex structure of a bacterial class 2 histone deacetylase homologue with a trifluoromethylketone inhibitor

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

Nielsen, Tine Kragh; Hildmann, Christian; Riester, Daniel

2007-04-01

The crystal structure of HDAH FB188 in complex with a trifluoromethylketone at 2.2 Å resolution is reported and compared to a previously determined inhibitor complex. Histone deacetylases (HDACs) have emerged as attractive targets in anticancer drug development. To date, a number of HDAC inhibitors have been developed and most of them are hydroxamic acid derivatives, typified by suberoylanilide hydroxamic acid (SAHA). Not surprisingly, structural information that can greatly enhance the design of novel HDAC inhibitors is so far only available for hydroxamic acids in complex with HDAC or HDAC-like enzymes. Here, the first structure of an enzyme complex with amore » nonhydroxamate HDAC inhibitor is presented. The structure of the trifluoromethyl ketone inhibitor 9,9,9-trifluoro-8-oxo-N-phenylnonanamide in complex with bacterial FB188 HDAH (histone deacetylase-like amidohydrolase from Bordetella/Alcaligenes strain FB188) has been determined. HDAH reveals high sequential and functional homology to human class 2 HDACs and a high structural homology to human class 1 HDACs. Comparison with the structure of HDAH in complex with SAHA reveals that the two inhibitors superimpose well. However, significant differences in binding to the active site of HDAH were observed. In the presented structure the O atom of the trifluoromethyl ketone moiety is within binding distance of the Zn atom of the enzyme and the F atoms participate in interactions with the enzyme, thereby involving more amino acids in enzyme–inhibitor binding.« less

Atmospheric Carbon Dioxide Record from Mauna Loa (1958-2008)

DOE Data Explorer

Keeling, R. F. [Scripps Institution of Oceanography, University of California, La Jolla, California; Piper, S. C. [Scripps Institution of Oceanography, University of California, La Jolla, California; Bollenbacher, A. F. [Scripps Institution of Oceanography, University of California, La Jolla, California; Walker, J. S. [Scripps Institution of Oceanography, University of California, La Jolla, California

2009-02-01

Air samples at Mauna Loa are collected continuously from air intakes at the top of four 7-m towers and one 27-m tower. Four air samples are collected each hour for the purpose of determining the CO2 concentration. Determinations of CO2 are made by using a Siemens Ultramat 3 nondispersive infrared gas analyzer with a water vapor freeze trap. This analyzer registers the concentration of CO2 in a stream of air flowing at ~0.5 L/min. Every 30 minutes, the flow is replaced by a stream of calibrating gas or "working reference gas". In December 1983, CO2-in-N2 calibration gases were replaced with the currently used CO2-in-air calibration gases. These calibration gases and other reference gases are compared periodically to determine the instrument sensitivity and to check for possible contamination in the air-handling system. These reference gases are themselves calibrated against specific standard gases whose CO2 concentrations are determined manometrically. Greater details about the sampling methods at Mauna Loa are given in Keeling et al. (1982) and Keeling et al. (2002).

Continuous field measurements of δD in water vapor by open-path Fourier transform infrared spectrometry

NASA Astrophysics Data System (ADS)

Wang, Wei; Liu, Wenqing; Zhang, Tianshu

2012-12-01

The stable isotopes in atmospheric water vapor contain rich information on the hydrologic cycles and gaseous exchange processes between biosphere and atmosphere. About one-week field experiment was conducted to continuously measure the isotope composition of water vapor in ambient air using an open-path FTIR system. Mixing ratios of H2 16O and HD16O were measured simultaneously. Analysis of water vapor isotopes revealed that the variations of H2 16O and HD16O were highly related. Mixing ratios of both isotopes varied considerably on a daily timescale or between days, with no obvious diurnal cycle, whereas the deuterium isotopic [delta]D showed clear diel cycle. The results illustrated that the correlation between [delta]D and H2O mixing ratio was relatively weak, which was also demonstrated by the Keeling plot analysis with the whole data. Yet the further Keeling analysis on a daily timescale displayed more obvious linear relationship between [delta]D and the total H2O concentration. All daily isotopic values of evapotranspiration source were obtained, with the range between -113.93±10.25‰ and -245.63±17.61‰ over the observation period.

Advanced Technology Composite Fuselage: Program Overview

NASA Technical Reports Server (NTRS)

Ilcewicz, L. B.; Smith, P. J.; Hanson, C. T.; Walker, T. H.; Metschan, S. L.; Mabson, G. E.; Wilden, K. S.; Flynn, B. W.; Scholz, D. B.; Polland, D. R.;

A Compendium of Portage Studies

DTIC Science & Technology

1982-02-01

M = 1.5W + 2.0(W+L)(L/W)2 + E(W+L)(1.5V2 + 0.35VG) (1) where M = metabolic cost (watts) W = subject weight, nude (kg) L = external load (kg) E...footing factor V = velocity ( m /sec) G = grade or slope (%) While it may not always result in an accurate prediction, Formula 1 does incorporate...Randall, R.B. Ray, S.N. Redfearn, J.W.T. Reid, A.M. Renbourne, E.T. Ress, M . Richardson, D.T. Roy, B.N. Saha, P.N. Sanders, J.H. Sen, R.N. Sen

Identification and Characterization of Genomic Amplifications in Ovarian Serous Carcinoma

DTIC Science & Technology

2009-01-01

Powell B, Mills GB, Gray JW. PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet 1999; 21:99-102. 26. Ma YY, Wei SJ, Lin YC, Lung JC, Chang TC...Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A...McCormick F, Gray JW. Chromosome aberrations in solid tumors. Nat Genet 2003;34:369–76. 3. Wang TL, Diaz LA, Jr, Romans K, Bardelli A, Saha S, Galizia

Shapes of Spectral Lines of Nonuniform Plasma of Electric Arc Discharge Between Copper Electrodes

NASA Astrophysics Data System (ADS)

Babich, Ida L.; Boretskij, Viacheslav F.; Veklich, Anatoly N.

2007-09-01

The radial profiles of the temperature and electron density in the plasma of the free burning electric arc between copper electrodes are studied by optical spectroscopy techniques. The electron density and the temperature in plasma as initial parameters were used in the calculation of the plasma composition in local thermodynamic equilibrium (LTE) assumption. We used the Saha's equation for copper, nitrogen and oxygen, dissociation equation for nitrogen and oxygen, the equation of plasma electrical neutrality and Dalton's law as well. So, it would be possible to determine the amounts of metal vapours in plasma.

46 CFR 69.183 - Figures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... fresh and tropical waters. EC01FE91.046 W=1/48 of the distance from the top of the flat keel to the... though the second deck were the freeboard deck. EC01FE91.047 k=a distance between 21 inches and six feet... inches and six feet six inches. a=the distance between the line of the second deck and the uppermost part...

46 CFR 69.183 - Figures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... fresh and tropical waters. EC01FE91.046 W=1/48 of the distance from the top of the flat keel to the... though the second deck were the freeboard deck. EC01FE91.047 k=a distance between 21 inches and six feet... inches and six feet six inches. a=the distance between the line of the second deck and the uppermost part...

77 FR 39629 - Certifications and Exemptions Under the International Regulations for Preventing Collisions at...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-05

... 32 CFR Part 706 Marine safety, Navigation (water), and Vessels. For the reasons set forth in the... stbd of keel dk in number of; dk in Rule meters; Sec. light in in meters; in meters; meters; Sec. Rule meters; Rule 30(a)(ii) 2(g), meters; Sec. Sec. 3(b), Rule 21(a) 2(K), 30(a)(i) 21(e), Rule Annex I 3(b...

76 FR 12859 - Certifications and Exemptions Under the International Regulations for Preventing Collisions at...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-09

..., Navigation (water), and Vessels. For the reasons set forth in the preamble, the Navy amends part 706 of title... masthead ship's keel in in number of; in meters; Rule 30(a) in light in sides in meters; meters; Rule 30(a) Rule (ii) meters; meters; meters; Rule 21(a) Sec. (i) 21(e), Sec. 2 Sec. Sec. 2(K), Rule (g), Annex 3(b...

SRMS maneuvers the ICC-VLD during STS-127 / Expedition 20 Joint Operations

NASA Image and Video Library

2009-07-19

S127-E-006934 (19 July 2009) --- Backdropped by a blue and white Earth, the remote manipulator system (RMS) arm of the Space Shuttle Endeavour, is about to hand off the Integrated Cargo Carrier (ICC) to the International Space Station (out of frame). The ICC is an unpressurized flat bed pallet and keel yoke assembly that was carried into space in the shuttle's payload bay.

Microbial Effects in Promoting the Smectite to Illite Reaction: Role of Organic Matter Intercalated in the Interlayer

DTIC Science & Technology

2007-01-01

organic matter in the smectite to illite reaction. For example, Small etal. (1994) demonstrated that potassium oxalate and potassium acetate in...potassium oxalate and potassium acetate on this reaction (Small 1994). This study supplements our previous study in that microbes play an...Keeling, J.L., Raven, M.D., and Gates, W.P, (2000) Geology and characterization of two hydrothermal nontronites from weathered metamorphic rocks at

Flower power: its association with bee power and floral functional morphology in papilionate legumes

PubMed Central

Córdoba, Silvina A.; Cocucci, Andrea A.

2011-01-01

Background and Aims A test was made of the hypothesis that papilionate legume flowers filter pollinators according to their ability to exert strength to open flowers to access rewards. In addition, interactions with pollen vectors were expected to explain the structural complexity of the architecture of these flowers since operative flower strength may be determined by a combination of morphological traits which form part of an intrafloral functional module. Methods Six papilionate species were studied: Collaea argentina, Desmodium uncinatum, Galactia latisiliqua, Lathyrus odoratus, Spartium junceum and Tipuana tipu. Measurements were made of the strength needed to open keels and the strength that pollinators were capable of exerting. Morphological traits of all petals were also measured to determine which of them could be either mutually correlated or correlated with operative strength and moment of strength and participated in a functional module. Key Results It was observed that pollinators were capable in all cases of exerting forces higher and often several times higher than that needed to access floral rewards, and no association could be detected between floral operative strength and strength exerted by the corresponding pollinators. On the other hand, strong and significant correlations were found among morphometric traits and, of these, with operative strength and moment. This was particularly evident among traits of the keel and the wings, presumably involved in the functioning of the floral moveable mechanism. Conclusions Though visitors are often many times stronger than the operative strength of the flowers they pollinate, exceptionally weak bees such as Apis mellifera cannot open the strongest flowers. On the other hand, strong correlations among certain petal morphometric traits (particularly between the keel and wings) give support to the idea that an intrafloral module is associated with the functioning of the mechanism of these legume flowers. In

Measurement and evolution of the thickness distribution and morphology of deformed features of Antarctic sea ice

NASA Astrophysics Data System (ADS)

Tin, Tina

Antarctic sea ice thickness data obtained from drilling on sea ice floes were examined with the goal of enhancing our capability to estimate ice thickness remotely, especially from air- or space-borne altimetry and shipboard visual observations. The state of hydrostatic equilibrium of deformed ice features and the statistical relationships between ice thickness and top surface roughness were examined. Results indicate that ice thickness may be estimated fairly reliably from surface measurements of snow elevation on length scales of ≥100 m. Examination of the morphology of deformed ice features show that Antarctic pressure ridges are flatter and less massive than Arctic pressure ridges and that not all surface features (ridge sails) are associated with features underwater (ridge keels). I propose that the differences in morphology are due to differences in sampling strategies, parent ice characteristics and the magnitude and duration of driving forces. As a result of these findings, the existing methodology used to estimate ice thickness from shipboard visual observations was modified to incorporate the probability that a sail is associated with a keel underwater, and the probability that keels may be found under level surfaces. Using the improved methodology, ice thickness was estimated from ship observations data obtained during two cruises in the Ross Sea, Antarctica. The dynamic and thermodynamic processes involved in the development of the ice prior to their observation were examined employing a regional sea ice-mixed layer-pycnocline model. Both our model results and previously published ice core data indicate that thermodynamic thickening is the dominant process that determines the thickness of first year ice in the central Ross Sea, although dynamic thickening also plays a significant role. Ice core data also indicate that snow ice forms a significant proportion of the total ice mass. For ice in the northeast Ross Sea in the summer, model results and

Design, Development, and Integration of A Space Shuttle Orbiter Bay 13 Payload Carrier

NASA Technical Reports Server (NTRS)

Spencer, Susan H.; Phillips, Michael W.; Upton, Lanny (Technical Monitor)

2002-01-01

Bay 13 of the Space Shuttle Orbiter has been limited to small sidewall mounted payloads and ballast. In order to efficiently utilize this space, a concept was developed for a cross-bay cargo carrier to mount Orbital Replacement Units (ORU's) for delivery to the International Space Station and provide additional opportunities for science payloads, while meeting the Orbiter ballast requirements. The Lightweight Multi-Purpose Experiment Support Structure (MPESS) Carrie (LMC) was developed and tested by NASA's Marshall Space Flight Center and the Boeing Company. The Multi-Purpose Experiment Support Structure (MPESS), which was developed for the Spacelab program was modified, removing the keel structure and relocating the sill trunnions to fit in Bay 13. Without the keel fitting, the LMC required a new and innovative concept for transferring Y loads into the Orbiter structure. Since there is no keel fitting available in the Bay 13 location, the design had to utilize the longeron bridge T-rail to distribute the Y loads. This concept has not previously been used in designing Shuttle payloads. A concept was developed to protect for Launch-On-Need ORU's, while providing opportunities for science payloads. Categories of potential ORU's were defined, and Get-Away Special (GAS) payloads of similar mass properties were provided by NASA's Goddard Space Flight Center. Four GAS payloads were manifest as the baseline configuration, preserving the capability to swap up to two ORU's for the corresponding science payloads, after installation into the Orbiter cargo bay at the pad, prior to closeout. Multiple configurations were considered for the analytical integration, to protect for all defined combinations of ORU's and GAS payloads. The first physical integration of the LMC war performed by Goddard Space Flight Center and Kennedy Space Center at an off-line facility at Kennedy Space Center. This paper will discuss the design challenges, structural testing, analytical and physical

Space Station Freedom Central Thermal Control System Evolution

NASA Technical Reports Server (NTRS)

Bullock, Richard; Olsson, Eric

1990-01-01

The objective of the evolution study is to review the proposed growth scenarios for Space Station Freedom and identify the major CTCS hardware scars and software hooks required to facilitate planned growth and technology obsolescence. The Station's two leading evolutionary configurations are: (1) the Research and Development node, where the fundamental mission is scientific research and commercial endeavors, and (2) the Transportation node, where the emphasis is on supporting Lunar and Mars human exploration. These two nodes evolve from the from the assembly complete configuration by the addition of manned modules, pocket labs, resource nodes, attached payloads, customer servicing facility, and an upper and lower keel and boom truss structure. In the case of the R & D node, the role of the dual keel will be to support external payloads for scientific research. In the case of the Transportation node, the keel will support the Lunar (LTV) and Mars (MTV) transportation vehicle service facilities In addition to external payloads. The transverse boom is extended outboard of the alpha gimbal to accommodate the new solar dynamic arrays for power generation, which will supplement the photovoltaic system. The design, development, deployment, and operation of SSF will take place over a 30 year time period and new Innovations and maturation in technologies can be expected. Evolutionary planning must include the obsolescence and insertion of the new technologies over the life of the program, and the technology growth issues must be addressed in parallel with the development of the baseline thermal control system. Technologies that mature and are available within the next 10 years are best suited for evolutionary consideration as the growth phase begins in the year 2000. To increase TCS capability to accommodate growth using baseline technology would require some penalty in mass, volume, EVA time, manifesting, and operational support. To be cost effective the capabilities of

Design strategies of sea urchin teeth: structure, composition and micromechanical relations to function.

PubMed

Wang, R Z; Addadi, L; Weiner, S

1997-04-29

The teeth of sea urchins comprise a variety of different structural entities, all of which are composed of magnesium-bearing calcite together with a small amount of organic material. The teeth are worn down continuously, but in such a way that they remain sharp and functional. Here we describe aspects of the structural, compositional and micromechanical properties of the teeth of Paracentrotus lividus using scanning electron microscopy, infrared spectrometry, atomic absorption. X-ray diffraction and microindentation. The S-shaped single crystalline calcitic fibres are one of the main structural elements of the tooth. They extend from the stone part to the keel. The diameter of the fibres increases gradually from less than 1 micron at the stone tip to about 20 microns at the keel end, while their MgCO3 contents decrease from about 13 mol% to about 4.5 mol%. Each fibre is coated by a thin organic sheath and surrounded by polycrystalline calcitic discs containing as much as 35 mol% MgCO3. This structure constitutes a unique kind of gradient fibre-reinforced ceramic matrix composite, whose microhardness and toughness decrease gradually from the stone part to the keel. Primary plates are also important structural elements of the tooth. Each primary plate has a very unusual sandwich-like structure with a calcitic envelope surrounding a thin apparently amorphous CaCO3 layer. This central layer, together with the primary plate/disc interface, improves the toughness of this zone by stopping and blunting cracks. The self-sharpening function of the teeth is believed to result from the combination of the geometrical shape of the main structural elements and their spatial arrangement, the interfacial strength between structural elements, and the hardness gradient extending from the working stone part to the surrounding zones. The sea urchin tooth structure possesses an array of interesting functional design features, some of which may possibly be applicable to materials science.

X-ray absorption microtomography (microCT) and small beam diffraction mapping of sea urchin teeth.

PubMed

Stock, S R; Barss, J; Dahl, T; Veis, A; Almer, J D

2002-07-01

Two noninvasive X-ray techniques, laboratory X-ray absorption microtomography (microCT) and X-ray diffraction mapping, were used to study teeth of the sea urchin Lytechinus variegatus. MicroCT revealed low attenuation regions at near the tooth's stone part and along the carinar process-central prism boundary; this latter observation appears to be novel. The expected variation of Mg fraction x in the mineral phase (calcite, Ca(1-x)Mg(x)CO(3)) cannot account for all of the linear attenuation coefficient decrease in the two zones: this suggested that soft tissue is localized there. Transmission diffraction mapping (synchrotron X-radiation, 80.8 keV, 0.1 x 0.1mm(2) beam area, 0.1mm translation grid, image plate area detector) simultaneously probed variations in 3-D and showed that the crystal elements of the "T"-shaped tooth were very highly aligned. Diffraction patterns from the keel (adaxial web) and from the abaxial flange (containing primary plates and the stone part) differed markedly. The flange contained two populations of identically oriented crystal elements with lattice parameters corresponding to x=0.13 and x=0.32. The keel produced one set of diffraction spots corresponding to the lower x. The compositions were more or less equivalent to those determined by others for camarodont teeth, and the high Mg phase is expected to be disks of secondary mineral epitaxially related to the underlying primary mineral element. Lattice parameter gradients were not noted in the keel or flange. Taken together, the microCT and diffraction results indicated that there was a band of relatively high protein content, of up to approximately 0.25 volume fraction, in the central part of the flange and paralleling its adaxial and abaxial faces. X-ray microCT and microdiffraction data used in conjunction with protein distribution data will be crucial for understanding the properties of various biocomposites and their mechanical functions.

Evapotranspiration flux partitioning using an Iso-SPAC model in a temperate grassland ecosystem

NASA Astrophysics Data System (ADS)

Wang, P.

2014-12-01

To partition evapotranspiration (ET) into soil evaporation and vegetation transpiration (T), a new numerical Iso-SPAC (coupled heat, water with isotopic tracer in Soil-Plant-Atmosphere-Continuum) model was developed and applied to a temperate-grassland ecosystem in central Japan. Several models of varying complexity have been tested with the aim of obtaining the close to true value for the isotope composition of leaf water and transpiration flux. The agreement between the model predictions and observations demonstrates that the Iso-SPAC model with a steady-state assumption for transpiration flux can reproduce seasonal variations of all the surface energy balance components，leaf and ground surface temperature as well as isotope data (canopy foliage and ET flux). This good performance was confirmed not only at diurnal timescale but also at seasonal timescale. Thus, although the non-steady-state behavior of isotope budget in a leaf and isotopic diffusion between leaf and stem or root is exactly important, the steady-state assumption is practically acceptable for seasonal timescale as a first order approximation. Sensitivity analysis both in physical flux part and isotope part suggested that T/ET is relatively insensitive to uncertainties/errors in assigned model parameters and measured input variables, which illustrated the partitioning validity. Estimated transpiration fractions using isotope composition in ET flux by Iso-SPAC model and Keeling plot are generally in good agreement, further proving validity of the both approaches. However, Keeling plot approach tended to overestimate the fraction during an early stage of glowing season and a period just after clear cutting. This overestimation is probably due to insufficient fetch and influence of transpiration from upwind forest. Consequently, Iso-SPAC model is more reliable than Keeling plot approach in most cases.The T/ET increased with grass growth, and the sharp reduction caused by clear cutting was well

Application of the Saha Equation to High Temperature ( or = 6000K) Rocket Exhaust

DTIC Science & Technology

1992-11-01

SAIR FORCE MATERIEL COMMAND EDWARDS AIR FORCE BASE CA 93524-7001 0 NOTICE When U.S. Government drawings, specifications, or other data are used for any...or any other person or corporation, or conveying any rights or permission to man- ufacture, use or sell any patented invention that may be related...iniferson Pv S. Ze :oh 2.n ardt~uý!ger.P ernck cc~o f - )..s gt CC ’C5C3. -I AGENCY USE O"LY (Leave blk) 2. REPORT DATE 3. REPORT TYPE AND DATES COVERED

Application of the Saha Equation to High Temperature ( or = 6000K) rocket Exhaust

DTIC Science & Technology

1993-03-01

specifications, or other data are used for any purpose other than a definitely related G )vernment procurement operation, the fact that the Government may have...any way licensing the holder or any other person or corporation, or conveying any rights or permission to manufacture, use or sell any patented...I" Office of M tiVt, ,nt pdo iki qet P p•eV ¢.k Re wtoW PSCjft t (0 IC4 0 1661. OWI .h-togtO n 1,1 ?V1,rj "I. AGENCY USE ONLY (Leave blank) [. REPORT

The Use of Ground Penetrating Radar to extend the Results of Archaeological Excavation

NASA Astrophysics Data System (ADS)

Utsi, E.

2009-04-01

archaeological material. The GPR survey has added significantly to the excavation results and hence to the potential interpretation of the site. Since it will not be possible either to continue the former excavation or to investigate the adjacent land, the information provided by the radar provides a unique insight. [1] Utsi, V (1988) "Ground Radar" in ‘Excavation of a Romano-British Villa at Wortley, Gloucs.' University of Keele Department of Adult & Continuing Education, Keele, 4th interim report. [2] Utsi, V & Utsi, E (1989) "Ground radar survey" in ‘Excavation of a Romano-British Villa at Wortley, Gloucs.' University of Keele, Department of Adult & Continuing Education, Keele, 5th interim report. [3] Utsi Electronics Ltd (2007) "Ground Penetrating Radar Survey of Part of Wortley Romano-British Villa" report to David Wilson, Director, Archaeological Excavation Training School, Cambridge UK.

Spring Ankle with Regenerative Kinetics to Build a New Generation of Transtibial Prostheses

DTIC Science & Technology

2009-07-01

fiber keel. This feature can provide an alternative if the electronics fail in a field condition. We are focused on developing the most durable...step forward in design of new prosthesis 22 14. Discovery Channel, 2008, “Toad research could leapfrog to new muscle model”, show was called...turning on the proportional myoelectric control. The pneumatic muscles supplied 36% plantar flexor torque and 123% dorsi flexor torque. Challenges

Argo Navis

NASA Astrophysics Data System (ADS)

Murdin, P.

2000-11-01

(the Ship) a large southern constellation representing the ship Argo of Jason and the Argonauts in Greek mythology whose brightest stars were cataloged by Ptolemy (c. AD 100-175) in the Almagest. It was divided up by the French astronomer Nicolas L de Lacaille (1713-62), who charted the southern sky in 1751-2, into the constellations Carina (the Keel), Vela (the Sails), Puppis (the Poop or Stern)...

Cross Body Thruster Control and Modeling of a Body of Revolution Autonomous Underwater Vehicle

DTIC Science & Technology

2011-03-01

Leonardo da Vinci envisioned submersible troop transports, assault craft, and diving rigs in the early sixteenth century. Figure 1. Da...BLOCK DIAGRAM 90 THIS PAGE INTENTIONALLY LEFT BLANK 91 LIST OF REFERENCES [1] Museo Galileo, “ Leonardo da Vinci – Studies on Keels of...appl=LIR&xsl=paginamanoscritto&li ngua=ENG&chiave=101406. [Accessed: 10 October 2010]. [2] Museo Galileo, “ Leonardo da Vinci – Machine for Raising

Measures of Time-Sharing Skill and Gender as Predictors of Flight Simulator Performance.

DTIC Science & Technology

1979-01-01

well as overall e- quations including gender as a variable. Besides gender in the overall equations, measures of time-sharing skill were the best ...study indicated the best predictors of dual or whole-task performance were other dual-tasks. Furthermore, the particular components involved in a dual...switching between tasks, or the use of efficient response strategies " (Damos and Wickens, 1977, p.2). Attentional flexibility. According to Keele

Laser induced breakdown spectroscopy (LIBS) applied to stratigrafic elemental analysis and optical coherence tomography (OCT) to damage determination of cultural heritage Brazilian coins

NASA Astrophysics Data System (ADS)

M. Amaral, Marcello; Raele, Marcus P.; Z. de Freitas, Anderson; Zahn, Guilherme S.; Samad, Ricardo E.; D. Vieira, Nilson, Jr.; G. Tarelho, Luiz V.

2009-07-01

This work presents a compositional characterization of 1939's Thousand "Réis" and 1945's One "Cruzeiro" Brazilian coins, forged on aluminum bronze alloy. The coins were irradiated by a Q-switched Nd:YAG laser with 4 ns pulse width and energy of 25mJ emitting at 1064nm reaching 3.1010Wcm-2 (assured condition for stoichiometric ablation), forming a plasma in a small fraction of the coin. Plasma emission was collected by an optical fiber system connected to an Echelle spectrometer. The capability of LIBS to remove small fraction of material was exploited and the coins were analyzed ablating layer by layer from patina to the bulk. The experimental conditions to assure reproductivity were determined by evaluation of three plasma paramethers: ionization temperature using Saha-Boltzmann plot, excitation temperature using Boltzmann plot, plasma density using Saha-Boltzmann plot and Stark broadening. The Calibration-Free LIBS technique was applied to both coins and the analytical determination of elemental composition was employed. In order to confirm the Edict Law elemental composition the results were corroborated by Neutron Activation Analysis (NAA). In both cases the results determined by CF-LIBS agreed to with the Edict Law and NAA determination. Besides the major components for the bronze alloy some other impurities were observed. Finally, in order to determine the coin damage made by the laser, the OCT (Optical Coherence Tomography) technique was used. After tree pulses of laser 54μg of coin material were removed reaching 120μm in depth.

Mechanistic insights into epigenetic modulation of ethanol consumption.

PubMed

Ponomarev, Igor; Stelly, Claire E; Morikawa, Hitoshi; Blednov, Yuri A; Mayfield, R Dayne; Harris, R Adron

2017-05-01

There is growing evidence that small-molecule inhibitors of epigenetic modulators, such as histone deacetylases (HDAC) and DNA methyltransferases (DNMT), can reduce voluntary ethanol consumption in animal models, but molecular and cellular processes underlying this behavioral effect are poorly understood. We used C57BL/6J male mice to investigate the effects of two FDA-approved drugs, decitabine (a DNMT inhibitor) and SAHA (an HDAC inhibitor), on ethanol consumption using two tests: binge-like drinking in the dark (DID) and chronic intermittent every other day (EOD) drinking. Decitabine but not SAHA reduced ethanol consumption in both tests. We further investigated decitabine's effects on the brain's reward pathway by gene expression profiling in the ventral tegmental area (VTA), using RNA sequencing and electrophysiological recordings from VTA dopaminergic neurons. Decitabine-induced decreases in EOD drinking were associated with global changes in gene expression, implicating regulation of cerebral blood flow, extracellular matrix organization, and neuroimmune functions in decitabine actions. In addition, an in vivo administration of decitabine shortened ethanol-induced excitation of VTA dopaminergic neurons in vitro, suggesting that decitabine reduces ethanol drinking via changes in the reward pathway. Taken together, our data suggest a contribution of both neuronal and non-neuronal mechanisms in the VTA in the regulation of ethanol consumption. Decitabine and other epigenetic compounds have been approved for cancer treatment, and understanding their mechanisms of actions in the brain may assist in repurposing these drugs and developing novel therapies for central disorders, including drug addiction. Copyright © 2017 Elsevier Inc. All rights reserved.

Naturally occurring benzoic acid derivatives retard cancer cell growth by inhibiting histone deacetylases (HDAC)

PubMed Central

Anantharaju, Preethi G.; Reddy, Bandi Deepa; Padukudru, Mahesh A.; Kumari Chitturi, CH. M.; Vimalambike, Manjunath G.

2017-01-01

ABSTRACT Histone deacetylases (HDACs), which modulate the expression of genes, are potential therapeutic targets in several cancers. Targeted inhibition of HDAC prevents the expression of oncogenes thereby help in the treatment of cancers. Hence, several pharmaceutical companies developed inhibitors of HDAC and tested them in preclinical models and in clinical trials. SAHA (suberanilohydroxamic acid) is one such HDAC inhibitor developed for treating breast and colorectal carcinomas. However, due to poor efficacy in clinical trials the utility of SAHA for treating cancers was discouraged. Similarly another HDAC inhibitor Trichostatin-A (TSA) also showed promising results in clinical trials but exhibited severe adverse effects, which dampened the interest of using this molecule for cancer treatment. Therefore, search for developing a potent HDAC inhibitor with minimal side effects still continues. Hence, in this study we have screened benzoic acid and benzoic acid derivatives with hydroxylic (-OH) groups and methoxy (-OCH3) groups for their efficacy to bind to the TSA binding site of HDAC using molecular docking studies. Molecules that showed much stronger affinity (than TSA) to HDAC were tested for inhibiting HDAC expressing cultured cancer cells. DHBA but not Dimethoxy Benzoic Acid (DMBA) inhibited HDAC activity, leading to cancer cell growth inhibition through the induction of ROS and cellular apoptosis mediated by Caspase-3. In addition, DHBA arrested cells in G2/M phase of the cell cycle and elevated the levels of sub-G0-G1 cell population. In summary, results of this study report that DHBA could be a strong HDAC inhibitor and inhibit cancer cell growth more effectively. PMID:28506198

Advanced Technology Composite Fuselage - Repair and Damage Assessment Supporting Maintenance

NASA Technical Reports Server (NTRS)

Flynn, B. W.; Bodine, J. B.; Dopker, B.; Finn, S. R.; Griess, K. H.; Hanson, C. T.; Harris, C. G.; Nelson, K. M.; Walker, T. H.; Kennedy, T. C.;

Modelling sea ice dynamics

NASA Astrophysics Data System (ADS)

Murawski, Jens; Kleine, Eckhard

2017-04-01

Sea ice remains one of the frontiers of ocean modelling and is of vital importance for the correct forecasts of the northern oceans. At large scale, it is commonly considered a continuous medium whose dynamics is modelled in terms of continuum mechanics. Its specifics are a matter of constitutive behaviour which may be characterised as rigid-plastic. The new developed sea ice dynamic module bases on general principles and follows a systematic approach to the problem. Both drift field and stress field are modelled by a variational property. Rigidity is treated by Lagrangian relaxation. Thus one is led to a sensible numerical method. Modelling fast ice remains to be a challenge. It is understood that ridging and the formation of grounded ice keels plays a role in the process. The ice dynamic model includes a parameterisation of the stress associated with grounded ice keels. Shear against the grounded bottom contact might lead to plastic deformation and the loss of integrity. The numerical scheme involves a potentially large system of linear equations which is solved by pre-conditioned iteration. The entire algorithm consists of several components which result from decomposing the problem. The algorithm has been implemented and tested in practice.

Radiographic measurement of internal organs in Spix's macaws (Cyanopsitta spixii).

PubMed

Rettmer, Helen; Deb, Amrita; Watson, Ryan; Hatt, Jean-Michel; Hammer, Sven

2011-12-01

Radiology is an important diagnostic instrument in avian medicine, but standard measurement ranges for the objective evaluation of radiographs of birds are rare. To establish radiographic reference ranges for the critically endangered Spix's macaw (Cyanopsitta spixii), we measured radiographic silhouettes of the heart, liver, kidneys, spleen, proventriculus, and keel of the sternum on 29 radiographs taken under standardized conditions in adult and juvenile, clinically healthy birds. Ratios were determined for the proventricular diameter-to-keel height, the width of the heart to the width of the thorax, and for the "hourglass shape" (ratio of the width of the heart to the width of the liver). No significant differences were found between the sexes among the adult birds. Compared with adult birds, juvenile females had a significantly larger heart width (19.8 +/- 1.4 mm versus 21.2 +/- 0.7 mm), ratio of the heart width to the thorax width (0.86 +/- 0.08 versus 0.94 +/- 0.09), and horizontal width of the spleen (7.7 +/- 0.6 mm versus 8.5 +/- 0.4 mm). Results of radiographic measurements in the Spix's macaws were comparable to those published from other psittacine species. These reference ranges will facilitate a more objective radiographic evaluation of captive Spix's macaws.

A new species of Vargapupa Páll-Gergely, 2015 and a new synonym of Pseudopomatias Möllendorff, 1885 (Gastropoda: Caenogastropoda: Pupinidae).

PubMed

Páll-Gergely, Barna

2016-07-21

Revision of the genus Pseudopomatias Möllendorff, 1885 and its relatives (Páll-Gergely et al. 2015) resulted in the recognition of four genera, which agree in the (usually slender) turriform, spindle-shaped or almost cylindrical shell and the regularly ribbed teleoconch, except sometimes for the last half whorl. The genus Vargapupa Páll-Gergely, 2015, which differs from Pseudopomatias by possessing a basal keel, includes two species, one from Vietnam, and another from Laos.

A new species of the genus Bryodemella (s. str.) Yin, 1982 from China (Orthoptera: Acridoidea: Oedipodidae).

PubMed

Zhang, Yu-Long; Zhi, Yong-Chao; Zhang, Dao-Chuan

2018-04-23

A new species (i.e. Bryodemella (s. str.) rufifemura sp. nov. from China is described in this paper. It is similar to Bryodemella (s. str.) diamesum (Bei-Bienko, 1930), but differs from the latter by red inner side of hind femur, median keel of pronotum indistinct in metazoan, and vertical diameter of eye shorter than subocular groove in female.  The type specimens are deposited in the Museum of Hebei University (MHU), China.

Trauma is Danger

DTIC Science & Technology

2011-01-01

self interactions and thereby neglect most traumatic injuries , the Danger model abandons this classical concept [ 2 ]. The Danger model theorizes that...June 2011 References 1. Keel M, Trentz O: Pathophysiology of polytrauma. Injury 2005, 36:691-709. 2 . Matzinger P: Tolerance, danger, and the extended... ischemia - reperfusion . J Exp Med 2005, 201:1135-1143. 27. Huang LF, Yao YM, Zhang LT, Dong N, Yu Y, Sheng ZY: The effect of high- mobility group box 1

Defense Small Business Innovation Research Program (SBIR). Volume 1. Army Abstracts of Phase 1 Awards from FY 1988 SBIR Solicitation

DTIC Science & Technology

1989-05-01

CONSTRUCTION). CONCEPT ANALYSIS CORP 14789 KEEL ST PLYMOUTH, MI 48170 CONTRACT NUMBER: DAHO -88-C-0942 DR’S WALDEN & GLANCE TITLE: MISSILE GEOMETRY PACKAGE TOPIC...COUNTING STUDY CAN BE UTILIZED TO EVALUATE THE EFFECTIVENESS OF AN EXPLOSION MONITORING SYSTEM. E SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM - PHASE... EXPLOSIVE OR GROUND PENETRATING MUNITIONS ARE TO BE EVALUATED. IN THAT CASE THE SYSTEM WILL BE ENHANCED WITH SEISMIC SENSORS. THE SEISMIC SIGNALS MAY

A Determination of Air-Sea Gas Exchange and Upper Ocean Biological Production From Five Noble Gases and Tritiugenic Helium-3

DTIC Science & Technology

2007-09-01

limitations due to so-called "bottle effects" produced by confining production to a single bottle, eliminating grazers, trace metal contamination from the...1, b - 2/3) (Levich, 1962 ) or can be determined by modeling studies of characteristic bubble populations (a = 0.7, b = 0.35) (Keeling, 1993). In this...artifacts associated with the early sampling method. In addition, some of the samples with large supersaturations may have been contaminated with

Dual keel Space Station payload pointing system design and analysis feasibility study

NASA Technical Reports Server (NTRS)

Smagala, Tom; Class, Brian F.; Bauer, Frank H.; Lebair, Deborah A.

1988-01-01

A Space Station attached Payload Pointing System (PPS) has been designed and analyzed. The PPS is responsible for maintaining fixed payload pointing in the presence of disturbance applied to the Space Station. The payload considered in this analysis is the Solar Optical Telescope. System performance is evaluated via digital time simulations by applying various disturbance forces to the Space Station. The PPS meets the Space Station articulated pointing requirement for all disturbances except Shuttle docking and some centrifuge cases.

A new species of Oileus Kaup (Coleoptera, Passalidae) from Guatemala, with a key to the species of the genus

PubMed Central

Cano, Enio B.; Schuster, Jack C.

2012-01-01

Abstract Oileus gasparilomi sp. n. is described from nine specimens from the mountains of Quiché in Guatemala, from cloud forest at 1795 m elevation. This represents the second species of the genus for Guatemala, differing from the closely related Mexican species Oileus rimator (Truqui) in having a straight anterior clypeal border, the postocular sulcus divided by a keel and the pronotum almost straight (not clearly bilobed). A key to the species of Oileus is given. PMID:22679385

Know Yourself, Define Your Enemy: Presidential Rhetoric and American Strategic Culture

DTIC Science & Technology

2016-06-10

Commander Gareth Prendergast received his commission from the Queen in 2000. Upon qualification in role as a Navigator on the Tornado GR4 fighter...On returning to the Tornado , he successfully deployed the first UK combat air assets in support of the humanitarian crisis in Iraq and...subsequently commanded the RAF Tornado detachment. Wing Commander Prendergast read for a Masters in International Law at Lancaster University and holds a Bachelor degree with honors from Keele University in International Relations.

Identification (ID) Cards for Members of the Uniformed Services, Their Dependents, and Other Eligible Individuals

DTIC Science & Technology

1992-12-30

Encl 5) Cayman Islands CJ Central African Republic CT Chad CD Chile CI China CH Christmas Island KT Clipperton Islands IP Cocos (Keeling) Islands CK...PA Puerto Rico PR Rhode Island RI South Carolina SC South Dakota SD Tennessee TN Federated States of Marshall Islands , Palau TT Texas TX Utah UT...Vermont VT Virginia VA Virgin Islands VI Washington WA West Virginia WV Wisconsin WI Wyoming WY Block 17. ZIP Code. Enter the correct nine-digit ZIP Code

Components of High-Level Vision: A Cognitive Neuroscience Analysis and Accounts of Neurological Syndromes

DTIC Science & Technology

1989-02-28

evidence that only one region of space can be attended to at a time (K. Cave and Kosslyn, in press; Downing and Pinker, 1985; LaBerge , 1983; Larsen...97131 New York NY 10027 Dr Steven Grossberg Or Howard Hock 50 Hyde Street Department of Psychology Newton Highland MA 02161 Florida Atlantic University...hU.m Unterstty University r Georgia Pittsburg* l 71213 Athens GA,- AI2-? Dr Stuart 9lapp Dr Steven W. Keele Department of Psychology Psychology

Arctic Acoustic Workshop Proceedings, 14-15 February 1989.

DTIC Science & Technology

1989-06-01

measurements. The measurements reported by Levine et al. (1987) were taken from current and temperature sensors moored in two triangular grids . The internal...requires a resampling of the data series on a uniform depth-time grid . Statistics calculated from the resampled series will be used to test numerical...from an isolated keel. Figure 2: 2-D Modeling Geometry - The model is based on a 2-D Cartesian grid with an axis of symmetry on the left. A pulsed

Defense AT&L (Volume 35, Number 5, September-October 2006)

DTIC Science & Technology

2006-10-01

percent of production. The criti- Defense AT&L: September-October 2006 8 cal path elements driving the IOT &E schedule are not pro- duction hardware...reduced costs, and successful completion of work in the scheduled time. 30 The Commodity Approach to Aircraft Protection Systems Capt. Bill Chubb, USN The...piece of Littoral Combat Ship Two during the ship’s keel laying ceremony. The Navy’s second Littoral Combat Ship is scheduled for commissioning in

The rights of the medically uninsured: an analysis of social justice and disparate health outcomes.

PubMed

Chandler, Michelle

2006-01-01

As technological advances in the United States continue to improve the effectiveness of medical interventions, expectations among Americans of both improved health and extended life expectancy have also increased. At the same time, many of the population continue to lack the insurance necessary to access even the most basic healthcare services (Institute of Medicine, 2004; Tunzi, 2004; Saha & Bindman, 2001). With approximately 18,000 avoidable deaths attributed annually to inadequate medical coverage and 43.6 million individuals currently without insurance benefits, the need to address the disparity in access to treatment and a means of social justice in the distribution of health care is all too clear (Crispen & Whalen, 2004). As a nation relying on market mechanisms to regulate the costs and quality of available health resources (Baldor, 2003; Saha&Bindman, 2001), the welfare of society as a whole may soon be threatened by the provision of marginal services to a select minority as increasing numbers of the uninsured continue to experience less favorable clinical outcomes and higher mortality rates (Tunzi, 2004; Litaker & Cebul, 2003; Jackson, 2001; Sox, Burstin, Edwards, O'Neil et al., 1998). The author will first examine the consequences of being among the growing number of uninsured individuals in the United States. Attention will then be given to exploring the social justice issues inherent in this critical problem and evaluating these issues through the perspective of both libertarian and feminist theory. Using these theories, innovative strategies for attaining distributive justice in the provision of health care will be offered with recommendations for utilizing these alternative approaches to develop and implement future health policy.

Evaluation of 6-([18F] fluoroacetamido)-1-hexanoic-anilide (18F-FAHA) as imaging probe in tumor xenograft mice model

NASA Astrophysics Data System (ADS)

Li, Fiona; Cho, Sung Ju; Yu, Lihai; Hudson, Robert H. E.; Luyt, Leonard G.; Pin, Christopher L.; Kovacs, Michael S.; Koropatnick, James; Lee, Ting-Yim

2016-03-01

Alteration in genetic expression is as important as gene mutation in cancer development and proliferation. Epigenetic changes affect gene expression without altering the DNA sequence. Histone deacetylase (HDAC), an enzyme facilitating histone remodelling, can lead to silencing of tumor suppressor genes making HDAC inhibitors viable anticancer drugs against tumors with increased activity of the enzyme. In this study we evaluated 18F-fluroacetamido-1-hexanoicanilide (18F-FAHA), an artificial HDAC substrate, as imaging probe of HDAC activity of human tumor xenografts in immunocompromised host mice. Human breast and melanoma cell lines, MDA-MB-468 and MDA-MB-435 respectively, known to overexpress HDAC activity were xenografted into immunocompromised mice and HDAC activity was imaged using 18F-FAHA. The melanoma group was treated with saline, SAHA (suberoylanilide hydroxamic acid, an approved anticancer HDAC inhibitor) in DMSO, or DMSO as positive control. Tracer kinetic modelling and SUV were used to estimate HDAC activity from dynamic PET data. Both breast tumor and melanoma group showed great variability in binding rate constant (BRC) of 18F-FAHA suggesting highly variable inter- and intra-tumoral HDAC activity. For the SAHA treated melanoma group, HDAC activity, as monitored by BRC of 18F-FAHA, decreased more than the two (positive and negative) control groups but not tumor growth. Our preliminary study showed that noninvasive PET imaging with 18F-FAHA has the potential to identify patients for whom treatment with HDAC inhibitors are appropriate, to assess the effectiveness of that treatment as an early marker of target reduction, and also eliminate the need for invasive tissue biopsy to individualize treatment.

Chromatin remodeling modulates radiosensitivity of the daughter cells derived from cell population exposed to low- and high-LET irradiation

PubMed Central

Chen, Xiaoyan; Zhu, Lin; Zhang, Hang; Wang, Chen; Shao, Chunlin

2017-01-01

Radiation effects are dependent of linear energy transfer (LET), but it is still obscure whether the daughter cells (DCs) derived from irradiated population are radioresistance and much less the underlying mechanism. With the measurements of survival, proliferation and γH2AX foci, this study shows that the DCs from γ-ray irradiated cells (DCs-γ) became more radioresistant than its parent control without irradiation, but the radiosensitivity of DCs from α-particle irradiated cells (DCs-α) was not altered. After irradiation with equivalent doses of γ-rays and α-particles, the foci number of histone H3 lysine 9 dimethylation (H3K9me3) and the activity of histone deacetylase (HDAC) in DCs-γ was extensively higher than these in DCs-α and its parent control, indicating that a higher level of heterochromatin was formed in DCs-γ but not in DCs-α. Treatment of cells with SAHA (an inhibitor of HDAC) decreased the level of heterochromatin domains by inhibiting the expressions of H3K9m3 and HP-1a proteins and triggering the expression of acetylated core histone H3 (Ac-H3). When cells were treated with SAHA, the radioresistance phenotype of DCs-γ was eliminated so that the radiosensitivities of DCs-γ, DCs-α and their parent cells approached to same levels. Our current results reveal that γ-rays but not α-particles could induce chromatin remodeling and heterochromatinization which results in the occurrence of radioresistance of DCs, indicating that the combination treatment of irradiation and HDAC inhibitor could serve as a potential cancer therapy strategy, especially for the fraction radiotherapy of low-LET irradiation. PMID:28881774

Sequential treatment of CD34+ cells from patients with primary myelofibrosis with chromatin-modifying agents eliminate JAK2V617F-positive NOD/SCID marrow repopulating cells

PubMed Central

Wang, Xiaoli; Zhang, Wei; Tripodi, Joseph; Lu, Min; Xu, Mingjiang; Najfeld, Vesna; Li, Yan

2010-01-01

Because primary myelofibrosis (PMF) originates at the level of the pluripotent hematopoietic stem cell (HSC), we examined the effects of various therapeutic agents on the in vitro and in vivo behavior of PMF CD34+ cells. Treatment of PMF CD34+ cells with chromatin-modifying agents (CMAs) but not hydroxyurea, Janus kinase 2 (JAK2) inhibitors, or low doses of interferon-α led to the generation of greater numbers of CD34+ chemokine (C-X-C motif) receptor (CXCR)4+ cells, which were capable of migrating in response to chemokine (C-X-C motif) ligand (CXCL)12 and resulted in a reduction in the proportion of hematopoietic progenitor cells (HPCs) that were JAK2V617F+. Furthermore, sequential treatment of PMF CD34+ cells but not normal CD34+ cells with decitabine (5-aza-2′-deoxycytidine [5azaD]), followed by suberoylanilide hydroxamic acid (SAHA; 5azaD/SAHA), or trichostatin A (5azaD/TSA) resulted in a higher degree of apoptosis. Two to 6 months after the transplantation of CMAs treated JAK2V617F+ PMF CD34+ cells into nonobese diabetic/severe combined immunodeficient (SCID)/IL-2Rγnull mice, the percentage of JAK2V617F/JAK2total in human CD45+ marrow cells was dramatically reduced. These findings suggest that both PMF HPCs, short-term and long-term SCID repopulating cells (SRCs), are JAK2V617F+ and that JAK2V617F+ HPCs and SRCs can be eliminated by sequential treatment with CMAs. Sequential treatment with CMAs, therefore, represents a possible effective means of treating PMF at the level of the malignant SRC. PMID:20858855

Differential effects of histone deacetylase inhibitors on cellular drug transporters and their implications for using epigenetic modifiers in combination chemotherapy.

PubMed

Valdez, Benigno C; Li, Yang; Murray, David; Brammer, Jonathan E; Liu, Yan; Hosing, Chitra; Nieto, Yago; Champlin, Richard E; Andersson, Borje S

2016-09-27

HDAC inhibitors, DNA alkylators and nucleoside analogs are effective components of combination chemotherapy. To determine a possible mechanism of their synergism, we analyzed the effects of HDAC inhibitors on the expression of drug transporters which export DNA alkylators. Exposure of PEER lymphoma T-cells to 15 nM romidepsin (Rom) resulted in 40%-50% reduction in mRNA for the drug transporter MRP1 and up to ~500-fold increase in the MDR1 mRNA within 32-48 hrs. MRP1 protein levels concomitantly decreased while MDR1 increased. Other HDAC inhibitors - panobinostat, belinostat and suberoylanilide hydroxamic acid (SAHA) - had similar effects on these transporters. The protein level of MRP1 correlated with cellular resistance to busulfan and chlorambucil, and Rom exposure sensitized cells to these DNA alkylators. The decrease in MRP1 correlated with decreased cellular drug export activity, and increased level of MDR1 correlated with increased export of daunorubicin. A similar decrease in the level of MRP1 protein, and increase in MDR1, were observed when mononuclear cells derived from patients with T-cell malignancies were exposed to Rom. Decreased MRP1 and increased MDR1 expressions were also observed in blood mononuclear cells from lymphoma patients who received SAHA-containing chemotherapy in a clinical trial. This inhibitory effect of HDAC inhibitors on the expression of MRP1 suggests that their synergism with DNA alkylating agents is partly due to decreased efflux of these alkylators. Our results further imply the possibility of antagonistic effects when HDAC inhibitors are combined with anthracyclines and other MDR1 drug ligands in chemotherapy.

Analysing the floral elements of the lost tree of Easter Island: a morphometric comparison between the remaining ex-situ lines of the endemic extinct species Sophora toromiro.

PubMed

Püschel, Thomas A; Espejo, Jaime; Sanzana, María-José; Benítez, Hugo A

2014-01-01

Sophora toromiro (Phil) Skottsb. is a species that has been extinct in its natural habitat Easter Island (Rapa Nui) for over 50 years. However, seed collections carried out before its extinction have allowed its persistence ex-situ in different botanical gardens and private collections around the world. The progenies of these diverse collections have been classified in different lines, most of them exhibiting high similarity as corroborated by molecular markers. In spite of this resemblance observed between the different lines, one of them (Titze) has dissimilar floral elements, thus generating doubts regarding its species classification. The floral elements (wing, standard and keel) belonging to three different S. toromiro lines and two related species were analyzed using geometric morphometrics. This method was applied in order to quantify the floral shape variation of the standard, wing, and keel between the different lines and control species. Geometric morphometrics analyses were able to distinguish the floral elements at both intra (lines) and inter-specific levels. The present results are on line with the cumulative evidence that supports the Titze line as not being a proper member of the S. toromiro species, but probably a hybridization product or even another species of the Edwardsia section. The reintroduction programs of S. toromiro should consider this information when assessing the authenticity and origin of the lines that will be used to repopulate the island.

A new species of the Southeast Asian genus Opisthotropis (Serpentes: Colubridae: Natricinae) from western Hunan, China

PubMed Central

Ren, Jin-Long; Wang, Kai; Jiang, Ke; Guo, Peng; Li, Jia-Tang

2017-01-01

A new species of natricine snake of the Southeast Asian genus Opisthotropis Günther, 1872 is described from western Hunan Province of China based on both mitochondrial DNA and morphological data. The new species is morphologically most similar and genetically most closely related to O. cheni Zhao, 1999 and O. latouchii (Boulenger, 1899), but possesses considerable genetic divergence (p-distance 5.1%-16.7%) and can be differentiated from all other congeners by a combination of the following morphological characters: (1) body size large (total length 514-586 mm) and strongly built; (2) dorsal scale rows 17 throughout, feebly keeled anteriorly and moderately keeled posteriorly; (3) ventral scales 147-152, subcaudal scales 54-62; (4) preocular absent, loreal elongated and touching orbit; (5) supralabials 8-9, fifth and sixth entering obit; (6) anterior temporals short, length 1.74-2.04 times longer than width; (7) maxillary teeth subequal, 28-30; (8) dorsal surface of head with distinct irregular yellow stripes and markings edged with ochre; (9) body with clear black and yellow longitudinal streaks, partly fused to several lighter patches or thicker stripes anteriorly; and (10) venter pale yellow, with asymmetric blackish speckles along outer margin. We present an updated diagnostic key to all members of the genus Opisthotropis, and recommendations on the ecological study for the group are provided. PMID:29181900

Evolution of clog formation with time in columns permeated with synthetic landfill leachate

NASA Astrophysics Data System (ADS)

VanGulck, Jamie F.; Rowe, R. Kerry

2004-11-01

Laboratory column tests conducted to gain insight regarding the biological and chemical clogging mechanisms in a porous medium are presented. To seed the porous medium with landfill bacteria, a mixture of Keele Valley Landfill and synthetic leachate permeated through the column under anaerobic conditions for the first 9 days of operation. After this, 100% synthetic leachate was used. The synthetic leachate approximated Keele Valley Landfill leachate in chemical composition but contained negligible suspended solids and bacteria compared with real leachate. The removal of volatile fatty acids (VFAs), primarily acetate, in leachate as it passed through the medium was highly correlated with the precipitation of calcium carbonate (CaCO 3(s)) from solution. The columns experienced a decrease in drainable porosity from an initial value of about 0.38 to less than 0.1 after steady state chemical oxygen demand (COD) removal, resulting in a five-order magnitude decrease in hydraulic conductivity. The decrease in drainable porosity prior to steady state COD removal was primarily due to the growth of a biofilm on the medium surface. After steady state COD removal, calcium precipitation was at least equally responsible for the decrease in drainable porosity as biofilm growth. Clog composition analyses showed that CaCO 3(s) was the dominant clog constituent and that 99% of the carbonate in the clog material was bound to calcium.

Advanced technology commercial fuselage structure

NASA Technical Reports Server (NTRS)

Ilcewicz, L. B.; Smith, P. J.; Walker, T. H.; Johnson, R. W.

1991-01-01

Boeing's program for Advanced Technology Composite Aircraft Structure (ATCAS) has focused on the manufacturing and performance issues associated with a wide body commercial transport fuselage. The primary goal of ATCAS is to demonstrate cost and weight savings over a 1995 aluminum benchmark. A 31 foot section of fuselage directly behind the wing to body intersection was selected for study purposes. This paper summarizes ATCAS contract plans and review progress to date. The six year ATCAS program will study technical issues for crown, side, and keel areas of the fuselage. All structural details in these areas will be included in design studies that incorporate a design build team (DBT) approach. Manufacturing technologies will be developed for concepts deemed by the DBT to have the greatest potential for cost and weight savings. Assembly issues for large, stiff, quadrant panels will receive special attention. Supporting technologies and mechanical tests will concentrate on the major issues identified for fuselage. These include damage tolerance, pressure containment, splices, load redistribution, post-buckled structure, and durability/life. Progress to date includes DBT selection of baseline fuselage concepts; cost and weight comparisons for crown panel designs; initial panel fabrication for manufacturing and structural mechanics research; and toughened material studies related to keel panels. Initial ATCAS studies have shown that NASA's Advanced Composite Technology program goals for cost and weight savings are attainable for composite fuselage.

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

Socolow, R.H.; Anderson, D.; Harte, J.

Thirteen papers are included in this volume. The titles and authors are: From Physics to Development Strategies by Jose Goldemberg; Rewards and Penalties of Monitoring the Earth by Charles D. Keeling; Science and Nonscience Concerning Human-Caused Climate Warming by J. D. Mahlman; Consumption of Materials in the United States, 1990--1995 by Grecia Matos and Lorie Wagner; Future Technologies for Energy-Efficient Iron and Steel Making by Jeroen de Beer, Ernst Worrell, and Kornelis Blok; The O{sub 2} Balance of the Atmosphere: A Tool for Studying the Fate of Fossil Fuel CO{sub 2} by Michael L. Bender, Mark Battle, and Ralph F.more » Keeling; Mexican Electric End-Use Efficiency: Experiences to Date by Rafael Friedmann and Claudia Sheinbaum; Drinking Water in Developing Countries by Ashok Gadgil; Engineering-Economic Studies of Energy Technologies to Reduce Greenhouse Gas Emissions: Opportunities and Challenges by Marilyn A. Brown, Mark D. Levine, Joseph P. Romm, Arthur H. Rosenfeld, and Jonathan G. Koomey; Climate Change Mitigation in the Energy and Forestry Sectors of Developing Countries by Jayant A. Sathaye and N. H. Ravindranath; Toward a Productive Divorce: Separating DOE Cleanups from Transition Assistance by M. Russell; Recycling Metals for the Environment by Iddo K. Wernick and Nickolas J. Themelis; and Environmentally Conscious Chemical Process Design by J. A. Cano-Ruiz and G. J. McRae.« less

Correlates of weapon carrying in school among adolescents in three countries.

PubMed

Stickley, Andrew; Koyanagi, Ai; Koposov, Roman; Blatný, Marek; Hrdlička, Michal; Schwab-Stone, Mary; Ruchkin, Vladislav

2015-01-01

To determine the factors associated with weapon carrying in school among Czech, Russian, and US adolescents. Logistic regression was used to analyze data drawn from the Social and Health Assessment (SAHA). Violent behavior (perpetration / victimization) was linked to adolescent weapon carrying in all countries. Substance use was associated with weapon carrying among boys in all countries. Greater parental warmth reduced the odds for weapon carrying among Czech and Russian adolescents. Associating with delinquent peers was important for weapon carrying only among US adolescents. Factors associated with weapon carrying in school vary among countries although violent behavior and substance use may be associated with weapon carrying across countries.

Blackbody emission from laser breakdown in high-pressure gases.

PubMed

Bataller, A; Plateau, G R; Kappus, B; Putterman, S

2014-08-15

Laser induced breakdown of pressurized gases is used to generate plasmas under conditions where the atomic density and temperature are similar to those found in sonoluminescing bubbles. Calibrated streak spectroscopy reveals that a blackbody persists well after the exciting femtosecond laser pulse has turned off. Deviation from Saha's equation of state and an accompanying large reduction in ionization potential are observed at unexpectedly low atomic densities-in parallel with sonoluminescence. In laser breakdown, energy input proceeds via excitation of electrons whereas in sonoluminescence it is initiated via the atoms. The similar responses indicate that these systems are revealing the thermodynamics and transport of a strongly coupled plasma.

Blackbody Emission from Laser Breakdown in High-Pressure Gases

NASA Astrophysics Data System (ADS)

Bataller, A.; Plateau, G. R.; Kappus, B.; Putterman, S.

2014-08-01

Laser induced breakdown of pressurized gases is used to generate plasmas under conditions where the atomic density and temperature are similar to those found in sonoluminescing bubbles. Calibrated streak spectroscopy reveals that a blackbody persists well after the exciting femtosecond laser pulse has turned off. Deviation from Saha's equation of state and an accompanying large reduction in ionization potential are observed at unexpectedly low atomic densities—in parallel with sonoluminescence. In laser breakdown, energy input proceeds via excitation of electrons whereas in sonoluminescence it is initiated via the atoms. The similar responses indicate that these systems are revealing the thermodynamics and transport of a strongly coupled plasma.

The Coast Artillery Journal. Volume 60, Number 1, January 1924

DTIC Science & Technology

1924-01-01

mainmast toppled just befol’e the ship turned turtle . Of the total of twenty-four 600 lb. bombs which were dropped from 10.000 feet, seventeen functioned...eighteen minutes after being ,truck, the rirg;lIia turned turtle to port and began to settle. The (’onfined air burst the sealllS along her keel. At 12 :2...generally as- sumed, not stated, and is for that reason nebulous and uncertain. 2. Economy of force--concentration of effectives, avoidance of dissemination

Survey of Technology with Possible Applications to United States Coast Guard Buoy Tenders. Volume 2. Literature Abstracts.

DTIC Science & Technology

1987-09-01

WORK VESSELS TECHNICAL AND OVERVIEW ARTICLES Arendt, John W., "A Specialty Item (The anchor-handling tug on the marine pipeline)", Fourth International...yard. Marier, John B. "What’s Ahead in Shallow Water Seismic Vessel Design", Ocean Industry, June 1983, (’Digicon Definition’) "Marine Fabricators...paper indicated that such a system would out-perform bilge keels by a substantial margin, while costing 20% less. A-32 Lewison , G.R.G., "Optimum Design of

Sensory Sensitivities and Discriminations and Their Roles in Aviation

DTIC Science & Technology

1992-11-30

SO YORK U N IVE E RS IT Y FACULTY OF ARTS 4700 KEELE STREET * NORTH YORK 9 ONTARIO * CANADA @ M3J 1P3 macaque lateral geniculate nucleus severely...Brain 110, 1675-1698. 35. Merigan WH & Maunsell JHR (1990) Macaque vision after magnocellular lateral geniculate lesions. Visual Neuroscience 5, 347-352...order. In the first experiment, the subject’s task was to judge whether the stimulus would arrive sooner or later than the mean of the stimulus set (of 64

Hair loss in women.

PubMed

Camacho-Martínez, Francisco M

2009-03-01

Female pattern hair loss (FPHL) is a clinical problem that is becoming more common in women. Female alopecia with androgen increase is called female androgenetic alopecia (FAGA) and without androgen increase is called female pattern hair loss. The clinical picture of typical FAGA begins with a specific "diffuse loss of hair from the parietal or frontovertical areas with an intact frontal hairline." Ludwig called this process "rarefaction." In Ludwig's classification of hair loss in women, progressive type of FAGA, 3 patterns were described: grade I or minimal, grade II or moderate, and grade III or severe. Ludwig also described female androgenetic alopecia with male pattern (FAGA.M) that should be subclassified according to Ebling's or Hamilton-Norwood's classification. FAGA.M may be present in 4 conditions: persistent adrenarche syndrome, alopecia caused by an adrenal or an ovarian tumor, posthysterectomy, and as an involutive alopecia. A more recent classification (Olsen's classification of FPHL) proposes 2 types: early- and late-onset with or without excess of androgens in each. The diagnosis of FPHL is made by clinical history, clinical examination, wash test, dermoscopy, trichoscan, trichograms and laboratory test, especially androgenic determinations. Topical treatment of FPHL is with minoxidil, 2-5% twice daily. When FPHL is associated with high levels of androgens, systemic antiandrogenic therapy is needed. Persistent adrenarche syndrome (adrenal SAHA) and alopecia of adrenal hyperandrogenism is treated with adrenal suppression and antiandrogens. Adrenal suppression is achieved with glucocorticosteroids. Antiandrogens therapy includes cyproterone acetate, drospirenone, spironolactone, flutamide, and finasteride. Excess release of ovarian androgens (ovarian SAHA) and alopecia of ovarian hyperandrogenism is treated with ovarian suppression and antiandrogens. Ovarian suppression includes the use of contraceptives containing an estrogen, ethinylestradiol, and a

A Review of the Growth Habits and Restoration Issues for Clitoria fragrans and Polygonella basiramia

DTIC Science & Technology

2007-06-01

ERDC/CRREL TR-07-6 2 Figure 1. Alpha impact area on Avon Park Air Force Range, showing the locations of Clitoria fragrans ( pigeon wing • ) and...herb belonging to the pea family (Fig. 3–5). One of about 35 species in the Clitoria genus (USDA 2007), C. fragrans is limited mainly to the rapidly...chasmogamous flowers have a typical zygomorphic pea family arrangement, with a large 3.5- to 5-cm-long wing petal and a small white keel petal forming a boat

Space Shuttle Project

NASA Image and Video Library

1995-10-20

A Great Blue Heron seems oblivious to the tremendous spectacle of light and sound generated by a Shuttle liftoff, as the Space Shuttle Columbia (STS-73) soars skyward from Launch Pad 39B. Columbia's seven member crew's mission included continuing experimentation in the Marshall managed payloads including the United States Microgravity Laboratory 2 (USML-2) and the keel-mounted accelerometer that characterizes the very low frequency acceleration environment of the orbiter payload bay during space flight, known as the Orbital Acceleration Research Experiment (OARE).

KSC-02pp1760

NASA Image and Video Library

2002-11-10

KENNEDY SPACE CENTER, FLA. - Mr. and Mrs. Sean O'Keefe (center) pose with officials of the Chickasaw Nation. Second from left is Lt. Gov. Jefferson Keel with his wife, Carol (far left). Second from right is Gov. Bill Anoatubby with his wife, Janice (far right). STS-113 Mission Specialist John Herrington is a tribally enrolled Chickasaw and the world's first Native American astronaut. Kennedy Space Center hosted more than 350 Native Americans in STS-113 prelaunch events surrounding the historic mission assignment of Herrington.

Maternal Exposure of Rats to Isoflurane during Late Pregnancy Impairs Spatial Learning and Memory in the Offspring by Up-Regulating the Expression of Histone Deacetylase 2.

PubMed

Luo, Foquan; Hu, Yan; Zhao, Weilu; Zuo, Zhiyi; Yu, Qi; Liu, Zhiyi; Lin, Jiamei; Feng, Yunlin; Li, Binda; Wu, Liuqin; Xu, Lin

2016-01-01

Increasing evidence indicates that most general anesthetics can harm developing neurons and induce cognitive dysfunction in a dose- and time-dependent manner. Histone deacetylase 2 (HDAC2) has been implicated in synaptic plasticity and learning and memory. Our previous results showed that maternal exposure to general anesthetics during late pregnancy impaired the offspring's learning and memory, but the role of HDAC2 in it is not known yet. In the present study, pregnant rats were exposed to 1.5% isoflurane in 100% oxygen for 2, 4 or 8 hours or to 100% oxygen only for 8 hours on gestation day 18 (E18). The offspring born to each rat were randomly subdivided into 2 subgroups. Thirty days after birth, the Morris water maze (MWM) was used to assess learning and memory in the offspring. Two hours before each MWM trial, an HDAC inhibitor (SAHA) was given to the offspring in one subgroup, whereas a control solvent was given to those in the other subgroup. The results showed that maternal exposure to isoflurane impaired learning and memory of the offspring, impaired the structure of the hippocampus, increased HDAC2 mRNA and downregulated cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) mRNA, N-methyl-D-aspartate receptor 2 subunit B (NR2B) mRNA and NR2B protein in the hippocampus. These changes were proportional to the duration of the maternal exposure to isoflurane and were reversed by SAHA. These results suggest that exposure to isoflurane during late pregnancy can damage the learning and memory of the offspring rats via the HDAC2-CREB -NR2B pathway. This effect can be reversed by HDAC2 inhibition.

ELEVATION OF C-FLIP IN CASTRATE-RESISTANT PROSTATE CANCER ANTAGONIZES THERAPEUTIC RESPONSE TO ANDROGEN-RECEPTOR TARGETED THERAPY

PubMed Central

McCourt, Clare; Maxwell, Pamela; Mazzucchelli, Roberta; Montironi, Rodolfo; Scarpelli, Marina; Salto-Tellez, Manuel; O’Sullivan, Joe M.; Longley, Daniel B.; Waugh, David J.J.

2012-01-01

Purpose To characterize the importance of cellular Fas-associated death domain (FADD)-like interleukin 1β-converting enzyme (FLICE) inhibitory protein (c-FLIP), a key regulator of caspase 8 (FLICE)-promoted apoptosis, in modulating the response of prostate cancer (CaP) cells to androgen receptor (AR)-targeted therapy. Experimental Design c-FLIP expression was characterized by immunohistochemical analysis of prostatectomy tissue. The functional importance of c-FLIP to survival and modulating response to bicalutamide was studied by molecular and pharmacological interventions. Results c-FLIP expression was increased in high-grade prostatic intra-epithelial neoplasia (HGPIN) and CaP tissue relative to normal prostate epithelium (P<0.001). Maximal c-FLIP expression was detected in castrate-resistant CaP (CRPC) (P<0.001). In vitro, silencing of c-FLIP induced spontaneous apoptosis and increased 22Rv1 and LNCaP cell sensitivity to bicalutamide, determined by flow cytometry, PARP cleavage and caspase activity assays. The histone deacetylase inhibitors (HDACi), droxinostat and SAHA, also down-regulated c-FLIP expression, induced caspase-8 and caspase-3/7 mediated apoptosis and increased apoptosis in bicalutamide-treated cells. Conversely, the elevated expression of c-FLIP detected in the CRPC cell line VCaP underpinned their insensitivity to bicalutamide and SAHA in vitro. However, knockdown of c-FLIP induced spontaneous apoptosis in VCaP cells, indicating its relevance to cell survival and therapeutic resistance. Conclusion c-FLIP reduces the efficacy of AR-targeted therapy and maintains the viability of CaP cells. A combination of HDACi with androgen-deprivation therapy (ADT) may be effective in early-stage disease, using c-FLIP expression as a predictive biomarker of sensitivity. Direct targeting of c-FLIP however may be relevant to enhance the response of existing and novel therapeutics in CRPC. PMID:22623731

[Research on the identification method of LTE condition in the laser-induced plasma].

PubMed

Fan, Juan-juan; Huang, Dan; Wang, Xin; Zhang, Lei; Ma, Wei-guang; Dong, Lei; Yin, Wang-bao; Jia, Suo-tang

2014-12-01

Because of the poor accuracy of the commonly used Boltzmann plot method and double-line method, the Boltzmann-Maxwell distribution combined with the Saha-Eggert formula is proposed to improve the measurement accuracy of the plasma temperature; the simple algorithm for determining the linewidth of the emission line was established according to the relationship between the area and the peak value of the Gaussian formula, and the plasma electron density was calculated through the Stark broadening of the spectral lines; the method for identifying the plasma local thermal equilibrium (LTE) condition was established based on the McWhirter criterion. The experimental results show that with the increase in laser energy, the plasma temperature and electron density increase linearly; when the laser energy changes within 127~510 mJ, the plasma electron density changes in the range of 1.30532X10(17)~1.87322X10(17) cm(-3), the plasma temperature changes in the range of 12586~12957 K, and all the plasma generated in this experiment meets the LTE condition threshold according to the McWhirter criterion. For element Al, there exist relatively few observable lines at the same ionization state in the spectral region of the spectrometer, thus it is unable to use the Boltzmann plane method to calculate temperature. One hundred sets of Al plasma spectra were used for temperature measurement by employing the Saha-Boltzmann method and the relative standard deviation (RSD) value is 0.4%, and compared with 1.3% of the double line method, the accuracy has been substantially increased. The methods proposed can be used for rapid plasma temperature and electron density calculation, the LTE condition identification, and are valuable in studies such as free calibration, spectral effectiveness analysis, spectral temperature correction, the best collection location determination, LTE condition distribution in plasma, and so on.

Even Keeled: A Practical Approach to Living with Someone with Bipolar II Disorder

ERIC Educational Resources Information Center

Neal, Philip

2008-01-01

Bipolar II disorder can be better understood and addressed by applying appropriate psychological principles. One such principle is that, on a very basic level, emotion is neither good nor bad. It is however, the expressed reaction of the mind to its environment. From this perspective, emotion is very useful. Emotionality often gets a bad rap as…

Stability of Nonstationary Cooling of Pure Hydrogen Gas with Respect to the Number of Discrete Levels Taken into Account

NASA Astrophysics Data System (ADS)

Belova, O. M.; Bychkov, K. V.

2018-03-01

The effect of the number K of atomic hydrogen levels taken into account on the cooling of the gas behind a shock front is studied. The calculations are done for the conditions in the atmospheres of long-period Mira Ceti type variables. K ranges from 2 to 25. The electron temperature Te(t; K) and ionization state x(r,K) asymptotically approach limiting functions Te(t) and x(t) that are independent of K. After the maximum electron temperature is reached, a partial equilibrium phase sets in, during which the populations of the highly excited discrete levels with principal quantum numbers ≥ 8 obey the Saha equation for the instantaneous electron temperature and density.

Role of growth media and chemical enhancers in secondary metabolites production from Aspergillus carbonarius (NRL-369) and their pharmaceutical potentials.

PubMed

Khan, Abid Ali; Bacha, Nafess; Ahmad, Bashir; Cox, R J; Bakht, Jehan

2016-07-01

The present study investigates the effect of different growth media and chemical enhancer on silent genes in Aspergillus carbonarius (NRL-369) for secondary metabolites production and its in vitro biological activities. Results revealed that Aspergillus carbonarius (NRL-369) grown in Czapeak yeast extract broth medium produced more metabolites compared with other media. Chemical epigenetic modifiers (suberoyl-anilide hydroxamic acid (SAHA) and 5-azacytidine (5-AZA) at concentration of 15mM were effective for the expression of silent genes resulting in increased secondary metabolites production. Secondary metabolites extracted in ethyl acetate and fractionized in n-Hexane showed variable degree of growth inhibitions of the tested microorganisms. Similarly, these samples were also active against brine shrimps and Lemna.

Galilean symmetry in a noncommutative gravitational quantum well

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

Saha, Anirban

2010-06-15

A thorough analysis of Galilean symmetries for the gravitational well problem on a noncommutative plane is presented. A complete closure of the one-parameter centrally extended Galilean algebra is realized for the model. This implies that the field theoretic model constructed to describe noncommutative gravitational quantum well in [A. Saha, Eur. Phys. J. C 51, 199 (2007).] is indeed independent of the coordinate choice. Hence the energy spectrum predicted by the model can be associated with the experimental results to establish the upper bound on a time-space noncommutative parameter. Interestingly, noncommutativity is shown to increase the gravitational pull on the neutronmore » trapped in the gravitational well.« less

Quinolone-based HDAC inhibitors.

PubMed

Balasubramanian, Gopalan; Kilambi, Narasimhan; Rathinasamy, Suresh; Rajendran, Praveen; Narayanan, Shridhar; Rajagopal, Sridharan

2014-08-01

HDAC inhibitors emerged as promising drug candidates in combating wide variety of cancers. At present, two of the compounds SAHA and Romidepsin were approved by FDA for cutaneous T-cell lymphoma and many are in various clinical phases. A new quinolone cap structure was explored with hydroxamic acid as zinc-binding group (ZBG). The pan HDAC inhibitory and antiproliferative activities against three human cancer cell lines HCT-116 (colon), NCI-H460 (lung) and U251 (glioblastoma) of the compounds (4a-4w) were evaluated. Introduction of heterocyclic amines in CAP region increased the enzyme inhibitory and antiproliferative activities and few of the compounds tested are metabolically stable in both MLM and HLM.

Carbamates as Potential Prodrugs and a New Warhead for HDAC Inhibition.

PubMed

King, Kristina; Hauser, Alexander-Thomas; Melesina, Jelena; Sippl, Wolfgang; Jung, Manfred

2018-02-02

We designed and synthesized carbamates of the clinically-approved HDAC (histone deacetylase) inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) in order to validate our previously-proposed hypothesis that these carbamates might serve as prodrugs for hydroxamic acid containing HDAC inhibitors. Biochemical assays proved our new compounds to be potent inhibitors of histone deacetylases in vitro, and they also showed antiproliferative effects in leukemic cells. These results, as well as stability analysis led to the suggestion that the intact carbamates are inhibitors of histone deacetylases themselves, representing a new zinc-binding warhead in HDAC inhibitor design. This suggestion was further supported by the synthesis and evaluation of a carbamate derivative of the HDAC6-selective inhibitor bufexamac.

Calculations of current-induced forces on moored tankers, using the theory of manoeuvring ships

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

Mirza, S.

1996-12-31

The knowledge of current induced loads on moored tankers is important in the design of mooring lines. Normally, these current loads are determined from controlled laboratory experiments and field tests or from the Oil Companies International Marine Forum (OCIMF) data (1977). Chakrabarti (1995) mentions that the validity of some of this data is doubtful, and he conducted some tank tests. To save time involved in preparation of elaborate tank tests, it will be useful to have some analytical tools to calculate the current induced loads. In this paper, an attempt has been made to calculate the lateral forces in currentmore » only conditions, using the theory of manoeuvring ships. The manoeuvring model was developed by Wellicome (1981). The sway forces on the hull are modelled by conformal transformation of the hull into a circle plane and applying the flow field. The forces on the bilge keel are modelled by vortex panel method. The results for the simulation are compared with the test results of Chakrabarti (1995). There is good correlation between the experimental and theoretical results for the case of hull with bilge keels. This is true for the streaming flow velocity up to an angle of 45 to the longitudinal direction of the hull. For the case of bare hull, the computational model grossly underpredicts the sway forces. This may be due to the dominance of viscous forces than the potential ones.« less

A basal stress parameterization for modeling landfast ice

NASA Astrophysics Data System (ADS)

Lemieux, Jean-François; Tremblay, L. Bruno; Dupont, Frédéric; Plante, Mathieu; Smith, Gregory C.; Dumont, Dany

2015-04-01

Current large-scale sea ice models represent very crudely or are unable to simulate the formation, maintenance and decay of coastal landfast ice. We present a simple landfast ice parameterization representing the effect of grounded ice keels. This parameterization is based on bathymetry data and the mean ice thickness in a grid cell. It is easy to implement and can be used for two-thickness and multithickness category models. Two free parameters are used to determine the critical thickness required for large ice keels to reach the bottom and to calculate the basal stress associated with the weight of the ridge above hydrostatic balance. A sensitivity study was conducted and demonstrates that the parameter associated with the critical thickness has the largest influence on the simulated landfast ice area. A 6 year (2001-2007) simulation with a 20 km resolution sea ice model was performed. The simulated landfast ice areas for regions off the coast of Siberia and for the Beaufort Sea were calculated and compared with data from the National Ice Center. With optimal parameters, the basal stress parameterization leads to a slightly shorter landfast ice season but overall provides a realistic seasonal cycle of the landfast ice area in the East Siberian, Laptev and Beaufort Seas. However, in the Kara Sea, where ice arches between islands are key to the stability of the landfast ice, the parameterization consistently leads to an underestimation of the landfast area.

DEBCat: A Catalog of Detached Eclipsing Binary Stars

NASA Astrophysics Data System (ADS)

Southworth, J.

2015-07-01

Detached eclipsing binary star systems are our primary source of measured physical properties of normal stars. I introduce DEBCat: a catalog of detached eclipsing binaries with mass and radius measurements to the 2% precision necessary to put useful constraints on theoretical models of stellar evolution. The catalog was begun in 2006, as an update of the compilation by Andersen (1991). It now contains over 170 systems, and new results are added on appearance in the refereed literature. DEBCat is available at: http://www.astro.keele.ac.uk/jkt/debcat/.

A History of the Rock Island District Corps of Engineers, 1866-1975

DTIC Science & Technology

1975-06-01

to St. Paul because the Rock Island location was " unhealthy."fi Rock Island was in the middle of a major flood at the time; cholera and typhoid...that he invested in , and laid out. a town site a long the sh ore near the present cit :--· of Daven- port, Iowa. The basis for this rumor can be found...Lake Pepin by adding a false keel and installing a sail he bought from a fisherman for $2.5049 These were the first examples of Meigs’ tinkering

The unexpected discovery of blind snakes (Serpentes: Typhlopidae) in Micronesia: Two new species of Ramphotyphlops from the Caroline Islands

USGS Publications Warehouse

Wynn, A.H.; Reynolds, R.P.; Buden, D.W.; Falanruw, M.; Lynch, B.

2012-01-01

Two new blind snakes in the genus Ramphotyphlops are described from Ulithi (R. hatmaliyeb sp. nov.) and Ant Atoll (R. adocetus sp. nov.) in the Caroline Islands, the first blind snake species known from Micronesia east of Palau (excluding Ramphotyphlops braminus). Both species are unusual in being known only from small, low-lying atolls. They can be distinguished from other Ramphotyphlops by the combination of 22 scale rows over the length of the body; a wedge-shaped snout, without a keratinized keel; and a broad, pyriform (R. adocetus) or ovate (R. hatmaliyeb) rostral scale.

The unexpected discovery of blind snakes (Serpentes: Typhlopidae) in Micronesia: two new species of Ramphotyphlops from the Caroline Islands

USGS Publications Warehouse

Wynn, Addison H.; Reynolds, Robert P.; Buden, Donald W.; Falanruw, Marjorie; Lynch, Brian

2012-01-01

Two new blind snakes in the genus Ramphotyphlops are described from Ulithi (R. hatmaliyeb sp. nov.) and Ant Atoll (R. adocetus sp. nov.) in the Caroline Islands, the first blind snake species known from Micronesia east of Palau (excluding Ramphotyphlops braminus). Both species are unusual in being known only from small, low-lying atolls. They can be distinguished from other Ramphotyphlops by the combination of 22 scale rows over the length of the body; a wedge-shaped snout, without a keratinized keel; and a broad, pyriform (R. adocetus) or ovate (R. hatmaliyeb) rostral scale.

Disseminated lymphoma of presumptive T-cell origin in a great horned owl (Bubo virginianus).

PubMed

Malka, Shachar; Crabbs, Torrie; Mitchell, Elizabeth B; Zehnder, Ashley; Kent, Michael S; Lowenstine, Linda J; Hawkins, Michelle G

2008-09-01

A geriatric male great horned owl (Bubo virginianus) that was a resident at a raptor center was presented for examination because of stridor and weight loss. Results of physical examination, diagnostic imaging, and biopsy were consistent with disseminated lymphoma involving the oropharynx, neck region (including thyroid and parathyroid glands), keel, spleen, and liver. Attempts to treat the owl with chlorambucil failed, and the owl was euthanatized 5 months later. Neoplastic cells from this owl were immunoreactive to CD-3 antibody, suggesting the lymphoma was of T-cell origin.

A new species of the genus Opisthotropis Gunther, 1872 (Squamata: Colubridae: Natricinae) from Guangdong Province, China.

PubMed

Yang, Jian-huan; Sung, Yik-hei; Chan, Bosco Pui-Lok

2013-01-01

A new natricid snake of the genus Opisthotropis Gunther, 1872, Opisthotropis laui sp. nov., is described from Mt. Gudou, Jiangmen City, Guangdong Province, China. The new species can be distinguished from other congeners by the combination of the following characters: dorsal scales weakly keeled throughout, in 25:23:23 rows; 10 supralabials; 11 infralabials; two internasals, longer than wide, not touching the loreal; one loreal, not touching the eye; one preocular; two postoculars; one anterior temporal scale; 152 ventrals; 53 subcaudals; body and tail dark olive above, with light yellow crossbars.

[Significance of bone mineral density and modern cementing technique for in vitro cement penetration in total shoulder arthroplasty].

PubMed

Pape, G; Raiss, P; Kleinschmidt, K; Schuld, C; Mohr, G; Loew, M; Rickert, M

2010-12-01

Loosening of the glenoid component is one of the major causes of failure in total shoulder arthroplasty. Possible risk factors for loosening of cemented components include an eccentric loading, poor bone quality, inadequate cementing technique and insufficient cement penetration. The application of a modern cementing technique has become an established procedure in total hip arthroplasty. The goal of modern cementing techniques in general is to improve the cement-penetration into the cancellous bone. Modern cementing techniques include the cement vacuum-mixing technique, retrograde filling of the cement under pressurisation and the use of a pulsatile lavage system. The main purpose of this study was to analyse cement penetration into the glenoid bone by using modern cement techniques and to investigate the relationship between the bone mineral density (BMD) and the cement penetration. Furthermore we measured the temperature at the glenoid surface before and after jet-lavage of different patients during total shoulder arthroplasty. It is known that the surrounding temperature of the bone has an effect on the polymerisation of the cement. Data from this experiment provide the temperature setting for the in-vitro study. The glenoid surface temperature was measured in 10 patients with a hand-held non-contact temperature measurement device. The bone mineral density was measured by DEXA. Eight paired cadaver scapulae were allocated (n = 16). Each pair comprised two scapulae from one donor (matched-pair design). Two different glenoid components were used, one with pegs and the other with a keel. The glenoids for the in-vitro study were prepared with the bone compaction technique by the same surgeon in all cases. Pulsatile lavage was used to clean the glenoid of blood and bone fragments. Low viscosity bone cement was applied retrogradely into the glenoid by using a syringe. A constant pressure was applied with a modified force sensor impactor. Micro-computed tomography

Optical diagnosis and theoretical simulation of laser induced lead plasma spectrum

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

Hong Bofu; Chuan Songchen; Bao Yuanman

2012-01-15

Plasmas generated during incipient laser ablation of lead in air were studied using emission spectroscopy and fast photography by an intensified charge coupled device (ICCD) camera. An improved plasma emission model was introduced, invoking one-dimensional radiative transfer, to describe the observed emission spectra, while taking into account Gaussian intensity distribution of the laser used to form plasma. The effects of different parameters to the fitting results are discussed. The plasma temperature got by Saha-Boltzmann plot method and the electron number density got by line broadening method were compared with the fitting results. We also found that the distribution of plasmamore » temperature is more uniform than that of the electron number density in the radial direction.« less

Opacity and transport measurements reveal that dilute plasma models of sonoluminescence are not valid.

PubMed

Khalid, Shahzad; Kappus, Brian; Weninger, Keith; Putterman, Seth

2012-03-09

A strong interaction between a nanosecond laser and a 70 μm radius sonoluminescing plasma is achieved. The overall response of the system results in a factor of 2 increase in temperature as determined by its spectrum. Images of the interaction reveal that light energy is absorbed and trapped in a region smaller than the sonoluminescence emitting region of the bubble for over 100 ns. We interpret this opacity and transport measurement as demonstrating that sonoluminescencing bubbles can be 1000 times more opaque than what follows from the Saha equation of statistical mechanics in the ideal plasma limit. To address this discrepancy, we suggest that the effects of strong Coulomb interactions are an essential component of a first principles theory of sonoluminescence.

Opacity and Transport Measurements Reveal That Dilute Plasma Models of Sonoluminescence Are Not Valid

NASA Astrophysics Data System (ADS)

Khalid, Shahzad; Kappus, Brian; Weninger, Keith; Putterman, Seth

2012-03-01

A strong interaction between a nanosecond laser and a 70 μm radius sonoluminescing plasma is achieved. The overall response of the system results in a factor of 2 increase in temperature as determined by its spectrum. Images of the interaction reveal that light energy is absorbed and trapped in a region smaller than the sonoluminescence emitting region of the bubble for over 100 ns. We interpret this opacity and transport measurement as demonstrating that sonoluminescencing bubbles can be 1000 times more opaque than what follows from the Saha equation of statistical mechanics in the ideal plasma limit. To address this discrepancy, we suggest that the effects of strong Coulomb interactions are an essential component of a first principles theory of sonoluminescence.

Structure optimization and preliminary bioactivity evaluation of N-hydroxybenzamide-based HDAC inhibitors with Y-shaped cap.

PubMed

Yu, Chenggong; He, Feng; Qu, Ying; Zhang, Qiuqiong; Lv, Jiahui; Zhang, Xiangna; Xu, Ana; Miao, Pannan; Wu, Jingde

2018-05-01

Histone deacetylase inhibitors (HDACIs) are effective small molecules in the treatment of human cancers. In our continuing efforts to develop novel N-hydroxyterephthalamide-based HDACIs, herein we report the design and development of a new class of N-hydroxybenzamide-based HDACIs. In this new class of analogs, we inserted an ethylene moiety in the linker and used indole as a part of the Y-shaped cap group. Biological characterization identified compounds 4o, 4p, 4q and 4t to show improved HDAC inhibition, while no isoform selectivity for HDACs was observed. These compounds also exhibited improved anti-proliferative activity against multiple cancer cell lines when compared to their parent compound and positive control SAHA. Copyright © 2018 Elsevier Ltd. All rights reserved.

Relativistic effects in electron impact ionization from the p-orbital

NASA Astrophysics Data System (ADS)

Haque, A. K. F.; Uddin, M. A.; Basak, A. K.; Karim, K. R.; Saha, B. C.; Malik, F. B.

2006-06-01

The parameters of our recent modification of BELI formula (MBELL) [A.K.F. Haque, M.A. Uddin, A.K. Basak, K.R. Karim, B.C. Saha, Phys. Rev. A 73 (2006) 012708] are generalized in terms of the orbital quantum numbers nl to evaluate the electron impact ionization (EII) cross sections of a wide range of isoelectronic targets (H to Ne series) and incident energies. For both the open and closed p-shell targets, the present MBELL results with a single parameter set, agree nicely with the experimental cross sections. The relativistic effect of ionization in the 2p subshell of U82+ for incident energies up to 250 MeV is well accounted for by the prescribed parameters of the model.

Electron impact ionization from p-orbital targets

NASA Astrophysics Data System (ADS)

Saha, Bidhan; Basak, Arun K.; Alfaz Uddin, M.

2006-05-01

Electron impact ionization cross sections are evaluated using a modified version [1] of the BELL formula [2] for a wide range of isoelectronic targets, ranging from Li to Ne targets with both the open and closed shell configurations. In this report the MBELL parameters are generalized for treating the orbital quantum numbers nl dependency; its accuracy has been tested by evaluating cross sections for a wider range of species and energies. Details will be presented at the meeting. [1] A. K. F. Haque, M. A. Uddin, A. K. Basak, K. R. Karim and B. C. Saha, Phys. Rev. A73, 012708 (2005). [2] K. L. Bell, H. B. Gilbody, J. G. Hughes, A. E. Kingston, and F. J. Smith, J. Phys. Chem. Ref. Data 12, 891 (1983).

GIS-technologies application for calculation of potential soil loss of Marha River basin (Republic of Saha)

NASA Astrophysics Data System (ADS)

Shynbergenov, Y.; Maltsev, K.; Sihanova, N.

2018-01-01

In the article the presentation of estimation methods of potential soil loss in the conditions of Siberia with application of geographical information systems is resulted. For the reference area of the Marha river basin, which is a part of the Lena river catchment, there was created a specialized geographic information database of potential soil erosion, with scale of 1: 1,000,000. Digital elevation model “GMTED2010” and the hydroset layer corresponding to the scale of 1: 1,000,000 are taken to calculate the soil loss values. The formation of the geobase data is considered in detail being constructed on the basis of the multiplicative structure which reflects the main parameters of the relief (slope steepness, exposition, slope length, erosion potential of the relief), soil, climatic characteristics and modern types of land cover. At the quantitative level with sufficiently high degree of spatial detail results were obtained for calculating the potential erosion of soils. The average value of potential soil loss in the basin without taking into account the factor of land cover types, was 12.6 t/ha/yr. The calculations carried out, taking into account the types of land cover obtained from remote sensing data from outer space resulted in an appreciable reduction of the soil loss values (0.04 t/ha/yr.).

Bilateral custom-fit total knee arthroplasty in a patient with poliomyelitis.

PubMed

Tardy, Nicolas; Chambat, Pierre; Murphy, Colin G; Fayard, Jean-Marie

2014-09-01

In limbs affected by poliomyelitis, total knee arthroplasty results in satisfactory pain relief. However, the risk of failure is high, especially if the preoperative quadriceps power is low. Therefore, treating osteoarthritis in the current patient represented a challenging procedure. A 66-year-old man presented with tricompartmental osteoarthritis of both knees, with valgus deformity of 14° on the left knee and 11° on the right knee. He walked with a bilateral knee recurvatum of 30° and a grade 1 quadriceps power. The authors treated both knees with cemented custom-fit hinged total knee arthroplasty with 30° of recurvatum in the tibial keel. Clinical scores showed good results 1 year postoperatively, especially on the subjective data of quality of life and function. At follow-up, radiographs showed good total knee arthroplasty positioning on the right side and a small mechanical loosening at the end of the tibial keel on the left side. Only 5 studies (Patterson and Insall; Moran; Giori and Lewallen; Jordan et al; and Tigani et al) have reported total knee arthroplasty results in patients with poliomyelitis. This study reports an original case of bilateral custom-fit hinged total knee arthroplasty in a patient with poliomyelitis. To the authors' knowledge, this is the first report of this type of procedure in the literature. The key point is the degree of recurvatum that is needed to allow walking, avoiding excessive constraints on the implants that can lead to early mechanical failure. Copyright 2014, SLACK Incorporated.

Why arboreal snakes should not be cylindrical: body shape, incline and surface roughness have interactive effects on locomotion.

PubMed

Jayne, Bruce C; Newman, Steven J; Zentkovich, Michele M; Berns, H Matthew

2015-12-01

Depending on animal size, shape, body plan and behaviour, variation in surface structure can affect the speed and ease of locomotion. The slope of branches and the roughness of bark both vary considerably, but their combined effects on the locomotion of arboreal animals are poorly understood. We used artificial branches with five inclines and five peg heights (≤40 mm) to test for interactive effects on the locomotion of three snake species with different body shapes. Unlike boa constrictors (Boa constrictor), corn snakes (Pantherophis guttatus) and brown tree snakes (Boiga irregularis) can both form ventrolateral keels, which are most pronounced in B. irregularis. Increasing peg height up to 10 mm elicited more of the lateral undulatory behaviour (sliding contact without gripping) rather than the concertina behaviour (periodic static gripping) and increased the speed of lateral undulation. Increased incline: (1) elicited more concertina locomotion, (2) decreased speed and (3) increased the threshold peg height that elicited lateral undulation. Boiga irregularis was the fastest species, and it used lateral undulation on the most surfaces, including a vertical cylinder with pegs only 1 mm high. Overall, B. constrictor was the slowest and used the most concertina locomotion, but this species climbed steep, smooth surfaces faster than P. guttatus. Our results illustrate how morphology and two different aspects of habitat structure can have interactive effects on organismal performance and behaviour. Notably, a sharper keel facilitated exploiting shorter protrusions to prevent slipping and provide propulsion, which became increasingly important as surface steepness increased. © 2015. Published by The Company of Biologists Ltd.

High resolution sea ice modeling for the region of Baffin Bay and the Labrador Sea

NASA Astrophysics Data System (ADS)

Zakharov, I.; Prasad, S.; McGuire, P.

2016-12-01

A multi-category numerical sea ice model (CICE) with a data assimilation module was implemented to derive sea ice parameters in the region of Baffin Bay and the Labrador Sea with resolution higher than 10 km. The model derived ice parameters include concentration, ridge keel measurement, thickness and freeboard. The module for assimilation of ice concentration uses data from the Advance Microwave Scanning Radiometer (AMSR-E) and OSI SAF data. The sea surface temperature (SST) data from AMSRE-AVHRR and Operational SST and Sea Ice Analysis (OSTIA) system were used to correct the SST computed by a mixed layer slab ocean model that is used to determine the growth and melt of sea ice. The ice thickness parameter from the model was compared with the measurements from Soil Moisture Ocean Salinity - Microwave Imaging Radiometer using Aperture Synthesis (SMOS-MIRAS). The freeboard measures where compared with the Cryosat-2 measurements. A spatial root mean square error computed for freeboard measures was found to be within the uncertainty limits of the observation. The model was also used to estimate the correlation parameter between the ridge and the ridge keel measurements in the region of Makkovik Bank. Also, the level ice draft estimated from the model was in good agreement with the ice draft derived from the upward looking sonar (ULS) instrument deployed in the Makkovik bank. The model corrected with ice concentration and SST from remote sensing data demonstrated significant improvements in accuracy of the estimated ice parameters. The model can be used for operational forecast and climate research.

Southern Ocean Seasonal Net Production from Satellite, Atmosphere, and Ocean Data Sets

NASA Technical Reports Server (NTRS)

Keeling, Ralph F.; Campbell, J. (Technical Monitor)

2002-01-01

A new climatology of monthly air-sea O2 flux was developed using the net air-sea heat flux as a template for spatial and temporal interpolation of sparse hydrographic data. The climatology improves upon the previous climatology of Najjar and Keeling in the Southern Hemisphere, where the heat-based approach helps to overcome limitations due to sparse data coverage. The climatology is used to make comparisons with productivity derived from CZCS images. The climatology is also used in support of an investigation of the plausible impact of recent global warming an oceanic O2 inventories.

Description of a new genus of Elaphidiini with two new species (Coleoptera, Cerambycidae, Cerambycinae).

PubMed

Santos-Silva, Antonio; Galileo, Maria Helena M

2017-03-27

Elaphidiini Thomson, 1864 is a large tribe of Cerambycidae composed of 92 genera with species distributed from Canada to southern South America. Lingafelter (1998) performed a generic level phylogenetic analysis of the tribe and provided a key to the known genera. According to Lingafelter, Elaphidiini is characterized as follows: mesally-spined antenna (lost in some taxa), narrow metepisternum with a centrally positioned keel, strongly sclerotized below and membranous above; prosternal process between procoxae slightly to strongly expanded at apex (rarely linear and unexpanded); terminal palpomeres much wider at apex than base; and coarsely faceted eyes (with few exceptions).

Two new Dolichothele Mello-Leitão, 1923 species from Brazil and Bolivia (Araneae, Theraphosidae)

PubMed Central

Revollo, Irene Soliz; Júnior, Pedro Ismael da Silva; Bertani, Rogério

2017-01-01

Abstract Two new species of Dolichothele Mello-Leitão, 1923 are described from Brazil and Bolivia, D. mottai sp. n. from Distrito Federal and the state of Goiás, Brazil, and D. camargorum sp. n. from the state of Rondônia, Brazil, and the La Paz region, Bolivia. Males of the two new species resemble Dolichothele bolivianum (Vol, 2001) in having a small subapical keel on the distal embolus and females in particular by the short spermatheca. Dolichothele bolivianum is redescribed, and its geographical distribution is herein restricted to Bolivia and the state of Mato Grosso in Brazil. PMID:29362529

The transportation depot: An orbiting vehicle support facility

NASA Technical Reports Server (NTRS)

Kaszubowski, Martin J.; Ayers, J. Kirk

1992-01-01

This paper describes the details of an effort to produce conceptual designs for an orbiting platform, called a transportation depot, to handle assembly and processing of lunar, Martian, and related vehicles. High-level requirements for such a facility were established, and several concepts were developed to meet those requirements. By showing that the critical rigid-body momentum characteristics of each concept are similar to those of the dual-keel space station, some insight was gained about the controllability and utility of this type of facility. Finally, several general observations were made that highlight the advantages and disadvantages of particular design features.

Climate Change and Sustainability Open Educational Resources: Lessons learned and challenges to tackle

NASA Astrophysics Data System (ADS)

Robinson, Zoe; Whitfield, Stephen; Gertisser, Ralf; Krause, Stefan; McKay, Deirdre; Pringle, Jamie; Szkornik, Katie; Waller, Richard

2010-05-01

The UK's Higher Education Academy Subject Centre for Geography, Earth and Environmental Sciences (GEES) is currently running a project entitled ‘C-Change in GEES: Open licensing of climate change and sustainability resources in the Geography, Earth and Environmental Sciences' as part of a national Open Educational Resource project. The C-Change project aims to explore the challenges involved in ‘repurposing' existing teaching materials on the topics of climate change and sustainability to make them open access. This project has produced an open access resource of diverse climate change and sustainability-related teaching materials across the subjects of Geography, Earth and Environmental Sciences. The process of repurposing existing face-to-face teaching resources requires consideration of a wide variety of issues including the Intellectual Property Rights (IPR) associated with images and other material included in the teaching resources, in addition to issues of quality, accessibility and usability of resources. Open access education is an issue that will have implications across the whole of the organizational structure of a university, from legal advisors with commitments to University research and enterprise activities, to the academics wishing to produce open access resources, through to all levels of senior management. The attitudes, concerns and openness to Open Educational Resources of stakeholders from all positions within a HE institution will have implications for the participation of that institution within the OER movement. The many barriers to the whole-scale adoption of Open Educational Resources within the UK Higher Education system and the willingness of UK Higher Education Institutions to engage in the OER movement include institutional perspectives on the IPR of teaching materials developed by members of staff within the institution and financial viability, in addition to more sceptical attitudes of potential contributors. Keele University is

On the actual variety of plate dynamical mechanisms and how mantle evolution affected them through time, from core formation to the Indian collision

NASA Astrophysics Data System (ADS)

Osmaston, Miles

2010-05-01

If horizontal plate motions were driven by thermal convection of the mantle, they would display the action of slow-to-change body forces. Yet rapid changes of spreading rate and direction, and ridge jumps, are well-documented for the past 130Ma. Also convection cannot readily cause rotations of a plate (e.g. Africa) about a pole within the plate or near it. And plate motions, especially that of India, scarcely fit a convective pattern. To address these problems we look first at mantle motivation at both ends of earth history, beginning with core formation. I then introduce 3 important properties of mantle materials, whose neglect by mantle modellers has surely impaired the value of their work, but whose recognition illuminates the present plate dynamical situation and provides the Earth with a heat engine that is not thermal convection. Finally I sketch the intervening changes in behaviour over time, the sharpest of which brought about the rise of atmospheric oxygen at ~2.25Ga. Core formation. As the very high specific angular momentum of mean planetary material (>105-fold relative to solar) can only be achieved if the planets were wholly accreted in presence of the nebula [1], the iron percolation model is ruled out, because it takes too long. This validates the A.E.Ringwood model (1960-1978) involving nebular H reaction with erupting FeO. The iron then loads the downgoing limb of what is then not a truly thermal convection system. Huge volumes of reaction water were produced, giving the early Earth a wet mantle, a (diminishing) feature that we'll see has constrained mantle behaviour ever since. Plate dynamics since 150Ma. Multiple plate dynamical evidence [2], which will be rapidly re-presented here, shows that currently (a) the Earth has a 2-layer mantle system with a boundary at ~660km and (b) that most cratons have tectospheric keels that reach right to that boundary, or nearly so. The argument is the simple and persuasive one (even to seismologists) of mantle

Thermodynamics of atomic and ionized hydrogen: analytical results versus equation-of-state tables and Monte Carlo data.

PubMed

Alastuey, A; Ballenegger, V

2012-12-01

We compute thermodynamical properties of a low-density hydrogen gas within the physical picture, in which the system is described as a quantum electron-proton plasma interacting via the Coulomb potential. Our calculations are done using the exact scaled low-temperature (SLT) expansion, which provides a rigorous extension of the well-known virial expansion-valid in the fully ionized phase-into the Saha regime where the system is partially or fully recombined into hydrogen atoms. After recalling the SLT expansion of the pressure [A. Alastuey et al., J. Stat. Phys. 130, 1119 (2008)], we obtain the SLT expansions of the chemical potential and of the internal energy, up to order exp(-|E_{H}|/kT) included (E_{H}≃-13.6 eV). Those truncated expansions describe the first five nonideal corrections to the ideal Saha law. They account exactly, up to the considered order, for all effects of interactions and thermal excitations, including the formation of bound states (atom H, ions H^{-} and H_{2}^{+}, molecule H_{2},⋯) and atom-charge and atom-atom interactions. Among the five leading corrections, three are easy to evaluate, while the remaining ones involve well-defined internal partition functions for the molecule H_{2} and ions H^{-} and H_{2}^{+}, for which no closed-form analytical formula exist currently. We provide accurate low-temperature approximations for those partition functions by using known values of rotational and vibrational energies. We compare then the predictions of the SLT expansion, for the pressure and the internal energy, with, on the one hand, the equation-of-state tables obtained within the opacity program at Livermore (OPAL) and, on the other hand, data of path integral quantum Monte Carlo (PIMC) simulations. In general, a good agreement is found. At low densities, the simple analytical SLT formulas reproduce the values of the OPAL tables up to the last digit in a large range of temperatures, while at higher densities (ρ∼10^{-2} g/cm^{3}), some

Association of Dermatoglyphic Peculiarities with Dental Caries in Preschool Children of Lucknow, India

PubMed Central

Saha, Sabyasachi; Jagannath, GV; Singh, Sanjay; Saha, Sonali; Garg, Nishita

2016-01-01

ABSTRACT Background: Dermatoglyphics refers to study of the intricate dermal ridge configurations on the skin covering the palmar and plantar surfaces of hand and feet. The basis of considering dermatoglyphic patterns as genetic marker for dental caries is that the epithelium of finger buds as well as enamel has ectodermal origin, and both develop at the same time of intrauterine life. Aim: To assess the relationship between fingerprint patterns and dental caries among preschool children of Lucknow city. Study design: This study was of cross-sectional design. Materials and methods: The study group comprised 512 preschool children 2-6 years of age. The prevalence of caries was recorded using "Dentition status and treatment needs" (WHO basic oral health assessment form, 1997). They were divided into three groups as follows: Group I (dmft score = 0-2), group II (dmft score = 3-4) and group III (dmft score ≥5). The handprints of each child were taken using a stamp pad. The fingertip patterns were analyzed according to the classical method and were classified according to the topological method. The frequency of occurrence of type of dermatoglyphic pattern on fingertip of each digit was noted. Statistics: Chi-square test was used to test the significant difference in proportions. Means were compared using Student’s t-test and analysis of variance (ANOVA) or F-test. Results: Subjects belonging to groups II and III showed maximum occurrence of whorl pattern on all digits. Group I subjects had maximum occurrence of arch pattern. All the variables had statistically significant value, with a degree of divergence of specific dermatoglyphic patterns among all three groups. Conclusion: The dental caries susceptibility of an individual increased with incidence of whorl pattern and it decreased with incidence of arch pattern. How to cite this article: Singh E, Saha S, Jagannath GV, Singh S, Saha S, Garg N. Association of Dermatoglyphic Peculiarities with Dental Caries in

Comparative molecular dynamics simulations of histone deacetylase-like protein: binding modes and free energy analysis to hydroxamic acid inhibitors.

PubMed

Yan, Chunli; Xiu, Zhilong; Li, Xiaohui; Li, Shenmin; Hao, Ce; Teng, Hu

2008-10-01

Histone deacetylases (HDACs) play an important role in gene transcription, and inhibitors of HDACs can induce cell differentiation and suppress cell proliferation in tumor cells. Histone deacetylase1 (HDAC1) binds suberanilohydroxamic acid (SAHA) and 7-phenyl-2, 4, 6-hepta-trienoyl hydroxamic acid (CG-1521) with moderately low affinity (DeltaG = -8.6 and -7.8 kcal mol(-1)). The structurally related (E)-2-(3-(3-(hydroxyamino)-3-oxoprop-1-enyl)phenyl)-N(1),N(3)-diphenylmalonamide (SK-683), a Trichostatin A (TSA)-like HDAC1 inhibitor, and TSA are bound to the HDAC1 with -12.3 and -10.3 kcal mol(-1) of DeltaG, higher binding free energies than SAHA and CG-1521. Histone deacetylase-like protein (HDLP), an HDAC homologue, shows a 35.2% sequence identity of HDLP and human HDAC1. Molecular dynamics simulation and the molecular mechanics/generalized-Born surface area (MM-GBSA) free energy calculations were applied to investigate the factors responsible for the relatively activity of these four inhibitors to HDLP. In addition, computational alanine scanning of the binding site residues was carried out to determine the contribution components from van der Waals, electrostatic interaction, nonpolar and polar energy of solvation as well as the effects of backbones and side-chains with the MM-GBSA method. MM-GBSA methods reproduced the experimental relative affinities of the four inhibitors in good agreement (R(2) = 0.996) between experimental and computed binding energies. The MM-GBSA calculations showed that, the number of hydrogen bonds formed between the HDLP and inhibitors, which varied in the system studied, and electrostatic interactions determined the magnitude of the free energies for HDLP-inhibitor interactions. The MM-GBSA calculations revealed that the binding of HDLP to these four hydroxamic acid inhibitors is mainly driven by van der Waals/nonpolar interactions. This study can be a guide for the optimization of HDAC inhibitors and future design of new therapeutic

Quantum statistical mechanics of dense partially ionized hydrogen.

NASA Technical Reports Server (NTRS)

Dewitt, H. E.; Rogers, F. J.

1972-01-01

The theory of dense hydrogenic plasmas beginning with the two component quantum grand partition function is reviewed. It is shown that ionization equilibrium and molecular dissociation equilibrium can be treated in the same manner with proper consideration of all two-body states. A quantum perturbation expansion is used to give an accurate calculation of the equation of state of the gas for any degree of dissociation and ionization. In this theory, the effective interaction between any two charges is the dynamic screened potential obtained from the plasma dielectric function. We make the static approximation; and we carry out detailed numerical calculations with the bound and scattering states of the Debye potential, using the Beth-Uhlenbeck form of the quantum second virial coefficient. We compare our results with calculations from the Saha equation.

Electron Impact K-shell Ionization Cross Sections at high energies

NASA Astrophysics Data System (ADS)

Haque, A. K. F.; Sarker, M. S. I.; Patoary, M. A. R.; Shahjahan, M.; Ismail Hossain, M.; Alfaz Uddin, M.; Basak, A. K.; Saha, Bidhan

2008-10-01

A simple modification of the empirical model of Deutsh et. al. [1] by incorporating both the ionic [2] and relativistic corrections [3] is proposed for evaluating the electron impact K -shell ionization cross sections of neutral atomic targets. Present results for 30 atomic targets with atomic number Z=1 -- 92 for incident energies up to E=2 GeV, agree well with available experimental cross sections. Comparisons with other theoretical findings will also be presented at the conference. [1] H. Deutsh, K. Becker, T. D. Mark, Int. J. Mass Spect. 177, 47 (1998). [2] M. A. Uddin, A. K. F. Haque, M. M. Billah, A. K. Basak, K. R. Karim, B. C. Saha, Phys. Rev. A 71, 032715 (2005).; Phys. Rev. A 73, 012708 (2006). [3] M. Gryzinski, Phys. Rev 138, 336 (1965).

Electron Impact Inner-shell Ionization including relativistic corrections.

NASA Astrophysics Data System (ADS)

Saha, Bidhan C.; Alfaz Uddin, M.; Basak, Arun K.

2007-04-01

We report a simple method to evaluate the electron impact inner-shell ionization cross sections at ultra high energy regime; there still remains a sparse cross sections due to lack of reliable method. To extend the validity domains of the siBED model [1] in terms of targets and incident energies in this work we modified the RQIBED model [2], and denoted it as MUIBED. It is examined for the description of the experimental EIICS data of various target atoms up to E=250MeV. Details will be presented at the meeting. [1] W. M. Huo, Phys. Rev A 64, 042719 (2001). [2] M. A. Uddin, A. K. F. Haque, M. S. Mahbub, K. R. Karim, A. K. Basak and B. C. Saha, Phys. Rev. A 71, 032715 (2005).

Solar H-alpha features with hot onsets. III. Long fibrils in Lyman-alpha and with ALMA

NASA Astrophysics Data System (ADS)

Rutten, R. J.

2017-02-01

In H-alpha most of the solar surface is covered by dense canopies of long opaque fibrils, but predictions for quiet-Sun observations with ALMA have ignored this fact. Comparison with Ly-alpha suggests that the extraordinary opacity of H-alpha fibrils is caused by hot precursor events. Application of a recipe that assumes momentary Saha-Boltzmann extinction during their hot onset to millimeter wavelengths suggests that ALMA will observe H-alpha-like fibril canopies, not acoustic shocks underneath, and will yield data more interesting than if these canopies were transparent. An additional file is available at the end of the PDF file of this article.This study is offered as compliment to M.W.M. de Graauw. Our ways, objects, instruments and spectral domains parted after the 1970 eclipse but converge here.

Three-dimensional model of an ultramafic feeder system to the Nikolai Greenstone mafic large igneous province, central Alaska Range

USGS Publications Warehouse

Glen, J.M.G.; Schmidt, J.M.; Connard, G.G.

2011-01-01

The Amphitheater Mountains and southern central Alaska Range expose a thick sequence of Triassic Nikolai basalts that is underlain by several mafic-ultramafic complexes, the largest and best exposed being the Fish Lake and Tangle (FL-T) mafic-ultramafic sills that flank the Amphitheater Mountains synform. Three-dimensional (3-D) modeling of gravity and magnetic data reveals details of the structure of the Amphitheater Mountains, such as the orientation and thickness of Nikolai basalts, and the geometry of the FL-T intrusions. The 3-D model (50 ?? 70 km) includes the full geographic extent of the FL-T complexes and consists of 11 layers. Layer surfaces and properties (density and magnetic susceptibility) were modified by forward and inverse methods to reduce differences between the observed and calculated gravity and magnetic grids. The model suggests that the outcropping FL-T sills are apparently connected and traceable at depth and reveals variations in thickness, shape, and orientation of the ultramafic bodies that may identify paths of magma flow. The model shows that a significant volume (2000 km3) of ultramafic material occurs in the subsurface, gradually thickening and plunging westward to depths exceeding 4 km. This deep ultramafic material is interpreted as the top of a keel or root system that supplied magma to the Nikolai lavas and controlled emplacement of related magmatic intrusions. The presence of this deep, keel-like structure, and asymmetry of the synform, supports a sag basin model for development of the Amphitheater Mountains structure and reveals that the feeders to the Nikolai are much more extensive than previously known. Copyright 2011 by the American Geophysical Union.

Development of a design methodology for pipelines in ice scoured seabeds

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

Clark, J.I.; Paulin, M.J.; Lach, P.R.

1994-12-31

Large areas of the continental shelf of northern oceans are frequently scoured or gouged by moving bodies of ice such as icebergs and sea ice keels associated with pressure ridges. This phenomenon presents a formidable challenge when the route of a submarine pipeline is intersected by the scouring ice. It is generally acknowledged that if a pipeline, laid on the seabed, were hit by an iceberg or a pressure ridge keel, the forces imposed on the pipeline would be much greater than it could practically withstand. The pipeline must therefore be buried to avoid direct contact with ice, but itmore » is very important to determine with some assurance the minimum depth required for safety for both economical and environmental reasons. The safe burial depth of a pipeline, however, cannot be determined directly from the relatively straight forward measurement of maximum scour depth. The major design consideration is the determination of the potential sub-scour deformation of the ice scoured soil. Forces transmitted through the soil and soil displacement around the pipeline could load the pipeline to failure if not taken into account in the design. If the designer can predict the forces transmitted through the soil, the pipeline can be designed to withstand these external forces using conventional design practice. In this paper, the authors outline a design methodology that is based on phenomenological studies of ice scoured terrain, both modern and relict, laboratory tests, centrifuge modeling, and numerical analysis. The implications of these studies, which could assist in the safe and economical design of pipelines in ice scoured terrain, will also be discussed.« less

Eidinemacheilus proudlovei, a new subterranean loach from Iraqi Kurdistan (Teleostei; Nemacheilidae).

PubMed

Freyhof, Jörg; Abdullah, Younis Sabir; Ararat, Korsh; Ibrahim, Hamad; Geiger, Matthias F

2016-10-04

Eidinemacheilus proudlovei, new species, is described from subterranean waters in the Little Zab River drainage in Iraqi Kurdistan. After the discovery of E. smithi in 1976, E. proudlovei is the second troglomorphic nemacheilid loach found in the Middle East and the second species placed in Eidinemacheilus. Eidinemacheilus proudlovei is distinguished from E. smithi by having 8+8 or 8+7 branched caudal-fin rays, no adipose keel on the caudal peduncle, enlarged jaws and a fully developed head canal system. It furthers differs substantially in its DNA barcode (>8% K2P distance) from all other nemacheilid loaches in the Middle East, Europe and Western India.

Spalled, aerodynamically modified moldavite from Slavice, Moravia, Czechoslovakia

USGS Publications Warehouse

Chao, E.C.T.

1964-01-01

A Czechoslovakian tektite or moldavite shows clear, indirect evidence of aerodynamic ablation. This large tektite has the shape of a teardrop, with a strongly convex, deeply corroded, but clearly identifiable front and a planoconvex, relatively smooth, posterior surface. In spite of much erosion and corrosion, demarcation of the posterior and the anterior part of the specimen (the keel) is clearly preserved locally. This specimen provides the first tangible evidence that moldavites entered the atmosphere cold, probably at a velocity exceeding 5 kilometers per second; the result was selective heating of the anterior face and perhaps ablation during the second melting. This provides evidence of the extraterrestial origin of moldavites.

Very low luminosity active galaxies and the X-ray background

NASA Technical Reports Server (NTRS)

Elvis, M.; Soltan, A.; Keel, W. C.

1984-01-01

The properties of very low luminosity active galactic nuclei are not well studied, and, in particular, their possible contribution to the diffuse X-ray background is not known. In the present investigation, an X-ray luminosity function for the range from 10 to the 39th to 10 to the 42.5th ergs/s is constructed. The obtained X-ray luminosity function is integrated to estimate the contribution of these very low luminosity active galaxies to the diffuse X-ray background. The construction of the X-ray luminosity function is based on data obtained by Keel (1983) and some simple assumptions about optical and X-ray properties.

The Development of a Conical Composite Energy Absorber for Use in the Attenuation of Crash/Impact Loads

NASA Technical Reports Server (NTRS)

Littell, Justin D.

2014-01-01

A design for a novel light-weight conical shaped energy absorbing (EA) composite subfloor structure is proposed. This composite EA is fabricated using repeated alternating patterns of a conical geometry to form long beam structures which can be implemented as aircraft subfloor keel beams or frame sections. The geometrical features of this conical design, along with the hybrid composite materials used in the manufacturing process give a strength tailored to achieve a constant 25-40 g sustained crush load, small peak crush loads and long stroke limits. This report will discuss the geometrical design and fabrication methods, along with results from static and dynamic crush testing of 12-in. long subcomponents.

Water-the Nation's Fundamental Climate Issue A White Paper on the U.S. Geological Survey Role and Capabilities

USGS Publications Warehouse

Lins, Harry F.; Hirsch, Robert M.; Kiang, Julie

2010-01-01

Of all the potential threats posed by climatic variability and change, those associated with water resources are arguably the most consequential for both society and the environment (Waggoner, 1990). Climatic effects on agriculture, aquatic ecosystems, energy, and industry are strongly influenced by climatic effects on water. Thus, understanding changes in the distribution, quantity and quality of, and demand for water in response to climate variability and change is essential to planning for and adapting to future climatic conditions. A central role of the U.S. Geological Survey (USGS) with respect to climate is to document environmental changes currently underway and to develop improved capabilities to predict future changes. Indeed, a centerpiece of the USGS role is a new Climate Effects Network of monitoring sites. Measuring the climatic effects on water is an essential component of such a network (along with corresponding effects on terrestrial ecosystems). The USGS needs to be unambiguous in communicating with its customers and stakeholders, and with officials at the Department of the Interior, that although modeling future impacts of climate change is important, there is no more critical role for the USGS in climate change science than that of measuring and describing the changes that are currently underway. One of the best statements of that mission comes from a short paper by Ralph Keeling (2008) that describes the inspiration and the challenges faced by David Keeling in operating the all-important Mauna Loa Observatory over a period of more than four decades. Ralph Keeling stated: 'The only way to figure out what is happening to our planet is to measure it, and this means tracking changes decade after decade and poring over the records.' There are three key ideas that are important to the USGS in the above-mentioned sentence. First, to understand what is happening requires measurement. While models are a tool for learning and testing our understanding

Deep seated inclusions in kimberlites from Kharamai field and some kimberlite fields of Prianabarie.

NASA Astrophysics Data System (ADS)

Ashchepkov, I. V.; Kuligin, S. S.; Afanasiev, V. P.; Vladykin, N. V.; Kostrovitsky, S. I.; Lelyukh, M. I.; Vavilov, M. A.; Nigmatulina, E. N.; Palessky, S. V.

2012-04-01

The problem of the thickness of the lithospheric keel in the northern part of Yakutia is critical for the diamond grade. Reported delamination of the SCLM (Griffin et al., 2005)which is not supported by the geophysical methods (Koulakov et al ., 2011) was checked in number of localities in circum Anabar region. Pyropes, chrome-diopside, omphacites, enstatite, chromites and ilmenites from concentrate three kimberlitic pipes of the Kharamai field revealed compositional variations typical for thick SCLM: pyropes to 13% Of cr2O3 in the association with chromites (to 60% Of cr2O3.) low- Al - Cr diopsides and enstatite, omphacites, Cr-pargasite and K-Na richterite and picroilmenites (to 20% Of MgO). The pyropes belong to lherzolite filed (Sobolev et al., 1973) as those published only in the low-chromium part relate to Ca- Fe to pyroxenite magmatic trend (Tychkov et al., 2008) which is typical for the majority of Mesozoic (especially Jurassic) kimberlitic pipes in Prianabarie and other northern parts of Yakutia. Thermo-barometric reconstructions using four methods of monomineral thermobarometry reveal the thickness of lithospheric keel not less than 200 km which coinsides with the determined thickness of the SCLM beneath nearest Ary- Mastakh filed (Khardakh pipe). Straya Rechka and Kuranakh fields (Universitetskaya, Tudovaya , Los kimberlites etc). But the pipes in Evenkiyskaya kimberlite group (including Malysh and Tuzic pipes) carry material dominantly from the upper part of the SCLM, sub-calcium garnets are rare. Relatively high oxidation state, determined according to chromite, pyroxenes and pyropes are in accord with the rather low diamond grades. However some other Jurassic pipes in northern part of the Siberian craton reveal sufficiently deep mantle roots evidencing about lack of the delamination of mantle keel after Siberian PT superplume. The trace elements determined for the pyropes show variations and belong to the melt metasomatized groups I the middle and

Assessing the hydraulic connection between fresh water aquifers and unconventional gas production using methane and stable isotopes

NASA Astrophysics Data System (ADS)

Iverach, Charlotte P.; Cendón, Dioni I.; Hankin, Stuart I.; Lowry, Dave; Fisher, Rebecca E.; France, James L.; Nisbet, Euan G.; Baker, Andy; Kelly, Bryce F. J.

2015-04-01

Unconventional gas developments pose a risk to groundwater quality and quantity in adjacent or overlying aquifers. To manage these risks there is a need to measure the background concentration of indicator groundwater chemicals and to map pathways of hydraulic connectivity between aquifers. This study presents methane (CH4) concentration and isotopic composition, dissolved organic carbon concentration ([DOC]) and tritium (3H) activity data from an area of expanding coal seam gas (CSG) exploration and production (Condamine Catchment, south-east Queensland, Australia). The target formation for gas production within the Condamine Catchment is the Walloon Coal Measures (WCM). This is a 700 m thick, low-rank CSG resource, which consists of numerous thin discontinuous lenses of coal separated by very fine-to medium-grained sandstone, siltstone, and mudstone, with minor calcareous sandstone, impure limestone and ironstone. The thickness of the coal makes up less than 10% of the total thickness of the unit. The WCM are overlain by sandstone formations, which form part of the Great Artesian Basin (GAB). The Condamine Alluvium fills a paleo-valley carved through the above formations. A combination of groundwater and degassing air samples were collected from irrigation bores and government groundwater monitoring boreholes. Degassing air samples were collected using an SKC 222-2301 air pump, which pumped the gas into 3 L Tedlar bags. The groundwater was analysed for 3H and [DOC]. A mobile CH4 survey was undertaken to continuously sample air in and around areas of agricultural and unconventional gas production. The isotopic signature of gas from the WCM was determined by sampling gas that was off-gassing from a co-produced water holding pond as it was the largest emission that could be directly linked to the WCM. This was used to determine the source signature of the CH4 from the WCM. We used Keeling plots to identify the source signature of the gas sampled. For the borehole

Relative contribution of combined kinetic and exchange energy terms vs the electronic component of molecular electrostatic potential in hardness potential derivatives.

PubMed

Bhattacharjee, Rituparna; Roy, Ram Kinkar

2013-11-14

The relative contribution of the sum of kinetic [(10/9)CFρ(r)2/3] and exchange energy [(4/9)CXρ(r)1/3] terms to that of the electronic part of the molecular electrostatic potential [Vel(r)] in the variants of hardness potential is investigated to assess the proposed definition of Δ+h(k) = −[VelN+1(k) – VelN(k)] and Δ–h(k) = −[VelN(k) – VelN–1(k)] (Saha; et al. J. Comput. Chem. 2013, 34, 662). Some substituted benzenes and polycyclic aromatic hydrocarbons (PAHs) (undergoing electrophilic aromatic substitution), carboxylic acids, and their derivatives are chosen to carry out the theoretical investigation as stated above. Intra- and intermolecular reactivity trends generated by Δ+h(k) and Δ–h(k) are found to be satisfactory and are correlated reasonably well with experimental results.

On the Use of Hydrogen Recombination Energy during Common Envelope Events

NASA Astrophysics Data System (ADS)

Ivanova, Natalia

2018-05-01

In this Letter we discuss what happens to hydrogen recombination energy that is released during regular common envelope (CE) events as opposed to self-regulated CE events. We show that the amount of recombination energy that can be transferred away by either convection or radiation from the regions where recombination takes place is negligible. Instead, recombination energy is destined to be used either to help CE expansion, as a work term, or to accelerate local fluid elements. The exceptions are donors that initially have very high entropy material, S/(k B N A) > 37 mol g‑1. The analysis and conclusions are independent of specific stellar models or evolutionary codes, and rely on fundamental properties of stellar matter such as the equation of state, Saha equation, and opacities, as well as on stellar structure equations and the mixing length theory of convection.

Hα features with hot onsets. I. Ellerman bombs

NASA Astrophysics Data System (ADS)

Rutten, R. J.

2016-05-01

Ellerman bombs are transient brightenings of the wings of the Balmer lines that uniquely mark reconnection in the solar photosphere. They are also bright in strong Ca II and ultraviolet lines and in ultraviolet continua, but they are not visible in the optical continuum and the Na I D and Mg I b lines. These discordant visibilities invalidate all published Ellerman bomb modeling. I argue that the assumption of Saha-Boltzmann lower-level populations is informative to estimate bomb-onset opacities for these diverse diagnostics, even and especially for Hα, and employ such estimates to gauge the visibilities of Ellerman bomb onsets in all of them. They constrain Ellerman bomb formation to temperatures 10 000-20 000 K and hydrogen densities around 1015 cm-3. Similar arguments likely hold for Hα visibility in other transient phenomena with hot and dense onsets.

Preliminary Development and Testing of a Self-Injecting Gallium MPD Thruster

NASA Technical Reports Server (NTRS)

Thomas, Robert E.; Burton, Rodney L.; Polzin, Kurt A.

2008-01-01

Discharge current and terminal voltage measurements were performed on a gallium electromagnetic thruster at discharge currents in the range of 20-54 kA. It was found that the arc impedance has a value of 6-7 m(Omega) at peak current. The absence of high-frequency oscillations in the terminal voltage trace indicates lack of the "onset" condition often seen in MPD arcs, suggesting that a sufficient number of charge carriers are present for current conduction. The mass ablated per pulse was not measured experimentally; however the mass flow rate was calculated using an ion current assumption and an anode power balance. Measurement of arc impedance predicts a temperature of 3.5 eV which from Saha equilibrium corresponds to Z = 2.0 - 3.5, and assuming Z = 2 yields an Isp of 3000 s and thrust efficiency of 50%.

Molybdenum electron impact width parameter measurement by laser-induced breakdown spectroscopy

NASA Astrophysics Data System (ADS)

Sternberg, E. M. A.; Rodrigues, N. A. S.; Amorim, J.

2016-01-01

In this work, we suggest a method for electron impact width parameter calculation based on Stark broadening of emission lines of a laser-ablated plasma plume. First, electron density and temperature must be evaluated by means of the Saha-Boltzmann plot method for neutral and ionized species of the plasma. The method was applied for laser-ablated molybdenum plasma plume. For molybdenum plasma electron temperature, which varies around 10,000 K, and electron density, which reaches values around 1018 cm-3, and considering that total measured line broadening was due experimental and Stark broadening mainly, electron impact width parameter of molybdenum emission lines was determined as (0.01 ± 0.02) nm. Intending to validate the presented method, it was analyzed the laser-ablated aluminum plasma plume and the obtained results were in agreement with the predicted on the literature.

Inner-shell Ionization With Relativistic Corrections By Electron Impact

NASA Astrophysics Data System (ADS)

Saha, Bidhan; Patoary, M. A. R.; Alfaz Uddin, M.; Haque, A. K. F.; Basak, Arun K.

2007-06-01

A simple method is proposed and tested by evaluating the electron impact inner-shell ionization cross sections of various targets up to ultra high energy region. In this energy region there are not many calculations due to lack of reliable method. In this work we extend the validity of the siBED model [1] in terms of targets and incident energies. The extension of our earlier RQIBED model [2] is also reported here and we examined its findings for the description of the experimental EIICS data of various targets up to E=1000 MeV. Details will be presented at the meeting. [1] W. M. Huo, Phys. Rev A 64, 042719 (2001). [2] M. A. Uddin, A. K. F. Haque, M. S. Mahbub, K. R. Karim, A. K. Basak and B. C. Saha, Phys. Rev. A 71, 032715 (2005).

Standard Reference Line Combined with One-Point Calibration-Free Laser-Induced Breakdown Spectroscopy (CF-LIBS) to Quantitatively Analyze Stainless and Heat Resistant Steel.

PubMed

Fu, Hongbo; Wang, Huadong; Jia, Junwei; Ni, Zhibo; Dong, Fengzhong

2018-01-01

Due to the influence of major elements' self-absorption, scarce observable spectral lines of trace elements, and relative efficiency correction of experimental system, accurate quantitative analysis with calibration-free laser-induced breakdown spectroscopy (CF-LIBS) is in fact not easy. In order to overcome these difficulties, standard reference line (SRL) combined with one-point calibration (OPC) is used to analyze six elements in three stainless-steel and five heat-resistant steel samples. The Stark broadening and Saha - Boltzmann plot of Fe are used to calculate the electron density and the plasma temperature, respectively. In the present work, we tested the original SRL method, the SRL with the OPC method, and intercept with the OPC method. The final calculation results show that the latter two methods can effectively improve the overall accuracy of quantitative analysis and the detection limits of trace elements.

Natural Variation in the Carbon Oxidation State and Oxidative Ratio of a Deciduous Forest

NASA Astrophysics Data System (ADS)

Masiello, C. A.; Calligan, L. J.; Gallagher, M. E.; Hockaday, W. C.; Robertson, G. P.

2007-12-01

Here we report natural variability in the oxidative ratio (OR) and carbon oxidation state (Cox) of a temperate, deciduous forest measured on an annual basis via elemental analysis of leaf litter. The OR of the terrestrial biosphere is a key component in O2 -based calculations of the biosphere's uptake of fossil fuel CO2 (eg [ Keeling, et al., 1996]). Ecosystem OR has been assumed to be invariant; however, small OR variations may cause significant shifts in the calculated size of the terrestrial biospheric C sink [ Randerson, et al., 2006]. Accurate measurements of OR are necessary for the accurate apportionment of fossil fuel CO2 between the atmosphere, oceans, and terrestrial biosphere. Ecosystem OR is linearly related to Cox, a parameter which can be easily measured via elemental analysis, calorimetry, or solid state nuclear magnetic resonance [ Masiello, et al., 2007]. We are measuring Cox and OR at the three deciduous forest sites within the Kellogg Biological Station NSF LTER (lter.kbs.msu.edu). We report OR from litter collected from three forest sites from 1998-2003, a time series which covers periods of both normal and low precipitation. We also report error introduced in the Cox to OR conversion via a range of plausible assumptions about ecosystem N cycling. Keeling, R. F., et al. (1996), Global and hemispheric CO2 sinks deduced from changes in atmospheric O2 concentration, Nature, 381, 218-221. Masiello, C.A. et al. (in review 2007) Two new approaches for measuring ecosystem carbon oxidation state and oxidative ratio. J.G.R. Biogeosciences. Randerson, J. T., et al. (2006), Is carbon within the global terrestrial biosphere becoming more oxidized? Implications for trends in atmospheric O2, Global Change Biology, 12, 260-271.

Carbon isotope systematics of Turrialba volcano, Costa Rica, using a portable cavity ring-down spectrometer

NASA Astrophysics Data System (ADS)

Malowany, K. S.; Stix, J.; de Moor, J. M.; Chu, K.; Lacrampe-Couloume, G.; Sherwood Lollar, B.

2017-07-01

Over the past two decades, activity at Turrialba volcano, Costa Rica, has shifted from hydrothermal to increasingly magmatic in character, with enhanced degassing and eruption potential. We have conducted a survey of the δ13C signatures of gases at Turrialba using a portable field-based CRDS with comparison to standard IRMS techniques. Our δ13C results of the volcanic plume, high-temperature vents, and soil gases reveal isotopic heterogeneity in the CO2 gas composition at Turrialba prior to its recent phase of eruptive activity. The isotopic value of the regional fault system, Falla Ariete (-3.4 ± 0.1‰), is in distinct contrast with the Central crater gases (-3.9 ± 0.1‰) and the 2012 high-temperature vent (-4.4 ± 0.2‰), an indication that spatial variability in δ13C may be linked to hydrothermal transport of volcanic gases, heterogeneities in the source composition, or magmatic degassing. Isotopic values of CO2 samples collected in the plume vary from δ13C of -5.2 to -10.0‰, indicative of mixing between atmospheric CO2 (-9.2 ± 0.1‰), and a volcanic source. We compare the Keeling method to a traditional mixing model (hyperbolic mixing curve) to estimate the volcanic source composition at Turrialba from the plume measurements. The predicted source compositions from the Keeling and hyperbolic methods (-3.0 ± 0.5‰ and -3.9 ± 0.4‰, respectively) illustrate two potential interpretations of the volcanic source at Turrialba. As of the 29 October 2014, Turrialba has entered a new eruptive period, and continued monitoring of the summit gases for δ13C should be conducted to better understand the dominant processes controlling δ13C fractionation at Turrialba.

Field measurements of del13C in ecosystem respiration

NASA Astrophysics Data System (ADS)

van Asperen, Hella; Sabbatini, Simone; Nicolini, Giacomo; Warneke, Thorsten; Papale, Dario; Notholt, Justus

2014-05-01

Stable carbon isotope del13C-measurements are extensively used to study ecological and biogeochemical processes in ecosystems. Above terrestrial ecosystems, atmospheric del13C can vary largely due to photosynthetic fractionation. Photosynthetic processes prefer the uptake of the lighter isotope 12C (in CO2), thereby enriching the atmosphere in 13C and depleting the ecosystem carbon. At night, when ecosystem respiratory fluxes are dominant, 13C-depleted CO2 is respired and thereby depletes the atmospheric del13C-content. Different ecosystems and different parts of one ecosystem (type of plant, leaves, and roots) fractionate and respire with a different del13C-ratio signature. By determining the del13C-signature of ecosystem respiration in temporal and spatial scale, an analysis can be made of the composition of respiratory sources of the ecosystem. A field study at a dry cropland after harvest (province of Viterbo, Lazio, Italy) was performed in the summer of 2013. A FTIR (Fourier Transform Infrared Spectrometer) was set up to continuously measure CO2-, CH4-, N2O-, CO- and del13C-concentrations. The FTIR was connected to 2 different flux measurements systems: a Flux Gradient system (sampling every half hour at 1.3m and 4.2m) and 2 flux chambers (measured every hour), providing a continuous data set of the biosphere-atmosphere gas fluxes and of the gas concentrations at different heights. Keeling plot intercept values of respiratory CO2, measured by the Flux Gradient system at night, were determined to be between -25‰ and -20‰. Keeling plot intercept values of respiratory CO2, measured by the flux chamber system, varied between -24‰ and -29‰, and showed a clear diurnal pattern, suggesting different (dominant) respiratory processes between day and night.

Suspension freezing of bottom sediment and biota in the Northwest Passage and implications for Arctic Ocean sedimentation

USGS Publications Warehouse

Reimnitz, E.; Marincovich, L.; McCormick, M.; Briggs, W.M.

1992-01-01

No evidence was seen for entrainment by bottom adfreezing, bluff slumping, river flooding, dragging ice keels, or significant eolian transport from land to sea. Muddy sediment with pebbles and cobbles, algae with holdfasts, ostracodes with appendages, and well-preserved mollusks and sea urchins were collected from two sites in a 50 km long stretch of turbid ice. These materials indicate that suspension freezing reaching to a water depth of 25-30 m during the previous fall was responsible for entrainment. This mechanism requires rapid ice formation in open, shallow water during a freezing storm, when the ocean becomes supercooled, and frazil and anchor ice attach to and ultimately lift sediment and living organisms to the sea surface. -from Authors

Microwave spectroscopy of high-L Rydberg states of nickel

NASA Astrophysics Data System (ADS)

Lindsay, Mark D.; Keele, Julie A.; Woods, Shannon L.; Lundeen, Stephen R.

2010-03-01

High-L non-penetrating Rydberg levels of nickel display a fine structure pattern consisting of six levels for each value of L. This pattern was studied recently with the optical RESIS technique, determining initial values of the quadrupole moment and polarizabilities of the ^2D5/2 ground state of Ni^+ [1]. Measurements are now in progress using the microwave RESIS technique [2], which promises much more precise measurements of the fine structure and of the related core properties, including the permanent hexadecapole moment.[4pt] [1] Julie A. Keele, et. al., to be published, Phys. Rev. A[0pt] [2] M.E. Hanni, et. al., Phys. Rev. A 78, 062510 (2008)

A new rock dwelling Hemidactylus (Squamata: Gekkonidae) from Chhattisgarh, India.

PubMed

Murthy, B H C K; Bauer, Aaron; Lajmi, Aparna; Agarwal, Ishan; Giri, Varad B

2015-09-25

A distinct new species of gecko of the genus Hemidactylus is described from the Kanker district of Chhattisgarh State, east-central India. This large-sized (SVL average 81.33±13.40 to at least 98.0 mm) Hemidactylus is characterized by a dorsum with small granules, intermixed with 10-12 rows of irregularly arranged, slightly larger, rounded, weakly-keeled tubercles at midbody; 10-12 and 13-15 subdigital lamellae on the first and fourth digits, respectively, of both manus and pes; a single enlarged postcloacal tubercle on either side of the tail; 10-12 femoral pores on each thigh separated by 5-8 poreless scales; 12-14 supralabials and 10-12 infralabials.

Vignapandeyana (Fabaceae), a new species from northern Western Ghats, India.

PubMed

Gaikwad, Sayajirao; Gore, Ramchandra; Randive, Sonali

2015-01-01

Vigna subg. Ceratotropis (Piper) Verdc. represents a homogenous and distinct group of species with highly specialized complex floral characters. It is most diverse in Asia. India, with 24 species, represents a secondary center of species diversity of the subgenus. A new species, Vignapandeyana RD Gore, SP Gaikwad & SD Randive, is described from hill slopes of the northern Western Ghats of India. It resembles Vignayadavii Gaikwad et al. and Vignadalzelliana (Kuntze) Verdc. but differs from the latter in its dimorphic shoots (some subterranean, with cleistogamous flowers) and densely hairy pods, from the former by its curved style, flattened style beak, foveolate seed coat and absence of standard protuberance and horn-like keel pocket in cleistogamous flowers.

Magnetic shield for turbomolecular pump of the Magnetized Plasma Linear Experimental device at Saha Institute of Nuclear Physics.

PubMed

Biswas, Subir; Chattopadhyay, Monobir; Pal, Rabindranath

2011-01-01

The turbo molecular pump of the Magnetized Plasma Linear Experimental device is protected from damage by a magnetic shield. As the pump runs continuously in a magnetic field environment during a plasma physics experiment, it may get damaged owing to eddy current effect. For design and testing of the shield, first we simulate in details various aspects of magnetic shield layouts using a readily available field design code. The performance of the shield made from two half cylinders of soft iron material, is experimentally observed to agree very well with the simulation results.

Aneurysmal SubArachnoid Hemorrhage—Red Blood Cell Transfusion And Outcome (SAHaRA): a pilot randomised controlled trial protocol

PubMed Central

English, Shane W; Fergusson, D; Chassé, M; Lauzier, F; Griesdale, D; Algird, A; Kramer, A; Tinmouth, A; Lum, C; Sinclair, J; Marshall, S; Dowlatshahi, D; Boutin, A; Pagliarello, G; McIntyre, L A

2016-01-01

Introduction Anaemia is common in aneurysmal subarachnoid haemorrhage (aSAH) and is a potential critical modifiable factor affecting secondary injury. Despite physiological evidence and management guidelines that support maintaining a higher haemoglobin level in patients with aSAH, current practice is one of a more restrictive approach to transfusion. The goal of this multicentre pilot trial is to determine the feasibility of successfully conducting a red blood cell (RBC) transfusion trial in adult patients with acute aSAH and anaemia (Hb ≤100 g/L), comparing a liberal transfusion strategy (Hb ≤100 g/L) with a restrictive strategy (Hb ≤80 g/L) on the combined rate of death and severe disability at 12 months. Methods Design This is a multicentre open-label randomised controlled pilot trial at 5 academic tertiary care centres. Population We are targeting adult aSAH patients within 14 days of their initial bleed and with anaemia (Hb ≤110 g/L). Randomisation Central computer-generated randomisation, stratified by centre, will be undertaken from the host centre. Randomisation into 1 of the 2 treatment arms will occur when the haemoglobin levels of eligible patients fall to ≤100 g/L. Intervention Patients will be randomly assigned to either a liberal (threshold: Hb ≤100 g/L) or a restrictive transfusion strategy (threshold: Hb ≤80 g/L). Outcome Primary: Centre randomisation rate over the study period. Secondary: (1) transfusion threshold adherence; (2) study RBC transfusion protocol adherence; and (3) outcome assessment including vital status at hospital discharge, modified Rankin Score at 6 and 12 months and Functional Independence Measure and EuroQOL Quality of Life Scale scores at 12 months. Outcome measures will be reported in aggregate. Ethics and dissemination The study protocol has been approved by the host centre (OHSN-REB 20150433-01H). This study will determine the feasibility of conducting the large pragmatic RCT comparing 2 RBC transfusion strategies examining the effect of a liberal strategy on 12-month outcome following aSAH. Trial registration number NCT02483351; Pre-results. PMID:27927658

Histone deacetylase inhibitors suppress RSV infection and alleviate virus-induced airway inflammation.

PubMed

Feng, Qiuqin; Su, Zhonglan; Song, Shiyu; Χu, Hui; Zhang, Bin; Yi, Long; Tian, Man; Wang, Hongwei

2016-09-01

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and young children. However, the majority of RSV-infected patients only show mild symptoms. Different severities of infection and responses among the RSV-infected population indicate that epigenetic regulation as well as personal genetic background may affect RSV infectivity. Histone deacetylase (HDAC) is an important epigenetic regulator in lung diseases. The present study aimed to explore the possible connection between HDAC expression and RSV-induced lung inflammation. To address this question, RSV-infected airway epithelial cells (BEAS‑2B) were prepared and a mouse model of RSV infection was established, and then treated with various concentrations of HDAC inhibitors (HDACis), namely trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA). Viral replication and markers of virus-induced airway inflammation or oxidative stress were assessed. The activation of the nuclear factor-κB (NF-κB), cyclo-oxygenase-2 (COX-2), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling pathways was evaluated by western blot analysis. Our results showed that RSV infection in airway epithelial cells (AECs) significantly decreased histone acetylation levels by altering HDAC2 expression. The treatment of RSV-infected AECs with HDACis significantly restricted RSV replication by upregulating the interferon-α (IFN-α) related signaling pathways. The treatment of RSV-infected AECs with HDACis also significantly inhibited RSV-induced pro-inflammatory cytokine release [interleukin (IL)-6 and IL-8] and oxidative stress-related molecule production [malondialdehyde (MDA), and nitrogen monoxide (NO)]. The activation of NF-κB, COX-2, MAPK and Stat3, which orchestrate pro‑inflammatory gene expression and oxidative stress injury, was also significantly inhibited. Our in vivo study using a mouse model of

Histone deacetylase inhibitors suppress RSV infection and alleviate virus-induced airway inflammation

PubMed Central

Feng, Qiuqin; Su, Zhonglan; Song, Shiyu; Xu, Hui; Zhang, Bin; Yi, Long; Tian, Man; Wang, Hongwei

2016-01-01

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in infants and young children. However, the majority of RSV-infected patients only show mild symptoms. Different severities of infection and responses among the RSV-infected population indicate that epigenetic regulation as well as personal genetic background may affect RSV infectivity. Histone deacetylase (HDAC) is an important epigenetic regulator in lung diseases. The present study aimed to explore the possible connection between HDAC expression and RSV-induced lung inflammation. To address this question, RSV-infected airway epithelial cells (BEAS-2B) were prepared and a mouse model of RSV infection was established, and then treated with various concentrations of HDAC inhibitors (HDACis), namely trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA). Viral replication and markers of virus-induced airway inflammation or oxidative stress were assessed. The activation of the nuclear factor-κB (NF-κB), cyclo-oxygenase-2 (COX-2), mitogen-activated protein kinase (MAPK) and signal transducer and activator of transcription 3 (STAT3) signaling pathways was evaluated by western blot analysis. Our results showed that RSV infection in airway epithelial cells (AECs) significantly decreased histone acetylation levels by altering HDAC2 expression. The treatment of RSV-infected AECs with HDACis significantly restricted RSV replication by upregulating the interferon-α (IFN-α) related signaling pathways. The treatment of RSV-infected AECs with HDACis also significantly inhibited RSV-induced pro-inflammatory cytokine release [interleukin (IL)-6 and IL-8] and oxidative stress-related molecule production [malondialdehyde (MDA), and nitrogen monoxide (NO)]. The activation of NF-κB, COX-2, MAPK and Stat3, which orchestrate pro-inflammatory gene expression and oxidative stress injury, was also significantly inhibited. Our in vivo study using a mouse model of RSV infection

Excited atoms in the free-burning Ar arc: treatment of the resonance radiation

NASA Astrophysics Data System (ADS)

Golubovskii, Yu; Kalanov, D.; Gortschakow, S.; Baeva, M.; Uhrlandt, D.

2016-11-01

The collisional-radiative model with an emphasis on the accurate treatment of the resonance radiation transport is developed and applied to the free-burning Ar arc plasma. This model allows for analysis of the influence of resonance radiation on the spatial density profiles of the atoms in different excited states. The comparison of the radial density profiles obtained using an effective transition probability approximation with the results of the accurate solution demonstrates the distinct impact of transport on the profiles and absolute densities of the excited atoms, especially in the arc fringes. The departures from the Saha-Boltzmann equilibrium distributions, caused by different radiative transitions, are analyzed. For the case of the DC arc, the local thermodynamic equilibrium (LTE) state holds close to the arc axis, while strong deviations from the equilibrium state on the periphery occur. In the intermediate radial positions the conditions of partial LTE are fulfilled.

Spectroscopic investigations of microwave generated plasmas

NASA Technical Reports Server (NTRS)

Hawley, Martin C.; Haraburda, Scott S.; Dinkel, Duane W.

1991-01-01

The study deals with the plasma behavior as applied to spacecraft propulsion from the perspective of obtaining better design and modeling capabilities. The general theory of spectroscopy is reviewed, and existing methods for converting emission-line intensities into such quantities as temperatures and densities are outlined. Attention is focused on the single-atomic-line and two-line radiance ratio methods, atomic Boltzmann plot, and species concentration. Electronic temperatures for a helium plasma are determined as a function of pressure and a gas-flow rate using these methods, and the concentrations of ions and electrons are predicted from the Saha-Eggert equations using the sets of temperatures obtained as a function of the gas-flow rate. It is observed that the atomic Boltzmann method produces more reliable results for the electronic temperature, while the results obtained from the single-line method reflect the electron temperatures accurately.

Design, synthesis, and evaluation of cyclic amide/imide-bearing hydroxamic acid derivatives as class-selective histone deacetylase (HDAC) inhibitors.

PubMed

Shinji, Chihiro; Maeda, Satoko; Imai, Keisuke; Yoshida, Minoru; Hashimoto, Yuichi; Miyachi, Hiroyuki

2006-11-15

A series of hydroxamic acid derivatives bearing a cyclic amide/imide group as a linker and/or cap structure, prepared during our structural development studies based on thalidomide, showed class-selective potent histone deacetylase (HDAC)-inhibitory activity. Structure-activity relationship studies indicated that the steric character of the substituent introduced at the cyclic amide/imide nitrogen atom, the presence of the amide/imide carbonyl group, the hydroxamic acid structure, the shape of the linking group, and the distance between the zinc-binding hydroxamic acid group and the cap structure are all important for HDAC-inhibitory activity and class selectivity. A representative compound (30w) showed potent p21 promoter activity, comparable with that of trichostatin A (TSA), and its cytostatic activity against cells of the human prostate cell line LNCaP was more potent than that of the well-known HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA).

Too Fast, Too Furious: A Galaxy's Fatal Plunge

NASA Astrophysics Data System (ADS)

2004-01-01

Trailing 200,000-light-year-long streamers of seething gas, a galaxy that was once like our Milky Way is being shredded as it plunges at 4.5 million miles per hour through the heart of a distant cluster of galaxies. In this unusually violent collision with ambient cluster gas, the galaxy is stripped down to its skeletal spiral arms as it is eviscerated of fresh hydrogen for making new stars. The galaxy's untimely demise is offering new clues to solving the mystery of what happens to spiral galaxies in a violent universe. Views of the early universe show that spiral galaxies were once much more abundant in rich clusters of galaxies. But they seem to have been vanishing over cosmic time. Where have these "missing bodies" gone? Astronomers are using a wide range of telescopes and analysis techniques to conduct a "CSI" or Crime Scene Investigator-style look at what is happening to this galaxy inside its cluster's rough neighborhood. "It's a clear case of galaxy assault and battery," says William Keel of the University of Alabama. "This is the first time we have a full suite of results from such disparate techniques showing the crime being committed, and the modus operandi." Keel and colleagues are laying out the "forensic evidence" of the galaxy's late life, in a series of presentations today in Atlanta, Ga., at the 203rd meeting of the American Astronomical Society. Astronomers have assembled the evidence by combining a variety of diagnostic observations from telescopes analyzing the galaxy's appearance in X-ray, optical, and radio light. Parallel observations at different wavelengths trace how stars, gas, and dust are being tossed around and torn from the fragile galaxy, called C153. Though such "distressed" galaxies have been seen before, this one's demise is unusually swift and violent. The galaxy belongs to a cluster of galaxies that slammed into another cluster about 100 million years ago. This galaxy took the brunt of the beating as it fell along a trajectory

The medical officer's journal: HMAS Sydney 1913-1922. An Australian Naval record of surgery and anaesthesia at the time of the outbreak of World War I.

PubMed

McDonald, J M; Todd, E M

2014-07-01

The Medical Officer's Journal of HMAS Sydney was a record kept by the ship's Surgeon, Leonard Darby, of the conditions on the ship and the health, diseases, injuries and treatment of the sailor's under his care. Records of anaesthesia and surgery indicate chloroform was mostly administered as was ether occasionally. There was some use of intravenous and subcutaneous fluids for resuscitation. The journal also provides an eyewitness account of the Sydney-Emden battle on 9 November 1914 which occurred off the Cocos Keeling Islands and was a famous first victory for the young Australian Navy, making headlines around the world. The treatment of the many injured, mostly Germans, is described; with the two Australian surgeons and the surviving German surgeon working together.

The Mauna Loa carbon dioxide record: lessons for long-term Earth observations

USGS Publications Warehouse

Sundquist, Eric T.; Keeling, Ralph F.

2009-01-01

The Mauna Loa carbon dioxide record is an iconic symbol of the human capacity to alter the planet. Yet this record would not have been possible without the remarkable work of one man, Charles David Keeling. We describe three emergent themes that characterized his work: (1) his desire to study and understand the processes that control atmospheric CO2 and the global carbon cycle, (2) his campaign to identify and minimize systematic measurement error, and (3) his tenacious efforts to maintain continuous funding despite changing government priorities and institutions. In many ways, the story of the Mauna Loa record demonstrates that distinctions between research and “routine” measurements are not very useful in long-term monitoring of Earth properties and processes.

Measurements of induced radioactivity in some LDEF samples

NASA Technical Reports Server (NTRS)

Moss, C. E.; Reedy, R. C.

1992-01-01

Twenty-six stainless steel trunnion samples, five aluminum end support retainer plate samples, two aluminum keel plate samples, and two titanium clips were analyzed. The shielded high purity germanium detectors used had efficiencies of 33, 54, and 80 percent at 1332 keV. Detector efficiencies as a function of energy and corrections for self-absorption in the samples were determined with calibrated sources and unactivated control samples. Several measurements were made on most samples. In the trunnion samples, Mn-54 and Co-57 were seen and limits were obtained for other isotopes. The results agree well with 1-D activation calculations for an anisotropic trapped proton model. In the aluminum and titanium samples, Na-22 was detected. Other results are presented.

A Comparative Analysis of Pitch Detection Methods Under the Influence of Different Noise Conditions.

PubMed

Sukhostat, Lyudmila; Imamverdiyev, Yadigar

2015-07-01

Pitch is one of the most important components in various speech processing systems. The aim of this study was to evaluate different pitch detection methods in terms of various noise conditions. Prospective study. For evaluation of pitch detection algorithms, time-domain, frequency-domain, and hybrid methods were considered by using Keele and CSTR speech databases. Each of them has its own advantages and disadvantages. Experiments have shown that BaNa method achieves the highest pitch detection accuracy. The development of methods for pitch detection, which are robust to additive noise at different signal-to-noise ratio, is an important field of research with many opportunities for enhancement the modern methods. Copyright © 2015 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Taxonomic status of Tropiocolotes cf. steudneri with a description of a new species of Tropiocolotes (Reptilia: Squamata: Gekkonidae) in southern Iran.

PubMed

Rajabizadeh, Mahdi; Faizi, Hiva; Anderson, Steven C; Zarrintab, Mohammad; Nazarov, Roman

2018-03-01

We review the status of an Iranian gecko population previously referred to Tropiocolotes cf. steudneri and describe it as a new species, Tropiocolotes hormozganensis sp. nov. We discuss the taxonomic history of this population and compare its characters with those of the other species in the genus. The new species is distinguished from other species of Tropiocolotes by possessing weakly keeled dorsal scales and smooth ventral scales, having imbricate scales on dorsal and ventral tail, possessing clearly tricarinatesubdigital scales, 48-55 dorsal scales, two pairs of postmental shields, of which the second pair is about half of the size of the first, 100-107 scales longitudinally along underside of body, 15-19 scales across head and 16-19 subdigital lamellae.

Processes of lithosphere evolution: New evidence on the structure of the continental crust and uppermost mantle

USGS Publications Warehouse

Artemieva, I.M.; Mooney, W.D.; Perchuc, E.; Thybo, H.

2002-01-01

We discuss the structure of the continental lithosphere, its physical properties, and the mechanisms that formed and modified it since the early Archean. The structure of the upper mantle and the crust is derived primarily from global and regional seismic tomography studies of Eurasia and from global and regional data on seismic anisotropy. These data as documented in the papers of this special issue of Tectonophysics are used to illustrate the role of different tectonic processes in the lithospheric evolution since Archean to present. These include, but are not limited to, cratonization, terrane accretion and collision, continental rifting (both passive and active), subduction, and lithospheric basal erosion due to a relative motion of cratonic keels and the convective mantle. ?? 2002 Elsevier Science B.V. All rights reserved.

Automatic three-dimensional measurement of large-scale structure based on vision metrology.

PubMed

Zhu, Zhaokun; Guan, Banglei; Zhang, Xiaohu; Li, Daokui; Yu, Qifeng

2014-01-01

All relevant key techniques involved in photogrammetric vision metrology for fully automatic 3D measurement of large-scale structure are studied. A new kind of coded target consisting of circular retroreflective discs is designed, and corresponding detection and recognition algorithms based on blob detection and clustering are presented. Then a three-stage strategy starting with view clustering is proposed to achieve automatic network orientation. As for matching of noncoded targets, the concept of matching path is proposed, and matches for each noncoded target are found by determination of the optimal matching path, based on a novel voting strategy, among all possible ones. Experiments on a fixed keel of airship have been conducted to verify the effectiveness and measuring accuracy of the proposed methods.

RS Ophiuchi: The Gift that Keeps on Giving

NASA Astrophysics Data System (ADS)

Starrfield, S.

2008-12-01

RS Oph experienced its sixth recorded outburst in 2006 and was observed in virtually every wavelength region from hard X-rays to the radio. Each observation, especially those with instruments that have come online since its last outburst in 1985, provided new and exciting information about the explosion. As a result, some of us organized a second workshop on the RS Oph outburst and it was held in June 2007 at Keele University. I gave the lead off talk in which I presented a number of questions to be discussed during the workshop, a brief summary of what had been discovered in previous outbursts concentrating on the ultraviolet studies with IUE, and a few observations of the 2006 outburst concentrating on the results from Swift and HST.

Measurements of induced radioactivity in some LDEF samples

NASA Technical Reports Server (NTRS)

Moss, C. E.; Reedy, R. C.

1991-01-01

Twenty-six stainless steel trunnion samples, five aluminum end support retainer plate samples, two aluminum keel plate samples, and two titanium clips were analyzed. The shielded high purity germanium detectors used had efficiencies of 33, 54, and 80 pcts. at 1332 keV. Detector efficiencies as a function of energy and corrections for self absorption in the samples were determined with calibrated sources, unactivated control samples, and calculations. Several measurements were made on most samples. In the trunnion samples, Mn-54 and Co-57 were seen and limits were obtained for other isotopes. The results agree well with 1-D activation calculations for an anisotropic trapped proton model. In the aluminum samples, Na-22 and Be-7 were seen. Other results are presented.

Proposed CMG momentum management scheme for space station

NASA Technical Reports Server (NTRS)

Bishop, L. R.; Bishop, R. H.; Lindsay, K. L.

1987-01-01

A discrete control moment gyro (CMG) momentum management scheme (MMS) applicable to spacecraft with principal axes misalignments, such as the proposed NASA dual keel space station, is presented in this paper. The objective of the MMS is to minmize CMG angular momentum storage requirements for maintaining the space station near local vertical in the presence of environmental disturbances. It utilizes available environmental disturbances, namely gravity gradient torques, to minimize CMG momentum storage. The MMS is executed once per orbit and generates a commanded torque equilibrium attitude (TEA) time history which consists of a yaw, pitch and roll angle command profile. Although the algorithm is called only once per orbit to compute the TEA profile, the space station will maneuver several discrete times each orbit.

Adaptive momentum management for large space structures

NASA Technical Reports Server (NTRS)

Hahn, E.

1987-01-01

Momentum management is discussed for a Large Space Structure (LSS) with the structure selected configuration being the Initial Orbital Configuration (IOC) of the dual keel space station. The external forces considered were gravity gradient and aerodynamic torques. The goal of the momentum management scheme developed is to remove the bias components of the external torques and center the cyclic components of the stored angular momentum. The scheme investigated is adaptive to uncertainties of the inertia tensor and requires only approximate knowledge of principle moments of inertia. Computational requirements are minimal and should present no implementation problem in a flight type computer and the method proposed is shown to be effective in the presence of attitude control bandwidths as low as .01 radian/sec.

M6-C artificial disc placement.

PubMed

Coric, Domagoj; Parish, John; Boltes, Margaret O

2017-01-01

There has been a steady evolution of cervical total disc replacement (TDR) devices over the last decade resulting in surgical technique that closely mimics anterior cervical discectomy and fusion as well as disc design that emphasizes quality of motion. The M6-C TDR device is a modern-generation artificial disc composed of titanium endplates with tri-keel fixation as well as a polyethylene weave with a polyurethane core. Although not yet approved by the FDA, M6-C has finished a pilot and pivotal US Investigational Device Exemption (IDE) study. The authors present the surgical technique for implantation of a 2-level M6-C cervical TDR device. The video can be found here: https://youtu.be/rFEAqINLRCo .

Vigna pandeyana (Fabaceae), a new species from northern Western Ghats, India

PubMed Central

Gaikwad, Sayajirao; Randive, Sonali

2015-01-01

Abstract Background Vigna subg. Ceratotropis (Piper) Verdc. represents a homogenous and distinct group of species with highly specialized complex floral characters. It is most diverse in Asia. India, with 24 species, represents a secondary center of species diversity of the subgenus. New information A new species, Vigna pandeyana RD Gore, SP Gaikwad & SD Randive, is described from hill slopes of the northern Western Ghats of India. It resembles Vigna yadavii Gaikwad et al. and Vigna dalzelliana (Kuntze) Verdc. but differs from the latter in its dimorphic shoots (some subterranean, with cleistogamous flowers) and densely hairy pods, from the former by its curved style, flattened style beak, foveolate seed coat and absence of standard protuberance and horn-like keel pocket in cleistogamous flowers. PMID:25829861

HUBBLE SPACE TELESCOPE ON TRACK FOR MEASURING THE EXPANSION RATE OF THE UNIVERSE

NASA Technical Reports Server (NTRS)

2002-01-01

Two international teams of astronomers, using NASA's Hubble Space Telescope, are reporting major progress in converging on an accurate measurement of the Universe's rate of expansion -- a value which has been debated for over half a century. These new results yield ranges for the age of the Universe from 9-12 billion years, and 11-14 billion years, respectively. The goal of the project is to measure the Hubble Constant to ten percent accuracy. The Hubble Space Telescope Key Project team, an international group of over 20 astronomers, is led by Wendy Freedman of Carnegie Observatories, Pasadena, CA, Robert Kennicutt, University of Arizona, Tucson, AZ, and Jeremy Mould, Mount Stromlo and Siding Springs Observatory, Australia. The group's interim results, announced at a meeting held at the Space Telescope Science Institute (STScI) in Baltimore, Maryland, are consistent with their preliminary result, announced in 1994, of 80 kilometers per second per megaparsec (km/sec/Mpc), based on observations of a galaxy in the Virgo cluster. 'We have five different ways of measuring the Hubble Constant with HST,' said Dr. Freedman. 'The results are coming in between 68 and 78 km/sec/Mpc.' (For example, at an expansion rate of 75 km/sec/Mpc, galaxies appear to be receding from us at a rate of 162,000 miles per hour for every 3.26 million light-years farther out we look). Two months ago, a second team, led by Allan Sandage, also of the Carnegie Observatories, Abhijit Saha, STScI, Gustav Tammann and Lukas Labhardt, Astronomical Institute, University of Basel, Duccio Macchetto and Nino Panagia, STScI/European Space Agency, reported a slower expansion rate of 57 km/sec/Mpc. The value of the Hubble Constant allows astronomers to calculate the expansion age of the Universe, the time elapsed since the Big Bang. Astronomers have been arguing recently whether the time since the Big Bang is consistent with the ages of the oldest stars. The ages are calculated from combining the expansion

Pulsed electromagnetic gas acceleration

NASA Technical Reports Server (NTRS)

Jahn, R. G.; Vonjaskowsky, W. F.; Clark, K. E.

1975-01-01

Terminal voltage measurements with long cathodes in a high power, quasi-steady MPD discharge show that the critical current for the onset of voltage fluctuations, which was previously shown to be a function of cathode area, approaches an asymptote for cathodes of very large surface area. Floating potential measurements and photographs of the discharge luminosity indicate that the fluctuations are confined to the vicinity of the cathode and hence reflect a cathode emission process rather than a fundamental limit on MPD performance. Photoelectric measurements of particular argon neutral and ion transitions show that the higher electronic states are populated more heavily than would be calculated on the basis of Saha-Boltzmann equilibrium at the local electron temperature and number density. Preliminary optical depth measurements show that for a current of 4 kA and an argon mass flow of 12 g/sec, a population inversion exists between the upper and lower states of the 4880 A argon ion transition.

Wiedemann-Franz ratio in high-pressure and low-temperature thermal xenon plasma with 10% caesium

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

Novakovic, N.V.; Milic, B.S.; Stojilkovic, S.M.

1995-12-31

Theoretical investigations of various transport properties of low-temperature noble-gas plasmas with additives has aroused a continuous interest over a considerable spall of time, due to numerous applications. In this paper the results of a theoretical evaluation of electrical conductivity, thermal conductivity and their ratio (the Wiedemann-Franz ratio) in xenon plasma with 10% of argon and 10% of caesium are presented, for the temperature range from 2000 K to 20000 K, and for pressures equal to or 5, 10, and 15 time higher than the normal atmospheric pressure. The plasma was regarded as weakly non-ideal and in the state of localmore » thermodynamical equilibrium with the assumption that the equilibrium is attained with the pressure kept constant. The plasma composition was determined on the ground of a set of Saha equations; the ionization energy lowerings were expressed with the aid of a modified plasma Debye radius r*{sub D} (rather than the standard r{sub D}), as proposed previously.« less

Differential protein acetylation induced by novel histone deacetylase inhibitors.

PubMed

Glaser, K B; Li, J; Pease, L J; Staver, M J; Marcotte, P A; Guo, J; Frey, R R; Garland, R B; Heyman, H R; Wada, C K; Vasudevan, A; Michaelides, M R; Davidsen, S K; Curtin, M L

2004-12-17

Histone deacetylase (HDAC) inhibitors induce the hyperacetylation of nucleosomal histones in carcinoma cells resulting in the expression of repressed genes that cause growth arrest, terminal differentiation, and/or apoptosis. In vitro selectivity of several novel hydroxamate HDAC inhibitors including succinimide macrocyclic hydroxamates and the non-hydroxamate alpha-ketoamide inhibitors was investigated using isolated enzyme preparations and cellular assays. In vitro selectivity for the HDAC isozymes (HDAC1/2, 3, 4/3, and 6) was not observed for these HDAC inhibitors or the reference HDAC inhibitors, MS-275 and SAHA. In T24 and HCT116 cells these compounds caused the accumulation of acetylated histones H3 and H4; however, the succinimide macrocyclic hydroxamates and the alpha-ketoamides did not cause the accumulation of acetylated alpha-tubulin. These data suggest "selectivity" can be observed at the cellular level with HDAC inhibitors and that the nature of the zinc-chelating moiety is an important determinant of activity against tubulin deacetylase.

Multi-charge-state molecular dynamics and self-diffusion coefficient in the warm dense matter regime

NASA Astrophysics Data System (ADS)

Fu, Yongsheng; Hou, Yong; Kang, Dongdong; Gao, Cheng; Jin, Fengtao; Yuan, Jianmin

2018-01-01

We present a multi-ion molecular dynamics (MIMD) simulation and apply it to calculating the self-diffusion coefficients of ions with different charge-states in the warm dense matter (WDM) regime. First, the method is used for the self-consistent calculation of electron structures of different charge-state ions in the ion sphere, with the ion-sphere radii being determined by the plasma density and the ion charges. The ionic fraction is then obtained by solving the Saha equation, taking account of interactions among different charge-state ions in the system, and ion-ion pair potentials are computed using the modified Gordon-Kim method in the framework of temperature-dependent density functional theory on the basis of the electron structures. Finally, MIMD is used to calculate ionic self-diffusion coefficients from the velocity correlation function according to the Green-Kubo relation. A comparison with the results of the average-atom model shows that different statistical processes will influence the ionic diffusion coefficient in the WDM regime.

Diffusion of external magnetic fields into the cone-in-shell target in the fast ignition

NASA Astrophysics Data System (ADS)

Sunahara, Atsushi; Morita, Hiroki; Johzaki, Tomoyuki; Nagatomo, Hideo; Fujioka, Shinsuke; Hassanein, Ahmed; Firex Project Team

2017-10-01

We simulated the diffusion of externally applied magnetic fields into cone-in-shell target in the fast ignition. Recently, in the fast ignition scheme, the externally magnetic fields up to kilo-Tesla is used to guide fast electrons to the high-dense imploded core. In order to study the profile of the magnetic field, we have developed 2D cylindrical Maxwell equation solver with Ohm's law, and carried out simulations of diffusion of externally applied magnetic fields into a cone-in-shell target. We estimated the conductivity of the cone and shell target based on the assumption of Saha-ionization equilibrium. Also, we calculated the temporal evolution of the target temperature heated by the eddy current driven by temporal variation of magnetic fields, based on the accurate equation of state. Both, the diffusion of magnetic field and the increase of target temperature interact with each other. We present our results of temporal evolution of the magnetic field and its diffusion into the cone and shell target.

Influence of the plasma environment on atomic structure using an ion-sphere model

DOE PAGES

Belkhiri, Madeny Jean; Fontes, Christopher John; Poirier, Michel

2015-09-03

Plasma environment effects on atomic structure are analyzed using various atomic structure codes. To monitor the effect of high free-electron density or low temperatures, Fermi-Dirac and Maxwell-Boltzmann statistics are compared. After a discussion of the implementation of the Fermi-Dirac approach within the ion-sphere model, several applications are considered. In order to check the consistency of the modifications brought here to extant codes, calculations have been performed using the Los Alamos Cowan Atomic Structure (cats) code in its Hartree-Fock or Hartree-Fock-Slater form and the parametric potential Flexible Atomic Code (fac). The ground-state energy shifts due to the plasma effects for themore » six most ionized aluminum ions have been calculated using the fac and cats codes and fairly agree. For the intercombination resonance line in Fe 22+, the plasma effect within the uniform electron gas model results in a positive shift that agrees with the MCDF value of B. Saha et al.« less

Influence of the plasma environment on atomic structure using an ion-sphere model

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

Belkhiri, Madeny Jean; Fontes, Christopher John; Poirier, Michel

Plasma environment effects on atomic structure are analyzed using various atomic structure codes. To monitor the effect of high free-electron density or low temperatures, Fermi-Dirac and Maxwell-Boltzmann statistics are compared. After a discussion of the implementation of the Fermi-Dirac approach within the ion-sphere model, several applications are considered. In order to check the consistency of the modifications brought here to extant codes, calculations have been performed using the Los Alamos Cowan Atomic Structure (cats) code in its Hartree-Fock or Hartree-Fock-Slater form and the parametric potential Flexible Atomic Code (fac). The ground-state energy shifts due to the plasma effects for themore » six most ionized aluminum ions have been calculated using the fac and cats codes and fairly agree. For the intercombination resonance line in Fe 22+, the plasma effect within the uniform electron gas model results in a positive shift that agrees with the MCDF value of B. Saha et al.« less

Electron Impact Ionization of Heavier Ions including relativistic effects

NASA Astrophysics Data System (ADS)

Saha, B. C.; Haque, A. K. F.; Uddin, M. A.; Basak, A. K.

2006-11-01

The demands of the electron impact ionization cross sections in diverse fields are enormous. And this is hard to fulfill either by experimental or ab initio calculations. So various analytical and semi-classical models are applied for a rapid generation of ionization cross sections accurately. We have applied a modified version [1] of the Bell et. al. equations [2] including both the ionic and relativistic corrections. In this report we show how to generalize the MBELL parameters for treating the orbital quantum numbers nl dependency; the accuracy of the procedure is tested by evaluating cross sections for various species and energies. Detail results will be presented at the meeting. [1] A. K. F. Haque, M. A. Uddin, A. K. Basak, K. R. Karim and B. C. Saha, Phys. Rev. A73, 052703 (2006). [2] K. L. Bell, H. B. Gilbody, J. G. Hughes, A. E. Kingston, and F. J. Smith, J. Phys. Chem. Ref. Data 12, 891 (1983).

Notch3 overexpression enhances progression and chemoresistance of urothelial carcinoma.

PubMed

Zhang, Heng; Liu, Limei; Liu, Chungang; Pan, Jinhong; Lu, Gensheng; Zhou, Zhansong; Chen, Zhiwen; Qian, Cheng

2017-05-23

Abnormal activation of Notch signaling is involved in the etiology of various diseases, including cancer, but the association between Notch3 expression in urothelial cancer and clinical outcome remains unclear, and the molecular mechanisms underlying Notch3 signaling activation are not well defined. In this study we examined 59 urothelial cancer patients and found that Notch3 was more highly expressed in human urothelial cancer tissues than in non-tumorous bladder tissue samples, with Notch3 overexpression being associated with poor clinical outcome. Notch3 knockdown resulted in decreased proliferation of urothelial cancer cells in vitro and decreased xenograft tumor growth in vivo. In addition, Notch3 knockdown rendered urothelial cancer cells more sensitive to cisplatin. Furthermore, suberoylanilide hydroxamic acid (SAHA, a histone deacetylase [HDAC] inhibitor) induced acetylation of NOTCH3, downregulated Notch 3, prevented urothelial cancer cell proliferation, and induced cell cycle arrest. Taken together, these data suggested that Notch 3 overexpression promotes growth and chemoresistance in urothelial cancer.

Notch3 overexpression enhances progression and chemoresistance of urothelial carcinoma

PubMed Central

Zhang, Heng; Liu, Limei; Liu, Chungang; Pan, Jinhong; Lu, Gensheng; Zhou, Zhansong; Chen, Zhiwen; Qian, Cheng

2017-01-01

Abnormal activation of Notch signaling is involved in the etiology of various diseases, including cancer, but the association between Notch3 expression in urothelial cancer and clinical outcome remains unclear, and the molecular mechanisms underlying Notch3 signaling activation are not well defined. In this study we examined 59 urothelial cancer patients and found that Notch3 was more highly expressed in human urothelial cancer tissues than in non-tumorous bladder tissue samples, with Notch3 overexpression being associated with poor clinical outcome. Notch3 knockdown resulted in decreased proliferation of urothelial cancer cells in vitro and decreased xenograft tumor growth in vivo. In addition, Notch3 knockdown rendered urothelial cancer cells more sensitive to cisplatin. Furthermore, suberoylanilide hydroxamic acid (SAHA, a histone deacetylase [HDAC] inhibitor) induced acetylation of NOTCH3, downregulated Notch 3, prevented urothelial cancer cell proliferation, and induced cell cycle arrest. Taken together, these data suggested that Notch 3 overexpression promotes growth and chemoresistance in urothelial cancer. PMID:28416766