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.

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

(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.

SAHA-induced TRAIL-sensitisation of Multiple Myeloma cells is enhanced in 3D cell culture.

PubMed

Arhoma, A; Chantry, A D; Haywood-Small, S L; Cross, N A

2017-11-15

Multiple Myeloma (MM) is currently incurable despite many novel therapies. Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) is a potential anti-tumour agent although effects as a single agent are limited. In this study, we investigated whether the Histone Deacetylase (HDAC) inhibitor SAHA can enhance TRAIL-induced apoptosis and target TRAIL resistance in both suspension culture, and 3D cell culture as a model of disseminated MM lesions that form in bone. The effects of SAHA and/or TRAIL in 6 Multiple Myeloma cell lines were assessed in both suspension cultures and in an Alginate-based 3D cell culture model. The effect of SAHA and/or TRAIL was assessed on apoptosis by assessment of nuclear morphology using Hoechst 33342/Propidium Iodide staining. Viable cell number was assessed by CellTiter-Glo luminescence assay, Caspase-8 and -9 activities were measured by Caspase-Glo™ assay kit. TRAIL-resistant cells were generated by culture of RPMI 8226 and NCI-H929 by acute exposure to TRAIL followed by selection of TRAIL-resistant cells. TRAIL significantly induced apoptosis in a dose-dependent manner in OPM-2, RPMI 8226, NCI-H929, U266, JJN-3 MM cell lines and ADC-1 plasma cell leukaemia cells. SAHA amplified TRAIL responses in all lines except OPM-2, and enhanced TRAIL responses were both via Caspase-8 and -9. SAHA treatment induced growth inhibition that further increased in the combination treatment with TRAIL in MM cells. The co-treatment of TRAIL and SAHA reduced viable cell numbers all cell lines. TRAIL responses were further potentiated by SAHA in 3D cell culture in NCI-H929, RPMI 8226 and U266 at lower TRAIL + SAHA doses than in suspension culture. However TRAIL responses in cells that had been selected for TRAIL resistance were not further enhanced by SAHA treatment. SAHA is a potent sensitizer of TRAIL responses in both TRAIL sensitive and resistant cell lines, in both suspension and 3D culture, however SAHA did not sensitise TRAIL-sensitive cell populations that had been selected for TRAIL-resistance from initially TRAIL-sensitive populations. SAHA may increase TRAIL sensitivity in insensitive cells, but not in cells that have specifically been selected for acquired TRAIL-resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

Facility shows benefit of staying single.

PubMed

Baillie, Jonathan

2010-08-01

Construction of the new 513-bed PFI-funded hospital in Pembury near Tunbridge Wells in Kent, a pound 227 million acute healthcare facility that, on its completion in the autumn of 2011, will be the UK's first to offer 100% single-bed en suite accommodation, is ahead of schedule, "thanks to excellent teamwork and careful planning". During a visit to the now rapidly emerging healthcare facility, located in an Area of Outstanding Natural Beauty (AONB) in a wooded hillside location in the Weald of Kent which Nigel Keen, general manager for the PFI project company, described as "the most attractive site for a hospital I have ever worked on", HEJ editor Jonathan Baillie met key project personnel and discussed the impressive progress made to date.

UK's first NHS high-energy proton beam facility.

PubMed

Shaw, Phil

2017-05-01

With the UK's first high-energy Proton Beam Therapy Centre set to open next year at Manchester's The Christie, young patients with head and neck tumours, cancers close to the skull or spine, or a variety of soft tissue tumours, and adults with cancers difficult to treat using 'conventional' photon-based radiotherapy will, for the first time, be able to receive NHS proton beam therapy (PBT) without having to travel overseas. HEJ editor, Jonathan Baillie, visited the site of The Christie's new £135 million PBT Centre to find out more about the design and construction of a facility which interserve construction director for the North-West, Phil Shaw, describes as one of the most complex and specialist he has worked on.

Significant growth in. LED use predicted.

PubMed

Simpson, Mike

2012-03-01

Although LED lighting has its critics, a number of whom (see article 'LED--panacea or marketing hype', HEJ--February 2012) are concerned about what they claim are some manufacturers' 'exaggerated claims' about lighting efficiency and lamp lifetime, Philips Lighting believes that, such are the advances being made in this innovative lighting technology, that LED's overall share of the European lighting market will have risen from around 7% in 2008 to 25% by 2020 and that, a decade later, it will account for a remarkable 75% of lighting sales. In the UK, Philips' technical and design director for Lighting, Mike Simpson, told HEJ editor, Jonathan Baillie, healthcare estates and facilities managers are increasingly recognising the potential to save energy, reduce carbon emissions, and cut maintenance costs, using LED.

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.

Tolerogenic Dendritic Cells Generated by In Vitro Treatment With SAHA Are Not Stable In Vivo.

PubMed

Thewissen, Kristof; Broux, Bieke; Hendriks, Jerome J A; Vanhees, Mandy; Stinissen, Piet; Slaets, Helena; Hellings, Niels

2016-01-01

The aim of this study is to examine whether the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), can generate dendritic cells (DCs) with a stable tolerogenic phenotype to counteract autoimmune responses in an animal model of multiple sclerosis. We investigated if the tolerogenic potency of DCs could be increased by continuous treatment during in vitro differentiation toward DCs compared to standard 24-h in vitro treatment of already terminally differentiated DCs. We show that in vitro treatment with SAHA reduces the generation of new CD11c(+) DCs out of mouse bone marrow. SAHA-generated DCs show reduced antigen-presenting function as evidenced by a reduction in myelin endocytosis, a decreased MHC II expression, and a failure to upregulate costimulatory molecules upon LPS challenge. In addition, SAHA-generated DCs display a reduction in proinflammatory cytokines and molecules involved in apoptosis induction, inflammatory migration, and TLR signaling, and they are less immunostimulatory compared to untreated DCs. We demonstrated that the underlying mechanism involves a diminished STAT1 phosphorylation and was independent of STAT6 activation. Although in vitro results were promising, SAHA-generated DCs were not able to alleviate the development of experimental autoimmune encephalomyelitis in mice. In vitro washout experiments demonstrated that the tolerogenic phenotype of SAHA-treated DCs is reversible. Taken together, while SAHA potently boosts tolerogenic properties in DCs during the differentiation process in vitro, SAHA-generated DCs were unable to reduce autoimmunity in vivo. Our results imply that caution needs to be taken when developing DC-based therapies to induce tolerance in the context of autoimmune disease.

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.

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.

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

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.

The HDAC inhibitor SAHA does not rescue CFTR membrane expression in Cystic Fibrosis.

PubMed

Bergougnoux, Anne; Petit, Aurélie; Knabe, Lucie; Bribes, Estelle; Chiron, Raphaël; De Sario, Albertina; Claustres, Mireille; Molinari, Nicolas; Vachier, Isabelle; Taulan-Cadars, Magali; Bourdin, Arnaud

2017-07-01

The development of suitable Cystic Fibrosis (CF) models for preclinical bench tests of therapeutic candidates is challenging. Indeed, the validation of molecules to rescue the p.Phe508del-CFTR channel (encoded by the Cystic Fibrosis Transmembrane conductance Regulator gene carrying the p.Phe508del mutation) requires taking into account their overall effects on the epithelium. Suberoylanilide Hydroxamic Acid (SAHA), a histone deacetylase inhibitor (HDACi), was previously shown to be a CFTR corrector via proteostasis modulation in CFTR-deficient immortalized cells. Here, we tested SAHA effects on goblet cell metaplasia using an ex vivo model based on the air-liquid interface (ALI) culture of differentiated airway epithelial cells obtained by nasal scraping from CF patients and healthy controls. Ex vivo epithelium grew successfully in ALI cultures with significant rise in the expression of CFTR and of markers of airway epithelial differentiation compared to monolayer cell culture. SAHA decreased CFTR transcript and protein levels in CF and non-CF epithelia. Whereas SAHA induced lysine hyperacetylation, it did not change histone modifications at the CFTR promoter. SAHA reduced MUC5AC and MUC5B expression and inhibited goblet epithelial cell differentiation. Similar effects were obtained in CF and non-CF epithelia. All the effects were fully reversible within five days from SAHA withdrawal. We conclude that, ex vivo, SAHA modulate the structure of airway epithelia without specific effect on CFTR gene and protein suggesting that HDACi cannot be useful for CF treatment. Copyright © 2017. Published by Elsevier Ltd.

Simultaneous acquisition sequence for improved hepatic pharmacokinetics quantification accuracy (SAHA) for dynamic contrast-enhanced MRI of liver.

PubMed

Ning, Jia; Sun, Yongliang; Xie, Sheng; Zhang, Bida; Huang, Feng; Koken, Peter; Smink, Jouke; Yuan, Chun; Chen, Huijun

2018-05-01

To propose a simultaneous acquisition sequence for improved hepatic pharmacokinetics quantification accuracy (SAHA) method for liver dynamic contrast-enhanced MRI. The proposed SAHA simultaneously acquired high temporal-resolution 2D images for vascular input function extraction using Cartesian sampling and 3D large-coverage high spatial-resolution liver dynamic contrast-enhanced images using golden angle stack-of-stars acquisition in an interleaved way. Simulations were conducted to investigate the accuracy of SAHA in pharmacokinetic analysis. A healthy volunteer and three patients with cirrhosis or hepatocellular carcinoma were included in the study to investigate the feasibility of SAHA in vivo. Simulation studies showed that SAHA can provide closer results to the true values and lower root mean square error of estimated pharmacokinetic parameters in all of the tested scenarios. The in vivo scans of subjects provided fair image quality of both 2D images for arterial input function and portal venous input function and 3D whole liver images. The in vivo fitting results showed that the perfusion parameters of healthy liver were significantly different from those of cirrhotic liver and HCC. The proposed SAHA can provide improved accuracy in pharmacokinetic modeling and is feasible in human liver dynamic contrast-enhanced MRI, suggesting that SAHA is a potential tool for liver dynamic contrast-enhanced MRI. Magn Reson Med 79:2629-2641, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

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.

Better protecting staff working alone.

PubMed

Swindlehurst, Darren

2016-08-01

Established four and a half years ago as a wholly-owned subsidiary of Dutch-headquartered personal security and critical communications solutions provider, Atus BV, Hereford-based Atus Systems has since established a strong UK-wide client base supplying personal pagers, wireless personal alarm units, and the associated infrastructure, predominantly to high secure mental health facilities, prisons, and detention centres. Recent months, however, mark a new chapter for it, with the launch of a 'unique' lone worker protection system able to identify such personnel's location even when they are indoors and out of range of GPS coverage, and a sophisticated two-way enterprise critical messaging system. As HEJ editor, Jonathan Baillie, discovered from MD, Darren Swindlehurst, the company will target both systems squarely at the NHS and private healthcare providers, as well as at its more 'traditional' customers.

Move signals the 'start of new era'.

PubMed

Baillie, Jonathan

2012-10-01

Thirty-one years after its establishment in a small office in Wigan, independent life safety equipment manufacturer, C-TEC, has moved into a new 75,000 ft2 factory, 'the size of three football pitches', marking the start of what founder and MD, Andrew Foster, dubs 'the next phase in our exciting development'. The past year has also seen the firm busy on the new product front, with the launch of a 'revolutionary' new range of touchscreen-controlled analogue addressable fire alarms panels which the company claims will put it 'way ahead of the competition', and, in response to demand from nursing and care home operator customers, the introduction of a range of components designed to facilitate dementia care as an extension to its well-established Quantec addressable call system. HEJ editor, Jonathan Baillie, reports.

Dementia-friendly design resource.

PubMed

Baillie, Jonathan

2014-02-01

Although estimates suggest that, on average, some 30 per cent of all patients in general acute medical wards may have some form of dementia, Stirling University's Dementia Services Development Centre (DSDC), one of the leading international knowledge centres working to improve the lives of dementia sufferers, says progress in designing healthcare facilities that address such patients' needs has been 'patchy at best'. With the number of individuals living with dementia expected to double in the next 25 years, the DSDC has recently worked with Edinburgh-based architects, Burnett Pollock Associates, to develop an online resource that clearly illustrates, via 15 simulated 'dementia-friendly' healthcare 'spaces', some of the key principles to consider when designing effectively for this fast-growing group. HEJ editor, Jonathan Baillie, attended the launch of the so-called 'Virtual Hospital'.

ProCure21+ should speed scheme starts.

PubMed

Baillie, Jonathan

2010-11-01

This October saw the launch of the new ProCure21+ National Framework under which, the Department of Health (DH) team behind the new scheme claims, the NHS can potentially save a further pound 200 million of public money on top of the substantial sums saved under predecessor, ProCure21, via faster, more streamlined procurement, design, planning, and construction, of publicly-funded healthcare schemes. HEJ editor Jonathan Baillie discussed, with the DH's senior responsible officer (SRO) and P21+ team leader Peter Sellars, the background to the new Framework's introduction, the success of its forerunner, and the additional benefits that ProCure21 + (which is backed by organisations incuding HM Treasury, the National Audit Office, and the Office of Government Commerce) should bring to the entire healthcare building supply chain.

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.

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.

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

SAHA Suppresses Peritoneal Fibrosis in Mice

PubMed Central

Io, Kumiko; Nishino, Tomoya; Obata, Yoko; Kitamura, Mineaki; Koji, Takehiko; Kohno, Shigeru

2015-01-01

♦ Objective: Long-term peritoneal dialysis causes peritoneal fibrosis in submesothelial areas. However, the mechanism of peritoneal fibrosis is unclear. Epigenetics is the mechanism to induce heritable changes without any changes in DNA sequences. Among epigenetic modifications, histone acetylation leads to the transcriptional activation of genes. Recent studies indicate that histone acetylation is involved in the progression of fibrosis. Therefore, we examined the effect of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, on the progression of peritoneal fibrosis in mice. ♦ Methods: Peritoneal fibrosis was induced by the injection of chlorhexidine gluconate (CG) into the peritoneal cavity of mice every other day for 3 weeks. SAHA, or a dimethylsulfoxide and saline vehicle, was administered subcutaneously every day from the start of the CG injections for 3 weeks. Morphologic peritoneal changes were assessed by Masson’s trichrome staining, and fibrosis-associated factors were assessed by immunohistochemistry. ♦ Results: In CG-injected mice, a marked thickening of the submesothelial compact zone was observed. In contrast, the administration of SAHA suppressed the progression of submesothelial thickening and type III collagen accumulation in CG-injected mice. The numbers of fibroblast-specific protein-1-positive cells and α-smooth muscle actin α-positive cells were significantly decreased in the CG + SAHA group compared to that of the CG group. The level of histone acetylation was reduced in the peritoneum of the CG group, whereas it was increased in the CG + SAHA group. ♦ Conclusions: Our results indicate that SAHA can suppress peritoneal thickening and fibrosis in mice through up-regulation of histone acetylation. These results suggest that SAHA may have therapeutic potential for treating peritoneal fibrosis. PMID:24584598

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

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 inhibitors can be used as lead compounds and as a chemical tool to study HDAC related cancer biology. The observed enhancement of selectivity upon modifying the linker region of the non-selective inhibitor SAHA shows that modifying current drugs, like SAHA, could lead to substantial improvement in its pharmacodynamic properties.

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 of interest were: Thermodynamics, transport theory and statistical mechanics in the context of continuum modeling discrete systems; Statistical mechanics and dynamics of fluid flows; Continuum mechanics of complex fluids and deformable solids with microstructure; Fundamentals of fracture, defect dynamics, fatigue, and fracture dynamics; Statics and dynamics of dislocations, dislocation mediated phase transitions and plasticity; Granular materials: statics and dynamics; Physics and mechanics of earthquakes; Transport in composite materials; and Continuum theory of soft matter systems of biological motivation and living structures. The scientific program consisted of General Lectures and Research Communications. The four General Lectures (40 min + 5 min) introduced the most recent ideas and advances in the fields covered. The 25 Research Communications reported new results and methods in these fields and were presented orally (30 min + 5 min). In addition there were 15 posters which also presented interesting results and five of these posters were selected by a special committee chaired by David J Bergman to contribute to this proceedings. The selected five posters were presented by Moutushi D Choudhury, Morten Grova, Arya Paul, Arnab Saha and Amartya Sarkar. We were happy to note that 32 scientists from ten countries and a large number of students (both from India and other countries) participated in this symposium. The talks and poster sessions generated a lot of discussions, arguments and collaborations. The articles that appear in this proceedings are based on the invited talks and selected poster presentations. We would like to thank the Journal of Physics Conference Series (IOP Publishing) for publishing the proceedings of the conference. We would also like to thank all the contributors to this proceedings for their kind co-operation and the referees for their prompt and active support. A number of invited participants (Amit Acharya, Alexander Altland, Kamal K Bardhan, Davide Bigoni, Andrej Cherkaev, Hikaru Kawamura, Subhasish Mazumder, Srutarshi Pradhan, Jacques Prost, Sriram Ramaswamy, Ping Sheng, Asok K Sen) were unable to contribute to this proceedings volume; on the other hand, although Kamal could not participate in the symposium, he contributed to the proceedings volume. We are grateful to Lucilla de Arcangelis, Kamal K Bardhan, Abhik Basu, Jayanta K Bhattacharjee, Andrej Cherkaev, Yilong Han, Alex Hansen, Takahiro Hatano, Esin Inan, Hikaru Kawamura, Pradeep K Mohanty, Akio Nakahara, Surajit Sengupta, Ping Sheng, Sujata Tarafdar and Uwe Tauber for reviewing the papers submitted to this proceedings volume. We would like to take this opportunity to thank all the members of the organizing committee and acknowledge the financial support received from the Centre for Applied Mathematics and Computational Science, Saha Institute of Nuclear Physics, Kolkata. We look forward to meeting you all at the next event in this series, CMDS 13, to be held in 2014/2015 in Utah, USA. Bikas K ChakrabartiChairman of CMDS 12Kolkata, 8 August 2011 Editors of the proceedings Abhik Basu abhik.basu@saha.ac.inBikas K Chakrabarti bikask.chakrabarti@saha.ac.inAnjan Kumar Chandra anjan.chandra@saha.ac.inSaha Institute of Nuclear Physics, Sector-I, Block - AF, Bidhannagar, Kolkata 700064, India

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

Changing times, similar challenges.

PubMed

Baillie, Jonathan

2013-11-01

With IHEEM celebrating its 70th Anniversary this month, HEJ editor, Jonathan Baillie, recently met the Institute's oldest surviving Past-President, Lawrence Turner OBE, who, having in 1964 established a small engineering business producing some of the NHS's earliest nurse call systems from the basement of his three-storey West Midlands home, has since seen the company, Static Systems Group, grow to become one of the U.K. market-leaders in its field. The Institute's President from 1979-1981, he looked back, during a fascinating two-hour discussion, at his time in the role, talked through some of the key technological and other changes he has seen in the past five decades, reflected on an interesting and varied career, and considered some of the very different current-day challenges that today's IHEEM President, and the Institute as a whole, face.

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

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

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.

What can be done to reduce false alarms?

PubMed

Baillie, Jonathan

2013-05-01

Although (the Department for Communities and Local Government's 'Fire statistics' reveal) the number of such incidents has fallen every year since 2006/07, UK fire and rescue services still attended over 312,400 'false fire alarms,' i.e. instances where, on arriving at a site, they found no fire, in 2011/12. Such incidents have been a significant concern for healthcare facilities teams, and for the fire and rescue services serving them, for many years, and, although the past decade has seen determined efforts to substantially reduce the number bearing fruit, many believe far too many still occur. HEJ editor, Jonathan Baillie, reports on a recent London roundtable discussion staged by two leading fire detection and alarm equipment specialists, Apollo Fire Detectors, and Static Systems Group, with IHEEM, which brought together experts to discuss what more can be done to minimise false fire alarms.

Is the jury still out on PFI contracts?

PubMed

Baillie, Jonathan

2012-02-01

Last September Andrew Lansley claimed that some NHS Trusts occupying PFI healthcare facilities had been 'landed with deals they could not afford', seemingly attributing much of the blame for a scenario where the Department of Health said 22 Trusts in England alone could be at significant financial risk to Labour, which, in the 1990s, greatly expanded a public/private funding partnership originally introduced by the Tories a decade earlier. Two key factors critics claim have put such Trusts 'at risk' are the 'inflexibility' of some PFI contracts, which makes varying terms difficult mid-contract, and the fact that many of the earlier deals were inexpertly negotiated by the 'public sector side'. HEJ editor Jonathan Baillie sought the views of Malcolm Austwick, a partner at top commercial law firm, DAC Beachcroft (see panel below), with extensive experience in the legal complexities of PFI, on whether or not the initiative's 'pros' do indeed outweigh the 'cons'.

Bringing a military approach to teaching.

PubMed

Baillie, Jonathan

2015-03-01

Despite having only established the company nine years ago, the founders of Kidderminster-based Avensys Medical believe the company now offers not only one of the UK's most comprehensive maintenance, repair, consultancy, and equipment audit services for medical and dental equipment, but also one of the most tailored training portfolios for electro-biomedical (EBME) engineers working in healthcare settings to enable them to get the best out of such equipment, improve patient safety, optimise service life, and save both the NHS and private sector money. As HEJ editor, Jonathan Baillie, discovered on meeting one of the two co-founders, ex-Royal Electrical and Mechanical Engineers (REME) artificer sergeant-major (ASM) and MoD engineering trainer, Robert Strange, many of the company's key trainers have a strong military background, and it is the rigorous and disciplined approach this enables them to bring to their training that he believes singles the company out.

Plenty of challenges, great opportunities.

PubMed

Northey, Chris

2014-10-01

Under the Presidency of Greg Markham, who took up the role two years ago this month, IHEEM has continued to significantly raise its profile among key opinion formers, strengthening its ties with influential bodies such as the Department of Health, the Sustainable Development Unit, The Department for Business, Innovation & Skills, ProCure21+, and the Engineering Council, and with parliamentarians, senior civil servants, its international counterparts, and the architectural and construction supply chains. Taking over the Presidency this month, highly experienced public health engineer, Chris Northey, will thus have much to build on. As he told HEJ editor, Jonathan Baillie, during a recent meeting at his employer, ChapmanBDSP's London offices, he is particularly looking forward to 'giving something back to the building services profession and the wider healthcare estates sector', having 'come a long way professionally' since beginning his working life, aged 17, as an apprentice plumbing and heating engineer in his father's Cornwall-based company.

Touchscreen device to 'calm and de-stress'.

PubMed

Kuijpers, Erik; Datema, Cor

2014-10-01

A highly experienced former psychiatric nurse until recently innovation manager at the Geestelijke Gezondheidszorg Eindhoven (GGZe)--the Eindhoven Mental Health Institute in the Netherlands, and a PhD holder in physics who spent several years at Philips Healthcare, have jointly developed an interactive 'communication wall' designed primarily as a communication tool for, and as a means to help 'de-stress', patients in inpatient mental health facilities during periods of acute anxiety. Erik Kuijpers and Cor Datema will show a version of their 'Cowall' on the Britplas stand at this month's Healthcare Estates 2014. As HEJ editor, Jonathan Baillie, discovered, when he met them during one of their recent trips to the UK, late in 2013 they formed a company, Recornect, to market the system, and to provide consultancy to those keen to specify the latest technology for mental and acute healthcare settings. Their Cowall has already seen installations in mainland Europe, and the pair are now seriously targeting the UK.

Poor commissioning discussed in depth.

PubMed

Towse, Bob; Whitby, Robin; Wignall, Stephen; Barrass, Chris; Newman, Alan; Shaw, Christopher; Johnston-Stuart, Chris; James, Chris

2014-05-01

Last October's Healthcare Estates 2013 conference saw one of the first day's 'Engineering' sessions debate the topic, 'Why do so many buildings disappoint their owners and occupants?' Much of the discussion centered on the problems caused by 'inadequate management of the commissioning process'. A roundtable debate jointly staged recently in London by IHEEM and the B&ES, the leading U.K. trade association for building services engineering contractors, took the debate forward. As HEJ editor, Jonathan Baillie reports, the discussions confirmed that one of the key contributors to poor commissioning is a failure to involve specialist building services contractors sufficiently early. It was also agreed that finding a really effective 'client-side' project manager, with the panoply of skills and experience the role requires, can be 'a tough ask'. In this issue of HEJ we report on the debate's first 'half'; in June's edition, we will cover 'part two' of a lively, forthright, and positive debate.

Tough by name, tough by nature.

PubMed

Baillie, Jonathan

2015-04-01

Few beds, one would imagine, could withstand three-quarters of a ton landing on them, but this was the challenge successfully met by a box bed from a furniture manufacturer for challenging behaviour environments, Tough Furniture, when, to reassure a customer that the bed could accommodate 30-stone patients, 13 of the company's staff jumped repeatedly on it to ensure that it would survive intact in a real-world setting. Such testing may seem extreme, but is vital, since much of the company's furniture is destined for environments where patients will abuse, and indeed attempt to destroy, components. As MD David Vesty explained to HEJ editor, Jonathan Baillie, when he visited the company's Shropshire headquarters, it is through manufacturing premium quality cabinet furniture that is both attractive and distinctly non-institutional, but will equally withstand the harshest use, that the company has ensured that its products can live up to the brand name.

Integrating Requirements Engineering, Modeling, and Verification Technologies into Software and Systems Engineering

DTIC Science & Technology

2007-10-28

Software Engineering, FASE󈧉, volume 3442 of Lecture Notes in Computer Science, pages 175--189. Springer, 2005. Andreas Bauer, Martin Leucker, and Jonathan ...of Personnel receiving masters degrees NAME Markus Strohmeier Gerrit Hanselmann Jonathan Streit Ernst Sassen 4Total Number: Names of personnel...developed and documented mainly within the master thesis by Jonathan Streit [Str06]: • Jonathan Streit. Development of a programming language like tem

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

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 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

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.

The Floor of Saha E

NASA Image and Video Library

2009-10-27

Diverse textures on the floor of Saha E which could be the result of impact melt coating boulders and other deposits on the floor of the crater on the lunar farside in this image taken by NASA Lunar Reconnaissance Orbiter.

Inhibition mechanism of SAHA in HDAC: a revisit.

PubMed

Zhou, Jingwei; Wu, Ruibo; Luo, Hai-Bin

2015-11-28

SAHA (vorinostat, Merck) is a famous clinical drug for zinc-containing histone deacetylase (HDAC) targets against cancer and several other human disorders, whose inhibition mechanism (namely the protonation mechanism) upon binding to HDAC has been debated for more than ten years. It is very challenging to verify experimentally and is still controversial theoretically. The popular "Class-dependent" (namely "Tyr-dependent") hypothesis is that the deprotonation of SAHA is mostly regulated by the conserved Tyr308 in class I HDAC while it is replaced by the His843 in class IIa HDAC. Herein, by elaborate QM(DFT)/MM MD simulations, we exclude the prevalent "Class-dependent" mechanism and advance a novel "Metal-dependent" mechanism, where the remote second metal site (K(+) in most HDAC and Ca(2+) in HDAC2) determines the protonation of SAHA. This proof-of-principle "Metal-dependent" mechanism opens up a new avenue to utilize the second metal site for isoform-selective inhibitor design.

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.

77 FR 40345 - Intent to Grant an Exclusive Patent License

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-09

... William V. Stoecker, Hernan F. Gomez, Jonathan A. Green, and David L. McGlasson; U.S. Patent Number 7,927... Including Noninvasive Sample Collection,'' by William V. Stoecker, Hernan F. Gomez, Jonathan A. Green, and.... Stoecker, Hernan F. Gomez, Jonathan A. Green, and David L. McGlasson. FOR FURTHER INFORMATION CONTACT...

KSC00pp0138

NASA Image and Video Library

2000-01-31

NASA Administrator Dan Goldin (left) shares a laugh with VIP 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. Behind Goldin is astronaut Doug Wheelock; behind Jonathan is his mother, Penny. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99

KSC-00pp0137

NASA Image and Video Library

2000-01-31

NASA Administrator Dan Goldin (left) listens intently to 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. Behind Goldin is astronaut Doug Wheelock; behind Jonathan is his mother, Penny. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99

KSC-00pp0138

NASA Image and Video Library

2000-01-31

NASA Administrator Dan Goldin (left) shares a laugh with VIP 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. Behind Goldin is astronaut Doug Wheelock; behind Jonathan is his mother, Penny. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99

KSC00pp0137

NASA Image and Video Library

2000-01-31

NASA Administrator Dan Goldin (left) listens intently to 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. Behind Goldin is astronaut Doug Wheelock; behind Jonathan is his mother, Penny. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99

KSC00pp0135

NASA Image and Video Library

2000-01-31

NASA Administrator Dan Goldin (left) watches as 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA, shakes hands with astronaut Dog Wheelock. Behind Jonathan is his mother, Penny. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99

KSC-00pp0135

NASA Image and Video Library

2000-01-31

NASA Administrator Dan Goldin (left) watches as 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA, shakes hands with astronaut Dog Wheelock. Behind Jonathan is his mother, Penny. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99

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.

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.

SAHA-based novel HDAC inhibitor design by core hopping method.

PubMed

Zang, Lan-Lan; Wang, Xue-Jiao; Li, Xiao-Bo; Wang, Shu-Qing; Xu, Wei-Ren; Xie, Xian-Bin; Cheng, Xian-Chao; Ma, Huan; Wang, Run-Ling

2014-11-01

The catalytic activity of the histone deacetylase (HDAC) is directly relevant to the pathogenesis of cancer, and HDAC inhibitors represented a promising strategy for cancer therapy. SAHA (suberoanilide hydroxamic acid), an effective HDAC inhibitor, is an anti-cancer agent against T-cell lymphoma. However, SAHA has adverse effects such as poor pharmacokinetic properties and severe toxicities in clinical use. In order to identify better HDAC inhibitors, a compound database was established by core hopping of SAHA, which was then docked into HDAC-8 (PDB ID: 1T69) active site to select a number of candidates with higher docking score and better interaction with catalytic zinc ion. Further ADMET prediction was done to give ten compounds. Molecular dynamics simulation of the representative compound 101 was performed to study the stability of HDAC8-inhibitor system. This work provided an approach to design novel high-efficiency HDAC inhibitors with better ADMET properties. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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.

Texture, Textuality and Political Discourse: A Study of Lexical Cohesion in Nigeria's President Goodluck Jonathan's Inaugural Address, May, 2011

ERIC Educational Resources Information Center

Enyi, Amaechi Uneke; Chitulu, Mark Ononiwu

2015-01-01

This study, entitled, "Texture and textuality in Political Discourse: A Study of Cohesive Devices in President Goodluck Jonathan's Inaugural Address-May, 2011" was an analysis of the lexical cohesive devices employed by Nigeria's President Goodluck Jonathan in crafting his May, 2011's Presidential Inaugural Address (PIA). Guided by the…

KSC-00pp0134

NASA Image and Video Library

2000-01-31

NASA Administrator Dan Goldin (center) talks to 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. In the background, between them, are Jonathan's mother, Penny; his grandfather, John Janocka; and his sister, Jaimie. At left is Mrs. Goldin. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99

KSC-00pp0136

NASA Image and Video Library

2000-01-31

NASA Administrator Dan Goldin (left) shares a light moment during his meeting with 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. Behind Goldin is astronaut Doug Wheelock; behind Jonathan is his mother, Penny. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99

KSC-00pp0132

NASA Image and Video Library

2000-01-31

NASA Administrator Dan Goldin (center) greets 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. In the background, between them, are Jonathan's mother, Penny; his grandfather, John Janocka; and his sister, Jaimie.. At left is Mrs. Goldin. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99

KSC00pp0134

NASA Image and Video Library

2000-01-31

NASA Administrator Dan Goldin (center) talks to 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. In the background, between them, are Jonathan's mother, Penny; his grandfather, John Janocka; and his sister, Jaimie. At left is Mrs. Goldin. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99

KSC00pp0132

NASA Image and Video Library

2000-01-31

NASA Administrator Dan Goldin (center) greets 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. In the background, between them, are Jonathan's mother, Penny; his grandfather, John Janocka; and his sister, Jaimie.. At left is Mrs. Goldin. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99

KSC00pp0136

NASA Image and Video Library

2000-01-31

NASA Administrator Dan Goldin (left) shares a light moment during his meeting with 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. Behind Goldin is astronaut Doug Wheelock; behind Jonathan is his mother, Penny. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99

NASA Administrator Dan Goldin greets 10-year-old VIP.

NASA Technical Reports Server (NTRS)

2000-01-01

NASA Administrator Dan Goldin (left) listens intently to 10-year- old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. Behind Goldin is astronaut Doug Wheelock; behind Jonathan is his mother, Penny. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS- 99.

NASA Administrator Dan Goldin greets 10-year-old VIP.

NASA Technical Reports Server (NTRS)

2000-01-01

NASA Administrator Dan Goldin (left) shares a light moment during his meeting with 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. Behind Goldin is astronaut Doug Wheelock; behind Jonathan is his mother, Penny. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99.

NASA Administrator Dan Goldin greets 10-year-old VIP.

NASA Technical Reports Server (NTRS)

2000-01-01

NASA Administrator Dan Goldin (left) watches as 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA, shakes hands with astronaut Dog Wheelock. Behind Jonathan is his mother, Penny. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99.

NASA Administrator Dan Goldin greets 10-year-old VIP.

NASA Technical Reports Server (NTRS)

2000-01-01

NASA Administrator Dan Goldin (left) shares a laugh with VIP 10- year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. Behind Goldin is astronaut Doug Wheelock; behind Jonathan is his mother, Penny. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS- 99.

High profile backing for GS1 drive.

PubMed

Hodgson, Glen

2016-09-01

At the 2016 GS1 UK Healthcare Conference in London, delegates heard from speakers including Pat Mills, the Department of Health's commercial director, on the ongoing work to embed GS1 standards throughout the NHS in England in line with the DH's eProcurement Strategy, published in April 2014. This mandated that any service or product procured by an English NHS acute Trust comply with the standards--one of the most obvious representations of which is on barcodes--'to enable Trusts to manage their non-pay spending by adopting master procurement data, automating the exchange of such data, and benchmarking their procurement against other Trusts and healthcare providers'. One of six 'demonstrator site' Trusts to provide a speaker at the 2016 GS1 UK national conference to report on their progress to date was Leeds Teaching Hospitals NHS Trust. Shortly after, HEJ editor, Jonathan Baillie, spoke to the Trust's associate director, Commercial and Procurement, Chris Slater, and to head of Healthcare at GS1 UK, Glen Hodgson.

Never Die Alone: Death and Birth in Pure Land Buddhism : Jonathan Watts and Yoshiharu Tomatsu, editors, 2008, Jodo Shu Press (Tokyo, 978-4-883-63041-7, 175 pp.).

PubMed

Maymind, Ilana

2017-09-01

This is a review of a collection of six essays. These essays, with the exception of one, are written by the followers of Shin Buddhism (Pure Land Buddhism). The last essay in this collection is written from the perspective of Theravada Buddhism rather than Mahayana Buddhism. This collection is a result of the initiative by Rev. Yoshiharu Tomatsu who, as a Buddhist priest, has acquired hands-on experience in dealing with grieving Temple members and became acutely aware of the discrepancy between a medical system and a ritualistic Buddhist system. While a medical system overlooks the spiritual needs of the dying, a Buddhist temple system neglects the spiritual needs of the living. This book ensued from a project that was initiated in 2006 and focused on the above-mentioned missing links, aiming to bring into conversation medical and religious practitioners.

KSC00pp0133

NASA Image and Video Library

2000-01-31

NASA Administrator Dan Goldin (center) presents a bag of special gifts to 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. In the background, between them, are Jonathan's mother, Penny; his grandfather, John Janocka; and his sister, Jaimie.. At left is Mrs. Goldin. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99

KSC-00pp0133

NASA Image and Video Library

2000-01-31

NASA Administrator Dan Goldin (center) presents a bag of special gifts to 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. In the background, between them, are Jonathan's mother, Penny; his grandfather, John Janocka; and his sister, Jaimie.. At left is Mrs. Goldin. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99

NASA Administrator Dan Goldin greets 10-year-old VIP.

NASA Technical Reports Server (NTRS)

2000-01-01

NASA Administrator Dan Goldin (center) talks to 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. In the background, between them, are Jonathan's mother, Penny; his grandfather, John Janocka; and his sister, Jaimie. At left is Mrs. Goldin. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99.

NASA Administrator Dan Goldin greets 10-year-old VIP.

NASA Technical Reports Server (NTRS)

2000-01-01

NASA Administrator Dan Goldin (center) presents a bag of special gifts to 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. In the background, between them, are Jonathan's mother, Penny; his grandfather, John Janocka; and his sister, Jaimie.. At left is Mrs. Goldin. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99.

NASA Administrator Dan Goldin greets 10-year-old VIP.

NASA Technical Reports Server (NTRS)

2000-01-01

NASA Administrator Dan Goldin (center) greets 10-year-old Jonathan Pierce (right), who is garbed in a protective cooling suit designed by NASA. In the background, between them, are Jonathan's mother, Penny; his grandfather, John Janocka; and his sister, Jaimie.. At left is Mrs. Goldin. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99.

Cobalt-Base Alloy Gun Barrel Study

DTIC Science & Technology

2014-07-01

Cobalt-Base Alloy Gun Barrel Study by William S. de Rosset and Jonathan S. Montgomery ARL-RP-0491 July 2014 A reprint...21005-5069 ARL-RP-0491 July 2014 Cobalt-Base Alloy Gun Barrel Study William S. de Rosset and Jonathan S. Montgomery Weapons and Materials... Gun Barrel Study 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) William S. de Rosset and Jonathan S. Montgomery

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

EDITORIAL: Editorial from the new Editor-in-Chief for 2014 Editorial from the new Editor-in-Chief for 2014

NASA Astrophysics Data System (ADS)

Graham, W. G.

2014-02-01

I am honoured to take on the leadership of Plasma Sources Science and Technology (PSST) as the successor to Professor Mark J Kushner, with whom I have had the pleasure to work on the journal for many years. Under Mark's insightful and energetic leadership over the last six years, PSST has cemented its position as the journal of choice within its subject area and is now one of the most successful journals in the field. In this first issue of 2014, I would like to reflect on some of the events and achievements of 2013. At the start of the year the PSST Editorial Board, recognizing the vital importance of atomic, molecular and optical (AMO) data to low-temperature plasma physics, agreed that PSST would accept papers reporting such new data, generated through both experiment and theory. Jonathan Tennyson joined the Editorial Board to represent this area. In March Anne Bourdon joined the Associate Editor team and has since then played a key part in the journal's review process alongside our other Editors. During the autumn, PSST moved to a new editorial management system. In December Deborah O'Connell was awarded the 2013 Hershkowitz Early Career Award and Review and joins the Editorial Board as of 2014. I would also like to thank Miles Turner for his work in leading the drafting of a guide on the details necessary in the reporting of the results of computer simulations; the main conclusions of this report have been incorporated into the journal policy. Overall 2013 has been another successful year for PSST; paper submissions were up by 8% on the previous year and there was the highest ever number of downloads of PSST papers in one year. Another noteworthy feature of 2013 was the continuing improvement in publication times while maintaining our high standards for acceptance and providing expert feedback coupled with encouragement particularly to younger researchers and groups. Largely as a result of the hard work of our referees and Associate Editors, the average time from receipt-to-first decision of a paper is only 50 days. In 2014 we will continue to support the low-temperature plasma physics community through the publication of special topical issues. Those already scheduled for next year are: Transport in B-fields in low temperature plasmas, Guest Editors: Rod Boswell and Igor D Kaganovich Spots and patterns on electrodes of gas discharges, Guest Editors: Mikhail S Benilov and Ulrich Kogelschatz Interaction of electromagnetic waves with low temperature plasmas, Guest Editors: Osamu Sakai and Shahid Rauf We will also launch a new feature: LabTalks, a way in which our authors can showcase their group's work and communicate their research published in PSST to a wider audience. Full details are on the PSST website. Along with the leadership team, made up of Associate Editors, Anne, Nick and Richard and the great PSST staff at Institute of Physics Publishing, led by Alice Malhador, I will strive to grow, improve and deliver a journal which reflects the excellent science from the low-temperature plasma community. We hope we can continue to count on your vital support as authors and referees.

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...

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.

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

Coherent Risk-Adjusted Decisions Over Time: a Bilevel Programming Approach

DTIC Science & Technology

2015-03-23

AFRL-AFOSR-VA-TR-2015-0310 Coherent Risk-Adjusted Decisions Over Time: a Bilevel Programming Approach Jonathan Eckstein RUTGERS THE STATE UNIVERSITY...FA9550-11-1-0164 5b. GRANT NUMBER FA9550-11-1-0164 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Eckstein, Jonathan Ruszczynski, Andrzej 5d. PROJECT... Jonathan Eckstein a. REPORT U b. ABSTRACT U c. THIS PAGE U 19b. TELEPHONE NUMBER (Include area code) 848-445-0510 Standard Form 298 (Rev. 8/98

Defense Acquisition Research Journal. Volume 22, Number 1, Issue 72.

DTIC Science & Technology

2015-01-01

Capt Allen J. DeNeve, USAF, Lt Col Erin T. Ryan , USAF, Lt Col Jonathan D. Ritschel, USAF, and Christine Schubert Kabban The Effects of System...USAF, Lt Col Erin T. Ryan , USAF, Lt Col Jonathan D. Ritschel, USAF, and Christine Schubert Kabban A regression technique is used to predict cost...practices. Capt Allen J. DeNeve, USAF, Lt Col Erin T. Ryan , USAF, Lt Col Jonathan D. Ritschel, USAF, and Christine Schubert Kabban, in “Taming the

1. Historic American Buildings Survey 1900 OLDEST KNOWN PHOTOGRAPH OF ...

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

1. Historic American Buildings Survey 1900 OLDEST KNOWN PHOTOGRAPH OF THE JONATHAN HAGER HOUSE AVAILABLE TO THE CHAIRMAN OF RESTORATION - Jonathan Hager House (Foundation), Hagerstown, Washington County, MD

2. Historic American Buildings Survey 1900 OLDEST KNOWN PHOTOGRAPH OF ...

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

2. Historic American Buildings Survey 1900 OLDEST KNOWN PHOTOGRAPH OF THE JONATHAN HAGER HOUSE AVAILABLE TO THE CHAIRMAN OF RESTORATION - Jonathan Hager House (Foundation), Hagerstown, Washington County, MD

Evaluation of genetic variability in choosen apple (Malus x domestica Borkh.) cultivars by ISSR-PCR analysis.

PubMed

Smolik, M; Krzysztoszek, O

2010-07-01

The aim of the study was to determine the genetic variability in eight apple cultivars: Delikates, Cortland, James Grieve, Lired, Jonathan, Golden Delicious, Jonagold and Idared from the collection of Fruit Growing Research Station in Rajkowo of the West Pomeranian University of Technology, Szczecin. The cultivar Delikates was obtained from the crossing of two cultivars: Cortland and James Grieve, whereas cultivar Lired is a James Grieve's sport. The second one cultivar--Jonagold was obtained from the crossing of Jonathan and Golden Delicious. The cultivar Idared is a hybrid obtained from the crossing of Jonathan and Wagener. Out of 40 primers, 17 were chosen for the final study. Those amplified a total of 183 loci (872 amplicons) out of which 34 (18.5%) were monomorphic, 128 (69.5%) were polymorphic and 22 (12%) cultivar-specific. Specific ISSR products were detected for each apple cultivar. A dendrogram was constructed using the UPGMA method which revealed two distinct clusters: I--Delikates, Cortland, James Grieve and Lired, II--Jonathan, Golden Delicious, Jonagold and Idared. Genetic similarity between Delikates, Cortland and James Grieve was 68.6, 70.8%, respectively and between cultivar Jonagold, Jonathan and Golden Delicous was 79.8, 85.2%, respectively.

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.

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.

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

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.

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

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.

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.

KSC-00pp0139

NASA Image and Video Library

2000-01-31

Ten-year-old Jonathan Pierce (second from right), who is garbed in a protective cooling suit, without the helmet, which was designed by NASA, poses with (left to right) NASA Administrator Dan Goldin, Mrs. Goldin, and astronaut Doug Wheelock. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99

KSC00pp0139

NASA Image and Video Library

2000-01-31

Ten-year-old Jonathan Pierce (second from right), who is garbed in a protective cooling suit, without the helmet, which was designed by NASA, poses with (left to right) NASA Administrator Dan Goldin, Mrs. Goldin, and astronaut Doug Wheelock. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS-99

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.

NASA Administrator Dan Goldin greets 10-year-old VIP.

NASA Technical Reports Server (NTRS)

2000-01-01

Ten-year-old Jonathan Pierce (second from right), who is garbed in a protective cooling suit, without the helmet, which was designed by NASA, poses with (left to right) NASA Administrator Dan Goldin, Mrs. Goldin, and astronaut Doug Wheelock. Jonathan suffers from erythropoietic protoporphyria, a rare condition that makes his body unable to withstand ultraviolet rays. The suit allows him to be outside during the day, which would otherwise be impossible. Jonathan's trip was funded by the Make-A-Wish Foundation and included a visit to Disney World. He and his family were among a dozen VIPs at KSC to view the launch of STS- 99.

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.

Passive Detection of Misbehaving Name Servers

DTIC Science & Technology

2013-10-01

Passive Detection of Misbehaving Name Servers Leigh B. Metcalf Jonathan M. Spring October 2013 TECHNICAL REPORT CMU/SEI-2013-TR-010 ESC-TR...Detection of Misbehaving Name Servers 5. FUNDING NUMBERS FA8721-05-C-0003 6. AUTHOR(S) Leigh B. Metcalf and Jonathan M. Spring 7. PERFORMING

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

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)

The Mexican Education System, the Keystone to Combatting Crime and Improving Economic Well-Being

DTIC Science & Technology

2011-10-28

2 Nabeel Alsalam and Jonathan Schwabish. "A Description of the Immigrant Population:." Congress of the United States Congressional Budget Office... Nabeel , and Jonathan Schwabish. "A Description of the Immigrant Population:." Congress of the United States Congressional Budget Office, Last modified

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.

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.

Savage Exaggerations: Worshiping the Cosmology of Jonathan Kozol

ERIC Educational Resources Information Center

Winters, Marcus A.

2006-01-01

Jonathan Kozol has made a good living talking with students. His books chronicle travels among poor, minority children, most of them African Americans in struggling public schools. In the four decades that Kozol, now 70, has been writing books--11 so far--his message has hardly wavered: minority children are unsuccessful because rich, white…

Political Identity and Moral Education: A Response to Jonathan Haidt's "The Righteous Mind"

ERIC Educational Resources Information Center

Blum, Lawrence

2013-01-01

In "The Righteous Mind," Jonathan Haidt claims that liberals have a narrower moral outlook than conservatives--they are concerned with fairness and relief of suffering, which Haidt sees as individualistic values, while conservatives care about authority and loyalty too, values concerned with holding society together. I question…

77 FR 64967 - Senior Executive Service; Performance Review Board

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-24

... BROWN, STEPHANIE H BRYAN, WILLIAM N BURROWS, CHARLES W BUTTRESS, LARRY D CADIEUX, GENA E CALBOS, PHILIP..., JONATHAN A DRUMMOND, WILLIAM K DURANT, CHARLES K ECKROADE, WILLIAM A EHLI, CATHY L ELKIND, JONATHAN H ELY... GARCIA, ANNA M GASPEROW, LESLEY A GEERNAERT, GERALD L GEISER, DAVID W GELISKE, TERRY M GELLES, CHRISTINE...

75 FR 63525 - Audit and Financial Management Advisory Committee (AFMAC)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-15

... Street, SW., Office of the Chief Financial Officer Conference Room, 6th Floor, Washington, DC [email protected] , SBA, Office of Chief Financial Officer, 409 3rd Street, SW., Washington, DC 20416... Jonathan Carver, by fax or e-mail, in order to be placed on the agenda. Jonathan Carver, Chief Financial...

Attacking Apartheid Education: An interview with Jonathan Kozol

ERIC Educational Resources Information Center

Curriculum Review, 2005

2005-01-01

This article presents an interview with Jonathan Kozol. Topics discussed include: (1) On the root causes of school resegregation; (2) On strategies for solving the problem; (3) On guaranteeing education for all; (4) On forcing opponents of integration into the open; (5) On mechanisms for promoting integration; (6) On scripted curricula in…

Agricultural Exposures, Multiple Myeloma Etiology: Profile of Jonathan Hofmann

Cancer.gov

Tenure-track investigator Jonathan Hofmann, Ph.D., M.P.H., has established a research program in the Occupational and Environmental Epidemiology Branch focused on the role of agricultural exposures in the etiology of multiple myeloma and other cancers, and on understanding the biological mechanisms that influence the development and progression of multiple myeloma.

75 FR 60459 - Sunshine Act Notices

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-30

...: Thursday, September 23, 2010, at 10 a.m. PLACE: 999 E Street, NW., Washington, DC (Ninth Floor). STATUS... Democratic-Farmer-Labor Party by its counsel, Marc E. Elias, Esq. and Jonathan S. Berkon, Esq. of Perkins Coie, LLP. Draft Advisory Opinion 2010-19: Google by its counsel, Marc E. Elias, Esq. and Jonathan S...

Reflections on Jonathan Boston's Paper

ERIC Educational Resources Information Center

Devine, Nesta

2014-01-01

In this article, Nesta Devine responds to Jonathan Boston's article "Child Poverty in New Zealand: Why It Matters and How It Can Be Reduced" ("Educational Philosophy and Theory," v46 n9 p995-999, 2014). Devine wishes to consider Boston's position from two angles: one is to rehearse the point that these statistics are an…

Compilation of Theses Abstracts

DTIC Science & Technology

2004-12-01

Lieutenant, United States Navy Master of Business Administration–December 2004 Jonathan C. Byrom–Captain, United States Army Master of Business...Hyperspectral Imagery, Principal Components Analysis, Minimum Noise Transform ALTERNATE CONFIGURATIONS FOR BLOCKED-IMPURITY-BAND DETECTORS Jonathan C...Yew Sing Quek –Captain, Republic of Singapore Armed Forces B.E., Nanyang Technological University-Singapore, 1999 Master of Science in Combat

Five-grass pollen immunotherapy tablet: an update on the latest findings from clinical trials: an interview with Olivier de Beaumont.

PubMed

de Beaumont, Olivier; Wilkinson, Jonathan

2014-01-01

Interview by Jonathan Wilkinson (Managing Commissioning Editor, Future Science Group). Olivier de Beaumont became Doctor of Medicine at the University of Paris Descartes in 1993. In the same year, he also took a Master of Health Economics degree at Paris Dauphine University. He is also a Master of Business Administration, ESCP Paris, 1999. At Stallergenes, he has been serving as Vice President/Head of Corporate Clinical Development since 2005, responsible for the clinical development plan, clinical operations, biometry and pharmacovigilance. In 2011, he took the responsibility of Senior Vice President Global Medical Affairs responsible for medical information and education, medical communication and nonregistration clinical studies. In 2014 he became Senior Vice President Global Scientific and Medical Affairs. From 2002 to 2005 he led the European business development of the world's leading clinical research organization Quintiles, developing Phase I-IV clinical trial programs for pharmaceutical companies. Previous roles included: Chief Scientific Officer and cofounder of Direct Medica (2000-2002), product champion and lifecycle management at Aventis (1998-2000), medical affairs manager in oncology and respiratory diseases at corporate Rhone-Poulenc Rorer (1993-1998).

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.

The Ties that Bind: A Response to Jonathan Jansen

ERIC Educational Resources Information Center

Sehoole, Chika Trevor

2006-01-01

In his critique of academic writing about and public consumption of government policy and law, Jonathan Jansen uses his argument of the symbolic functions of education law and education policy as a basis for explaining the lack of progress in achieving equity and justice under "Brown v. Board of Education" (1954) in the United States and…

78 FR 69663 - Jonathan and Jayne Chase Troy Mills Hydroelectric Inc.; Notice of Transfer of Exemption

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

... Jayne Chase Troy Mills Hydroelectric Inc.; Notice of Transfer of Exemption 1. By letter filed October 15, 2013, Jonathan Chase informed the Commission that the exemption from licensing for the Troy Hydroelectric Project, FERC No. 13381, originally issued December 2, 2011,\\1\\ has been transferred to Troy Mills...

76 FR 31955 - Jonathan and Jayne Chase; Notice of Application Accepted for Filing With the Commission, Intent...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-02

.... c. Date filed: July 23, 2010. d. Applicant: Jonathan and Jayne Chase. e. Name of Project: Troy Hydropower Project. f. Location: On the Missisquoi River, in the Town of Troy, Orleans County, Vermont. The... filing and is now ready for environmental analysis. l. Project Description: The Troy Project would...

Radical Hope and Teaching: Learning Political Agency from the Politically Disenfranchised

ERIC Educational Resources Information Center

Edgoose, Julian

2009-01-01

If teaching is a political act, how can teachers hope to make a difference through their work? In this review essay, Julian Edgoose explores this question of hope in relation to three recent books: David Halpin's "Hope and Education," Jonathan Kozol's "Letters to a Young Teacher," and Jonathan Lear's "Radical Hope." Halpin describes how hope comes…

Modeling Civic Engagement: A Student Conversation with Jonathan Kozol

ERIC Educational Resources Information Center

Thacker, Peter; Christen, Richard S.

2006-01-01

Jonathan Kozol's visit to Portland, Oregon, in April 2005 included a dialogue with 55 urban middle and high school students about inequities in American schools. Students left this conversation with a stronger sense of the systemic impediments to equal education. They also felt that their voice had been heard on a topic of national import. This…

76 FR 23322 - Change in Bank Control Notices; Acquisitions of Shares of a Bank or Bank Holding Company

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-26

... Street, Dallas, Texas 75201-2272: 1. Jonathan Ross Kasling of Hughes Springs, Texas, Individually; Mayo Givens Kasling III of Hughes Springs, Texas, Individually; Jonathan Ross Kasling of Hughes Springs, Texas; Mayo Givens Kasling III of Hughes Springs, Texas; Mayo Givens Kasling, Jr. of Hughes Springs, Texas and...

Jonathan W. Amy and the Amy Facility for Instrumentation Development.

PubMed

Cooks, R Graham

2017-05-16

This Perspective describes the unique Jonathan Amy Facility for Chemical Instrumentation in the Department of Chemistry at Purdue University, tracing its history and mode of operation. It also describes aspects of the career of its namesake and some of his insights which have been central to analytical instrumentation development, improvement, and utilization, both at Purdue and nationally.

The Devil in Mr. Smith: A Conversation with Jonathan Z. Smith

ERIC Educational Resources Information Center

Smith, Jonathan Z.; Pearson, Thomas; Gallagher, Eugene V.; Jensen, Tim; Fujiwara, Satoko

2014-01-01

This interview was recorded in November 2012 in Jonathan Z. Smith's Hyde Park graystone. Professor Smith offers insights into how he thinks about his classroom teaching and his students' learning through descriptions of various assignments and classroom activities he has developed over more than forty years of teaching. The discussion…

Jonathan Dayton: Soldier-Statesmen of the Constitution. A Bicentennial Series No. 19.

ERIC Educational Resources Information Center

Army Center of Military History, Washington, DC.

Jonathan Dayton's practical approach to government evolved out of his military experiences during the Revolutionary War, and he became a supporter for the equal representation of the small states. This booklet on Dayton is one in a series on Revolutionary War soldiers who signed the United States Constitution. It covers his early life, his…

Resolved, to Immerse Students in a World of Ideas: The Virtues of Teaching Philosophical Analysis in the Literature Classroom.

ERIC Educational Resources Information Center

Lambert, Stephen, Jr.

1996-01-01

Provides an outline for an exercise for junior high and high school students that encourages them to develop a philosophy of life in the form of resolutions, similar to those written by Jonathan Swift, Benjamin Franklin, and Jonathan Edwards. Cites examples of resolutions written by students. (PA)

A Pragma-Stylistic Analysis of President Goodluck Ebele Jonathan Inaugural Speech

ERIC Educational Resources Information Center

Abuya, Eromosele John

2012-01-01

The study was an examination through the pragma-stylistic approach to meaning of the linguistic acts that manifest in the Inaugural Speech of Goodluck Ebele Jonathan as the democratically elected president in May 2011 General Elections in Nigeria. Hence, the study focused on speech acts type of locution, illocutionary and perlocutionary in the…

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 vivo pharmacokinetic properties.

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 release and in vivo pharmacokinetic properties. PMID:25579435

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.

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.

Teaching Eighteenth-Century Poetic Satire with a Competency-Based Approach: Jonathan Swift and Lady Mary Wortley Montagu

ERIC Educational Resources Information Center

Modia, María Jesús Lorenzo; Álvarez, Begoña Lasa

2011-01-01

The purpose of this essay is to analyse the teaching of literature with a competency-based approach. This is exemplified by means of a thorough study of a poetic duel between two relevant eighteenth-century writers, Jonathan Swift and Lady Mary Wortley Montagu, and more specifically, by means of the satires entitled respectively "The Lady's…

A Persistent Reformer: Jonathan Kozol's Work to Promote Equality in America. Adolescent Cultures, School and Society. Volume 59

ERIC Educational Resources Information Center

Ognibene, Richard, Ed.

2012-01-01

Jonathan Kozol has been a leading educational critic and social activist since 1967 when "Death at an Early Age," his book about racism in Boston's schools, was published and won a National Book Award. Since then, Kozol has written eleven more books which focus on such issues as segregation in schools and society, poverty, inequitable school…

A Microprocessor-Based Real-Time Simulator of a Turbofan Engine

DTIC Science & Technology

1988-01-01

NASA AVSCOM Technical Memorandum 100889 Technical Report 88-C-011 Lfl A Microprocessor-Based Real-Time Simulator of a Turbofan Engine CD I Jonathan S...Accession For NTIS GRA&I A MICROPROCESSOR-BASED REAL-TIME SIMULATOR DTIC TABUnannounced OF A TURBOFAN ENGINE Justifiaation, Jonathan S. Litt Propulsion...the F100 engine without augmentation (without afterburning). HYTESS is a simplified simulation written in FORTRAN of a generalized turbofan engine . To

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

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 treatment of osteosarcoma and chondrosarcoma might improve the rate of metastasis and survival of patients. Our results present an encouraging approach to loading PMMA with anti-neoplastic drugs. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Using Heart Rate to Predict Resilience and Susceptibility to PTSD in Soldiers

DTIC Science & Technology

2011-04-01

Predict Resilience and Susceptibility to PTSD in Soldiers Authors Brian Chung Jonathan Lanier Lolita M. Burrell Michael D. Matthews...AUTHOR(S) Brian Chung; Jonathan Lanier; Lolita Burrell; Michael Matthews 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING...members of the control group were matched with one of the trauma or PTSD victims based on age and sex and both individuals were shown the same

Tokenless Biometric Electronic Transactions Using an Audio Signature to Identify the Transaction Processor

DTIC Science & Technology

2002-05-28

28, 2002 Inventors: Hoffman; Ned (Sebastopol, CA); Pare, Jr.; David Ferrin (Berkeley, CA); Lee; Jonathan Alexander (Oakland, CA); Lapsley; Philip...Transaction Processor 5. FUNDING NUMBERS 6. AUTHOR(S) Hoffman, Ned; Pare Jr, David Ferrin; Lee, Jonathan Alexander; Lapsley, Philip Dean 7...408. 4845636 Jul., 1989 Walker 705/39. 4926480 May., 1990 Chaum 380/23. 4947028 Aug., 1990 Gorog 235/380. 4961142 Oct., 1990 Elliott et al. 364/408

Non-Lethal Weapons: A Technology Gap or Lack or Available Systems, Training, and Proper Application

DTIC Science & Technology

2016-06-10

Ibid., 190-191. 9 Jonathan D. Moreno, “Medical Ethics and Non-Lethal Weapons ,” The American Journal of Bioethics 4, no. 4 (Fall 2004): W1...Quarterly (Spring-Summer 2001): 18-22. Moreno, Jonathan D. “Medical Ethics and Non-Lethal Weapons .” The American Journal of Bioethics 4, no. 4 (Fall...NON-LETHAL WEAPONS : A TECHNOLOGY GAP OR LACK OF AVAILABLE SYSTEMS, TRAINING, AND PROPER APPLICATION A thesis presented to

APPS-IV Civil Works Data Extraction/Data Base Application Study

DTIC Science & Technology

1982-09-01

QA 1 2 3 889 ETL-031 0 APPS-IV civil works data extraction/data base application study (phase 1) Jonathan C. Howland Autometric, Incorporated 5205... STUDY FINAL REPORT (PHASE I) 6. PERFORMING ORG. REPORT NUMBER 900-0081 7. AUTHOR(@) S. CONTRACT ON GRANT NUMBER(B) DAAK70-8 I -C-026 1 Jonathan C...CAPIR system was applied to a flood damage potential study . The particular applications were structure mapping and land use interpretation. A Civil

The base rate principle and the fairness principle in social judgment

PubMed Central

Cao, Jack; Banaji, Mahzarin R.

2016-01-01

Meet Jonathan and Elizabeth. One person is a doctor and the other is a nurse. Who is the doctor? When nothing else is known, the base rate principle favors Jonathan to be the doctor and the fairness principle favors both individuals equally. However, when individuating facts reveal who is actually the doctor, base rates and fairness become irrelevant, as the facts make the correct answer clear. In three experiments, explicit and implicit beliefs were measured before and after individuating facts were learned. These facts were either stereotypic (e.g., Jonathan is the doctor, Elizabeth is the nurse) or counterstereotypic (e.g., Elizabeth is the doctor, Jonathan is the nurse). Results showed that before individuating facts were learned, explicit beliefs followed the fairness principle, whereas implicit beliefs followed the base rate principle. After individuating facts were learned, explicit beliefs correctly aligned with stereotypic and counterstereotypic facts. Implicit beliefs, however, were immune to counterstereotypic facts and continued to follow the base rate principle. Having established the robustness and generality of these results, a fourth experiment verified that gender stereotypes played a causal role: when both individuals were male, explicit and implicit beliefs alike correctly converged with individuating facts. Taken together, these experiments demonstrate that explicit beliefs uphold fairness and incorporate obvious and relevant facts, but implicit beliefs uphold base rates and appear relatively impervious to counterstereotypic facts. PMID:27325760

The base rate principle and the fairness principle in social judgment.

PubMed

Cao, Jack; Banaji, Mahzarin R

2016-07-05

Meet Jonathan and Elizabeth. One person is a doctor and the other is a nurse. Who is the doctor? When nothing else is known, the base rate principle favors Jonathan to be the doctor and the fairness principle favors both individuals equally. However, when individuating facts reveal who is actually the doctor, base rates and fairness become irrelevant, as the facts make the correct answer clear. In three experiments, explicit and implicit beliefs were measured before and after individuating facts were learned. These facts were either stereotypic (e.g., Jonathan is the doctor, Elizabeth is the nurse) or counterstereotypic (e.g., Elizabeth is the doctor, Jonathan is the nurse). Results showed that before individuating facts were learned, explicit beliefs followed the fairness principle, whereas implicit beliefs followed the base rate principle. After individuating facts were learned, explicit beliefs correctly aligned with stereotypic and counterstereotypic facts. Implicit beliefs, however, were immune to counterstereotypic facts and continued to follow the base rate principle. Having established the robustness and generality of these results, a fourth experiment verified that gender stereotypes played a causal role: when both individuals were male, explicit and implicit beliefs alike correctly converged with individuating facts. Taken together, these experiments demonstrate that explicit beliefs uphold fairness and incorporate obvious and relevant facts, but implicit beliefs uphold base rates and appear relatively impervious to counterstereotypic facts.

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.

Thomas Jonathan ’Stonewall’ Jackson Fought by the Old Testament, Lived by the New

DTIC Science & Technology

1992-04-15

the paternal Jacksons. Sometime in 1835, Laura went to live with their maternal relatives, the Neales.14 At seven years old, Jackson had become a...document may not be Maed for openi pub&hcdos unti it h- s been delrd by the appropriat militMs ftwvic@ o r~erment apncy. THOMAS JONATHAN "STONEWALL...SCHEDULE Distribution is unlimited. 4 PERFORMING ORGANIZATION REPORT NUMBER( S ) 5. MONITORING ORGANIZATION REPORT NUMBER( S ) 6a. NAME OF PERFORMING

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.

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.

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 of HDAC inhibitor treatment. PMID:23626839

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.

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.

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.

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.

Interobserver Variability in Injury Severity Scoring After Combat Trauma: Different Perspectives, Different Values?

DTIC Science & Technology

2015-07-01

MSc, MRCSEd; David N. Naumann, MB BChir, MRCS; Paul Guyver, MBBS, FRCS; Jonathan Bishop, PhD; Simon Davies, BN(Hons), DipIMC RCSEd, RGN; Jonathan...Smith, I. M. Naumann, D. N. Guyver, P. Bishop, J . Davies, S. Lundy, J . B. Bowley, D. M. 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER...McLeod J , et al. The role of trauma scoring in developing trauma clinical governance in the De- fence Medical Services. Philos Trans R Soc Lond B

Jonathan Osborne (1794-1864) MD FRCPI: a crypto-neurologist.

PubMed

Breathnach, Caoimhghín S

2009-08-01

Jonathan Osborne was born in Dublin and educated in Trinity College Dublin, where he became Professor of Materia Medica. As physician to Sir Patrick Dun's and Mercer Hospitals he reported extensively on those patients who came under his care. In his native city he is remembered for the instruments he devised, for his studies on dropsies (particularly albuminuric nephritis), and for his therapeutic approach to epilepsy and neuralgia. It is his thorough analysis of a patient with conduction aphasia in 1833, however, which has stood the test of time.

a New IAA Cosmic Study: Establishing a Radio Observatory on the Moon Farside

NASA Astrophysics Data System (ADS)

Heidmann, J.

2002-01-01

In 1998, the IAA decided to develop a new Cosmic Study following a suggestion by its President, M. Yarymovych, based on work I initiated in 1993. This project is jointly fully supported by G. Haerendel, Vice-President of the IAA and President of the COSPAR. After the Symposium " Protection of Part of a Celestial Body for the Scientific Benefit of Humankind: the Lunar Farside Crater SAHA Proposal", which I organized at the COSPAR 1998 Scientific Assembly, the IAA Space Science Committee endorsed also this study. I assembled a Committee including D. McNally, University of London Observatory, for Radio Protection, B. Reijnen, International Institute of Space Law, for Space Law, G. Genta, Politecnico di Torino, for Astronautics, J.-F. Lestrade, Paris-Meudon Observatory, for Radioastronomy, and C. Maccone, IAA SETI and Interstellar Space Exploration Committees, for Mission Management. We encourage contributions from workers in a wide range of interdisciplinary domains: space lawyers, space engineers, astronomers, policy-makers, economists, educationists, media analysts. I started to invite potential contributors from various sources such as programmes of recent conferences of IAF, IAA, IISL, COSPAR, IAU, NASA, ESA and other space agencies, together with news from journals such as Science, Nature, Space News. The basic philosophy is not to refrain from giving access to persons of different opinions, so that a balance can be presented, aiming at some synthetizing consensus. I shall be the Editor, submitting each paper to two referees and taking advice from the Committee in controversial cases.

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

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.

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.

SWiFT Software Quality Assurance Plan.

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

Berg, Jonathan Charles

This document describes the software development practice areas and processes which contribute to the ability of SWiFT software developers to provide quality software. These processes are designed to satisfy the requirements set forth by the Sandia Software Quality Assurance Program (SSQAP). APPROVALS SWiFT Software Quality Assurance Plan (SAND2016-0765) approved by: Department Manager SWiFT Site Lead Dave Minster (6121) Date Jonathan White (6121) Date SWiFT Controls Engineer Jonathan Berg (6121) Date CHANGE HISTORY Issue Date Originator(s) Description A 2016/01/27 Jon Berg (06121) Initial release of the SWiFT Software Quality Assurance Plan

Final report on SNAC 11

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

Huber, Patrick

2013-06-26

This report details how the $5,000 DOE grant to support the workshop titled “Sterile Neutrinos at the Crossroads” (or SNAC11) was allocated and spent. The SNAC11 workshop covered three days during which there were 28 talks, multiple discussion sessions, a poster session with 9 posters delivered, and an impromptu public lecture on the OPERA superluminal neutrino result by the former project manager of OPERA (this was the first official OPERA talk on the subject in North America). The workshop scientific agenda can be viewed at http://www.cpe.vt.edu/snac/program.html. Emerging out of the workshop discussions, was the idea to write a comprehensive whitemore » paper describing the current state of the light sterile neutrino. This effort soon became an international collaboration. The final document, titled “Light Sterile Neutrinos: A White Paper” has nearly 200 authors, is 267 pages long, and cites 730 unique references. It has been posted the preprint archive as arXiv:1204.5379 [hep-ph]. Workshop local organizing committee co-chairs, Patrick Huber and Jonathan Link, are the white paper’s head editors. The white paper’s sections and section editors are as follows: 1. Theory and Motivation (Gabriela Barenboim, Valencia and Werner Rodejohann, MPI Heidelberg) 2. Astrophysical Evidence (Kev Abazajian, UC Irvine and Yvonne Wong, Aachen) 3. Evidence from Oscillation Experiments (Joachim Kopp, FNAL and Bill Louis, LANL) 4. Global Picture (Thierry Lasserre, CEA Saclay and Thomas Schwetz, MPI Heidelberg) 5. Requirements for Future Measurements (Bonnie Fleming, Yale and Joe Formaggio, MIT) 6. Appendix: Possible Future Experiments (Patrick Huber, Virginia Tech and Jon Link, Virginia Tech) In all 56 people participated in the workshop, of these 11 were young scientists. The workshop was covered in a feature article in Science (Science, 334, (2011), 304-306.). The DOE award was spent, as budgeted, as contractual services to VT CPE, which is the unit within the University which organizes conferences. Specifically, the travel cost of the speakers P. Langacker, K. Schreckenbach and P. Vogel was covered as well as bus transportation to KURF and to/from the airport.« less

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.

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.

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.

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.

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...

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.

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.

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.

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.

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.

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...

ED15-0229-01

NASA Image and Video Library

2015-08-03

From left, former Desert Christian students Logan Francisco, Kyler Stephens and Jonathan Lokos and NASA Armstrong mentor Allen Parker show the elements of the experiment launched into space on Dec. 3.

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.

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

PREFACE: The 7th International Seminar on Geometry, Continua and Microstructures

NASA Astrophysics Data System (ADS)

Burton, David A.

2007-04-01

It gives me great pleasure to present the proceedings of the 7th International Seminar on Geometry, Continua and Microstructures (GCM 7). The conference took place on 25-27 September 2006 at Lancaster University and the local organisers were Robin Tucker, Tim Walton, myself and Jonathan Gratus of the Lancaster University Mathematical Physics Group. Modern field theories of mechanically and electrically responsive continua have a wealth of interesting applications in physics. Such theories provide effective macroscopic models of complex systems, such as living tissue and material with dynamical defects, that capture macroscopic consequences of microscopic phenomena. GCM is an interdisciplinary conference series, initiated by the Eringen medallist Gérard A Maugin, that brings together physicists and applied mathematicians who have interests in continuum mechanics and differential geometry and who aim to develop new and powerful methods for analysing the behaviour of complex mechanical systems. The earlier conferences in the series were held in Paris, Madrid, Mannheim, Turin, Sinaia and Belgrade. This volume addresses a variety of topics including the physics of saturated porous media, the relationship between growth in living tissue and molecular transport, the mechanics of polymer bonds, the macroscopic properties of damaged elastomers, the mechanics of carbon nanotubes, the geometry of balance systems in Continuum Thermodynamics and wave propagation in the material manifold. I would like to warmly thank the rest of the organising committee and the conference participants for making GCM 7 an enjoyable and rewarding occasion. Photographs may be found at http://www.lancs.ac.uk/depts/spc/conf/gcm7/wss/index.htm David A Burton Editor

Mitchell Receives 2013 Ronald Greeley Early Career Award in Planetary Science: Citation

NASA Astrophysics Data System (ADS)

McKinnon, William B.

2014-07-01

The Greeley Early Career Award is named for pioneering planetary scientist Ronald Greeley. Ron was involved in nearly every major planetary mission from the 1970s until his death and was extraordinarily active in service to the planetary science community. Ron's greatest legacies, however, are those he mentored through the decades, and it is young scientists whose work and promise we seek to recognize. This year's Greeley award winner is Jonathan L. Mitchell, an assistant professor at the University of California, Los Angeles (UCLA). Jonathan received his Ph.D. from the University of Chicago, and after a postdoc at the Institute for Advanced Studies in Princeton, he joined the UCLA faculty, where he holds a joint appointment in Earth and space sciences and in atmospheric sciences.

78 FR 9067 - Receipt of Applications for Endangered Species Permits

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-07

... County, Alabama. Permit Application Number: TE-91366A Applicant: Dr. Paul Stewart, Troy, Alabama...: TE-91373A Applicant: Jonathan Miller, Troy, Alabama. Applicant requests authorization to take...

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

ACHP | News

Science.gov Websites

significance of Juneteenth to the United States and its important role in the emancipation of persons in podium. Also speaking was NPS Director Jonathan Jarvis, who discussed the role of the federal government

Electric Sail (E-Sail) Tether Team

NASA Image and Video Library

2017-08-03

Electric Sail (E-Sail) Tether Team Discusses 6U CubeSat Test Article and Tether Deployment System (Right to left: Tom Bryan, Davis Hunter (student intern), Jonathan MacArthur (student intern), Charles Cowen, Mike Tinker)

Defense Waste Processing Facility Process Enhancements

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

Bricker, Jonathan

2010-11-01

Jonathan Bricker provides an overview of process enhancements currently being done at the Defense Waste Processing Facility (DWPF) at SRS. Some of these enhancements include: melter bubblers; reduction in water use, and alternate reductant.

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...

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

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…

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…

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

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

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.

75 FR 71785 - Senior Executive Service: Performance Review Board Members

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-24

.... Jonathan I. Carver, Chief Financial Officer and Associate Administrator for Performance Management. 3... Counsel. 5. Ana M. Ma, Chief of Staff. Karen G. Mills, Administrator. [FR Doc. 2010-29611 Filed 11-23-10...

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.

76 FR 5647 - Public Availability of U.S. Small Business Administration FY 2010 Service Contract Inventory

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-01

...-3499 or [email protected] . Dated: January 26, 2011. Jonathan I. Carver, Chief Financial Officer/Associate Administrator for Performance Management, Office of the Chief Financial Officer. [FR Doc. 2011...

4. Historic American Buildings Survey, Arthur C. Haskell, Photographer. 1935. ...

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

4. Historic American Buildings Survey, Arthur C. Haskell, Photographer. 1935. (e) Int-Staircase from Jonathan Watson House, formerly on High St., Medford. - Colonel Isaac Royall Slave Quarters, 15 George Street, Medford, Middlesex County, MA

77 FR 74273 - Qualification of Drivers; Exemption Applications; Vision

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-13

... (SD) Terry L. Anderson (PA) Sammy J. Barada (NE) Timothy Bradford (TN) Cody W. Cook (OK) Marvin R...) Thomas L. Oglesby (GA) Garrick Pitts (AR) Jonathan C. Rollings (IA) Preston S. Salisbury (MT) Victor M...

Electric Sail (E-Sail) Tether Team

NASA Image and Video Library

2017-08-03

Electric Sail (E-Sail) Tether Team with 6U CubeSat Prototypes and Current Version of Tether Deployer Test Article, (Right to left: Tom Bryan, Davis Hunter (student intern), Jonathan MacArthur (student intern), Charles Cowen, Mike Tinker)

75 FR 72780 - Information Collection Activity; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-26

... term ``critical infrastructure'' is defined in section 1016(e) of the USA Patriot Act of 2001 (42 U.S.C.... Jonathan Adelstein, Administrator, Rural Utilities Service. [FR Doc. 2010-29768 Filed 11-24-10; 8:45 am...

Monitoring methods and predictive models for water status in Jonathan apples.

PubMed

Trincă, Lucia Carmen; Căpraru, Adina-Mirela; Arotăriţei, Dragoş; Volf, Irina; Chiruţă, Ciprian

2014-02-01

Evaluation of water status in Jonathan apples was performed for 20 days. Loss moisture content (LMC) was carried out through slow drying of wholes apples and the moisture content (MC) was carried out through oven drying and lyophilisation for apple samples (chunks, crushed and juice). We approached a non-destructive method to evaluate LMC and MC of apples using image processing and multilayer neural networks (NN) predictor. We proposed a new simple algorithm that selects the texture descriptors based on initial set heuristically chosen. Both structure and weights of NN are optimised by a genetic algorithm with variable length genotype that led to a high precision of the predictive model (R(2)=0.9534). In our opinion, the developing of this non-destructive method for the assessment of LMC and MC (and of other chemical parameters) seems to be very promising in online inspection of food quality. Copyright © 2013 Elsevier Ltd. 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…

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)…

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

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…

AGU Publications Volunteers Feted At Elegant Editors' Evening

NASA Astrophysics Data System (ADS)

Panning, Jeanette

2013-01-01

The 2012 Fall Meeting Editors' Evening, held at the City Club of San Francisco, was hosted by the Publications Committee and is the premier social event for editors and associate editors attending the Fall Meeting. The evening commenced with a welcome from Carol Finn, incoming AGU president, in which she expressed her thanks to the editors and associate editors for volunteering their time to benefit AGU.

76 FR 58805 - Notice of Availability of Environmental Assessment; Jonathan and Jayne Chase

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-22

... hydropower project exemption for the Troy Hydroelectric Project, to be located on the Missisquoi River, in the Town of Troy in Orleans County, Vermont, and has prepared an Environmental Assessment (EA). In the...

What Is It All For? A Conversation With Jonathan Kozol

ERIC Educational Resources Information Center

Journal of Current Social Issues, 1976

1976-01-01

The main complaint with the current educational system in the U.S. is that public schools are classic examples of consumer fraud in the most literal sense--false labels, half empty packages, and dangerous contents. (Author/AM)

77 FR 22831 - Public Availability of U.S. Small Business Administration FY 2010 Service Contract Inventory

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-17

[email protected] . Dared: March 7, 2012. Jonathan I. Carver, Chief Financial Officer/Associate Administrator for Performance Management, Office of the Chief Financial Officer. [FR Doc. 2012-8997 Filed 4-16-12; 8...

78 FR 16563 - Public Availability of U.S. Small Business Administration FY 2012 Service Contract Inventory

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-15

[email protected] . Dated: January 28, 2013. Jonathan I. Carver, Chief Financial Officer/Associate Administrator for Performance Management, Office of the Chief Financial Officer. [FR Doc. 2013-05957 Filed 3-14-13...

1. Historic American Buildings Survey (Fed.) Stanely P. Mixon, Photographer ...

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

1. Historic American Buildings Survey (Fed.) Stanely P. Mixon, Photographer Mar. 27, 1940 (A) EXTERIOR, GENERAL VIEW FROM STREET BELOW) (JUST MADE INTO TENEMENTS & EXTERIOR COVERED WITH ASBESTOS SHINGLES) - Jonathan Latimer House, New London, New London County, CT

77 FR 37265 - Lending Limits

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-21

... the Currency (OCC) is amending its regulation governing lending limits for national banks to consolidate the lending limit rules applicable to national banks and savings associations and remove its...: Jonathan Fink, Assistant Director, Bank Activities and Structure Division, (202) 874-5300; Heidi M. Thomas...

Androgen Receptor Splice Variants and Resistance to Taxane Chemotherapy

DTIC Science & Technology

2017-10-01

presence or absence of androgen. Citations (published journal articles): Xichun Liu, Elisa Ledet, Dongying Li, Ary Dotiwala, Allie Steinberger...paper was published: Xichun Liu, Elisa Ledet, Dongying Li, Ary Dotiwala, Allie Steinberger, Jianzhuo Li, Yanfeng Qi, Yan Dong, Jonathan Silberstein

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.

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.

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.

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.

Conflicts of interest of editors of medical journals

PubMed Central

Minhajuddin, Abu

2018-01-01

Background Almost all medical journals now require authors to publicly disclose conflicts of interests (COI). The same standard and scrutiny is rarely employed for the editors of the journals although COI may affect editorial decisions. Methods We conducted a retrospective observational study to determine the prevalence and magnitude of financial relationships among editors of 60 influential US medical journals (10 each for internal medicine and five subspecialties: cardiology, gastroenterology, neurology, dermatology and allergy & immunology). Open Payments database was reviewed to determine the percentage of physician editors receiving payments and the nature and amount of these payments. Findings 703 unique physician editors were included in our analysis. 320/703 (46%) received 8659 general payments totaling $8,120,562. The median number of payments per editor was 9 (IQR 3–26) and the median amount per payment was $91 (IQR $21–441). The median total payment received by each editor in one year was $4,364 (IQR $319–23,143). 152 (48%) editors received payments more than $5,000 in a year, a threshold considered significant by the National Institutes of Health. COI policies for editors were available for 34/60 (57%) journals but only 7/34 (21%) publicly reported the disclosures and only 2 (3.%) reported the dollar amount received. Interpretation A significant number of editors of internal medicine and subspecialty medical journals have financial COI and very few are publicly disclosed. Specialty journal editors have more COI compared to general medicine journal editors. Current policies for disclosing COI for editors are inconsistent and do not comply with the recommended standards. PMID:29775468

New Editors Appointed for Sections of Journal of Geophysical Research

NASA Astrophysics Data System (ADS)

2009-04-01

New editors have been appointed for the Atmospheres, Biogeosciences, and Oceans sections of the Journal of Geophysical Research (JGR). Joost de Gouw (NOAA, Boulder, Colo.) and Renyi Zhang (Texas A&M, College Station) are filling the vacancies of retiring Atmospheres section editors John Austin and Jose Fuentes. De Gouw and Zhang join the continuing editors Steven Ghan and Yinon Rudich. Sara Pryor (Indiana University, Bloomington) is joining the Atmospheres section editorial board as an associate editor now; she will transition to editor in January 2010.

Journal Editors Celebrated at Editors' Evening

NASA Astrophysics Data System (ADS)

Panning, Jeanette

2014-02-01

At the Fall Meeting, the premiere social event for AGU's many journal editors is the annual Editors' Evening, an opportunity for members to celebrate and to recognize the efforts of retiring editors. At the event, AGU president Carol Finn welcomed all those in attendance and thanked them for volunteering their time for the benefit of AGU and the wider research community.

Examining Editor-Author Ethics: Real-World Scenarios from Interviews with Three Journal Editors

ERIC Educational Resources Information Center

Amare, Nicole; Manning, Alan

2009-01-01

Those who submit manuscripts to academic journals may benefit from a better understanding of how editors weigh ethics in their interactions with authors. In an attempt to ascertain and to understand editors' ethics, we interviewed 3 current academic journal editors of technical and/or business communication journals. We asked them about the…

Standards and Certification. Symposium.

ERIC Educational Resources Information Center

2002

This document contains three papers from a symposium on standards and certification in human resource development (HRD). "Implementing Management Standards in the UK" (Jonathan Winterton, Ruth Winterton) reports on a study that explored the implementation of management standards in 16 organizations and identified 36 key themes and…

PARTICLE SIZE DISTRIBUTIONS FROM SELECT RESIDENCES PARTICIPATING IN THE NERL RTP PM PANEL STUDY

EPA Science Inventory

Particle Size Distributions from Select Residences Participating in the NERL RTP PM Panel Study. Alan Vette, Ronald Williams, and Michael Riediker, U.S. Environmental Protection Agency, National Exposure Research Laboratory, Research Triangle Park, NC 27711; Jonathan Thornburg...

Strategies for Promoting Pluralism in Education and the Workplace.

ERIC Educational Resources Information Center

Welch, Lynne Brodie, Ed.; Cleckley, Betty Jane, Ed.; McClure, Marilyn, Ed.

The following papers are included: "Multiculturalism: A Matter of Essentiality" (Betty Jane Cleckley assisted by Boyd Evans and Jonathan Porter); "A Deconstructionist Approach to Multicultural Education" (Susan Marnell Weaver); "Intercultural Communication Competence: A Strategy for a Multicultural Campus" (Bertram W.…

Jonathan J. Stickel | NREL

Science.gov Websites

research interests in fluid mechanics, rheology, separation science, reaction engineering, mathematical -established Newtonian fluid mechanics and solution reaction kinetics do not apply to these biomass slurries , and reaction kinetics of the biomass slurries in order to develop predictive modeling capabilities

A life of cycles.

PubMed

Pycock, Jonathan

2015-03-07

Jonathan Pycock is one of three equine claims consultants with the Veterinary Defence Society. His career in equine reproduction, and lecturing on the same topic, has given him the opportunity to work and travel widely, and ensure his work/life balance stays in sync. British Veterinary Association.

Issue Information

PubMed Central

Moore, Allen; Beckerman, Andrew

2014-01-01

Front Cover: Skeleton of a Columbian mammoth (Mammuthus columbi) assembled from bones recovered at the La Brea Tar Pits in Los Angeles, California. Original photograph taken by Jonathan Drury. Reproduced by permission of David A. Gold, Department of Ecology and Evolutionary Biology, University of California, Los Angeles, CA.

ARC-2010-ACD10-0120-001

NASA Image and Video Library

2010-06-21

Singularity University Staff; Tasha McCauley, Manuel Zaera-Sanz, David Ayotte, Jose Cordeiro, Sarah Russell, Candi Sterling, Marco Chacin, Ola Abraham, Jonathan Badal, Eric Dahlstrom, Susan Fonseca-Klein, Emeline Paat-Dahlstrom, Keith Powers, Bruce Klein, Tracy Nguyen, Kelly Lewis, Ken Hurst, Paul Sieveke, Kathryn Myronuk, Andy Barry.

Students Who Create Jobs.

ERIC Educational Resources Information Center

Gibson, Robert

REAL Enterprises (Rural Entrepreneurship through Action Learning) brings classes in "school-based enterprise" to rural high schools in North and South Carolina, Georgia, and Washington State. Jonathan Sher, the founder of REAL Enterprises, believes that children learn better by doing, and that successful rural economic development requires an…

Moving Faces

ERIC Educational Resources Information Center

Journal of College Science Teaching, 2005

2005-01-01

A recent study by Zara Ambadar and Jeffrey F. Cohn of the University of Pittsburgh and Jonathan W. Schooler of the University of British Columbia, examined how motion affects people's judgment of subtle facial expressions. Two experiments demonstrated robust effects of motion in facilitating the perception of subtle facial expressions depicting…

Surprise

ERIC Educational Resources Information Center

Adler, Jonathan E.

2008-01-01

Surprise is of great value for learning, especially in cases where deep-seated preconceptions and assumptions are upset by vivid demonstrations. In this essay, Jonathan Adler explores the ways in which surprise positively affects us and serves as a valuable tool for motivating learning. Adler considers how students' attention is aroused and…

Growth and Regression through Language.

ERIC Educational Resources Information Center

Bartel, Roland

1983-01-01

Finds confirmation of the humanizing influence of language in anthropological and linguistic studies, in creation myths, and in the lives of individuals such as Anne Frank and Helen Keller. Sees in George Orwell's "1984" and Jonathan Swift's "Gulliver's Travels" examples of the dehumanization created by empty or deceptive…

Author Correction: Segregation of mitochondrial DNA heteroplasmy through a developmental genetic bottleneck in human embryos.

PubMed

Floros, Vasileios I; Pyle, Angela; Dietmann, Sabine; Wei, Wei; Tang, Walfred W C; Irie, Naoko; Payne, Brendan; Capalbo, Antonio; Noli, Laila; Coxhead, Jonathan; Hudson, Gavin; Crosier, Moira; Strahl, Henrik; Khalaf, Yacoub; Saitou, Mitinori; Ilic, Dusko; Surani, M Azim; Chinnery, Patrick F

2018-04-19

In the version of this Letter originally published, an author error led to the affiliations for Brendan Payne, Jonathan Coxhead and Gavin Hudson being incorrect. The correct affiliations are: Brendan Payne: 3 Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK. 6 Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK; this is a new affiliation 6 and subsequent existing affiliations have been renumbered. Jonathan Coxhead: 11 Genomic Core Facility, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK; this is a new affiliation 11 and subsequent existing affiliations have been renumbered. Gavin Hudson: 3 Wellcome Trust Centre for Mitochondrial Research, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK. In addition, in Fig. 2d, the numbers on the x-axis of the left plot were incorrectly labelled as negative; they should have been positive. These errors have now been corrected in all online versions of the Letter.

Frontiers of Knowledge: An Interview with 2017 Edward Novitski Prize Recipient Jonathan Hodgkin.

PubMed

Hodgkin, Jonathan

2017-12-01

The Genetics Society of America's Edward Novitski Prize recognizes a single experimental accomplishment or a body of work in which an exceptional level of creativity and intellectual ingenuity has been used to design and execute scientific experiments to solve a difficult problem in genetics. The 2017 winner, Jonathan Hodgkin, used elegant genetic studies to unravel the sex determination pathway in Caenorhabditis elegans He inferred the order of genes in the pathway and their modes of regulation using epistasis analyses-a powerful tool that was quickly adopted by other researchers. He expanded the number and use of informational suppressor mutants in C. elegans that are able to act on many genes. He also introduced the use of collections of wild C. elegans to study naturally occurring genetic variation, paving the way for SNP mapping and QTL analysis, as well as studies of hybrid incompatibilities between worm species. His current work focuses on nematode-bacterial interactions and innate immunity. Copyright © 2017 by the Genetics Society of America.

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

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 capacity of the iCMs into the heart muscle, when injected systemically.

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 evaluation of HDAC inhibitors. HDAC inhibition in combination with standard doxorubicin treatment offers promising potential for chemotherapeutic intervention in both canine and human OS.

Test Plans and Procedures for the Baseline SAF for BDS-D Sites (ModSAF). Volume 2

DTIC Science & Technology

1993-12-20

operations editor will no longer editor, appear in the EditorI Area. 64 I ADST/WDL/TR-93-W003271 VOLUME 2 of 2; Ver 1.0I 44200 Repeat steps 44120 thru...The unit operations 44200 to task the orange editor will no longer platoon to Move on the appear in the Editor route labeled "ort. Area. The vehicles

Strategic Studies Quarterly. Volume 2, Number 3, Fall 2008

DTIC Science & Technology

2008-01-01

Managing Editor Betty R. Littlejohn, Editorial Assistant Jerry L. Gantt, Content Editor Sherry Terrell , Editorial Assistant Steven C. Garst...factsheet.asp?id=107 . Ibid. 9. Lt Col Sebastian M. Convertino II, CDR Lou Anne DeMattei, and Lt Col Tammy Knierim, Flying and Fighting in...PhD, Editor-in-Chief L. Tawanda Eaves, Managing Editor Betty R. Littlejohn, Editorial Assistant Jerry L. Gantt, Content Editor Sherry Terrell

U.S. Army Research Laboratory Image Enhancement Test Bed User’s Manual

DTIC Science & Technology

2013-07-01

Web Services; ARL-TR- 6393; U.S. Army Research Laboratory: Adelphi, MD, March 2013. 2. Young, S. Susan; Driggers, Ronald G. Superresolution Image...Young, S. Susan; Theilke, Matthew.; Schuler, Jonathan M. Superresolution Performance for Undersampled Imagers. Optical Engineering 2005, 44 (01). 4

New Tech Measures Artery Health: Engevity Cuff

ScienceCinema

Maltz, Jonathan

2018-05-22

Jonathan Maltz, a Berkeley Lab scientist in the Molecular Biophysics and Integrated Bioimaging division, explains a new technology developed at Berkeley Lab that could soon make detecting the process of plaque buildup in vessels a routine part of a visit to the doctor and, perhaps, home healthcare settings.

Defining Purpose for Policy and Practice

ERIC Educational Resources Information Center

Kardos, Susan M.

2012-01-01

Jonathan Woocher's "Reinventing Jewish Education for the 21st Century" presents a vision for a reimagined system of Jewish education. The educational landscape is changing, Woocher says, both because of a myriad of contextual factors (economic, geopolitical, technological, sociological) and because of the very need for Jewish educational decision…

Mention Detection: Heuristics for the OntoNotes Annotations

DTIC Science & Technology

2011-01-01

Mention Detection: Heuristics for the OntoNotes annotations Jonathan K. Kummerfeld, Mohit Bansal, David Burkett and Dan Klein Computer Science...considered the provided parses and parses produced by the Berke - ley parser (Petrov et al., 2006) trained on the pro- vided training data. We added a

77 FR 10539 - National Institute of Dental & Craniofacial Research Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-22

... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health National Institute of Dental... unwarranted invasion of personal privacy. Name of Committee: National Institute of Dental and Craniofacial...: Jonathan Horsford, Ph.D., Scientific Review Officer, Natl Inst of Dental and Craniofacial Research...

The Controversy over Controversial Issues

ERIC Educational Resources Information Center

Zimmerman, Jonathan; Robertson, Emily

2018-01-01

Avoiding the discussion of controversial topics in U.S. classrooms deprives students of an important part of their learning. Jonathan Zimmerman and Emily Robertson, authors of "The Case for Contention: Teaching Controversial Issues in American Schools" (University of Chicago Press, 2017) say Americans are terrible at having informed,…

77 FR 65664 - Publication of Depreciation Rates

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-30

.... Central Office Transmission: a. Radio Systems 9.95 b. Circuit equipment 10.00 4. Information origination...--fiber 5.00 h. Conduit systems 3.50 i. Other 5.59 Dated: October 9, 2012. John Padalino, Acting... ending December 31, 2012. FOR FURTHER INFORMATION CONTACT: Jonathan P. Claffey, Deputy Assistant...

Gifted Education Press Quarterly. Volume 10, 1996.

ERIC Educational Resources Information Center

Gifted Education Press Quarterly, 1996

1996-01-01

This set of four newsletters discusses current issues in gifted education. The first issue includes: "The Underserved Young Gifted Child: Status of Programs and Research" (Joan Smutny); "The Home Education Model: An Alternative Program for the Gifted" (Karen Kendig) and "Jonathan Swift (1667-1745): A Need for Gifted…

77 FR 70796 - Privacy Act of 1974; Retirement of Department of Homeland Security Transportation Security...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-27

... privacy issues, please contact: Jonathan Cantor, (202-343-1717), Acting Chief Privacy Officer, Privacy... DEPARTMENT OF HOMELAND SECURITY Office of the Secretary Privacy Act of 1974; Retirement of Department of Homeland Security Transportation Security Administration System of Records AGENCY: Privacy...

America's Newcomers: An Immigrant Policy Handbook.

ERIC Educational Resources Information Center

Morse, Ann, Ed.

This handbook contains five research papers and extensive reference materials on general immigration, immigrant policy, and related federal and state programs. "Immigration and Immigrant Policy" (Jonathan C. Dunlap) presents an historical overview of U.S. immigration, 1820s-1980s; defines various immigrant statuses and eligibility of each for…

New Tech Measures Artery Health: Engevity Cuff

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

Maltz, Jonathan

2016-05-19

Jonathan Maltz, a Berkeley Lab scientist in the Molecular Biophysics and Integrated Bioimaging division, explains a new technology developed at Berkeley Lab that could soon make detecting the process of plaque buildup in vessels a routine part of a visit to the doctor and, perhaps, home healthcare settings.

Proceedings of the Annual Linguistics Conference (2nd, Irbid, Jordan, April 1983).

ERIC Educational Resources Information Center

Owens, Jonathan, Comp.; Abu-Salim, Issam, Comp.

A collection of conference papers includes: "More on Arabic Vowel Harmony: A Metrical-Suprasegmental Approach" (Issam Abu-Salim); "The Phonological Assimilation of Borrowing" (Saleh Suleiman); "On Getting a Head: A Problem in Dependency Grammar" (Jonathan Owens); "Negation in Jordanian Arabic: A Developmental…

United States Navy Oceanic Armed Reconnaissance System

DTIC Science & Technology

2011-12-12

This report was prepared by: Rahul Petrie Daniel Reese Kurtis Hoots Robert Taylor Drew Nash Bunny Cooper Jonathan Trdan-Schmidt Marshall...NPS – Cohort 311-102S, Team OARS: Mr. Marshall Rice, Mr. Rahul Petrie, Mr. Daniel Reese, Mr. Kurtis Hoots, Mr. Robert Taylor, Mr. Drew Nash

Editorial independence at medical journals owned by professional associations: a survey of editors.

PubMed

Davis, Ronald M; Müllner, Marcus

2002-10-01

The purpose of this study was to assess the degree of editorial independence at a sample of medical journals and the relationship between the journals and their owners. We surveyed the editors of 33 medical journals owned by not-for-profit organizations ("associations"), including 10 journals represented on the International Committee of Medical Journal Editors (nine of which are general medical journals) and a random sample of 23 specialist journals with high impact factors that are indexed by the Institute for Scientific Information. The main outcome measures were the authority to hire, fire, and oversee the work of the editor; the editor's tenure and financial compensation; control of the journal's budget; publication of material about the association; and the editor's perceptions about editorial independence and pressure over editorial content. Of the 33 editors, 23 (70%) reported having complete editorial freedom, and the remainder reported a high level of freedom (a score of > or = 8, where 10 equals complete editorial freedom and 1 equals no editorial freedom). Nevertheless, a substantial minority of editors reported having received at least some pressure in recent years over editorial content from the association's leadership (42%), senior staff (30%), or rank-and-file members (39%). The association's board of directors has the authority to hire (48%) or fire (55%) the editor for about half of the journals, and the editor reports to the board for 10 journals (30%). Twenty-three editors (70%) are appointed for a specific term (median term = 5 years). Three-fifths of the journals have no control over their profit, and the majority of journals use the association's legal counsel and/or media relations staff. Stronger safeguards are needed to give editors protection against pressure over editorial content, including written guarantees of editorial freedom and governance structures that support those guarantees. Strong safeguards are also needed because editors may have less freedom than they believe (especially if they have not yet tested their freedom in an area of controversy).

Reflections on 35 years with Applied Optics: outgoing editorial.

PubMed

Mait, Joseph N

2014-10-20

Applied Optics' Editor-in-Chief, Joseph N. Mait reflects on his experience as a reader, author, reviewer and eventual editor of the journal. Dr. Mait also introduces the incoming Editor-in-Chief, Ronald G. Driggers and acknowledges outgoing Division Editor, T.-C. Poon.

New Editors Appointed for Water Resources Research

NASA Astrophysics Data System (ADS)

2009-03-01

Praveen Kumar (University of Illinois at Urbana-Champaign), the newly appointed editor in chief of Water Resources Research (WRR), heads the new team of editors for the journal. The other editors are Tom Torgersen (University of Connecticut, Groton), who continues his editorship; Tissa Illangasekare (Colorado School of Mines, Golden); Graham Sander (Loughborough University, Loughborough, UK); and John Selker (Oregon State University, Corvallis). Hoshin Gupta (University of Arizona, Tucson) will join WRR at the end of 2009. The new editors will begin receiving submissions immediately. The incoming editorial board thanks outgoing editors Marc Parlange, Brian Berkowitz, Amilcare Porporato, and Scott Tyler, all of whom will assist during the transition.

78 FR 60009 - Environmental Impact Statement: Erie and Genesee Counties, New York

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-30

... and Genesee Counties, New York AGENCY: Federal Highway Administration (FHWA), DOT; New York State... counties of Erie and Genesee, New York (NYSDOT Project Identification Number: 5528.28). A Notice of Intent... CONTACT: Jonathan McDade, Division Administrator, Federal Highway Administration, New York Division, Leo W...

A New Direction in Psychology and Politics

ERIC Educational Resources Information Center

Goldstein, Evan R.

2008-01-01

Jonathan Haidt remembers reading "Metaphors We Live By", the influential book that George P. Lakoff, a professor of linguistics and cognitive science at the University of California at Berkeley, wrote with Mark L. Johnson, a professor of philosophy at the University of Oregon. The book drew on cognitive science, psychology, linguistics, and…

Student Teaching--An Experience of Change and Growth.

ERIC Educational Resources Information Center

Nicholsen, Jean

1980-01-01

Jonathan Livingston Seagull represents the concepts of change and growth in the elementary student teaching program at Indiana University-Purdue University. Student feedback indicates acceptance of the symbolism as it is used in materials and activities to reinforce the motto, "We can be free! We can learn to fly!" (CM)

76 FR 69793 - Audit and Financial Management Advisory (AFMAC)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-09

... Street SW., Office of the Chief Financial Officer, Washington, DC 20416. SUPPLEMENTARY INFORMATION... fax or email, in order to be placed on the agenda. Jonathan Carver, Chief Financial Officer, 409 3rd... Financial Officer, 409 3rd Street SW., Washington, DC 20416. For more information, please visit our Web site...

76 FR 64990 - Audit and Financial Management Advisory (AFMAC)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-19

... Street, SW., Office of the Chief Financial Officer, Washington, DC 20416. SUPPLEMENTARY INFORMATION..., in order to be placed on the agenda. Jonathan Carver, Chief Financial Officer, 409 3rd Street, SW... Chief Financial Officer, 409 3rd Street, SW., Washington, DC 20416. For more information, please visit...

77 FR 64373 - Audit and Financial Management Advisory (AFMAC)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-19

... the Chief Financial Officer Conference Room, 6th Floor, Washington, DC 20416. SUPPLEMENTARY.... Jonathan Carver, Chief Financial Officer, 409 3rd Street SW., 6th Floor, Washington, DC 20416, phone: (202...-1608, email: [email protected] ; SBA, Office of Chief Financial Officer, 409 3rd Street SW...

Twenty Superstars of Education

ERIC Educational Resources Information Center

Adams, Caralee

2006-01-01

In 2005, the staff at "Instruction" magazine conducted a survey to know the individuals who are most admired for their contributions to the field of education. This article presents the brief profiles of these individuals. These celebrities, authors, and teachers include Mel Levine, Oprah Winfrey, Hillary Clinton, Jonathan Kozol, Marilyn Burns,…

The Great American University: Maintaining Our Preeminence

ERIC Educational Resources Information Center

Cole, Jonathan R.

2011-01-01

American research universities are arguably the world's most powerful engines of innovation and discovery. Yet they are widely misunderstood and in danger of losing their capacity to drive economic progress and improve our lives. Jonathan Cole, John Mitchell Mason University Professor at Columbia University, notes that the preeminence of American…

78 FR 77492 - Hearings of the Judicial Conference Advisory Committee on Rules of Bankruptcy Procedure; Federal...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-23

... JUDICIAL CONFERENCE OF THE UNITED STATES Hearings of the Judicial Conference Advisory Committee on...: Advisory Committee on Rules of Bankruptcy Procedure, Judicial Conference of the United States. ACTION..., 2014, Chicago, IL. FOR FURTHER INFORMATION CONTACT: Jonathan C. Rose, Secretary and Chief Rules Officer...

77 FR 72885 - Meeting of the Judicial Conference Committee on Rules of Practice and Procedure

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-06

... JUDICIAL CONFERENCE OF THE UNITED STATES Meeting of the Judicial Conference Committee on Rules of Practice and Procedure AGENCY: Judicial Conference of the United States Advisory Committee on Rules of... CONTACT: Jonathan C. Rose, Secretary and Chief Rules Officer, Rules Committee Support Office...

77 FR 66481 - Hearings of the Judicial Conference Advisory Committee on Rules of Civil Procedure

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-05

... JUDICIAL CONFERENCE OF THE UNITED STATES Hearings of the Judicial Conference Advisory Committee on Rules of Civil Procedure AGENCY: Judicial Conference of the United States, Advisory Committee on Rules... Circle NE., Washington, DC 20544. FOR FURTHER INFORMATION CONTACT: Jonathan C. Rose, Chief Rules Officer...

78 FR 76177 - Meeting of the Judicial Conference Committee on Rules of Practice and Procedure

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-16

... JUDICIAL CONFERENCE OF THE UNITED STATES Meeting of the Judicial Conference Committee on Rules of Practice and Procedure AGENCY: Judicial Conference of the United States Advisory Committee on Rules of..., Phoenix, Arizona 85003. FOR FURTHER INFORMATION CONTACT: Jonathan C. Rose, Secretary and Chief Rules...

77 FR 72885 - Meeting of the Judicial Conference Committee on Rules of Practice and Procedure

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-06

... Procedure AGENCY: Judicial Conference of the United States Advisory Committee on Rules of Civil Procedure... Timberdell Road, Norman, OK 73019. FOR FURTHER INFORMATION CONTACT: Jonathan C. Rose, Secretary and Chief Rules Officer, Rules Committee Support Office, Administrative Office of the United States Courts...

Chronicle of Higher Education. Volume 51, Number 28, March 18, 2005

ERIC Educational Resources Information Center

Chronicle of Higher Education, 2005

2005-01-01

"Chronicle of Higher Education" presents an abundant source of news and information for college and university faculty members and administrators. This March 18, 2005 issue of "Chronicle of Higher Education" includes the following articles: (1) "After a Loss, Silence?" (Silin, Jonathan G.); (2) "Is Frantz Fanon…

Operations Assessment in Afghanistan is Broken: What Is to Be Done?

DTIC Science & Technology

2011-01-01

Connection between Assessment and End State. For operations in Afghanistan, the end state is, loosely speaking , a region (or district, or the en- tire country...was with them in Af- ghanistan. They are truly ferocious fighters and courteous colleagues. I am grateful to Ben Connable, Jonathan Schroden, Peter

Religiously Dedicated, an Uncommon Approach

ERIC Educational Resources Information Center

Haviland, Margaret; Eppler, Kevin; O'Brien, Jennifer

2017-01-01

Almost countercultural today, focusing on the humanities--examining what it means to be human, understanding our cultures, and learning to embrace what Jonathan Sacks calls the "Dignity of Difference"--provides students with the tools to reclaim our public spaces, our public dialogue, and our businesses and corporations from the venal,…

76 FR 30154 - Maritime Communications/Land Mobile, LLC, Licensee of Various Authorizations in the Wireless...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-24

... Mobile, LLC, Licensee of Various Authorizations in the Wireless Radio Services, Applicant for Modification of Various Authorizations in the Wireless Radio Services AGENCY: Federal Communications Commission... Confidential Treatment from Patricia J. Paoletta and Jonathan B. Mirsky, Counsel to Wireless Properties of...

Bipartisan, but Unfounded: The Assault on Teachers' Unions

ERIC Educational Resources Information Center

Kahlenberg, Richard D.

2012-01-01

Teachers' unions are under unprecedented bipartisan attack. The drumbeat is relentless, from governors in Wisconsin and Ohio to the film directors of "Waiting for 'Superman'" and "The Lottery"; from new lobbying groups like Michelle Rhee's StudentsFirst and Wall Street's Democrats for Education Reform to political columnists such as Jonathan Alter…

Undoing Appropriateness: Raciolinguistic Ideologies and Language Diversity in Education

ERIC Educational Resources Information Center

Flores, Nelson; Rosa, Jonathan

2015-01-01

In this article, Nelson Flores and Jonathan Rosa critique appropriateness-based approaches to language diversity in education. Those who subscribe to these approaches conceptualize standardized linguistic practices as an objective set of linguistic forms that are appropriate for an academic setting. In contrast, Flores and Rosa highlight the…

76 FR 72672 - Publication of Depreciation Rates

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-25

... cable--metal 5.10 g. Buried cable--fiber 5.00 h. Conduit systems 3.50 i. Other 5.50 Dated: November 19... ending December 31, 2011. FOR FURTHER INFORMATION CONTACT: Jonathan P. Claffey, Deputy Assistant... Avenue SW., Washington, DC 20250-1590. Telephone: (202) 720-9556. SUPPLEMENTARY INFORMATION: In 7 CFR...

The Research University in a Time of Discontent.

ERIC Educational Resources Information Center

Cole, Jonathan R., Ed.; And Others

This volume contains 19 papers on the current status of the research university particularly in light of diminished federal research support and of the opportunities and perils of the larger, international educational stage. The papers are: (1) "Balancing Acts: Dilemmas of Choice Facing Research Universities" (Jonathan R. Cole); (2)…

77 FR 70796 - Privacy Act of 1974; Retirement of Department of Homeland Security Transportation Security...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-27

...; email: [email protected] . For privacy issues please contact: Jonathan Cantor, (202-343-1717), Acting... DEPARTMENT OF HOMELAND SECURITY Office of the Secretary Privacy Act of 1974; Retirement of Department of Homeland Security Transportation Security Administration System of Records AGENCY: Privacy...

77 FR 70795 - Privacy Act of 1974; Retirement of Department of Homeland Security Transportation Security...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-27

... 20598-6036; email: [email protected] . For privacy issues please contact: Jonathan Cantor, (202-343... DEPARTMENT OF HOMELAND SECURITY Office of the Secretary Privacy Act of 1974; Retirement of Department of Homeland Security Transportation Security Administration System of Records AGENCY: Privacy...

Before and After: An Exploration into Narrative.

ERIC Educational Resources Information Center

Clark, Kelly

2003-01-01

Describes a project about narrative in art that combines a study of art history with art reproductions. Explains that the students create before and after pictures on postcards for famous works of art. States that students were asked to choose an artist such as Norman Rockwell, Edward Gorey, or Jonathan Green. (CMK)

Field implementation of fiber-reinforced polymer (FRP) deck panels.

DOT National Transportation Integrated Search

2017-06-01

Jeffery S. Volz, S.E., P.E., Ph.D., Kamal H. Khayat, PhD, P.Eng. http://orcid.org/0000-0003-1431-0715, Soo Duck Hwang, Ph.D. http://orcid.org/0000-0003-2178-1531, Hesham Tuwair, Ph.D., Jonathan T. Drury, Amy S. Crone : Although still in their infancy...

CrossTalk: The Journal of Defense Software Engineering. Volume 21, Number 7

DTIC Science & Technology

2008-07-01

However, when your staff ’s passion goes from Edelweiss [1] to Kewpie Station [2], be sure your protective structures fan, rather than extinguish, the... Kewpie Station.” Everybody Loves You. Velour, 2003. 3. August Rush. Dir. Kirsten Sheridan. Perf. Freddie Highmore, Keri Russell, Jonathan Rhys Meyers

Mexico and the Future.

DTIC Science & Technology

1995-09-25

analysis of the crisis as it developed during the Salinas years and the first months of the Zedillo presidency, see the preceding companion report to...Jonathan Fox’s excellent study of the short-lived Sistema Alimentario Mexicano and the lessons that can be learned from it: The Politics of Food in

Everyone's Challenge. Proceedings of the Literacy Conference (Edmonton, Alberta, October 9-12, 1990).

ERIC Educational Resources Information Center

Konrad, Abram G., Ed.

The following presentations are included in this report on conference proceedings: Conference Opening (Joyce Fairbairn); Greetings (John Gogo); Special Address (Ramon J. Hnatyshyn); "Paulo Freire on Adult Education," an interview and panel discussion (Carlos Torres et al.); Keynote Addresses (Jonathan Kozol, John Gogo, Peter Calamai,…

Terms of Inclusion: Unity and Diversity in Public Education

ERIC Educational Resources Information Center

Kantor, Harvey; Lowe, Robert

2007-01-01

In this review essay, Harvey Kantor and Robert Lowe explore the history of the culture wars in public education in the United States. Drawing on three books--David Tyack's "Seeking Common Ground," Jonathan Zimmerman's "Whose America?" and Amy Binder's "Contentious Curricula"--Kantor and Lowe review the history of…

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

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.

[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.

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

FRED user's manual

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

Shilling, J.

1984-02-01

FRED, the friendly editor, is a screen-based structured editor. This manual is intended to serve the needs of a wide range of users of the FRED text editor. Most users will find it sufficient to read the introductory material in section 2, supplemented with the full command set description in section 3. Advanced users may wish to change the keystroke sequences which invoke editor commands. Section 4 describes how to change key bindings and how to define command macros. Some users may need to modify a language description or create an entirely new language description for use with FRED. Sectionmore » 5 describes the format of the language descriptions used by the editor, and describes how to construct a language grammar. Section 6 describes known portability problems of the FRED editor and should concern only system installation personnel. The editor points out syntax errors in the file being edited and does automatic pretty printing.« less

EDT mode for JED -- An advanced Unix text editor

NASA Astrophysics Data System (ADS)

McIlwrath, B. K.; Page, C. G.

This note describes Starlink extended EDT emulation for the JED editor. It provides a Unix text editor which can utilise the advanced facilities of DEC VTn00, xterm and similar terminals. JED in this mode provides a reasonably good emulation of the VAX/VMS editor EDT in addition to many extra facilities.

Becoming an Online Editor: Perceived Roles and Responsibilities of Wikipedia Editors

ERIC Educational Resources Information Center

Littlejohn, Allison; Hood, Nina

2018-01-01

Introduction: We report on the experiences of a group of people as they become Wikipedia editors. We test Benkler's (2002) theory that commons-based production processes accelerate the creation of capital, questioning what knowledge production processes do people engage in as they become editors? The analysis positions the development of editing…

Emerging Perspectives on Editorial Ethics: An Interview with Chris Higgins

ERIC Educational Resources Information Center

Jackson, Liz

2017-01-01

Chris Higgins took on the roles of Editor of "Educational Theory," and Editor-in-Chief of the "Philosophy of Education Yearbook" published by the Philosophy of Education Society, in 2013, after having been an Associate Editor and Book Review Editor for "Educational Theory" for six years. Higgins worked closely with…

Authors and editors assort on gender and geography in high-rank ecological publications

PubMed Central

Belou, Rebecca M.

2018-01-01

Peer-reviewed publication volume and caliber are widely-recognized proxies for academic merit, and a strong publication record is essential for academic success and advancement. However, recent work suggests that publication productivity for particular author groups may also be determined in part by implicit biases lurking in the publication pipeline. Here, we explore patterns of gender, geography, and institutional rank among authors, editorial board members, and handling editors in high-impact ecological publications during 2015 and 2016. A higher proportion of lead authors had female first names (33.9%) than editorial board members (28.9%), and the proportion of female first names among handling editors was even lower (21.1%). Female editors disproportionately edited publications with female lead authors (40.3% of publications with female lead authors were handled by female editors, though female editors handled only 34.4% of all studied publications). Additionally, ecological authors and editors were overwhelmingly from countries in the G8, and high-ranking academic institutions accounted for a large portion of both the published work, and its editorship. Editors and lead authors with female names were typically affiliated with higher-ranking institutions than their male peers. This description of author and editor features provides a baseline for benchmarking future trends in the ecological publishing culture. PMID:29420647

Authors and editors assort on gender and geography in high-rank ecological publications.

PubMed

Manlove, Kezia R; Belou, Rebecca M

2018-01-01

Peer-reviewed publication volume and caliber are widely-recognized proxies for academic merit, and a strong publication record is essential for academic success and advancement. However, recent work suggests that publication productivity for particular author groups may also be determined in part by implicit biases lurking in the publication pipeline. Here, we explore patterns of gender, geography, and institutional rank among authors, editorial board members, and handling editors in high-impact ecological publications during 2015 and 2016. A higher proportion of lead authors had female first names (33.9%) than editorial board members (28.9%), and the proportion of female first names among handling editors was even lower (21.1%). Female editors disproportionately edited publications with female lead authors (40.3% of publications with female lead authors were handled by female editors, though female editors handled only 34.4% of all studied publications). Additionally, ecological authors and editors were overwhelmingly from countries in the G8, and high-ranking academic institutions accounted for a large portion of both the published work, and its editorship. Editors and lead authors with female names were typically affiliated with higher-ranking institutions than their male peers. This description of author and editor features provides a baseline for benchmarking future trends in the ecological publishing culture.

JSME: a free molecule editor in JavaScript.

PubMed

Bienfait, Bruno; Ertl, Peter

2013-01-01

A molecule editor, i.e. a program facilitating graphical input and interactive editing of molecules, is an indispensable part of every cheminformatics or molecular processing system. Today, when a web browser has become the universal scientific user interface, a tool to edit molecules directly within the web browser is essential. One of the most popular tools for molecular structure input on the web is the JME applet. Since its release nearly 15 years ago, however the web environment has changed and Java applets are facing increasing implementation hurdles due to their maintenance and support requirements, as well as security issues. This prompted us to update the JME editor and port it to a modern Internet programming language - JavaScript. The actual molecule editing Java code of the JME editor was translated into JavaScript with help of the Google Web Toolkit compiler and a custom library that emulates a subset of the GUI features of the Java runtime environment. In this process, the editor was enhanced by additional functionalities including a substituent menu, copy/paste, drag and drop and undo/redo capabilities and an integrated help. In addition to desktop computers, the editor supports molecule editing on touch devices, including iPhone, iPad and Android phones and tablets. In analogy to JME the new editor is named JSME. This new molecule editor is compact, easy to use and easy to incorporate into web pages. A free molecule editor written in JavaScript was developed and is released under the terms of permissive BSD license. The editor is compatible with JME, has practically the same user interface as well as the web application programming interface. The JSME editor is available for download from the project web page http://peter-ertl.com/jsme/

Preparing Students To Work on Newspaper Copy Desks: Are Educators Meeting Editors' Expectations?

ERIC Educational Resources Information Center

Auman, Ann E.; Cook, Betsy B.

A study surveyed two groups in the fall of 1994, journalism educators and newspaper editors. Educators completed a survey regarding the course content and skill areas emphasized in beginning level copy editing courses, while editors were asked to respond to questions regarding the skills they expect entry-level copy editors to have. Respondents…

MRAPs, Irregular Warfare, and Pentagon Reform

DTIC Science & Technology

2009-06-01

U P R E S S S TA F F COLONEL DAVID H. GURNEY, USMC (RET.) Director DR. JEFFREY D. SMOTHERMAN Executive Editor GEORGE C. MAERZ Supervisory Editor...LISA M. YAMBRICK Writer-Editor CALVIN B. KELLEY Writer-Editor MARTIN J. PETERS Production Supervisor TARA J. PAREKH Visual Design Editor O T H E R T I T ...L E S I N T H E S E R I E S Choosing War: The Decision to Invade Iraq and Its Aftermath Occasional Paper 5, April 2008 China’s Global Activism

Web-Based Media Contents Editor for UCC Websites

NASA Astrophysics Data System (ADS)

Kim, Seoksoo

The purpose of this research is to "design web-based media contents editor for establishing UCC(User Created Contents)-based websites." The web-based editor features user-oriented interfaces and increased convenience, significantly different from previous off-line editors. It allows users to edit media contents online and can be effectively used for online promotion activities of enterprises and organizations. In addition to development of the editor, the research aims to support the entry of enterprises and public agencies to the online market by combining the technology with various UCC items.

29 CFR 793.8 - “News editor.”

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 3 2013-07-01 2013-07-01 false âNews editor.â 793.8 Section 793.8 Labor Regulations... Exemption § 793.8 “News editor.” A news editor is an employee who gathers, edits and rewrites the news. He may also select and prepare news items for broadcast and present the news on the air. An employee who...

29 CFR 793.8 - “News editor.”

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 3 2011-07-01 2011-07-01 false âNews editor.â 793.8 Section 793.8 Labor Regulations... Exemption § 793.8 “News editor.” A news editor is an employee who gathers, edits and rewrites the news. He may also select and prepare news items for broadcast and present the news on the air. An employee who...

29 CFR 793.8 - “News editor.”

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 3 2012-07-01 2012-07-01 false âNews editor.â 793.8 Section 793.8 Labor Regulations... Exemption § 793.8 “News editor.” A news editor is an employee who gathers, edits and rewrites the news. He may also select and prepare news items for broadcast and present the news on the air. An employee who...

29 CFR 793.8 - “News editor.”

Code of Federal Regulations, 2010 CFR

2010-07-01

... 29 Labor 3 2010-07-01 2010-07-01 false âNews editor.â 793.8 Section 793.8 Labor Regulations... Exemption § 793.8 “News editor.” A news editor is an employee who gathers, edits and rewrites the news. He may also select and prepare news items for broadcast and present the news on the air. An employee who...

29 CFR 793.8 - “News editor.”

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 3 2014-07-01 2014-07-01 false âNews editor.â 793.8 Section 793.8 Labor Regulations... Exemption § 793.8 “News editor.” A news editor is an employee who gathers, edits and rewrites the news. He may also select and prepare news items for broadcast and present the news on the air. An employee who...

Academic Degradation and the Retreat of the Editors: Academic Irregularities and the Spreading of Academic Corruption from an Editor's Perspective

ERIC Educational Resources Information Center

Xun, Gong

2007-01-01

Against the backdrop of the grave academic crisis in China, editors have become the objects of wooing, favor-currying, connections-seeking, and collusions; they have been targeted for attacks, plots, extortions, and encroachments. Editing and publishing have become avenues for academic irregularities and academic corruption. Editors have the power…

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

Talking Cents: Public Discourse, State Oversight, and Democratic Education in East St. Louis

ERIC Educational Resources Information Center

Roseboro, Donyell L.; O'Malley, Michael P.; Hunt, John

2006-01-01

Since Jonathan Kozol's 1991 publication of "Savage Inequalities: Children in America's Schools," East St. Louis, Illinois, District 189 has endured unswerving criticism and study. While Kozol's work made publicly known the horrible conditions of schools in the district, it did not bring immediate relief. In 1994, the state appointed a…

The Vod Couple

ERIC Educational Resources Information Center

Schaffhauser, Dian

2009-01-01

This article features two high school chemistry teachers, Aaron Sams and Jonathan Bergmann, who have overturned conventional classroom instruction by using video podcasts to form the root of a new learning model. Thumbing through an issue of "MacWorld" a few years ago, Aaron Sams was struck by an article about an application called ProfCast that…

75 FR 22179 - Qualification of Drivers; Exemption Renewals; Vision

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-27

... Federal vision exemptions for Alberto Blanco, Michael B. Canedy, Larry A. Cossin, Charles W. Cox, Gary W. Ellis, Dennis J. Evers, Hector O. Flores, W. Roger Goold, Lee Guse, Steven W. Halsey, Clifford J. Harris, John C. Henricks, Thomas M. Leadbitter, John L. Lewis, Jonathan P. Lovel, Kent S. Reining, Enrique G...

77 FR 56262 - Qualification of Drivers; Exemption Applications; Vision

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-12

... (IL) Calvin D. Bills (VA) Joel W. Bryant (LA) Jonathan E. Carriaga (NM) Curtis E. Firari (WI) Percy L. Gaston (TX) Ronald M. Green (OH) Charles S. Huffman (KS) Richard Iocolano (NY) Daniel W. Johnson (NY) Charles R. Murphy (TX) Danny W. Nuckles (VA) Charles E. Queen (OH) Matias P. Quintanilla (CA) The...

78 FR 59080 - Audit and Financial Management Advisory Committee (AFMAC)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-25

... Administration, 409 3rd Street SW., Office of the Chief Financial Officer Conference Room, 6th Floor, Washington.... Jonathan Carver, Chief Financial Officer, 409 3rd Street SW., 6th Floor, Washington, DC 20416, phone: (202...-1608, email: [email protected] ; SBA, Office of Chief Financial Officer, 409 3rd Street SW...

78 FR 26680 - Audit and Financial Management Advisory Committee (AFMAC)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-07

... Administration, 409 3rd Street SW., Office of the Chief Financial Officer Conference Room, 6th Floor, Washington... placed on the agenda. Jonathan Carver, Chief Financial Officer, 409 3rd Street SW., 6th Floor, Washington... Donna Wood at (202) 619- 1608, email: [email protected] ; SBA, Office of Chief Financial Officer, 409...

76 FR 64421 - Senior Executive Service: Performance Review Board Members

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-18

... Financial Law and Lender Oversight 4. Pravina Raghavan, District Director, New York District Office 5. Tong Qin, Deputy Chief Financial Officer 6. Steven Smits, Associate Administrator for Capital Access 7. Jonathan Swain, Chief of Staff Karen G. Mills, Administrator. [FR Doc. 2011-26833 Filed 10-17-11; 8:45 am...

Attachment Styles and Acculturation of Christian Asian Indians: Impact on Life Satisfaction

ERIC Educational Resources Information Center

Isaac, Sherin K.

2008-01-01

Introduced by Jonathan Bowlby in the early 1960s, attachment theory seeks to explain an individual's depth of bonding with others throughout one's life. Attachment styles can affect family life, life interactions, career choices, friendships, relationships, marriage, and parenting (Turner, 2005). Attachment theory is composed of four different…

Teaching Economics Using Historical Novels: Jonathan Harr's "The Lost Painting"

ERIC Educational Resources Information Center

Cotti, Chad; Johnson, Marianne

2012-01-01

Undergraduate students are often interested in and benefit greatly from applications of economic principles. Historical novels drawn from real-world situations can engage students with economic concepts in new ways and provide a useful tool to help enhance instruction. In this article, the authors discuss the use of historical novels generally in…

Two Views: Do College Therapists Underdiagnose Bipolar II Disorder?

ERIC Educational Resources Information Center

Perry, Jonathan; Keyes, Lee

2014-01-01

On February 17, 2014, Dr. Jonathan Perry, former director of counseling at the University of Arkansas, sparked a lively debate on the listserv of the Association of University and College Counseling Center Directors (AUCCCD) by warning about the likelihood and dangers of underdiagnosing borderline II disorder. Standing out among the many…

Stochastic Estimation and Control of Queues Within a Computer Network

DTIC Science & Technology

2009-03-01

3]. And NS-2 is a network simulator developed at UC Berkely and is a well known, free, powerful network simulator tool. As will be more discussed...HA011118931033.aspx 7. James Trulove , “Broadband Networking”, CRC Press, 2nd edition, 2000 8. Jonathan Pengelly “MONTE CARLO METHODS” University of Otago

Teaching Applied Ethics to the Righteous Mind

ERIC Educational Resources Information Center

Murphy, Peter

2014-01-01

What does current empirically informed moral psychology imply about the goals that can be realistically achieved in college-level applied ethics courses? This paper takes up this question from the vantage point of Jonathan Haidt's Social Intuitionist Model of human moral judgment. I summarize Haidt's model, and then consider a variety of…

Planting the Seeds of Partnership: Parents as Instructors in Teacher Education

ERIC Educational Resources Information Center

Brown, Colleen; Cianca, Marie; Gladstone-Brown, Wendy; Wischnowski, Michael; Yingling, Jacalyn

2009-01-01

Brenda and Bob have told their family's story many times to professionals as they have navigated through the sometimes precarious waters of education and medicine in search of quality services for their son, Jonathan. Sometimes, along the way, especially when experiencing miscommunication and fragmentation, they've wondered to each other: Is…

Metabolic Signature of Antipsychotics Used in the Treatment of Autism

DTIC Science & Technology

2015-10-01

4. TITLE AND SUBTITLE Metabolic Signature of Antipsychotics used in the Treatment of Autism Metabolic Signature of Antipsychotics used in the...treatment of autism 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0611 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Nira Ben-Jonathan 5d. PROJECT NUMBER

How Gender Differences Shape Student Success in Honors

ERIC Educational Resources Information Center

Dinan, Susan E.

2016-01-01

In 2014, Jonathan Zimmerman published an op-ed in the "Christian Science Monitor" in which he wrote, "The last time I checked, [men] held most of the important positions of power and influence in American society. And yet, college admissions offices lower the standard for young men--effectively raising it for women--simply to make…

Reason, Education, and Liberalism: Family Resemblance within an Overlapping Consensus.

ERIC Educational Resources Information Center

Halliday, John

2001-01-01

Discusses recent debates concerning the nature of liberalism and its central feature of reason. Examines ideas from Jonathan, Hirst, Rawls, Gadamer, Wittgenstein, Taylor, and Ackerman. Suggests that the search for transcendental conceptions of justice and reason must be abandoned in favor of a more fluid curriculum structure. (Contains 18…

77 FR 72885 - Meeting of the Judicial Conference Committee on Rules of Practice and Procedure

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-06

... JUDICIAL CONFERENCE OF THE UNITED STATES Meeting of the Judicial Conference Committee on Rules of Practice and Procedure AGENCY: Judicial Conference of the United States Advisory Committee on Rules of... Science Drive, Durham, NC 27708. FOR FURTHER INFORMATION CONTACT: Jonathan C. Rose, Secretary and Chief...

78 FR 64012 - Meeting of the Judicial Conference Committee on Rules of Practice and Procedure

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-25

... JUDICIAL CONFERENCE OF THE UNITED STATES Meeting of the Judicial Conference Committee on Rules of Practice and Procedure AGENCY: Judicial Conference of the United States Advisory Committee on Rules of... Columbus Circle NE., Washington, DC 20544. FOR FURTHER INFORMATION CONTACT: Jonathan C. Rose, Secretary and...

78 FR 45564 - Meeting of the Judicial Conference Committee on Rules of Practice and Procedure

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-29

... States Courts, Washington, DC 20544, telephone (202) 502- 1820. Dated: July 24, 2013. Jonathan C. Rose... JUDICIAL CONFERENCE OF THE UNITED STATES Meeting of the Judicial Conference Committee on Rules of Practice and Procedure AGENCY: Judicial Conference of the United States Advisory Committee on Rules of...

77 FR 72885 - Meeting of the Judicial Conference Committee on Rules of Practice and Procedure

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-06

... JUDICIAL CONFERENCE OF THE UNITED STATES Meeting of the Judicial Conference Committee on Rules of Practice and Procedure AGENCY: Judicial Conference of the United States Advisory Committee on Rules of..., Coral Gables, FL 33146. FOR FURTHER INFORMATION CONTACT: Jonathan C. Rose, Secretary and Chief Rules...

Forecasting Foreign Currency Exchange Rates for Air Force Budgeting

DTIC Science & Technology

2015-03-26

FORECASTING FOREIGN CURRENCY EXCHANGE RATES FOR AIR FORCE BUDGETING THESIS MARCH 2015...States. AFIT-ENV-MS-15-M-178 FORECASTING FOREIGN CURRENCY EXCHANGE RATES FOR AIR FORCE BUDGETING THESIS Presented to the Faculty...FORECASTING FOREIGN CURRENCY EXCHANGE RATES FOR AIR FORCE BUDGETING Nicholas R. Gardner, BS Captain, USAF Committee Membership: Lt Col Jonathan

Freshwater harmful algal bloom exposure – an emerging health risk for recreational water users

EPA Science Inventory

Freshwater harmful algal bloom exposure – an emerging health risk for recreational water users Elizabeth D. Hilborn1, Virginia A. Roberts2, Lorraine C. Backer3, Jonathan S. Yoder2, Timothy J. Wade1, Michele C. Hlavsa2 1Environmental Public Health Division, Office of Researc...

77 FR 2774 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-19

... of Application for Approval of Discontinuance or Modification of a Railroad Signal System In... modification of a signal system. FRA has reopened and assigned the application Docket Number FRA-2003-15754. Applicant: Reading, Blue Mountain and Northern Railroad, Mr. Jonathan Barket, AVP, Communications & Signals...

59th Medical Wing Office of the Chief Scientists Research Highlights Flyer-April 2016

DTIC Science & Technology

2016-05-09

Occlusion of the Aorta (REBOA Inventors: Col Todd Rasmussen, MC, USAF MEDCOM USAMRMC and Jonathan Eliason, MD, University of Michigan) Is a fluoroscopy-free...thoracic aortic balloon occlusion system to control non-compressible hemorrh and assess the effect of an occluding aorta . Research to develop the

Huck Finn, Moral Language and Moral Education

ERIC Educational Resources Information Center

Schinkel, Anders

2011-01-01

The aim of this article is twofold. Against the traditional interpretation of "the conscience of Huckleberry Finn" (for which Jonathan Bennett's article with this title is the locus classicus) as a conflict between conscience and sympathy, I propose a new interpretation of Huck's inner conflict, in terms of Huck's mastery of (the) moral language…

Detection of Failure Progression in Cross-Ply Graphite/Epoxy during Fatigue through Acoustic Emission. Volume 1

DTIC Science & Technology

1989-11-01

ELECTE Jonathan Awerbuch MAY 2 6 1992William F. Ecldes m Donald L. Erdman A D Drexel University Department of Mechanical Engineering and Mechanics...17 2.8 References . ............. ................................. 17 M . EXPERIMENTAL PROCEDURE...90 6.7 On the Correspondence Between Event Intensities and M odes of Damage

Science Teaching Methods: A Rationale for Practices

ERIC Educational Resources Information Center

Osborne, Jonathan

2011-01-01

This article is a version of the talk given by Jonathan Osborne as the Association for Science Education (ASE) invited lecturer at the National Science Teachers' Association Annual Convention in San Francisco, USA, in April 2011. The article provides an explanatory justification for teaching about the practices of science in school science that…

Radio Frequency Emitter Geolocation Using Cubesats

DTIC Science & Technology

2014-03-27

CUBESATS Andrew J. Small, B.S.E.E. Captain, USAF Approved: //signed// Maj Marshall Haker , PhD (Chairman) //signed// Jonathan Black, PhD (Member) //signed...Cubesat, Direct Position Determination, Angle of Arrival, Time Difference of Arrival, Instantaneous Received Frequency U U U UU 101 Maj Marshall Haker (ENG) (937) 255-3636 x4603 marshall.haker@afit.edu

Home-Schooling in Oldtown: The Education of a Virtuous Citizenry

ERIC Educational Resources Information Center

Howard, William L.

2009-01-01

Harriet Beecher Stowe (1811-1896) was the beneficiary of a unique blend of educational influences. The daughter, sister, and wife of Congregational ministers, she inherited the faith of New England Puritanism and its subsequent redirection by Jonathan Edwards (1703-1758). Studying and then teaching at her sister Catharine's female seminary, she…

DEVELOP students attend conference

NASA Image and Video Library

2009-06-08

Last month, Madeline Brozen and Jason Jones of the DEVELOP Program at John C. Stennis Space Center joined members from the program's national office at Langley Research Center to attend the Southern Growth Policies Board annual conference in Biloxi. Pictured are (l to r): Karen Allsbrook, Jonathan Gleason, Gov. Haley Barbour, Madeline Brozen, Lindsay Rogers and Tracey Silcox.

The man behind the machine

NASA Astrophysics Data System (ADS)

Cerf, Vint

2018-01-01

As a practising computer scientist, I thought I had a fairly good grasp of Alan Turing’s many contributions to the field. But The Turing Guide by Jack Copeland, Jonathan Bowen, Mark Sprevak and Robin Wilson has opened up a universe of Turing's other pursuits I knew nothing about, inflating my admiration for him and his work.

Helping Ourselves, Helping Others

ERIC Educational Resources Information Center

Schuller, Tom

2012-01-01

Adult Learners' Week has whirled round again, but the author has been looking backwards. An invitation to speak at an event to mark the retirement of Richard Bolsin as General Secretary of the Workers' Educational Association prompted him at last to get hold of Jonathan Rose's "Intellectual Life of the British Working Classes." Rose's concern is…

Black Dean: Race, Reconciliation, and the Emotions of Deanship

ERIC Educational Resources Information Center

Jansen, Jonathan David

2005-01-01

In this article, Jonathan Jansen describes his experiences as a Black dean in the formerly all-White University of Pretoria in South Africa. The article shows how race, gender, history, and institutional culture constitute emotional terrain in which decanal leadership plays itself out in the volatile postapartheid era. In the context of South…

Diagnostic Classification Models: Are They Necessary? Commentary on Rupp and Templin (2008)

ERIC Educational Resources Information Center

Gorin, Joanna S.

2009-01-01

In their paper "Unique Characteristics of Diagnostic Classification Models: A Comprehensive Review of the Current State-of-the-Art," Andre Rupp and Jonathan Templin (2008) provide a comparative analysis of selected psychometric models useful for the analysis of multidimensional data for purposes of diagnostic score reporting. Recent assessment…

ANTIANDROGENIC EFFECTS OF VINCLOZOLIN ON MALE RATS ARE PARTIALLY ATTENUATED BY TESTOSTERONE PROPIONATE

EPA Science Inventory

ANTIANDROGENIC EFFECTS OF VINCLOZOLIN ON MALE RATS ARE PARTIALLY ATTENUATED BY TESTOSTERONE PROPIONATE

Cynthia Wolf1,2 , Joe Ostby1, Jonathan Furr 1, Gerald A. LeBlanc2, and L. Earl Gray, Jr.1
1 US Environmental Protection Agency, NHEERL, RTD, RTP, NC 27711, 2 Departmen...

MASCULINIZATION OF FEMALE RATS BY PRENATAL TESTOSTERONE PROPIONATE IS PARTIALLY ATTENUATED BY VINCLOZOLIN

EPA Science Inventory

MASCULINIZATION OF FEMALE RATS BY PRENATAL TESTOSTERONE PROPIONATE IS PARTIALLY ATTENUATED BY VINCLOZOLIN
Cynthia Wolf1,2, Gerald LeBlanc2, Andrew Hotchkiss3, Jonathan Furr1, L Earl Gray, Jr.1
1USEPA, Reproductive Toxicology Division, RTP, NC 27711, 2Dept. Molecular and En...

Excellence Gaps in Education: Expanding Opportunities for Talented Students

ERIC Educational Resources Information Center

Plucker, Jonathan A.; Peters, Scott J.

2016-01-01

In "Excellence Gaps in Education," Jonathan A. Plucker and Scott J. Peters shine a spotlight on "excellence gaps"--the achievement gaps among subgroups of students performing at the highest levels of achievement. Much of the focus of recent education reform has been on closing gaps in achievement between students from different…

TechEdSat 5 PhoneSat 5 Team Photo

NASA Image and Video Library

2016-07-28

TechEdSat 5 PhoneSat 5 Team photo on July 26, 2016. Taken in fron of the 1/3 scale Shuttle Orbiter Model, in front of the Parade Ground on Clark Road at NASA Research Park. Mark Murbach Sarosh Hussain Ali Guarneros Luna David Handy Jonathan Hanson Jakqueline Granillo Sarah Chu Alejandro Sales

78 FR 51597 - Modernizing the E-Rate Program for Schools and Libraries

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-20

... small a school they attend or how far they live from experts in their field of study. High-capacity... study by Austan Goolsbee and Jonathan Guryan found that E-rate support substantially increased the... statistically significant effect on student test scores. Have more recent studies suggested otherwise? We also...

Addressing Child Maltreatment in New Zealand: Is Poverty Reduction Enough?

ERIC Educational Resources Information Center

Dare, Tim; Vaithianathan, Rhema; De Haan, Irene

2014-01-01

Jonathan Boston provides an insightful analysis of the emergence and persistence of child poverty in New Zealand (Boston, 2014, "Educational Philosophy and Theory"). His remarks on why child poverty matters are brief but, as he reports, "there is a large and robust body of research on the harmful consequences of child poverty"…

PERIPUBERTAL DI (2-ETHYLHEXYL) PHTHALATE EXPOSURE INHIBITS ANDROGEN SENSITIVE TISSUE DEVELOPMENT AND DELAYS PUBERTY IN MALE SPRAGUE-DAWLEY RATS

EPA Science Inventory

PERIPUBERTAL DI (2-ETHYLHEXYL) PHTHALATE EXPOSURE INHIBITS ANDROGEN SENSITIVE TISSUE DEVELOPMENT AND DELAYS PUBERTY IN MALE SPRAGUE-DAWLEY RATS

Nigel Noriega, Jonathan Furr, Christy Lambright, Vickie Wilson, L. Earl Gray Jr.

The plasticizer Di (2-ethylhexyl) phtha...

What's Next? Perspectives from the Helm

ERIC Educational Resources Information Center

Howland, Jonathan

2016-01-01

In the fall of 2015, Jonathan Howland interviewed about a dozen independent school heads to inquire about novel programs and developments in their schools that, if they take root and flourish, could be "game changing"; about their vision of independent schools 40 years hence, in mid-21st-century America; and about impediments to reaching…

Compilation of K-12 Action Research Papers in Language Arts Education.

ERIC Educational Resources Information Center

Sherman, Thomas F.; Lundquist, Margaret

The papers in this compilation are the result of K-12 action research projects and were submitted in partial fulfillment for a variety of degrees from Winona State University (Minnesota). The compilation contains the following nine papers: "Will Playing Background Music in My Classroom Help Increase Student Spelling Scores?" (Jonathan L.…

Rosalind Driver studentships

NASA Astrophysics Data System (ADS)

1999-11-01

The School of Education at King's College London can now offer funded studentships to those wishing to undertake research in science education. These studentships, which are funded through the generous benefaction of the late Rosalind Driver, can be for a full-time student (over a maximum of three years) or several part-time students (a maximum of six years). Applications from anyone working in science education are welcome but preference will be given to those originating from practising science teachers. Applicants will be expected to register for the award of a MPhil/PhD or EdD and are normally expected to have a first degree. Preliminary ideas about a topic for investigation would also be helpful. Further details and application forms are obtainable from Chiz Dube, School of Education, King's College London, Franklin - Wilkins Building, Waterloo Road, London SE1 8WA (tel: 020-7848-3089, e-mail: chiz.dube@kcl.ac.uk). The deadline for the first round of applications was the middle of October, but preliminary informal enquiries may be made to Dr Jonathan Osborne at the School of Education (tel: 020-7848-3094, e-mail: jonathan.osborne@kcl.ac.uk).

[Jonathan Swift's asylum in Dublin--Ireland's introduction to institutional psychiatry 250 years ago].

PubMed

Reuber, M

1995-09-01

250 years ago, the satirical writer and clergyman Jonathan Swift from Dublin (1667-1745) founded the first Irish lunatic asylum. Rejecting the theories put forward by the English philosopher Thomas Hobbes and the doctor Thomas Willis, he was influenced by the ideas of the Scottish doctor and the "enlightened" thinker John Locke. Swift's St. Patrick's Hospital did not, however, realise a new philosophical concept: architecture and therapeutic approach of the new institution were clearly modelled on the much older Hospital of St. Mary of Bethlehem ( = Bedlam). Despite its conservative conceptual basis, the first institution dedicated to the mentally ill and intellectually subnormal in Ireland became a starting point for the apparantly unstoppable expansion of the, at one time, most comprehensive asylum system in the world. After Swift's Hospital had been enlarged twice at the tax-payers' expense (1778, 1793), the administration decided to relieve the institution by erecting the Richmond Asylum (1810), the first public asylum in Ireland. When this establishment also became overcrowded, in 1817, legislation was passed which led to the establishment of the oldest system of public asylums in Europe.

KENNEDY SPACE CENTER, FLA. -- Dr. Jonathan Clark, husband of STS-107 astronaut Laurel Clark, addresses the family members of the STS-107 astronauts, other dignitaries, members of the university community and the public gathered for the dedication ceremony of the Columbia Village at the Florida Institute of Technology in Melbourne, Fla. Each of the seven new residence halls in the complex is named for one of the STS-107 astronauts who perished during the Columbia accident -- Rick Husband, Willie McCool, Laurel Clark, Michael Anderson, David Brown, Kalpana Chawla, and Ilan Ramon.

NASA Image and Video Library

2003-10-28

KENNEDY SPACE CENTER, FLA. -- Dr. Jonathan Clark, husband of STS-107 astronaut Laurel Clark, addresses the family members of the STS-107 astronauts, other dignitaries, members of the university community and the public gathered for the dedication ceremony of the Columbia Village at the Florida Institute of Technology in Melbourne, Fla. Each of the seven new residence halls in the complex is named for one of the STS-107 astronauts who perished during the Columbia accident -- Rick Husband, Willie McCool, Laurel Clark, Michael Anderson, David Brown, Kalpana Chawla, and Ilan Ramon.

Editors on Unix

NASA Astrophysics Data System (ADS)

Clayton, C. A.

The purpose of this document is to give new users advice on how to choose which editor to use on Unix machines. Under Unix the default editors are considered to be unfriendly and many users prefer to use other more sophisticated alternatives. However, many such alternatives exist; there is not one single editor that everyone finds acceptable and hence each user must decide for himself or herself which to adopt.

The Lives and Hard Times of Magazine Editors in the Big Apple: A Report on the Society of Magazine Editors' Educators Seminar.

ERIC Educational Resources Information Center

English, John W.

This report chronicles the first Society of Magazine Editors' educators seminar, which was held in New York from May 13-17, 1974, and was attended by ten journalism faculty. The industry's concerns, as expressed through editors, are paper, printing, postage, people, and profit. The Magazine Publishers Association (MPA) seems mostly concerned with…

Views of Iranian medical journal editors on medical research publication.

PubMed

Etemadi, Arash; Raiszadeh, Farbod; Alaeddini, Farshid; Azizi, Fereidoun

2004-01-01

Medical journal editors play an important role in optimizing research publication. This study evaluates the views of Iranian medical journal editors, and their knowledge of medical publication standards. In May 2001, 51 editors from all journals approved by the Ministry of Health were invited to participate, 27 of whom completed the study. A self-administered questionnaire, based on the Uniform Requirements for Manuscripts Submitted to Biomedical Journals (URMS) was used which consisted of 28 questions in 9 subject fields. These fields included: peer review, conflicts of interest, authorship criteria, publication ethics, duplicate publication, mass media, advertising, competing manuscripts, and the Internet. The knowledge of the editors was assessed by a scoring system, with a range of -46 to +44 points. Twenty-three of the participants were editors-in-chief and 4 were managing editors. Their average age was 47.3 +/- 8.7 years and 25 were male. All journals were peer-reviewed, most having 2 or 3 reviewers for each manuscript. Of the journals, 92.6% accepted or rejected an article on the basis of the views of most reviewers and 52%, sometimes or always, used a statistician as a reviewer. Most of the editors believed that writing the first draft and designing the study are authorship criteria, and most of them believed that these 2 are stated in URMS. Seven journals (25.9%) never published advertisements. Among journals that sold advertisements, the most popular policy (85%) was the rejection of advertisements because they advertised harmful products. Out of 27 journals, 12 were accessible on the Internet, and 7 had independent websites. Of the editors, 81.5% thought that a website is useful for their journal. The average knowledge score of the editors was 6.5 +/- 7.5. None had a negative score, 33% scored zero, 45% obtained average scores and 22% obtained good scores. The results show that peer review is favored by all the editors studied, though it seems that journals do not follow clear-cut policies in this regard. Most of the editors, agreed with the statements of URMS to some extent and generally most have average to high knowledge of URMS.

How is research publishing going to progress in the next 20 years?: transcription of session for editors, associate editors, publishers and others with an interest in scientific publishing held at IADR meeting in Seattle on Wednesday, 20 March 2013.

PubMed

Eaton, Kenneth A; Rex Holland, G; Giannobile, William V; Hancocks, Stephen; Robinson, Peter G; Lynch, Christopher D

2014-03-01

On March 20th 2013, a one-hour session for Editors, Associate Editors, Publishers and others with an interest in scientific publishing was held at the IADR International Session in Seattle. Organised by Kenneth Eaton and Christopher Lynch (Chair and Secretary, respectively, of the British Dental Editors Forum), the meeting sought to bring together leading international experts in dental publishing, as well as authors, reviewers and students engaged in research. The meeting was an overwhelming success, with more than 100 attendees. A panel involving four leading dental editors led a discussion on anticipated developments in publishing dental research with much involvement and contribution from audience members. This was the third such meeting held at the IADR for Editors, Associate Editors, Publishers and others with an interest in scientific publishing. A follow-up session will take place in Cape Town on 25 June 2014 as part of the annual IADR meeting. The transcript of the Seattle meeting is reproduced in this article. Where possible speakers are identified by name. At the first time of mention their role/position is also stated, thereafter only their name appears. We are grateful to Stephen Hancocks Ltd. for their generous sponsorship of this event. For those who were not able to attend the authors hope this article gives a flavour of the discussions and will encourage colleagues to attend future events. Involvement is open to Editors, Associate Editors, Publishers and others with an interest in scientific publishing. It is a very open group and all those with an interest will be welcome to join in. Copyright © 2014 Elsevier Ltd. All rights reserved.

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, demonstrating the specificity of the method. Conclusions Viable FRAP assays were established for 11 representative bromodomain-containing proteins that broadly cover the bromodomain phylogenetic tree. Addition of SAHA can overcome weak binding to chromatin, and the use of tandem bromodomain constructs can eliminate masking effects of other chromatin binding domains. Together, these results demonstrate that FRAP assays offer a potentially pan-bromodomain method for generating cell-based assays, allowing the testing of compounds with respect to cell permeability, on-target efficacy and selectivity. PMID:25097667

From scientist to editor

NASA Astrophysics Data System (ADS)

Novoselov, Kostya S.; Pulizzi, Fabio

2018-06-01

Kostya S. Novoselov, professor of physics at the University of Manchester, UK, has been digging into the details of the life of an editor by asking Fabio Pulizzi, Chief Editor of Nature Nanotechnology, some inside information on his work.

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.

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.

Burke new Tectonics editor

NASA Astrophysics Data System (ADS)

Kevin C. Burke, National Academy of Sciences/ National Research Council (NAS/NRC), assumed responsibilities as Editor in Chief of the American Geophysical Union (AGU) journal Tectonics at the beginning of 1990, taking over from Raymond A. Price, Queens University, Kingston, Ontario. Asger Berthelsen, University of Copenhagen, Denmark, continues as the European Editor, and Paul F. Hoffman, Geological Society of Canada, assumes the task of North American Editor. Tectonics is a joint publication of AGU and the European Geophysical Society.

The Altar of Patriarchy in John Ehle's "The Winter People."

ERIC Educational Resources Information Center

Grimes, M. Katherine

In John Ehle's "The Winter People," the goddess Persephone is with Hades, and winter is upon the Appalachians in full force. Ehle's novel begins as Wayland Jackson and his daughter, Paula, arrive at the home of Collie Wright and her baby, Jonathan. The Jacksons' truck has broken down on their way from Pennsylvania to Tennessee following…

ARC-2010-ACD10-0019-005

NASA Image and Video Library

2010-01-26

Director's Colloquium; Dr Jonathan Trent, Physical Scientist with NASA Ames Bioengineering Branch presents 'OMEGA and the Future of Aviation Fuels) Abstract: Offshore Membrane Enclosures for Growing Algae (OMEGA) is an innovative approach to growing oil-producing, freshwater algea in off shore enclosures, using municipal wastewater that is currently dumped into the ocean at a rate of >35 billion gals/day.

ARC-2010-ACD10-0019-009

NASA Image and Video Library

2010-01-26

Director's Colloquium; Dr Jonathan Trent, Physical Scientist with NASA Ames Bioengineering Branch presents 'OMEGA and the Future of Aviation Fuels) Abstract: Offshore Membrane Enclosures for Growing Algae (OMEGA) is an innovative approach to growing oil-producing, freshwater algea in off shore enclosures, using municipal wastewater that is currently dumped into the ocean at a rate of >35 billion gals/day.

One Step Closer to the Marketplace for State-of-the-Art Wind Turbine

Science.gov Websites

engineer and project lead Jonathan Keller, the technology is meeting design projections and working as drivetrain design. The Energy Department funded more than half of the project's $3 million design, build, and test budget. The industry partners supplied expertise, hardware design, development and fabrication

Are We Holding Back Our Students that Possess the Potential to Excel?

ERIC Educational Resources Information Center

Phillips, Simone

2008-01-01

This is a study of high achieving students using information about gifted students that can apply to and benefit all students. This article places focus on the highly motivated student that is intrinsically motivated, persistently works hard, and achieves top grades, but may not qualify as "gifted". For example, Jonathan has an average…

Intern Programs | Contacts

Science.gov Websites

Phone CCI Jonathan Lewis Manager jdl@fnal.gov 1-630-840-3779 GEM Sandra Charles Manager scharles gdzurics@fnal.gov 1-630-687-2929 SIST Sandra Charles Manager sist@fnal.gov 1-630-840-4574 Laura Fields Committee Chair sist@fnal.gov 1-630-840-8491 TARGET Sandra Charles Manager scharles@fnal.gov 1-630-840-4574

Inescapable Bodies, Disquieting Perception: Why Adults Seek to Tame and Harness Swift's Excremental Satire in "Gulliver's Travels"

ERIC Educational Resources Information Center

Stallcup, Jackie E.

2004-01-01

Jonathan Swift's "Gulliver's Travels" is a complex, uninhibited, savage satire that concludes with the narrator's descent into madness--hardly a likely candidate for children's reading. In the nearly three hundred years since it was first published, however, "Gulliver's Travels" has become associated with children's literature, though it is…

Envisioning Schoolhouse Nostalgia and the Pastoral Retreat: A Rural Landscape Approach to Educational History

ERIC Educational Resources Information Center

Clark, Sara

2014-01-01

The role of nostalgia has been identified by those interested in the unique impact of one-room schoolhouses on historical memory and present-day fascination with the structures. Most notably, educational historian Jonathan Zimmerman explored the issue in "Small Wonder: The Little Red Schoolhouse in History and Memory" (2009). Zimmerman…

Modeling and Evaluating Emotions Impact on Cognition

DTIC Science & Technology

2013-07-01

Causality and Responsibility Judgment in Multi-Agent Interactions: Extended abstract. 23rd International Joint Conference on Artificial Inteligence ...responsibility judgment in multi-agent interactions." Journal of Artificial Intelligence Research v44(1), 223- 273. • Morteza Dehghani, Jonathan Gratch... Artificial Intelligence (AAAI’11). Grant related invited talks: • Keynote speaker, Workshop on Empathic and Emotional Agents at the International

Unraveling "Braid": Puzzle Games and Storytelling in the Imperative Mood

ERIC Educational Resources Information Center

Arnott, Luke

2012-01-01

"Unraveling Braid" analyzes how unconventional, non-linear narrative fiction can help explain the ways in which video games signify. Specifically, this essay looks at the links between the semiotic features of Jonathan Blow's 2008 puzzle-platform video game Braid and similar elements in Georges Perec's 1978 novel "Life A User's Manual," as well as…

The Fate of Intrapleurally Injected Bone Marrow-Derived Stem Cells in Mice with Pleural Mesothelioma

DTIC Science & Technology

2012-12-01

hepatocytes by the intrahepatic delivery of clonal human mesenchymal stem cells in fetal sheep . Hepatology, 46: 1935-1945, 2007. 4. Jongsma, J., van...Mice with Pleural Mesothelioma 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0574 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Jonathan M

NASA Dryden aircraft and avionics technicians install the nose cone on an inert Phoenix missile prior to a fit check on the center's F-15B research aircraft.

NASA Image and Video Library

2006-11-13

NASA Dryden aircraft and avionics technicians (from left) Bryan Hookland, Art Cope, Herman Rijfkogel and Jonathan Richards install the nose cone on a Phoenix missile prior to a fit check on the center's F-15B research aircraft.

Radical Reform in a Time of Uncertainty

ERIC Educational Resources Information Center

Sherman, Robert M.

2012-01-01

Jonathan Woocher opens his clarion call for a new paradigm in Jewish education with a nod to Samson Benderly, founding executive of the Bureau of Jewish Education in New York (BJENY), who at the beginning of the 20th century set out to design a communal system built upon the twin pillars of progressive educational theory and practice and cultural…

Corporal Punishment and the Pain Provoked by the Community of Enquiry Pedagogy in the University Classroom

ERIC Educational Resources Information Center

Murris, Karin

2014-01-01

Education for transformation and social justice calls for critical, reflective, imaginative and independent thinkers with enquiring minds and a strong sense of curiosity--the ends and means of what Jonathan Jansen calls a "pedagogy to disrupt" and Gert Biesta a "pedagogy of interruption". For this reason, I introduced an…

Slowing Entropy: Instructional Policy Design in New York City, 2011-12. Policy Brief #14-3

ERIC Educational Resources Information Center

Supovitz, Jonathan

2014-01-01

How do policymakers craft policies, particularly centered on the Common Core State Standards, to be more resilient and less likely to disintegrate during enactment? Researcher Jonathan Supovitz in "Slowing Entropy: Instructional Policy Design in New York City, 2011-12" examines the design of a New York City Department of Education policy…

Quantum Computing

DTIC Science & Technology

1998-04-01

information representation and processing technology, although faster than the wheels and gears of the Charles Babbage computation machine, is still in...the same computational complexity class as the Babbage machine, with bits of information represented by entities which obey classical (non-quantum...nuclear double resonances Charles M Bowden and Jonathan P. Dowling Weapons Sciences Directorate, AMSMI-RD-WS-ST Missile Research, Development, and

High Value Talent: Identifying, Developing, and Retaining Naval Special Warfare’s Best Leaders

DTIC Science & Technology

2012-06-01

Retaining Naval Special Warfare’s Best Leaders 6. AUTHOR(S) Walter H. Allman, Jonathan M. Fussell, Marty D. Timmons 5. FUNDING NUMBERS 7. PERFORMING ...ORGANIZATION NAME(S) AND ADDRESS(ES) Naval Postgraduate School Monterey, CA 93943-5000 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING...5 1. High Performers ...................................................................................5 2. High Potentials

75 FR 41524 - Notice of Determinations Regarding Eligibility To Apply for Worker Adjustment Assistance

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-16

... in the Federal Register under section 202(f)(3); or (B) Notice of an affirmative determination... certifications have been issued. The requirements of Section 222(a)(2)(B) (shift in production or services) of... Industries, Inc., d/ Los Angeles, CA....... December 2, 2008. b/a/Jonathan Martin. 73,075 ABB, Inc., Robotics...

Measuring Refractive Index Using the Focal Displacement Method (Postprint)

DTIC Science & Technology

2014-05-01

refractive in- dex data at wavelengths longer than 1.8 μm [19] (2.5 μm [20]). The CdMgTe and CdMnTe crystals were obtained from Brimrose Technology...increase its accuracy. The authors gratefully acknowledge Dr. Sudhir Trivedi ( Brimrose Corp.) for providing the CdMgTe and CdMnTe samples, Dr. Jonathan

Not Too Big to Fail: How Teacher Education Killed the Foundations

ERIC Educational Resources Information Center

Gabbard, David; Flint, Lori J.

2013-01-01

Nearly forty years ago, Jonathan Kozol wrote on the perennial question posed by children: "Why do I have to go to school?" Rightfully, in David Gabbard and Lori Flint's view, he admonishes those who would "act as though it were a foolish question." The authors of this article take issue, however, with his characterization…

A Comparative Revolution? An Argument for In-Depth Study of the Iranian Revolution in a Familiar Way

ERIC Educational Resources Information Center

White, Jonathan

2011-01-01

Although the curriculum changes of 2008 brought with them new GCSE specifications, Jonathan White was disappointed by the dated feel of some "Modern World" options, particularly the depth studies on offer. Drawing on his experience of teaching comparative history within the International Baccalaureate, and building on previous arguments…

"Gulliver's Travels" by Alfred Silver with Music by Stephen Naylor. Cue Sheet for Students.

ERIC Educational Resources Information Center

Waterfall, Milde; Flynn, Rosalind, Ed.

Designed to be used before and after attending a musical adaptation of Jonathan's Swift's "Gulliver's Travels" (performed by the Mermaid Theatre of Nova Scotia), this cue sheet presents information about the performance and suggests activities that can be done with classmates, friends, or family members. Beginning with an illustration of…

Emotions under discussion: gender, status and communication in online collaboration.

PubMed

Iosub, Daniela; Laniado, David; Castillo, Carlos; Fuster Morell, Mayo; Kaltenbrunner, Andreas

2014-01-01

Despite the undisputed role of emotions in teamwork, not much is known about the make-up of emotions in online collaboration. Publicly available repositories of collaboration data, such as Wikipedia editor discussions, now enable the large-scale study of affect and dialogue in peer production. We investigate the established Wikipedia community and focus on how emotion and dialogue differ depending on the status, gender, and the communication network of the [Formula: see text] editors who have written at least 100 comments on the English Wikipedia's article talk pages. Emotions are quantified using a word-based approach comparing the results of two predefined lexicon-based methods: LIWC and SentiStrength. We find that administrators maintain a rather neutral, impersonal tone, while regular editors are more emotional and relationship-oriented, that is, they use language to form and maintain connections to other editors. A persistent gender difference is that female contributors communicate in a manner that promotes social affiliation and emotional connection more than male editors, irrespective of their status in the community. Female regular editors are the most relationship-oriented, whereas male administrators are the least relationship-focused. Finally, emotional and linguistic homophily is prevalent: editors tend to interact with other editors having similar emotional styles (e.g., editors expressing more anger connect more with one another). Emotional expression and linguistic style in online collaboration differ substantially depending on the contributors' gender and status, and on the communication network. This should be taken into account when analyzing collaborative success, and may prove insightful to communities facing gender gap and stagnation in contributor acquisition and participation levels.

Microbial properties database editor tutorial

USDA-ARS?s Scientific Manuscript database

A Microbial Properties Database Editor (MPDBE) has been developed to help consolidate microbialrelevant data to populate a microbial database and support a database editor by which an authorized user can modify physico-microbial properties related to microbial indicators and pathogens. Physical prop...

Microbial Properties Database Editor Tutorial

EPA Science Inventory

A Microbial Properties Database Editor (MPDBE) has been developed to help consolidate microbial-relevant data to populate a microbial database and support a database editor by which an authorized user can modify physico-microbial properties related to microbial indicators and pat...

Meet the Editors: JGR-Atmospheres

NASA Astrophysics Data System (ADS)

Kumar, Mohi

2006-04-01

Three scientists were newly appointed and one scientist was reappointed last year as editors of JGR-Atmospheres. The three new editors, John Austin, Jose D. Fuentes, and Ruth Lieberman, along with returning editor Colin O'Dowd, would like to see several changes made to the journal. ``JGR-Atmospheres is still regarded as the highest-quality atmospheric science journal, having perhaps one of the most stringent and rigorous review processes,'' said O'Dowd. ``However, there is still room for improvement.''

[The Chilean Association of Biomedical Journal Editors].

PubMed

Reyes, H

2001-01-01

On September 29th, 2000, The Chilean Association of Biomedical Journal Editors was founded, sponsored by the "Comisión Nacional de Investigación Científica y Tecnológica (CONICYT)" (the Governmental Agency promoting and funding scientific research and technological development in Chile) and the "Sociedad Médica de Santiago" (Chilean Society of Internal Medicine). The Association adopted the goals of the World Association of Medical Editors (WAME) and therefore it will foster "cooperation and communication among Editors of Chilean biomedical journals; to improve editorial standards, to promote professionalism in medical editing through education, self-criticism and self-regulation; and to encourage research on the principles and practice of medical editing". Twenty nine journals covering a closely similar number of different biomedical sciences, medical specialties, veterinary, dentistry and nursing, became Founding Members of the Association. A Governing Board was elected: President: Humberto Reyes, M.D. (Editor, Revista Médica de Chile); Vice-President: Mariano del Sol, M.D. (Editor, Revista Chilena de Anatomía); Secretary: Anna María Prat (CONICYT); Councilors: Manuel Krauskopff, Ph.D. (Editor, Biological Research) and Maritza Rahal, M.D. (Editor, Revista de Otorrinolaringología y Cirugía de Cabeza y Cuello). The Association will organize a Symposium on Biomedical Journal Editing and will spread information stimulating Chilean biomedical journals to become indexed in international databases and in SciELO-Chile, the main Chilean scientific website (www.scielo.cl).

A scoping review of competencies for scientific editors of biomedical journals.

PubMed

Galipeau, James; Barbour, Virginia; Baskin, Patricia; Bell-Syer, Sally; Cobey, Kelly; Cumpston, Miranda; Deeks, Jon; Garner, Paul; MacLehose, Harriet; Shamseer, Larissa; Straus, Sharon; Tugwell, Peter; Wager, Elizabeth; Winker, Margaret; Moher, David

2016-02-02

Biomedical journals are the main route for disseminating the results of health-related research. Despite this, their editors operate largely without formal training or certification. To our knowledge, no body of literature systematically identifying core competencies for scientific editors of biomedical journals exists. Therefore, we aimed to conduct a scoping review to determine what is known on the competency requirements for scientific editors of biomedical journals. We searched the MEDLINE®, Cochrane Library, Embase®, CINAHL, PsycINFO, and ERIC databases (from inception to November 2014) and conducted a grey literature search for research and non-research articles with competency-related statements (i.e. competencies, knowledge, skills, behaviors, and tasks) pertaining to the role of scientific editors of peer-reviewed health-related journals. We also conducted an environmental scan, searched the results of a previous environmental scan, and searched the websites of existing networks, major biomedical journal publishers, and organizations that offer resources for editors. A total of 225 full-text publications were included, 25 of which were research articles. We extracted a total of 1,566 statements possibly related to core competencies for scientific editors of biomedical journals from these publications. We then collated overlapping or duplicate statements which produced a list of 203 unique statements. Finally, we grouped these statements into seven emergent themes: (1) dealing with authors, (2) dealing with peer reviewers, (3) journal publishing, (4) journal promotion, (5) editing, (6) ethics and integrity, and (7) qualities and characteristics of editors. To our knowledge, this scoping review is the first attempt to systematically identify possible competencies of editors. Limitations are that (1) we may not have captured all aspects of a biomedical editor's work in our searches, (2) removing redundant and overlapping items may have led to the elimination of some nuances between items, (3) restricting to certain databases, and only French and English publications, may have excluded relevant publications, and (4) some statements may not necessarily be competencies. This scoping review is the first step of a program to develop a minimum set of core competencies for scientific editors of biomedical journals which will be followed by a training needs assessment, a Delphi exercise, and a consensus meeting.

FloorspaceJS - A New, Open Source, Web-Based Geometry Editor for Building Energy Modeling (BEM): Preprint

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

Macumber, Daniel L; Horowitz, Scott G; Schott, Marjorie

Across most industries, desktop applications are being rapidly migrated to web applications for a variety of reasons. Web applications are inherently cross platform, mobile, and easier to distribute than desktop applications. Fueling this trend are a wide range of free, open source libraries and frameworks that make it incredibly easy to develop powerful web applications. The building energy modeling community is just beginning to pick up on these larger trends, with a small but growing number of building energy modeling applications starting on or moving to the web. This paper presents a new, open source, web based geometry editor formore » Building Energy Modeling (BEM). The editor is written completely in JavaScript and runs in a modern web browser. The editor works on a custom JSON file format and is designed to be integrated into a variety of web and desktop applications. The web based editor is available to use as a standalone web application at: https://nrel.github.io/openstudio-geometry-editor/. An example integration is demonstrated with the OpenStudio desktop application. Finally, the editor can be easily integrated with a wide range of possible building energy modeling web applications.« less

Inverse Scattering and Applications. Proceedings of Conference on Inverse Scattering on the Line, Held in Amherst, Massachusetts on June 7 - 13, 1990

DTIC Science & Technology

1990-01-01

J. Laurie Snell S. A. Amitsur, D. J. Saltman, and 2 Proceedings of the conference on G. B. Seligman , Editors integration, topology, and geometry in...Rational constructions of modules 17 Nonlinear partial differential equations. for simple Lie algebras, George B. Joel A. Smoller, Editor Seligman 18...number theory, Michael R. Stein and Linda Keen, Editor R. Keith Dennis, Editors 65 Logic and combinatorics, Stephen G. 84 Partition problems in

Editor's Choice Offered as a Service

NASA Astrophysics Data System (ADS)

Richman, Barbara T.

2010-06-01

Editor's Choice is now being offered as a service rather than on a subscription basis. As in the past, articles will be selected by collection editors with assistance from advisory panels. The selected articles will be listed on the AGU Web site (http://www.agu.org/pubs/journals/virtual/editors_choice/); these lists will be accessible to anyone. Those who are interested in reading the articles can access them through a personal or institutional subscription or can purchase them either individually or as part of a MultiChoice packet.

Rule-based support system for multiple UMLS semantic type assignments

PubMed Central

Geller, James; He, Zhe; Perl, Yehoshua; Morrey, C. Paul; Xu, Julia

2012-01-01

Background When new concepts are inserted into the UMLS, they are assigned one or several semantic types from the UMLS Semantic Network by the UMLS editors. However, not every combination of semantic types is permissible. It was observed that many concepts with rare combinations of semantic types have erroneous semantic type assignments or prohibited combinations of semantic types. The correction of such errors is resource-intensive. Objective We design a computational system to inform UMLS editors as to whether a specific combination of two, three, four, or five semantic types is permissible or prohibited or questionable. Methods We identify a set of inclusion and exclusion instructions in the UMLS Semantic Network documentation and derive corresponding rule-categories as well as rule-categories from the UMLS concept content. We then design an algorithm adviseEditor based on these rule-categories. The algorithm specifies rules for an editor how to proceed when considering a tuple (pair, triple, quadruple, quintuple) of semantic types to be assigned to a concept. Results Eight rule-categories were identified. A Web-based system was developed to implement the adviseEditor algorithm, which returns for an input combination of semantic types whether it is permitted, prohibited or (in a few cases) requires more research. The numbers of semantic type pairs assigned to each rule-category are reported. Interesting examples for each rule-category are illustrated. Cases of semantic type assignments that contradict rules are listed, including recently introduced ones. Conclusion The adviseEditor system implements explicit and implicit knowledge available in the UMLS in a system that informs UMLS editors about the permissibility of a desired combination of semantic types. Using adviseEditor might help accelerate the work of the UMLS editors and prevent erroneous semantic type assignments. PMID:23041716

Emotions under Discussion: Gender, Status and Communication in Online Collaboration

PubMed Central

Iosub, Daniela; Laniado, David; Castillo, Carlos; Fuster Morell, Mayo; Kaltenbrunner, Andreas

2014-01-01

Background Despite the undisputed role of emotions in teamwork, not much is known about the make-up of emotions in online collaboration. Publicly available repositories of collaboration data, such as Wikipedia editor discussions, now enable the large-scale study of affect and dialogue in peer production. Methods We investigate the established Wikipedia community and focus on how emotion and dialogue differ depending on the status, gender, and the communication network of the editors who have written at least 100 comments on the English Wikipedia's article talk pages. Emotions are quantified using a word-based approach comparing the results of two predefined lexicon-based methods: LIWC and SentiStrength. Principal Findings We find that administrators maintain a rather neutral, impersonal tone, while regular editors are more emotional and relationship-oriented, that is, they use language to form and maintain connections to other editors. A persistent gender difference is that female contributors communicate in a manner that promotes social affiliation and emotional connection more than male editors, irrespective of their status in the community. Female regular editors are the most relationship-oriented, whereas male administrators are the least relationship-focused. Finally, emotional and linguistic homophily is prevalent: editors tend to interact with other editors having similar emotional styles (e.g., editors expressing more anger connect more with one another). Conclusions/Significance Emotional expression and linguistic style in online collaboration differ substantially depending on the contributors' gender and status, and on the communication network. This should be taken into account when analyzing collaborative success, and may prove insightful to communities facing gender gap and stagnation in contributor acquisition and participation levels. PMID:25140870

Technical editing and the effective communication of scientific results

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

Pieper, G.W.; Picologlou, S.M.

1996-05-01

Communication of scientific results--whether for professional journals, poster sessions, oral presentations, or the popular press--is an essential part of any scientific investigation. The technical editor plays an important rolein ensuring that scientists express their results correctly and effectively. Technical editing comprises far more than simple proofreading. The editor`s tasks may range from restructuring whole parpagrphs and suggesting improved graphical aids to writing abstracts and preparing first drafts of proposals. The technical editor works closely with scientists to present complex ideas to differentaudiences, including fellow scentists, funding agencies, and the general public. New computer technologyhas also involved the technical editor notmore » only with on-line editing but also with preparing CD ROMs and World Wide Web pages.« less

Data Sharing: A New Editorial Initiative of the International Committee of Medical Journal Editors. Implications for the Editors´ Network.

PubMed

Alfonso, Fernando; Adamyan, Karlen; Artigou, Jean Yves; Aschermann, Michael; Boehm, Michael; Buendia, Alfonso; Chu, Pao Hsien; Cohen, Ariel; Cas, Livio Dei; Dilic, Mirza; Doubell, Anton; Echeverri, Dario; Enç, Nuray; Ferreira-González, Ignacio; Filipiak, Krzysztof J; Flammer, Andreas; Fleck, Eckart; Gatzov, Plamen; Ginghina, Carmen; Goncalves, Lino; Haouala, Habib; Hassanein, Mahmoud; Heusch, Gerd; Huber, Kurt; Hulín, Ivan; Ivanusa, Mario; Krittayaphong, Rungroj; Lau, Chu Pak; Marinskis, Germanas; Mach, François; Moreira, Luiz Felipe; Nieminen, Tuomo; Oukerraj, Latifa; Perings, Stefan; Pierard, Luc; Potpara, Tatjana; Reyes-Caorsi, Walter; Rim, Se Joong; Rødevand, Olaf; Saade, Georges; Sander, Mikael; Shlyakhto, Evgeny; Timuralp, Bilgin; Tousoulis, Dimitris; Ural, Dilek; Piek, J J; Varga, Albert; Lüscher, Thomas F

2017-06-01

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship -emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors´ Network of the European Society of Cardiology.

Data Sharing: A New Editorial Initiative of the International Committee of Medical Journal Editors. Implications for the Editors´ Network

PubMed Central

Alfonso, Fernando; Adamyan, Karlen; Artigou, Jean-Yves; Aschermann, Michael; Boehm, Michael; Buendia, Alfonso; Chu, Pao-Hsien; Cohen, Ariel; Cas, Livio Dei; Dilic, Mirza; Doubell, Anton; Echeverri, Dario; Enç, Nuray; Ferreira-González, Ignacio; Filipiak, Krzysztof J.; Flammer, Andreas; Fleck, Eckart; Gatzov, Plamen; Ginghina, Carmen; Goncalves, Lino; Haouala, Habib; Hassanein, Mahmoud; Heusch, Gerd; Huber, Kurt; Hulín, Ivan; Ivanusa, Mario; Krittayaphong, Rungroj; Lau, Chu-Pak; Marinskis, Germanas; Mach, François; Moreira, Luiz Felipe; Nieminen, Tuomo; Oukerraj, Latifa; Perings, Stefan; Pierard, Luc; Potpara, Tatjana; Reyes-Caorsi, Walter; Rim, Se-Joong; Rødevand, Olaf; Saade, Georges; Sander, Mikael; Shlyakhto, Evgeny; Timuralp, Bilgin; Tousoulis, Dimitris; Ural, Dilek; Piek, J. J.; Varga, Albert; Lüscher, Thomas F.

2017-01-01

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship - emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors´ Network of the European Society of Cardiology. PMID:28591318

Peer reviews and the role of a journal editor

USDA-ARS?s Scientific Manuscript database

Obtaining peer reviews for manuscripts submitted to scientific journals is becoming increasingly difficult. Changes to the system are necessary, and editors must cultivate and maintain a solid base of reviewers to help evaluate journal submissions. This article outlines some steps editors can and sh...

Training the Technical Editor.

ERIC Educational Resources Information Center

Cathcart, Margaret E.

The demand for skilled technical editors is growing as society places increasing emphasis on receiving accurate, concise, and complete technical data. Since many organizations do not have inhouse programs for training technical editors, a need exists to provide inexperienced people with basic editing skills. One organization has developed two…

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.

Entering the 60th year of Acta Astronautica

NASA Astrophysics Data System (ADS)

Chang, Yi-Wei; Chern, Jeng-Shing; Marec, Jean-Pierre

2014-04-01

The Acta Astronautica Journal was firstly published in 1955 as the official Journal of the International Astronautical Federation (IAF) with the title Astronautica Acta. It is entering its 60th year in 2014. In 1962, the Astronautica Acta became the official Journal of the International Academy of Astronautics (IAA) established in 1960. A total of 18 volumes had been published from 1955 to 1973 under the leadership of three Editor-in-Chiefs: F. Hecht, Theodore von Karman, and Martin Summerfield. In 1974, A.K. Oppenheim became the new Editor-in-Chief and several evolved changes were performed including change of the title to Acta Astronautica (for grammatical correctness), cover page change, and format change. From 1974 to 2010, another three Editor-in-Chiefs led the journal with 67 volumes published. They were A.K. Oppenheim, Jean-Pierre Marec, and Rupert Gerzer. The current Editor-in-Chief Jeng-Shing Chern (Rock) took over the job from 2011. Total pages and articles published in 2012 are 3586 and 356, respectively. Currently, the Acta Astronautica Editorial Board consists of one Editor-in-Chief, 15 Co-Editors, one Managing Editor and one Honorary Editor-in-Chief (Jean-Pierre Marec). After 59 years, the Acta Astronautica has become a well-known journal worldwide. Its current rank and impact factor are 7/63 and 0.701, respectively. This paper presents some of the details as well as new strategies and steps. In particular, supports from the IAA Academicians are mandatory and most welcome.

Quantifying the effect of editor-author relations on manuscript handling times.

PubMed

Sarigöl, Emre; Garcia, David; Scholtes, Ingo; Schweitzer, Frank

2017-01-01

In this article we study to what extent the academic peer review process is influenced by social relations between the authors of a manuscript and the editor handling the manuscript. Taking the open access journal PlosOne as a case study, our analysis is based on a data set of more than 100,000 articles published between 2007 and 2015. Using available data on handling editor, submission and acceptance time of manuscripts, we study the question whether co-authorship relations between authors and the handling editor affect the manuscript handling time , i.e. the time taken between the submission and acceptance of a manuscript. Our analysis reveals (1) that editors handle papers co-authored by previous collaborators significantly more often than expected at random, and (2) that such prior co-author relations are significantly related to faster manuscript handling. Addressing the question whether these shorter manuscript handling times can be explained by the quality of publications, we study the number of citations and downloads which accepted papers eventually accumulate. Moreover, we consider the influence of additional (social) factors, such as the editor's experience, the topical similarity between authors and editors, as well as reciprocal citation relations between authors and editors. Our findings show that, even when correcting for other factors like time, experience, and performance, prior co-authorship relations have a large and significant influence on manuscript handling times, speeding up the editorial decision on average by 19 days.

Powder based superdielectric materials for novel Capacitor design

DTIC Science & Technology

2017-06-01

SUPERDIELECTRIC MATERIALS FOR NOVEL CAPACITOR DESIGN by Clayton W. Petty June 2017 Thesis Advisor: Jonathan Phillips Second Reader: Anthony...thesis 4. TITLE AND SUBTITLE POWDER-BASED SUPERDIELECTRIC MATERIALS FOR NOVEL CAPACITOR DESIGN 5. FUNDING NUMBERS 6. AUTHOR(S) Clayton W...unlimited. POWDER-BASED SUPERDIELECTRIC MATERIALS FOR NOVEL CAPACITOR DESIGN Clayton W. Petty Lieutenant, Junior Grade, United States Navy B.S

75 FR 47585 - Jonathan and Jayne Chase; Notice of Application Tendered for Filing With the Commission and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-06

.... e. Name of Project: Troy Hydroelectric Project. f. Location: On the Missisquoi River, in the Town of Troy, Orleans County, Vermont. The project would not occupy lands of the United States. g. Filed... application is not ready for environmental analysis at this time. n. The Troy Project would consist of: (1...

Management of Information Technology Access Controls

DTIC Science & Technology

1991-01-01

Management Information Systems , (New York: American Elsevier Publishing Company, 1968), 8. 2. Webster’s Third New International Dictionary, Unabridged... Management Information Systems (New York: American Elsevier Publishing company, 1968), 37. 5. Ibid. 6. Ibid. 7. Gerald M. Ward and Jonathan D. Harris, "Data...Controls: A Visual Approach Through Integrated Management Information Systems . New York: American Elsevier Publishing Company, 1968. Brancheau, James C

AN APPROACH TO THE DEVELOPMENT OF MODELS TO QUANTITATIVELY ASSESS THE EFFECTS OF EXPOSURE TO ENVIRONMENTALLY RELEVANT LEVELS OF ENDOCRINE DISRUPTORS

EPA Science Inventory

An approach to the development of quantitative models to assess the effects of exposure to environmentally relevant levels of endocrine disruptors on homeostasis in adults.

Ben-Jonathan N, Cooper RL, Foster P, Hughes CL, Hoyer PB, Klotz D, Kohn M, Lamb DJ, Stancel GM.
<...

Reflections on Active Networking

DTIC Science & Technology

2005-01-01

Reflections on Active Networking Jonathan M. Smith CIS Department, University of Pennsylvania jms@cis.upenn.edu Abstract Interactions among...called “ Active Networking” came into being. It demonstrates the deep roots Active Networking has in the programming languages, networking and operating...broader research agenda, and the specific goals pursued in the SwitchWare project. I close by speculating on possible futures for Active Networking

Educator Effectiveness Series: Assessing School Climate. Q&A with Jonathan Cohen, Ph.D. REL Mid-Atlantic Webinar

ERIC Educational Resources Information Center

Cohen, Jonathan

2015-01-01

The REL Mid-Atlantic Webinar discussed the elements in a positive school climate and shared different methods for assessing school data, including the Comprehensive School Climate Inventory. The Q&A presented in this document address the questions participants had for Dr. Cohen following the webinar. The webinar recording and PowerPoint…

Doing What It Takes To Make Schools and Communities Drug Free. Conference Proceedings (2nd, Chicago, IL, March 26-28, 1992).

ERIC Educational Resources Information Center

North Central Regional Educational Lab., Elmhurst, IL.

Keynote addresses, issues forums, workshops, and panel discussions from a conference on making schools and communities drug free are summarized in this document. Keynote addresses by Jonathan Kozol, Protase Woodford, and Jeff Howard are summarized. Issues forums are included on the topics of building successful school and community partnerships;…

Worries Occasioned by Woocher's Conception of Jewish Education

ERIC Educational Resources Information Center

Pekarsky, Daniel

2012-01-01

Jonathan Woocher is to be commended for offering his thought-provoking "big picture" account of where the field of Jewish education has been and where, if it is to be successful, it needs to be going under the conditions of life in the 21st century. Woocher's capacity to use an array of relevant perspectives and literatures to illuminate the…

Understanding American Identity: An Introduction

DTIC Science & Technology

2017-12-01

and equality in American society is akin to a magnetic field; this force will either bring people together or force them apart. Jonathan Haidt...Hegemony: Problems and Possibilities,” The American Historical Review, 1985, 567–593. 55 3. Obstacle # 3: Subgroup Suppression When societies ... American identity narratives in U.S. history and contemporary society . The historic disagreement over the distribution of the fundamental American

INTER LABORATORY COMBAT HELMET BLUNT IMPACT TEST METHOD COMPARISON

DTIC Science & Technology

2018-03-26

HELMET BLUNT IMPACT TEST METHOD COMPARISON by Tony J. Kayhart Charles A. Hewitt and Jonathan Cyganik March 2018 Final...Report March 2016 – August 2017 Approved for public release; distribution is unlimited U.S. Army Natick Soldier Research ...INTER-LABORATORY COMBAT HELMET BLUNT IMPACT TEST METHOD COMPARISON 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

Trace a Vein: On Assessment for Learning

ERIC Educational Resources Information Center

Howland, Jonathan

2014-01-01

Author Jonathan Howland writes here that he is hardly the first to suggest that much of the testing going on in the educational system today appears dumb. The tidal change that brought schools the Common Core standards is a maneuver born of an admission: educators took their eye off the ball, testing for too much of the wrong thing--thin skills…

76 FR 33705 - Takes of Marine Mammals Incidental to Specified Activities; Marine Geophysical Survey in the...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-09

... determinations and including a proposed IHA. The notice initiated a 30-day public comment period. USGS plans to... Investigators are Drs. Jonathan R. Childs and Ginger Barth of the USGS. The vessel will be self-contained, and... conduct its analysis and make any determinations and therefore no further effort is needed by the...

JPL-20170811-CASSINf-0001a-A World Unveiled Cassini at TItan

NASA Image and Video Library

2017-08-11

A look at the Cassini-Huygens mission's discoveries at Saturn's moon Titan and a description of how flybys of Titan allowed the mission to change to new orbits repeatedly without wasting fuel. Featuring Linda Spilker, Cassini Project Scientist, JPL; Jonathan Lunine, Cassini Titan Scientist, Cornell University; and Elizabeth "Zibi" Turtle, Cassini Imaging Team, John Hopkins Applied Physics Laboratory.

78 FR 76177 - Meeting of the Judicial Conference Committee on Rules of Practice and Procedure

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-16

... Procedure. ACTION: Notice of open meeting. SUMMARY: The Committee on Rules of Practice and Procedure will hold a two-day meeting. The meeting will be open to public observation but not participation. DATES...: December 11, 2013. Jonathan C. Rose, Rules Committee Secretary. [FR Doc. 2013-29841 Filed 12-13-13; 8:45 am...

Data-Based Detection of Potential Terrorist Attacks: Statistical and Graphical Methods

DTIC Science & Technology

2010-06-01

Naren; Vasquez-Robinet, Cecilia; Watkinson, Jonathan: "A General Probabilistic Model of the PCR Process," Applied Mathematics and Computation 182(1...September 2006. Seminar, Measuring the effect of Length biased sampling, Mathematical Sciences Section, National Security Agency, 19 September 2006...Committee on National Statistics, 9 February 2007. Invited seminar, Statistical Tests for Bullet Lead Comparisons, Department of Mathematics , Butler

EFFECTS OF PRENATAL TESTOSTERONE PROPIONATE AND VINCLOZOLIN ON PERINATAL AND INFANTILE DEVELOPMENT OF MALE AND FEMALE RATS

EPA Science Inventory

Effects of Prenatal Testosterone Propionate and Vinclozolin on Perinatal and Infantile Development of Male and Female Rats
Cynthia Wolf1,2, Jonathan Furr1, Gerald A. LeBlanc2, and L. Earl Gray, Jr.1
1USEPA, NHEERL, RTD, EB, RTP, NC 27711, 2Dept. of Environmental and Molecu...

The Case for District-Based Reform: Leading, Building, and Sustaining School Improvement

ERIC Educational Resources Information Center

Supovitz, Jonathan A.

2006-01-01

In 1999, the Duval County (Fla.) school system set out to improve every school in the district. Over the next five years, the district achieved stunning results that have drawn nationwide attention. Jonathan A. Supovitz uses the unfolding story of Duval County to develop a sophisticated and thoughtful analysis of the role of the school district in…

"Finding Useful Questions: On Bayesian Diagnosticity, Probability, Impact, and Information Gain": Correction to Nelson (2005)

ERIC Educational Resources Information Center

Nelson, Jonathan D.

2007-01-01

Reports an error in "Finding Useful Questions: On Bayesian Diagnosticity, Probability, Impact, and Information Gain" by Jonathan D. Nelson (Psychological Review, 2005[Oct], Vol 112[4], 979-999). In Table 13, the data should indicate that 7% of females had short hair and 93% of females had long hair. The calculations and discussion in the article…

Building an Honors Education for the Twenty-First Century: Making Connections in and outside the Classroom

ERIC Educational Resources Information Center

Alger, Jonathan

2015-01-01

Jonathan Alger, president of James Madison University, reflects on his experience as a student who searched for an honors program in which it was "cool" for students to develop close mentoring relationships with faculty and where students were encouraged to seek both breadth and depth in their education. He realized he was seeking a…

High Accuracy Potential Energy Surface, Dipole Moment Surface, Rovibrational Energies and Line List Calculations for ^{14}NH_3

NASA Astrophysics Data System (ADS)

Coles, Phillip; Yurchenko, Sergei N.; Polyansky, Oleg; Kyuberis, Aleksandra; Ovsyannikov, Roman I.; Zobov, Nikolay Fedorovich; Tennyson, Jonathan

2017-06-01

We present a new spectroscopic potential energy surface (PES) for ^{14}NH_3, produced by refining a high accuracy ab initio PES to experimental energy levels taken predominantly from MARVEL. The PES reproduces 1722 matched J=0-8 experimental energies with a root-mean-square error of 0.035 cm-1 under 6000 cm^{-1} and 0.059 under 7200 cm^{-1}. In conjunction with a new DMS calculated using multi reference configuration interaction (MRCI) and H=aug-cc-pVQZ, N=aug-cc-pWCVQZ basis sets, an infrared (IR) line list has been computed which is suitable for use up to 2000 K. The line list is used to assign experimental lines in the 7500 - 10,500 cm^{-1} region and previously unassigned lines in HITRAN in the 6000-7000 cm^{-1} region. Oleg L. Polyansky, Roman I. Ovsyannikov, Aleksandra A. Kyuberis, Lorenzo Lodi, Jonathan Tennyson, Andrey Yachmenev, Sergei N. Yurchenko, Nikolai F. Zobov, J. Mol. Spec., 327 (2016) 21-30 Afaf R. Al Derzia, Tibor Furtenbacher, Jonathan Tennyson, Sergei N. Yurchenko, Attila G. Császár, J. Quant. Spectrosc. Rad. Trans., 161 (2015) 117-130

How Non-Daily Editors Describe Status and Function of Editorial Pages.

ERIC Educational Resources Information Center

Hynds, Ernest C.; Martin, Charles H.

1979-01-01

Results of a survey of 359 editors of nondaily newspapers indicates that most nondaily editors see their editorials and editorial pages as important segments of their newspapers and believe they can use them to help influence readers, particularly on local issues. (Author/GT)

Letter to the editor of TAAP, in response to letter from Anders et al.

EPA Science Inventory

To the Editor, Toxicology and Applied Pharmacology: We would like to address the letter to the editor submitted by Anders et al. regarding the substantive issues raised regarding our paper "Evaluation of two different metabolic hypotheses for dichloromethane toxicity using physi...

Growth and Consequences.

PubMed

Abbott, J Haxby

2016-08-01

In response to the growth of JOSPT, Editor-in-Chief J. Haxby Abbott introduces 3 new Associate Editors to the JOSPT Editorial Board, and announces the promotion of 1 outstanding Editorial Board member to an Editor role. J Orthop Sports Phys Ther 2016;46(8):610-612. doi:10.2519/jospt.2016.0111.

Professional Editing Strategies Used by Six Editors

ERIC Educational Resources Information Center

Bisaillon, Jocelyne

2007-01-01

Identifying the approach used by those revision experts par excellence--that is, professional editors--should enable researchers to better grasp the revision process. To further explore this hypothesis, the author conducted research among professional editors, six of whom she filmed as they engaged in their practice. An analysis of their work…

A "Situational" and "Coorientational" Measure of Specialized Magazine Editors' Perceptions of Readers.

ERIC Educational Resources Information Center

Jeffers, Dennis W.

A study was undertaken of specialized magazine editors' perceptions of audience characteristics as well as the perceived role of their publications. Specifically, the study examines the relationship between the editors' perceptions of reader problem recognition, level of involvement, constraint recognition, and possession of reference criteria and…

Editorial and Broadcasting Careers.

ERIC Educational Resources Information Center

Broido, Arnold; And Others

1982-01-01

Describes the jobs of the music publisher and editor, music magazine and book editor, film music editor, and music critic. Educational requirements, job availability, and the advantages and disadvantages of each are discussed. A tear-out chart of ten music career areas, listing salaries and personal and educational qualifications, is included. (AM)

Generating the Field: The Role of Editors in Disciplinary Formation

ERIC Educational Resources Information Center

Selfe, Cynthia; Villanueva, Victor; Parks, Steve

2017-01-01

In the following conversation, conducted asynchronously through email, three current and former editors discuss the role of publishing in creating a disciplinary identity. Speaking from the academic (Villanueva), digital (Selfe), and community (Parks), and, often crossing these three categories, the editors discuss how the field has failed to…

STEVE -- User Guide and Reference Manual

NASA Astrophysics Data System (ADS)

Fish, Adrian

This document describes an extended version of the EVE editor that has been tailored to the general Starlink user's requirements. This extended editor is STarlink Eve or STEve, and this document (along with it's introductory companion SUN/125) describes this editor, and offers additional help, advice and tips on general EVE usage.

Publishing and Journalism Careers

ERIC Educational Resources Information Center

Reed, Alfred; And Others

1977-01-01

If you like to work with words and notational symbols--or with describing, selecting, managing, and distributing the words and music of other people--then journalism or publishing as a whole may be your bailiwick. Describes the positions of music editor, music publisher, magazine/book editor, music critic, and freelance music writer. (Editor/RK)

Data Sharing: A New Editorial Initiative of the International Committee of Medical Journal Editors. Implications for the Editors' Network.

PubMed

Alfonso, Fernando; Adamyan, Karlen; Artigou, Jean-Yves; Aschermann, Michael; Boehm, Michael; Buendia, Alfonso; Chu, Pao-Hsien; Cohen, Ariel; Cas, Livio Dei; Dilic, Mirza; Doubell, Anton; Echeverri, Dario; Enç, Nuray; Ferreira-González, Ignacio; Filipiak, Krzysztof J; Flammer, Andreas; Fleck, Eckart; Gatzov, Plamen; Ginghina, Carmen; Goncalves, Lino; Haouala, Habib; Hassanein, Mahmoud; Heusch, Gerd; Huber, Kurt; Hulín, Ivan; Ivanusa, Mario; Krittayaphong, Rungroj; Lau, Chu-Pak; Marinskis, Germanas; Mach, François; Moreira, Luiz Felipe; Nieminen, Tuomo; Oukerraj, Latifa; Perings, Stefan; Pierard, Luc; Potpara, Tatjana; Reyes-Caorsi, Walter; Rim, Se-Joong; Rødevand, Olaf; Saade, Georges; Sander, Mikael; Shlyakhto, Evgeny; Timuralp, Bilgin; Tousoulis, Dimitris; Ural, Dilek; Piek, J J; Varga, Albert; Lüscher, Thomas F

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship - emphasizing the importance of responsibility and accountability -, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors' Network of the European Society of Cardiology. Copyright © 2017. Publicado por Masson Doyma México S.A.

ZED- A LINE EDITOR FOR THE DEC VAX

NASA Technical Reports Server (NTRS)

Scott, P. J.

1994-01-01

The ZED editor for the DEC VAX is a simple, yet powerful line editor for text, program source code, and non-binary data. Line editors can be superior to screen editors in some cases, such as executing complex multiple or conditional commands, or editing via slow modem lines. ZED excels in the area of text processing by using procedure files. For example, such procedures can reformat a file of addresses or remove all comment lines from a FORTRAN program. In addition to command files, ZED also features versatile search qualifiers, global changes, conditionals, on-line help, hexadecimal mode, space compression, looping, logical combinations of search strings, journaling, visible control characters, and automatic detabbing. The ZED editor was originally developed at Cambridge University in London and has been continuously enhanced since 1976. Users of the Cambridge implementation have devised such elaborate ZED procedures as chess games, calculators, and programs for evaluating Pi. This implementation of ZED strives to maintain the characteristics of the Cambridge editor. A complete ZED manual is included on the tape. ZED is written entirely in C for either batch or interactive execution on the DEC VAX under VMS 4.X and requires 80,896 bytes of memory. This program was released in 1988 and updated in 1989.

Adolescent Sexual Initiation through the Lens of Letters to the Editor Published in Polish Teenage Magazines

ERIC Educational Resources Information Center

Kopacz, Marek S.; Bajka-Kopacz, Aleksandra

2012-01-01

Almost all teenage magazines invite readers to submit questions concerning relationships, published as letters to the editor, popularly called "advice columns," often containing explicit questions about sexuality. This study aims to examine, firstly, how themes related to sexual initiation are presented in letters to the editor published…

Digital Alteration of Photographs in Magazines: An Examination of the Ethics.

ERIC Educational Resources Information Center

Reaves, Shiela

A study examined magazine editors' views of some of the ethical considerations posed by digital alteration of photographs. Subjects, 12 consumer news and specialty magazine editors, were interviewed by telephone and asked a series of questions concerning the ethics of digitally manipulating photographs. Results indicated that magazine editors were…

"Clones," Codes, and Conflicts of Interest in Cartooning: Cartoonists and Editors Look at Ethics.

ERIC Educational Resources Information Center

Riffe, Daniel; And Others

A study examined differences between political cartoonists and op-ed page editors on both traditional ethical issues (such as conflicts of interest) and the special, style-related concerns of editorial cartoonists. Hypotheses proposed were that editors and cartoonists (1) would condemn "cloning" or copying, reflecting an ethical…

29 CFR 793.11 - Combination announcer, news editor and chief engineer.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 29 Labor 3 2012-07-01 2012-07-01 false Combination announcer, news editor and chief engineer. 793...)(9) OF THE FAIR LABOR STANDARDS ACT Requirements for Exemption § 793.11 Combination announcer, news... as a news editor. In such cases, the primary employment test under the section 13(b)(9) exemption...

29 CFR 793.11 - Combination announcer, news editor and chief engineer.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 29 Labor 3 2014-07-01 2014-07-01 false Combination announcer, news editor and chief engineer. 793...)(9) OF THE FAIR LABOR STANDARDS ACT Requirements for Exemption § 793.11 Combination announcer, news... as a news editor. In such cases, the primary employment test under the section 13(b)(9) exemption...

29 CFR 793.11 - Combination announcer, news editor and chief engineer.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 29 Labor 3 2013-07-01 2013-07-01 false Combination announcer, news editor and chief engineer. 793...)(9) OF THE FAIR LABOR STANDARDS ACT Requirements for Exemption § 793.11 Combination announcer, news... as a news editor. In such cases, the primary employment test under the section 13(b)(9) exemption...

The Introductory Psychology Textbook Market: Perceptions of Authors and Editors.

ERIC Educational Resources Information Center

Griggs, Richard A.; Jackson, Sherri L.

1989-01-01

Surveys psychology textbook authors and editors on their perceptions of the introductory psychology textbook market. Finds that the textbook market is divided into three levels according to quality, and that authors and editors are not familiar with most textbooks. Notes that the growth of used book companies has adversely affected the market.…

A Lesson for Instructors: Top 10 Copy-Editing Skills.

ERIC Educational Resources Information Center

Auman, Ann

1995-01-01

Presents results of a survey of 164 newspaper editors regarding which skills they believe are crucial for entry-level copy editors to know, and in which areas they see the most deficiencies. Notes that the skills identified reflect the changing duties of the copy editor and the increasing complexities of the job. (SR)

Newspaper Ethics and Managing Editors: The Evolution of APME's Code.

ERIC Educational Resources Information Center

De Mott, John

A review of the 42-year development of the professional code of ethics of the Associated Press Managing Editors (APME) demonstrates an effort to elevate newspaper ethical standards around the country. Following the example of the American Society of Newspaper Editors in establishing its "Canons of Journalism" in 1923, the APME formed a…

Editorial

NASA Astrophysics Data System (ADS)

Audoly, Basile; Castañeda, Pedro Ponte; Kuhl, Ellen; Niordson, Christian; Sharma, Pradeep; Gao, Huajian

2016-02-01

After 12 years of distinguished service, Kaushik Bhattacharya has decided to step down as co-editor of the Journal of the Mechanics and Physics of Solids. A new editorial team, with Huajian Gao as editor and Basile Audoly, Pedro Ponte Castañeda, Ellen Kuhl, Christian Niordson and Pradeep Sharma as Associate Editors, will take over as of January 1, 2016.

Biosecurity and the review and publication of dual-use research of concern.

PubMed

Patrone, Daniel; Resnik, David; Chin, Lisa

2012-09-01

Dual-use research of concern (DURC) is scientific research with significant potential for generating information that could be used to harm national security, the public health, or the environment. Editors responsible for journal policies and publication decisions play a vital role in ensuring that effective safeguards exist to cope with the risks of publishing scientific research with dual-use implications. We conducted an online survey of 127 chief editors of life science journals in 27 countries to examine their attitudes toward and experience with the review and publication of dual-use research of concern. Very few editors (11) had experience with biosecurity review, and no editor in our study reported having ever refused a submission on biosecurity grounds. Most respondents (74.8%) agreed that editors have a responsibility to consider biosecurity risks during the review process, but little consensus existed among editors on how to handle specific issues in the review and publication of research with potential dual-use implications. More work is needed to establish consensus on standards for the review and publication of dual-use research of concern in life science journals.

Biosecurity and the Review and Publication of Dual-Use Research of Concern

PubMed Central

Resnik, David; Chin, Lisa

2012-01-01

Dual-use research of concern (DURC) is scientific research with significant potential for generating information that could be used to harm national security, the public health, or the environment. Editors responsible for journal policies and publication decisions play a vital role in ensuring that effective safeguards exist to cope with the risks of publishing scientific research with dual-use implications. We conducted an online survey of 127 chief editors of life science journals in 27 countries to examine their attitudes toward and experience with the review and publication of dual-use research of concern. Very few editors (11) had experience with biosecurity review, and no editor in our study reported having ever refused a submission on biosecurity grounds. Most respondents (74.8%) agreed that editors have a responsibility to consider biosecurity risks during the review process, but little consensus existed among editors on how to handle specific issues in the review and publication of research with potential dual-use implications. More work is needed to establish consensus on standards for the review and publication of dual-use research of concern in life science journals. PMID:22871221

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

Designing Epigenome Editors: Considerations of Biochemical and Locus Specificities.

PubMed

Sen, Dilara; Keung, Albert J

2018-01-01

The advent of locus-specific protein recruitment technologies has enabled a new class of studies in chromatin biology. Epigenome editors enable biochemical modifications of chromatin at almost any specific endogenous locus. Their locus specificity unlocks unique information including the functional roles of distinct modifications at specific genomic loci. Given the growing interest in using these tools for biological and translational studies, there are many specific design considerations depending on the scientific question or clinical need. Here we present and discuss important design considerations and challenges regarding the biochemical and locus specificities of epigenome editors. These include how to account for the complex biochemical diversity of chromatin; control for potential interdependency of epigenome editors and their resultant modifications; avoid sequestration effects; quantify the locus specificity of epigenome editors; and improve locus specificity by considering concentration, affinity, avidity, and sequestration effects.

Payments by US pharmaceutical and medical device manufacturers to US medical journal editors: retrospective observational study.

PubMed

Liu, Jessica J; Bell, Chaim M; Matelski, John J; Detsky, Allan S; Cram, Peter

2017-10-26

Objective  To estimate financial payments from industry to US journal editors. Design  Retrospective observational study. Setting  52 influential (high impact factor for their specialty) US medical journals from 26 specialties and US Open Payments database, 2014. Participants  713 editors at the associate level and above identified from each journal's online masthead. Main outcome measures  All general payments (eg, personal income) and research related payments from pharmaceutical and medical device manufacturers to eligible physicians in 2014. Percentages of editors receiving payments and the magnitude of such payments were compared across journals and by specialty. Journal websites were also reviewed to determine if conflict of interest policies for editors were readily accessible. Results  Of 713 eligible editors, 361 (50.6%) received some (>$0) general payments in 2014, and 139 (19.5%) received research payments. The median general payment was $11 (£8; €9) (interquartile range $0-2923) and the median research payment was $0 ($0-0). The mean general payment was $28 136 (SD $415 045), and the mean research payment was $37 963 (SD $175 239). The highest median general payments were received by journal editors from endocrinology ($7207, $0-85 816), cardiology ($2664, $0-12 912), gastroenterology ($696, $0-20 002), rheumatology ($515, $0-14 280), and urology ($480, $90-669). For high impact general medicine journals, median payments were $0 ($0-14). A review of the 52 journal websites revealed that editor conflict of interest policies were readily accessible (ie, within five minutes) for 17/52 (32.7%) of journals. Conclusions  Industry payments to journal editors are common and often large, particularly for certain subspecialties. Journals should consider the potential impact of such payments on public trust in published research. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Payments by US pharmaceutical and medical device manufacturers to US medical journal editors: retrospective observational study

PubMed Central

Bell, Chaim M; Matelski, John J; Detsky, Allan S; Cram, Peter

2017-01-01

Objective To estimate financial payments from industry to US journal editors. Design Retrospective observational study. Setting 52 influential (high impact factor for their specialty) US medical journals from 26 specialties and US Open Payments database, 2014. Participants 713 editors at the associate level and above identified from each journal’s online masthead. Main outcome measures All general payments (eg, personal income) and research related payments from pharmaceutical and medical device manufacturers to eligible physicians in 2014. Percentages of editors receiving payments and the magnitude of such payments were compared across journals and by specialty. Journal websites were also reviewed to determine if conflict of interest policies for editors were readily accessible. Results Of 713 eligible editors, 361 (50.6%) received some (>$0) general payments in 2014, and 139 (19.5%) received research payments. The median general payment was $11 (£8; €9) (interquartile range $0-2923) and the median research payment was $0 ($0-0). The mean general payment was $28 136 (SD $415 045), and the mean research payment was $37 963 (SD $175 239). The highest median general payments were received by journal editors from endocrinology ($7207, $0-85 816), cardiology ($2664, $0-12 912), gastroenterology ($696, $0-20 002), rheumatology ($515, $0-14 280), and urology ($480, $90-669). For high impact general medicine journals, median payments were $0 ($0-14). A review of the 52 journal websites revealed that editor conflict of interest policies were readily accessible (ie, within five minutes) for 17/52 (32.7%) of journals. Conclusions Industry payments to journal editors are common and often large, particularly for certain subspecialties. Journals should consider the potential impact of such payments on public trust in published research. PMID:29074628

The Dialectical Relationship between Place and Space in Education: How the Internet Is Changing Our Perceptions of Teaching and Learning

ERIC Educational Resources Information Center

Glassman, Michael; Burbidge, Jonathan

2014-01-01

In this essay Michael Glassman and Jonathan Burbidge explore the idea of a dialectical relationship between the traditional place(s) of teaching/learning settings and the challenges to our perceptions created by the new spaces of the Internet. The authors examine this topic in the context of a three-stage evolution of humans' relationship…

Joint Force Quarterly (Issue 71, 4th Quarter, October 2013)

DTIC Science & Technology

2013-01-01

for a better future and two perspectives in the on-going debate on missile defense in Europe. Drawing on...commended the students for their critical thinking skills and writing talent. In the winning Secretary of Defense essay, Colonel Jonathan Rice...Leadership: Priorities for 21st Century Defense T he Nation and its allies face a strategic turning point that necessitates the optimization of joint and

The History of the Nigerian Army and the Implications for the Future of Nigeria

DTIC Science & Technology

2002-05-31

Jonathan Agwunobi lists a few visible impacts of the politicization of the Nigerian Army: 1. Reduced its professional military aspirations 2...grazing and livestock migration put tremendous pressure on the environment. Other environmental threats include poaching and settlement within...wildlife for food has threatened the animal population in Nigeria. Consequently, Nigeria’s few remaining elephants , 11 buffalo, lions, leopards, and

How China Could Affect the Future of U.S. Defense Corporations

DTIC Science & Technology

2010-12-01

of Jonathan Galloway , who addressees among many things, the global implications of DMNCs by differentiating the driving mechanisms for these... Galloway , “The Military-Industrial Linkages of U.S.-Based Multinational Corporations,” International Studies Quarterly 16, no. 4, Multinational...individual percentages.56 Galloway states “it stands to reason that their managements will be interested in preserving the dynamic equilibrium between

The Simpsons: Public Choice in the Tradition of Swift and Orwell

ERIC Educational Resources Information Center

Considine, John

2006-01-01

The author disagrees with Homer Simpson who claims that "...cartoons don't have any deep meaning. They're just stupid drawings that give you a cheap laugh." He argues that The Simpsons have a deep meaning in the same way as the works of Jonathan Swift and George Orwell. The message in The Simpsons, Swift, and Orwell is that those in charge do not…

Use and Complications of Operative Control of Arterial Inflow in Combat Casualties with Traumatic Lower-extremity Amputations Caused by Improvised Explosive Devices

DTIC Science & Technology

2013-08-01

explosive devices Henrietta Poon, MRCS, Jonathan J. Morrison, MRCS, Jon C. Clasper, DPhil, FRCSEd(Orth), Mark J. Midwinter, MD, FRCS, and Jan O. Jansen...the IP group, compared with the EP, although this does not achieve statistical significance, likely owing to a lack of power within the study. The war

Variable Discretisation for Anomaly Detection using Bayesian Networks

DTIC Science & Technology

2017-01-01

UNCLASSIFIED DST- Group –TR–3328 1 Introduction Bayesian network implementations usually require each variable to take on a finite number of mutually...UNCLASSIFIED Variable Discretisation for Anomaly Detection using Bayesian Networks Jonathan Legg National Security and ISR Division Defence Science...and Technology Group DST- Group –TR–3328 ABSTRACT Anomaly detection is the process by which low probability events are automatically found against a

US Army Medical Department Journal, April-June 2005

DTIC Science & Technology

2005-06-01

systematically assess their practice, and identify Medical Education Directorate and the final link in the medical areas where education can effect...syndrome would nasogastric tube was drained intermittently and otherwise mandate decompressive fasciotomies of the affected extremities vented. Urine...AMEDD Continuum of Medical Education 12 COL John M. Powers, MC, USA The Medical Corps Assignment Process 16 COL Jonathan H. Jaffin, MC, USA, et al

AIDS Prevention and Control: Invited Presentations and Papers from the World Summit of Ministers of Health on Programmes for AIDS Prevention (London, England, January 26-28, 1988).

ERIC Educational Resources Information Center

World Health Organization, Geneva (Switzerland).

Papers from the World Summit of Ministers of Health on Programmes for AIDS Prevention in this book include: (1) "Global AIDS: Epidemiology, Impact, Projections, Global Strategy," (Jonathan Mann); (2) "Modes of Transmission: The Basis for Prevention Strategies," (Donald Acheson); (3) "National AIDS Information Programme in…

Explaining and Influencing Chinese Arms Transfers

DTIC Science & Technology

1995-02-01

this volume: Jonathan W. Pierce [] Secretary: Laura Hall [] Circulation Manager : Myma Morgan INSS publishes McNair Papers to provoke thought and inform...their affiliated factories were directed to decentralize their decision-making processes, grant more autonomy to managers , use excess capacity to...intimacy of ties between Moscow and 10 EXPLAINING AND INFLUENCING CHINESE ARMS TRANSFERS New Dehli , and concem that the United States was still in retreat

Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

DTIC Science & Technology

2016-11-01

Jonathan Purnell CONTRACTING ORGANIZATION: Oregon Health & Science University Portland, OR 97239-3098 REPORT DATE: November 2016 TYPE OF REPORT...ORGANIZATION NAME(S) AND ADDRESS(ES) Oregon Health & Science University 3181 SW S AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER SW Sam...current work to determine the association between fatty acid synthase (FAS) overexpression and intraprostatic fat as measured by in-vivo imaging using

Metabolic Signature of Antipsychotics used in the Treatment of Autism

DTIC Science & Technology

2013-10-01

used in the Treatment of Autism ”. PRINCIPAL INVESTIGATOR: Nira Ben-Jonathan CONTRACTING ORGANIZATION: University of Cincinnati...30September2012-29September2013 4. TITLE AND SUBTITLE Metabolic Signature of Antipsychotics used in the Treatment of Autism ”. 5a. CONTRACT... dopamine (DAR) and serotonin (5-HTR) receptors. The general consensus is that AAP cause metabolic disturbances by an exclusive action on the brain