TIP60 represses telomerase expression by inhibiting Sp1 binding to the TERT promoter

PubMed Central

Pandey, Amit Kumar; Xiuzhen, Magdalene Claire; Lee, Kwok Kin; Hora, Shainan; Zhang, Yanzhou; Kwok, Hui Si; Deng, Lih Wen; Tenen, Daniel G.; Kappei, Dennis

2017-01-01

HIV1-TAT interactive protein (TIP60) is a haploinsufficient tumor suppressor. However, the potential mechanisms endowing its tumor suppressor ability remain incompletely understood. It plays a vital role in virus-induced cancers where TIP60 down-regulates the expression of human papillomavirus (HPV) oncoprotein E6 which in turn destabilizes TIP60. This intrigued us to identify the role of TIP60, in the context of a viral infection, where it is targeted by oncoproteins. Through an array of molecular biology techniques such as Chromatin immunoprecipitation, expression analysis and mass spectrometry, we establish the hitherto unknown role of TIP60 in repressing the expression of the catalytic subunit of the human telomerase complex, TERT, a key driver for immortalization. TIP60 acetylates Sp1 at K639, thus inhibiting Sp1 binding to the TERT promoter. We identified that TIP60-mediated growth suppression of HPV-induced cervical cancer is mediated in part due to TERT repression through Sp1 acetylation. In summary, our study has identified a novel substrate for TIP60 catalytic activity and a unique repressive mechanism acting at the TERT promoter in virus-induced malignancies. PMID:29045464

Evaluation of trypanocidal activity of combinations of anti-sleeping sickness drugs with cysteine protease inhibitors.

PubMed

Steverding, Dietmar

2015-01-01

Chemotherapy of human African trypanosomiasis (HAT) is unsatisfactory because only a few drugs, with serious side effects and poor efficacy, are available. As drug combination regimes often achieve greater therapeutic efficacy than monotherapies, here the trypanocidal activity of the cysteine protease inhibitor K11777 in combination with current anti-HAT drugs using bloodstream forms of Trypanosoma brucei was investigated. Isobolographic analysis was used to determine the interaction between cysteine protease inhibitors (K11777, CA-074Me and CAA0225) and anti-HAT drugs (suramin, pentamidine, melarsoprol and eflornithine). Bloodstream forms of T. brucei were incubated in culture medium containing cysteine protease inhibitors or anti-HAT drugs alone or in combination at a 1:1 fixed-dose ratio. After 48 h incubation, live cells were counted, the 50% growth inhibition values determined and combination indices calculated. The general cytotoxicity of drug combinations was evaluated with human leukaemia HL-60 cells. Combinations of K11777 with suramin, pentamidine and melarsoprol showed antagonistic effects while with eflornithine a synergistic effect was observed. Whereas eflornithine antagonises with CA-074Me, an inhibitor inactivating the targeted TbCATL only under reducing conditions, it synergises with CAA0255, an inhibitor structurally related to CA-074Me which inactivates TbCATL independently of thiols. These findings indicate an essential role of thiols for the synergistic interaction between K11777 and eflornithine. Encouragingly, the K11777/eflornithine combination displayed higher trypanocidal than cytotoxic activity. The results of this study suggest that the combination of the cysteine protease inhibitor K11777 and eflornithine display promising synergistic trypanocidal activity that warrants further investigation of the drug combination as possible alternative treatment of HAT. Copyright © 2015 Elsevier Inc. All rights reserved.

VizieR Online Data Catalog: 5 exoplanet light and RV curves (Mancini+, 2018)

NASA Astrophysics Data System (ADS)

Mancini, L.; Esposito, M.; Covino, E.; Southworth, J.; Biazzo, K.; Bruni, I.; Ciceri, S.; Evans, D.; Lanza, A. F.; Poretti, E.; Sarkis, P.; Smith, A. M. S.; Brogi, M.; Affer, L.; Benatti, S.; Bignamini, A.; Boccato, C.; Bonomo, A. S.; Borsa, F.; Carleo, I.; Claudi, R.; Cosentino, R.; Damasso, M.; Desidera, S.; Giacobbe, P.; Gonzalez-Alvarez, E.; Gratton, R.; Harutyunyan, A.; Leto, G.; Maggio, A.; Malavolta, L.; Maldonado, J.; Martinez-Fiorenzano, A.; Masiero, S.; Micela, G.; Molinari, E.; Nascimbeni, V.; Pagano, I.; Pedani, M.; Piotto, G.; Rainer, M.; Scandariato, G.; Smareglia, R.; Sozzetti, A.; Andreuzzi, G.; Henning, T.

2018-02-01

Radial velocity measurements of HAT-P-3, HAT-P-12, HAT-P-22, WASP-39, and WASP-60 obtained with HARPS-N at the 3.5m TNG telescope. Light curves of transit events of the extrasolar planet HAT-P-3b, HAT-P-12b and WASP-60b. Two of the datasets were obtained using the Cassini 1.52m Telescope (Gunn r and Gunn i) at the Astronomical Observatory of Bologna in Loiano (Italy). Ten of the datasets were obtained using the Zeiss 1.23m telescope (Cousins R and Cousins I) at the German-Spanish Astronomical Centre at Calar Alto (Spain). Four of the datasets were obtained using the 2.2m telescope (Stromgren u, Gunn g, Gunn r, Johnson I) at the German-Spanish Astronomical Centre at Calar Alto (Spain). One of the datasets was obtained using the 2.5m Isaac Newton Telescope (INT) in La Palma (Spain). (4 data files).

Nucleosome Recognition by the Piccolo NuA4 Histone Acetyltransferase Complex†

PubMed Central

Berndsen, Christopher E.; Selleck, William; McBryant, Steven J.; Hansen, Jeffrey C.; Tan, Song; Demi, John M.

2007-01-01

The mechanisms by which multisubunit histone acetyltransferase (HAT) complexes recognize and perform efficient acetylation on nucleosome substrates are largely unknown. Here, we use a variety of biochemical approaches and compare histone-based substrates of increasing complexity to determine the critical components of nucleosome recognition by the MOZ, Ybf2/Sas3, Sas2, Tip60 family HAT complex, Piccolo NuA4 (picNuA4). We find the histone tails to be dispensable for binding to both nucleosomes and free histones and that the H2A, H3, and H2B tails do not influence the ability of picNuA4 to tetra-acetylate the H4 tail within the nucleosome. Most notably, we discovered that the histone-fold domain (HFD) regions of histones, particularly residues 21–52 of H4, are critical for tight binding and efficient tail acetylation. Presented evidence suggests that picNuA4 recognizes the open surface of the nucleosome on which the HFD of H4 is located. This binding mechanism serves to direct substrate access to the tails of H4 and H2A and allows the enzyme to be “tethered”, thereby increasing the effective concentration of the histone tail and permitting successive cycles of H4 tail acetylation. PMID:17274630

Tip60 degradation by adenovirus relieves transcriptional repression of viral transcriptional activator EIA.

PubMed

Gupta, A; Jha, S; Engel, D A; Ornelles, D A; Dutta, A

2013-10-17

Adenoviruses are linear double-stranded DNA viruses that infect human and rodent cell lines, occasionally transform them and cause tumors in animal models. The host cell challenges the virus in multifaceted ways to restrain viral gene expression and DNA replication, and sometimes even eliminates the infected cells by programmed cell death. To combat these challenges, adenoviruses abrogate the cellular DNA damage response pathway. Tip60 is a lysine acetyltransferase that acetylates histones and other proteins to regulate gene expression, DNA damage response, apoptosis and cell cycle regulation. Tip60 is a bona fide tumor suppressor as mice that are haploid for Tip60 are predisposed to tumors. We have discovered that Tip60 is degraded by adenovirus oncoproteins EIB55K and E4orf6 by a proteasome-mediated pathway. Tip60 binds to the immediate early adenovirus promoter and suppresses adenovirus EIA gene expression, which is a master regulator of adenovirus transcription, at least partly through retention of the virally encoded repressor pVII on this promoter. Thus, degradation of Tip60 by the adenoviral early proteins is important for efficient viral early gene transcription and for changes in expression of cellular genes.

The Stress-responsive Gene ATF3 Mediates Dichotomous UV Responses by Regulating the Tip60 and p53 Proteins*

PubMed Central

Cui, Hongmei; Li, Xingyao; Han, Chunhua; Wang, Qi-En; Wang, Hongbo; Ding, Han-Fei; Zhang, Junran; Yan, Chunhong

2016-01-01

The response to UV irradiation is important for a cell to maintain its genetic integrity when challenged by environmental genotoxins. An immediate early response to UV irradiation is the rapid induction of activating transcription factor 3 (ATF3) expression. Although emerging evidence has linked ATF3 to stress pathways regulated by the tumor suppressor p53 and the histone acetyltransferase Tip60, the role of ATF3 in the UV response remains largely unclear. Here, we report that ATF3 mediated dichotomous UV responses. Although UV irradiation enhanced the binding of ATF3 to Tip60, knockdown of ATF3 expression decreased Tip60 stability, thereby impairing Tip60 induction by UV irradiation. In line with the role of Tip60 in mediating UV-induced apoptosis, ATF3 promoted the death of p53-defective cells in response to UV irradiation. However, ATF3 could also activate p53 and promote p53-mediated DNA repair, mainly through altering histone modifications that could facilitate recruitment of DNA repair proteins (such as DDB2) to damaged DNA sites. As a result, ATF3 rather protected the p53 wild-type cells from UV-induced apoptosis. Our results thus indicate that ATF3 regulates cell fates upon UV irradiation in a p53-dependent manner. PMID:26994140

PRMT5-Dependent Methylation of the TIP60 Coactivator RUVBL1 Is a Key Regulator of Homologous Recombination.

PubMed

Clarke, Thomas L; Sanchez-Bailon, Maria Pilar; Chiang, Kelly; Reynolds, John J; Herrero-Ruiz, Joaquin; Bandeiras, Tiago M; Matias, Pedro M; Maslen, Sarah L; Skehel, J Mark; Stewart, Grant S; Davies, Clare C

2017-03-02

Protein post-translation modification plays an important role in regulating DNA repair; however, the role of arginine methylation in this process is poorly understood. Here we identify the arginine methyltransferase PRMT5 as a key regulator of homologous recombination (HR)-mediated double-strand break (DSB) repair, which is mediated through its ability to methylate RUVBL1, a cofactor of the TIP60 complex. We show that PRMT5 targets RUVBL1 for methylation at position R205, which facilitates TIP60-dependent mobilization of 53BP1 from DNA breaks, promoting HR. Mechanistically, we demonstrate that PRMT5-directed methylation of RUVBL1 is critically required for the acetyltransferase activity of TIP60, promoting histone H4K16 acetylation, which facilities 53BP1 displacement from DSBs. Interestingly, RUVBL1 methylation did not affect the ability of TIP60 to facilitate ATM activation. Taken together, our findings reveal the importance of PRMT5-mediated arginine methylation during DSB repair pathway choice through its ability to regulate acetylation-dependent control of 53BP1 localization. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Large Starspot Groups on HAT-P-11 in Activity Cycle 1

NASA Astrophysics Data System (ADS)

Morris, Brett M.; Hawley, Suzanne L.; Hebb, Leslie

2018-02-01

HAT-P-11 is a planet-hosting K4V star in the Kepler field, with an activity cycle that bear similarities to the Sun's. The chromospheric activity of HAT-P-11 indicates that a new activity cycle is beginning. We report ground-based observations with holographic diffuser photometry to measure the starspots of HAT-P-11 in its second observed magnetic activity cycle (Cycle 1). We find the area coverage of starspots within the transit chord for UTC 2017-10-30 is 14% --- which makes this transit the most spotted HAT-P-11 transit observed to date. We suggest that we are likely observing occultations of large spot groups appearing at the beginning of Cycle 1.

Exercise enhances cognitive function and neurotrophin expression in the hippocampus accompanied by changes in epigenetic programming in senescence-accelerated mice.

PubMed

Maejima, Hiroshi; Kanemura, Naohiko; Kokubun, Takanori; Murata, Kenji; Takayanagi, Kiyomi

2018-02-05

Aerobic exercise is known to increase expression of neurotrophins, particularly brain-derived neurotrophic factor (BDNF), in the hippocampus and to improve cognitive function. Exercise exerts neuroprotective effects in the hippocampus by inducing epigenetic changes, which play crucial roles in aging and neurodegenerative diseases. Specifically, the activity levels of histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate histone acetylation and modulate gene transcription. The objective of the present study was to assess the interactive effects of exercise and aging on cognitive function, expression of neurotrophins (BDNF and neurotrophin-4) and their receptors (tyrosine receptor kinase B and p75), and epigenetic regulations, including the activity of HATs and HADCs in the hippocampus. We used the senescence-accelerated mouse (SAM) model, specifically 13-month-old SAM resistant 1(SAMR1) and SAM prone 1 (SAMP1) lines. Mice were distributed into four groups based on accelerated senescence and exercise status. Mice in the exercise groups exercised on a treadmill for approximately 60min a day, 5days a week. Aerobic exercise for 4 weeks improved cognitive function, accompanied by an increase in BDNF expression and a decrease in p75 transcription in both SAMR1 and SAMP1. In addition, the exercise regimen activated both HAT and HDAC in the hippocampus. Therefore, the present study reveals that despite accelerated senescence, long-term exercise improved cognitive function, upregulated the expression of BDNF, and downregulated p75, a receptor involved in apoptotic signaling. Furthermore, long-term exercise enhanced activity of both HAT and HDAC, which may contribute to the transcriptional regulation underlying the improvement of cognitive function. Copyright © 2017 Elsevier B.V. All rights reserved.

Black Hats and White Hats: The Effect of Organizational Culture and Institutional Identity on the Twenty-third Air Force

DTIC Science & Technology

2006-12-01

comments, and insight. Finally, I must offer a special thank-you to Gen Norton Schwartz; Brig Gen Eric Fiel; Col Tracy “Moose” Amos; Col Dennis...the two communities, their institutional histories have played a significant role in their organizational development. According to Col Ken Pribyla...Low IIIs, UH-60 Blackhawks (the Army’s first operational company of UH-60s), CH-47C Chi- nooks from the 101st Airborne Division, and OH-6 Loach

NOTCH1 Inhibits Activation of ATM by Impairing the Formation of an ATM-FOXO3a-KAT5/Tip60 Complex.

PubMed

Adamowicz, Marek; Vermezovic, Jelena; d'Adda di Fagagna, Fabrizio

2016-08-23

The DNA damage response (DDR) signal transduction pathway is responsible for sensing DNA damage and further relaying this signal into the cell. ATM is an apical DDR kinase that orchestrates the activation and the recruitment of downstream DDR factors to induce cell-cycle arrest and repair. We have previously shown that NOTCH1 inhibits ATM activation upon DNA damage, but the underlying mechanism remains unclear. Here, we show that NOTCH1 does not impair ATM recruitment to DNA double-strand breaks (DSBs). Rather, NOTCH1 prevents binding of FOXO3a and KAT5/Tip60 to ATM through a mechanism in which NOTCH1 competes with FOXO3a for ATM binding. Lack of FOXO3a binding to ATM leads to the loss of KAT5/Tip60 association with ATM. Moreover, expression of NOTCH1 or depletion of ATM impairs the formation of the FOXO3a-KAT5/Tip60 protein complex. Finally, we show that pharmacological induction of FOXO3a nuclear localization sensitizes NOTCH1-driven cancers to DNA-damage-induced cell death. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Investigating the physical properties of transiting hot Jupiters with the 1.5-m Kuiper Telescope

NASA Astrophysics Data System (ADS)

Turner, Jake D.; Leiter, Robin M.; Biddle, Lauren I.; Pearson, Kyle A.; Hardegree-Ullman, Kevin K.; Thompson, Robert M.; Teske, Johanna K.; Cates, Ian T.; Cook, Kendall L.; Berube, Michael P.; Nieberding, Megan N.; Jones, Christen K.; Raphael, Brandon; Wallace, Spencer; Watson, Zachary T.; Johnson, Robert E.

2017-12-01

We present new photometric data of 11 hot Jupiter transiting exoplanets (CoRoT-12b, HAT-P-5b, HAT-P-12b, HAT-P-33b, HAT-P-37b, WASP-2b, WASP-24b, WASP-60b, WASP-80b, WASP-103b and XO-3b) in order to update their planetary parameters and to constrain information about their atmospheres. These observations of CoRoT-12b, HAT-P-37b and WASP-60b are the first follow-up data since their discovery. Additionally, the first near-UV transits of WASP-80b and WASP-103b are presented. We compare the results of our analysis with previous work to search for transit timing variations (TTVs) and a wavelength dependence in the transit depth. TTVs may be evidence of a third body in the system, and variations in planetary radius with wavelength can help constrain the properties of the exoplanet's atmosphere. For WASP-103b and XO-3b, we find a possible variation in the transit depths which may be evidence of scattering in their atmospheres. The B-band transit depth of HAT-P-37b is found to be smaller than its near-IR transit depth and such a variation may indicate TiO/VO absorption. These variations are detected from 2-4.6σ, so follow-up observations are needed to confirm these results. Additionally, a flat spectrum across optical wavelengths is found for five of the planets (HAT-P-5b, HAT-P-12b, WASP-2b, WASP-24b and WASP-80b), suggestive that clouds may be present in their atmospheres. We calculate a refined orbital period and ephemeris for all the targets, which will help with future observations. No TTVs are seen in our analysis with the exception of WASP-80b and follow-up observations are needed to confirm this possible detection.

Subunits of ADA-two-A-containing (ATAC) or Spt-Ada-Gcn5-acetyltrasferase (SAGA) Coactivator Complexes Enhance the Acetyltransferase Activity of GCN5.

PubMed

Riss, Anne; Scheer, Elisabeth; Joint, Mathilde; Trowitzsch, Simon; Berger, Imre; Tora, László

2015-11-27

Histone acetyl transferases (HATs) play a crucial role in eukaryotes by regulating chromatin architecture and locus specific transcription. GCN5 (KAT2A) is a member of the GNAT (Gcn5-related N-acetyltransferase) family of HATs. In metazoans this enzyme is found in two functionally distinct coactivator complexes, SAGA (Spt Ada Gcn5 acetyltransferase) and ATAC (Ada Two A-containing). These two multiprotein complexes comprise complex-specific and shared subunits, which are organized in functional modules. The HAT module of ATAC is composed of GCN5, ADA2a, ADA3, and SGF29, whereas in the SAGA HAT module ADA2b is present instead of ADA2a. To better understand how the activity of human (h) hGCN5 is regulated in the two related, but different, HAT complexes we carried out in vitro HAT assays. We compared the activity of hGCN5 alone with its activity when it was part of purified recombinant hATAC or hSAGA HAT modules or endogenous hATAC or hSAGA complexes using histone tail peptides and full-length histones as substrates. We demonstrated that the subunit environment of the HAT complexes into which GCN5 incorporates determines the enhancement of GCN5 activity. On histone peptides we show that all the tested GCN5-containing complexes acetylate mainly histone H3K14. Our results suggest a stronger influence of ADA2b as compared with ADA2a on the activity of GCN5. However, the lysine acetylation specificity of GCN5 on histone tails or full-length histones was not changed when incorporated in the HAT modules of ATAC or SAGA complexes. Our results thus demonstrate that the catalytic activity of GCN5 is stimulated by subunits of the ADA2a- or ADA2b-containing HAT modules and is further increased by incorporation of the distinct HAT modules in the ATAC or SAGA holo-complexes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The socio-economic burden of human African trypanosomiasis and the coping strategies of households in the South Western Kenya foci.

PubMed

Bukachi, Salome A; Wandibba, Simiyu; Nyamongo, Isaac K

2017-10-01

Human African Trypanosomiasis (HAT), a disease caused by protozoan parasites transmitted by tsetse flies, is an important neglected tropical disease endemic in remote regions of sub-Saharan Africa. Although the determination of the burden of HAT has been based on incidence, mortality and morbidity rates, the true burden of HAT goes beyond these metrics. This study sought to establish the socio-economic burden that households with HAT faced and the coping strategies they employed to deal with the increased burden. A mixed methods approach was used and data were obtained through: review of hospital records; structured interviews (152); key informant interviews (11); case narratives (12) and focus group discussions (15) with participants drawn from sleeping sickness patients in the south western HAT foci in Kenya. Quantitative data were analysed using descriptive statistics while qualitative data was analysed based on emerging themes. Socio-economic impacts included, disruption of daily activities, food insecurity, neglect of homestead, poor academic performance/school drop-outs and death. Delayed diagnosis of HAT caused 93% of the affected households to experience an increase in financial expenditure (ranging from US$ 60-170) in seeking treatment. Out of these, 81.5% experienced difficulties in raising money for treatment resorting to various ways of raising it. The coping strategies employed to deal with the increased financial expenditure included: sale of agricultural produce (64%); seeking assistance from family and friends (54%); sale/lease of family assets (22%); seeking credit (22%) and use of personal savings (17%). Coping strategies outlined in this study impacted negatively on the affected households leading to further food insecurity and impoverishment. Calculation of the true burden of disease needs to go beyond incidence, mortality and morbidity rates to capture socio-economic variables entailed in seeking treatment and coping strategies of HAT affected households.

Phosphorylation of Tip60 by GSK-3 determines the induction of PUMA and apoptosis by p53

PubMed Central

Charvet, Céline; Wissler, Manuela; Brauns-Schubert, Prisca; Wang, Shang-Jui; Tang, Yi; Sigloch, Florian C.; Mellert, Hestia; Brandenburg, Martin; Lindner, Silke E.; Breit, Bernhard; Green, Douglas R.; McMahon, Steven B.; Borner, Christoph; Gu, Wei; Maurer, Ulrich

2011-01-01

Summary Activation of p53 by DNA damage results in either cell cycle arrest, allowing DNA repair and cell survival, or induction of apoptosis. As these opposite outcomes are both mediated by p53 stabilization, additional mechanisms to determine this decision must exist. Here we show that glycogen synthase kinase-3 (GSK-3) is required for the p53-mediated induction of the pro-apoptotic BH3 only-protein PUMA, an essential mediator of p53-induced apoptosis. Inhibition of GSK-3 protected from cell death induced by DNA damage and promoted increased long-term cell survival. We demonstrate that GSK-3 phosphorylates serine 86 of the p53-acetyltransferase Tip60. A Tip60S86A mutant was less active to induce p53 K120 acetylation, Histone 4 acetylation and expression of PUMA. Our data suggest that GSK-3 mediated Tip60S86-phosphorylation provides a link between PI3K signaling and the choice for or against apoptosis induction by p53. PMID:21658600

Activation of p300 histone acetyltransferase activity and acetylation of the androgen receptor by bombesin in prostate cancer cells.

PubMed

Gong, J; Zhu, J; Goodman, O B; Pestell, R G; Schlegel, P N; Nanus, D M; Shen, R

2006-03-30

Androgen receptor signaling in prostate cancer cells is augmented by the androgen receptor (AR) coactivator p300, which transactivates and acetylates the AR in the presence of dihydrotestosterone (DHT). As prostate cancer (PC) cells progress to androgen independence, AR signaling remains intact, indicating that other factors stimulate AR activities in the absence of androgen. We previously reported that neuropeptide growth factors could transactivate the AR in the presence of very low concentrations of DHT. Here, we examine the involvement of p300 in neuropeptide activation of AR signaling. Transfection of increasing concentrations of p300 in the presence of bombesin into PC-3 cells resulted in a linear increase in AR transactivation, suggesting that p300 acts as a coactivator in neuropeptide-mediated AR transactivation. P300 is endowed with histone acetyltransferase (HAT) activity. Therefore, we examine the effect of bombesin on p300 HAT activity. At 4 h after the addition of bombesin, p300 HAT activity increased 2.0-fold (P<0.01). Incubation with neutral endopeptidase, which degrades bombesin, or bombesin receptor antagonists blocked bombesin-induced p300 HAT activity. To explore the potential signaling pathways involved in bombesin-induced p300 HAT activity, we examined Src and PKCdelta pathways that mediate bombesin signaling. Inhibitors of Src kinase activity or Src kinase siRNA blocked bombesin-induced p300 HAT activity, whereas PKCdelta inhibitors or PKCdelta siRNA significantly increased bombesin-induced p300 HAT activity suggesting that Src kinase and PKCdelta kinase are involved in the regulation of p300 HAT activity. As AR is acetylated in the presence of 100 nM DHT, we next examined whether bombesin-induced p300 HAT activity would result in enhanced AR acetylation. Bombesin-induced AR acetylation at the same motif KLKK observed in DHT-induced acetylation. Elimination of p300 using p300 siRNA reduced AR acetylation, demonstrating that AR acetylation was mediated by p300. AR acetylation results in AR transactivation and the expression of the AR-regulated gene prostate-specific antigen (PSA). Therefore, we examined bombesin-induced AR transactivation and PSA expression in the presence and absence of p300 siRNA and found inhibition of p300 expression reduced bombesin-induced AR transactivation and PSA expression. Together these results demonstrate that bombesin, via Src and PKCdelta signaling pathways, activates p300 HAT activity which leads to enhanced acetylation of AR resulting in increased expression of AR-regulated genes.

Regulation of Histone Acetyltransferase TIP60 Function by Histone Deacetylase 3

PubMed Central

Yi, Jingjie; Huang, Xiangyang; Yang, Yuxia; Zhu, Wei-Guo; Gu, Wei; Luo, Jianyuan

2014-01-01

The key member of the MOZ (monocyticleukaemia zinc finger protein), Ybf2/Sas3, Sas2, and TIP60 acetyltransferases family, Tat-interactive protein, 60 kD (TIP60), tightly modulates a wide array of cellular processes, including chromatin remodeling, gene transcription, apoptosis, DNA repair, and cell cycle arrest. The function of TIP60 can be regulated by SIRT1 through deacetylation. Here we found that TIP60 can also be functionally regulated by HDAC3. We identified six lysine residues as its autoacetylation sites. Mutagenesis of these lysines to arginines completely abolishes the autoacetylation of TIP60. Overexpression of HDAC3 increases TIP60 ubiquitination levels. However, unlike SIRT1, HDAC3 increased the half-life of TIP60. Further study found that HDAC3 colocalized with TIP60 both in the nucleus and the cytoplasm, which could be the reason why HDAC3 can stabilize TIP60. The deacetylation of TIP60 by both SIRT1 and HDAC3 reduces apoptosis induced by DNA damage. Knockdown of HDAC3 in cells increased TIP60 acetylation levels and increased apoptosis after DNA damage. Together, our findings provide a better understanding of TIP60 regulation mechanisms, which is a significant basis for further studies of its cellular functions. PMID:25301942

HAT1 induces lung cancer cell apoptosis via up regulating Fas.

PubMed

Han, Na; Shi, Lei; Guo, Qiuyun; Sun, Wei; Yu, Yang; Yang, Li; Zhang, Xiaoxi; Zhang, Mengxian

2017-10-27

The dysfunction of apoptosis is one of the factors contributing to lung cancer (LC) growth. Histone acetyltransferase HAT1 can up regulate cell apoptosis. This study aims to investigate the mechanism by which HAT1 induces LC cell (LCC) apoptosis via up regulating the expression of Fas. In this study, the surgically removed human LC tissues were collected. LCCs were isolated from the LC tissues and analyzed for the expression of HAT1 and Fas by RT-qPCR and Western blotting. We observed that the expression of Fas was negatively correlated with PAR2 in LCCs. Activation of PAR2 suppressed the expression of Fas in normal lung epithelial cells. The expression of HAT1 was lower and positively correlated with Fas expression and negatively correlated with PAR2 expression in LCCs. Activation of PAR2 suppressed Fas expression in lung epithelial cells via inhibiting HAT1. Restoration of HAT1 expression restored Fas expression in LCCs and induced LCC apoptosis. In conclusion, less expression of HAT1 in LCCs was associated with the pathogenesis of LC. Up regulation of HAT1 expression in LCCs can induce LCCs apoptosis, which may be a potential novel therapy for the treatment of LC.

Valproic acid exposure decreases Cbp/p300 protein expression and histone acetyltransferase activity in P19 cells

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

Lamparter, Christina L.

The teratogenicity of the antiepileptic drug valproic acid (VPA) is well established and its inhibition of histone deacetylases (HDAC) is proposed as an initiating factor. Recently, VPA-mediated HDAC inhibition was demonstrated to involve transcriptional downregulation of histone acetyltransferases (HATs), which was proposed to compensate for the increased acetylation resulting from HDAC inhibition. Cbp and p300 are HATs required for embryonic development and deficiencies in either are associated with congenital malformations and embryolethality. The objective of the present study was to characterize Cbp/p300 following VPA exposure in P19 cells. Consistent with previous studies, exposure to 5 mM VPA over 24 hmore » induced a moderate decrease in Cbp/p300 mRNA, which preceded a strong decrease in total cellular protein mediated by ubiquitin-proteasome degradation. Nuclear Cbp/p300 protein was also decreased following VPA exposure, although to a lesser extent. Total cellular and nuclear p300 HAT activity was reduced proportionately to p300 protein levels, however while total cellular HAT activity also decreased, nuclear HAT activity was unaffected. Using the Cbp/p300 HAT inhibitor C646, we demonstrated that HAT inhibition similarly affected many of the same endpoints as VPA, including increased reactive oxygen species and caspase-3 cleavage, the latter of which could be attenuated by pre-treatment with the antioxidant catalase. C646 exposure also decreased NF-κB/p65 protein, which was not due to reduced mRNA and was not attenuated with catalase pre-treatment. This study provides support for an adaptive HAT response following VPA exposure and suggests that reduced Cbp/p300 HAT activity could contribute to VPA-mediated alterations. - Highlights: • VPA exposure in vitro downregulates Cbp/p300 mRNA and induces protein degradation. • Cbp/p300 histone acetyltransferase activity is similarly reduced with VPA exposure. • Inhibition of Cbp/p300 acetyltransferase activity induces apoptosis, involving ROS. • This inhibition of activity also reduces NFκB expression independently of ROS. • Reduced Cbp/p300 acetyltransferase activity may contribute to VPA teratogenesis.« less

The HAT TRICK programme for improving physical activity, healthy eating and connectedness among overweight, inactive men: study protocol of a pragmatic feasibility trial

PubMed Central

Caperchione, Cristina M; Bottorff, Joan L; Oliffe, John L; Johnson, Steven T; Hunt, Kate; Sharp, Paul; Fitzpatrick, Kayla M; Price, Ryley; Goldenberg, S Larry

2017-01-01

Introduction Physical activity, healthy eating and maintaining a healthy weight are associated with reduced risk of cardiovascular disease, type 2 diabetes and cancer and with improved mental health. Despite these benefits, many men do not meet recommended physical activity guidelines and have poor eating behaviours. Many health promotion programmes hold little appeal to men and consequently fail to influence men’s health practices. HAT TRICK was designed as a 12-week face-to-face, gender-sensitised intervention for overweight and inactive men focusing on physical activity, healthy eating and social connectedness and was delivered in collaboration with a major junior Canadian ice hockey team (age range 16–20 years). The programme was implemented and evaluated to assess its feasibility. This article describes the intervention design and study protocol of HAT TRICK. Methods and analysis HAT TRICK participants (n=60) were men age 35 years, residing in the Okanagan Region of British Columbia, who accumulate 150 min of moderate to vigorous physical activity a week, with a body mass index of >25 kg/m2 and a pant waist size of >38’. Each 90 min weekly session included targeted health education and theory-guided behavioural change techniques, as well as a progressive (ie, an increase in duration and intensity) group physical activity component. Outcome measures were collected at baseline, 12 weeks and 9 months and included the following: objectively measured anthropometrics, blood pressure, heart rate, physical activity and sedentary behaviour, as well as self-reported physical activity, sedentary behaviour, diet, smoking, alcohol consumption, sleep habits, risk of depression, health-related quality of life and social connectedness. Programme feasibility data (eg, recruitment, satisfaction, adherence, content delivery) were assessed at 12 weeks via interviews and self-report. Ethics and dissemination Ethical approval was obtained from the University of British Columbia Okanagan Behavioural Research Ethics Board (reference no H1600736). Study findings will be disseminated through academic meetings, peer-reviewed publication, web-based podcasts, social media, plain language summaries and co-delivered community presentations. Trial registration number ISRCTN43361357,Pre results PMID:28882920

State of the Art in African Trypanosome Drug Discovery

PubMed Central

Jacobs, Robert T.; Nare, Bakela; Phillips, Margaret A.

2011-01-01

African sleeping sickness is endemic in sub-Saharan Africa where the WHO estimates that 60 million people are at risk for the disease. Human African trypanosomiasis (HAT) is 100% fatal if untreated and the current drug therapies have significant limitations due to toxicity and difficult treatment regimes. No new chemical agents have been approved since eflornithine in 1990. The pentamidine analog DB289, which was in late stage clinical trials for the treatment of early stage HAT recently failed due to toxicity issues. A new protocol for the treatment of late-stage T. brucei gambiense that uses combination nifurtomox/eflornithine (NECT) was recently shown to have better safety and efficacy than eflornithine alone, while being easier to administer. This breakthrough represents the only new therapy for HAT since the approval of eflornithine. A number of research programs are on going to exploit the unusual biochemical pathways in the parasite to identify new targets for target based drug discovery programs. HTS efforts are also underway to discover new chemical entities through whole organism screening approaches. A number of inhibitors with anti-trypanosomal activity have been identified by both approaches, but none of the programs are yet at the stage of identifying a preclinical candidate. This dire situation underscores the need for continued effort to identify new chemical agents for the treatment of HAT. PMID:21401507

Cleavage and Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by Human Airway Trypsin-Like Protease ▿

PubMed Central

Bertram, Stephanie; Glowacka, Ilona; Müller, Marcel A.; Lavender, Hayley; Gnirss, Kerstin; Nehlmeier, Inga; Niemeyer, Daniela; He, Yuxian; Simmons, Graham; Drosten, Christian; Soilleux, Elizabeth J.; Jahn, Olaf; Steffen, Imke; Pöhlmann, Stefan

2011-01-01

The highly pathogenic severe acute respiratory syndrome coronavirus (SARS-CoV) poses a constant threat to human health. The viral spike protein (SARS-S) mediates host cell entry and is a potential target for antiviral intervention. Activation of SARS-S by host cell proteases is essential for SARS-CoV infectivity but remains incompletely understood. Here, we analyzed the role of the type II transmembrane serine proteases (TTSPs) human airway trypsin-like protease (HAT) and transmembrane protease, serine 2 (TMPRSS2), in SARS-S activation. We found that HAT activates SARS-S in the context of surrogate systems and authentic SARS-CoV infection and is coexpressed with the viral receptor angiotensin-converting enzyme 2 (ACE2) in bronchial epithelial cells and pneumocytes. HAT cleaved SARS-S at R667, as determined by mutagenesis and mass spectrometry, and activated SARS-S for cell-cell fusion in cis and trans, while the related pulmonary protease TMPRSS2 cleaved SARS-S at multiple sites and activated SARS-S only in trans. However, TMPRSS2 but not HAT expression rendered SARS-S-driven virus-cell fusion independent of cathepsin activity, indicating that HAT and TMPRSS2 activate SARS-S differentially. Collectively, our results show that HAT cleaves and activates SARS-S and might support viral spread in patients. PMID:21994442

Chromospheric Activity of HAT-P-11: An Unusually Active Planet-hosting K Star

NASA Astrophysics Data System (ADS)

Morris, Brett M.; Hawley, Suzanne L.; Hebb, Leslie; Sakari, Charli; Davenport, James. R. A.; Isaacson, Howard; Howard, Andrew W.; Montet, Benjamin T.; Agol, Eric

2017-10-01

Kepler photometry of the hot Neptune host star HAT-P-11 suggests that its spot latitude distribution is comparable to the Sun’s near solar maximum. We search for evidence of an activity cycle in the Ca II H & K chromospheric emission S-index with archival Keck/HIRES spectra and observations from the echelle spectrograph on the Astrophysical Research Consortium 3.5 m Telescope at Apache Point Observatory. The chromospheric emission of HAT-P-11 is consistent with an ≳ 10 year activity cycle, which plateaued near maximum during the Kepler mission. In the cycle that we observed, the star seemed to spend more time near active maximum than minimum. We compare the {log}{R}{HK}{\\prime } normalized chromospheric emission index of HAT-P-11 with other stars. HAT-P-11 has unusually strong chromospheric emission compared to planet-hosting stars of similar effective temperature and rotation period, perhaps due to tides raised by its planet.

Development of new hard hat dimensions using user-centered design approach among oil palm harvesters.

PubMed

Mohd Shukoor, Nor Shuhada; Mohd Tamrin, Shamsul Bahri; Guan, Ng Yee; Mohd Suadi Nata, Dayana Hazwani

2018-05-22

Hard hats are among the personal protective equipment (PPE) used in many industries to reduce the impact of any falling object on the skull and also to prevent head and brain injuries. However, the practice of wearing a safety helmet during working hours is still low. This is due to the physical discomfort perceived by safety helmet users. Given the unpopularity of the current hard hat, the general perception of workers concerning its use and its measurements are the determining factors in the development of a new hard hat. A cross-sectional study was conducted in which 132 male oil palm harvesters between 19 and 60 years of age were selected from among the employees of the same oil palm harvesting company. A set of questionnaires was developed to collect their socio-demographic information as well as their perceptions of comfort and the prevalence of head injury. In addition, a set of measuring instruments, including Martin's anthropometry set, was used for head measurement and data collection in respect of the current hard hat. In this research, six respondents were randomly selected to attend an interview session for qualitative assessment.RESULTSBased on the questionnaires, the unpopularity in the use of the hard hat was largely influenced by factors related to poor design, in general, and, specifically, poor ventilation (64%), load (67% ), and physical discomfort (42% ). The measurements of the anthropometric parameters and the dimensions of the hard hat also showed a significant mismatch. The unpopularity of the current hard hat among oil palm harvesters stemmed from the discomfort from wearing, which showed that the development of a new hard hat could lead to better usage and the greater likelihood of wearing a hard hat throughout the working day.

Arabidopsis HD-Zip II transcription factors control apical embryo development and meristem function.

PubMed

Turchi, Luana; Carabelli, Monica; Ruzza, Valentino; Possenti, Marco; Sassi, Massimiliano; Peñalosa, Andrés; Sessa, Giovanna; Salvi, Sergio; Forte, Valentina; Morelli, Giorgio; Ruberti, Ida

2013-05-01

The Arabidopsis genome encodes ten Homeodomain-Leucine zipper (HD-Zip) II proteins. ARABIDOPSIS THALIANA HOMEOBOX 2 (ATHB2), HOMEOBOX ARABIDOPSIS THALIANA 1 (HAT1), HAT2, HAT3 and ATHB4 are regulated by changes in the red/far red light ratio that induce shade avoidance in most of the angiosperms. Here, we show that progressive loss of HAT3, ATHB4 and ATHB2 activity causes developmental defects from embryogenesis onwards in white light. Cotyledon development and number are altered in hat3 athb4 embryos, and these defects correlate with changes in auxin distribution and response. athb2 gain-of-function mutation and ATHB2 expression driven by its promoter in hat3 athb4 result in significant attenuation of phenotypes, thus demonstrating that ATHB2 is functionally redundant to HAT3 and ATHB4. In analogy to loss-of-function mutations in HD-Zip III genes, loss of HAT3 and ATHB4 results in organ polarity defects, whereas triple hat3 athb4 athb2 mutants develop one or two radialized cotyledons and lack an active shoot apical meristem (SAM). Consistent with overlapping expression pattern of HD-Zip II and HD-Zip III gene family members, bilateral symmetry and SAM defects are enhanced when hat3 athb4 is combined with mutations in PHABULOSA (PHB), PHAVOLUTA (PHV) or REVOLUTA (REV). Finally, we show that ATHB2 is part of a complex regulatory circuit directly involving both HD-Zip II and HD-Zip III proteins. Taken together, our study provides evidence that a genetic system consisting of HD-Zip II and HD-Zip III genes cooperates in establishing bilateral symmetry and patterning along the adaxial-abaxial axis in the embryo as well as in controlling SAM activity.

Predicting the Impact of Intervention Strategies for Sleeping Sickness in Two High-Endemicity Health Zones of the Democratic Republic of Congo.

PubMed

Rock, Kat S; Torr, Steve J; Lumbala, Crispin; Keeling, Matt J

2017-01-01

Two goals have been set for Gambian human African trypanosomiasis (HAT), the first is to achieve elimination as a public health problem in 90% of foci by 2020, and the second is to achieve zero transmission globally by 2030. It remains unclear if certain HAT hotspots could achieve elimination as a public health problem by 2020 and, of greater concern, it appears that current interventions to control HAT in these areas may not be sufficient to achieve zero transmission by 2030. A mathematical model of disease dynamics was used to assess the potential impact of changing the intervention strategy in two high-endemicity health zones of Kwilu province, Democratic Republic of Congo. Six key strategies and twelve variations were considered which covered a range of recruitment strategies for screening and vector control. It was found that effectiveness of HAT screening could be improved by increasing effort to recruit high-risk groups for screening. Furthermore, seven proposed strategies which included vector control were predicted to be sufficient to achieve an incidence of less than 1 reported case per 10,000 people by 2020 in the study region. All vector control strategies simulated reduced transmission enough to meet the 2030 goal, even if vector control was only moderately effective (60% tsetse population reduction). At this level of control the full elimination threshold was expected to be met within six years following the start of the change in strategy and over 6000 additional cases would be averted between 2017 and 2030 compared to current screening alone. It is recommended that a two-pronged strategy including both enhanced active screening and tsetse control is implemented in this region and in other persistent HAT foci to ensure the success of the control programme and meet the 2030 elimination goal for HAT.

Predicting the Impact of Intervention Strategies for Sleeping Sickness in Two High-Endemicity Health Zones of the Democratic Republic of Congo

PubMed Central

Torr, Steve J.; Lumbala, Crispin; Keeling, Matt J.

2017-01-01

Two goals have been set for Gambian human African trypanosomiasis (HAT), the first is to achieve elimination as a public health problem in 90% of foci by 2020, and the second is to achieve zero transmission globally by 2030. It remains unclear if certain HAT hotspots could achieve elimination as a public health problem by 2020 and, of greater concern, it appears that current interventions to control HAT in these areas may not be sufficient to achieve zero transmission by 2030. A mathematical model of disease dynamics was used to assess the potential impact of changing the intervention strategy in two high-endemicity health zones of Kwilu province, Democratic Republic of Congo. Six key strategies and twelve variations were considered which covered a range of recruitment strategies for screening and vector control. It was found that effectiveness of HAT screening could be improved by increasing effort to recruit high-risk groups for screening. Furthermore, seven proposed strategies which included vector control were predicted to be sufficient to achieve an incidence of less than 1 reported case per 10,000 people by 2020 in the study region. All vector control strategies simulated reduced transmission enough to meet the 2030 goal, even if vector control was only moderately effective (60% tsetse population reduction). At this level of control the full elimination threshold was expected to be met within six years following the start of the change in strategy and over 6000 additional cases would be averted between 2017 and 2030 compared to current screening alone. It is recommended that a two-pronged strategy including both enhanced active screening and tsetse control is implemented in this region and in other persistent HAT foci to ensure the success of the control programme and meet the 2030 elimination goal for HAT. PMID:28056016

PCAF interacts with tax and stimulates tax transactivation in a histone acetyltransferase-independent manner.

PubMed

Jiang, H; Lu, H; Schiltz, R L; Pise-Masison, C A; Ogryzko, V V; Nakatani, Y; Brady, J N

1999-12-01

Recent studies have shown that the p300/CREB binding protein (CBP)-associated factor (PCAF) is involved in transcriptional activation. PCAF activity has been shown strongly associated with histone acetyltransferase (HAT) activity. In this report, we present evidence for a HAT-independent transcription function that is activated in the presence of the human T-cell leukemia virus type 1 (HTLV-1) Tax protein. In vitro and in vivo GST-Tax pull-down and coimmunoprecipitation experiments demonstrate that there is a direct interaction between Tax and PCAF, independent of p300/CBP. PCAF can be recruited to the HTLV-1 Tax responsive element in the presence of Tax, and PCAF cooperates with Tax in vivo to activate transcription from the HTLV-1 LTR over 10-fold. Point mutations at Tax amino acid 318 (TaxS318A) or 319 to 320 (Tax M47), which have decreased or no activity on the HTLV-1 promoter, are defective for PCAF binding. Strikingly, the ability of PCAF to stimulate Tax transactivation is not solely dependent on the PCAF HAT domain. Two independent PCAF HAT mutants, which knock out acetyltransferase enzyme activity, activate Tax transactivation to approximately the same level as wild-type PCAF. In contrast, p300 stimulation of Tax transactivation is HAT dependent. These studies provide experimental evidence that PCAF contains a coactivator transcription function independent of the HAT activity on the viral long terminal repeat.

PCAF Interacts with Tax and Stimulates Tax Transactivation in a Histone Acetyltransferase-Independent Manner

PubMed Central

Jiang, Hua; Lu, Hanxin; Schiltz, R. Louis; Pise-Masison, Cynthia A.; Ogryzko, Vasily V.; Nakatani, Yoshihiro; Brady, John N.

1999-01-01

Recent studies have shown that the p300/CREB binding protein (CBP)-associated factor (PCAF) is involved in transcriptional activation. PCAF activity has been shown strongly associated with histone acetyltransferase (HAT) activity. In this report, we present evidence for a HAT-independent transcription function that is activated in the presence of the human T-cell leukemia virus type 1 (HTLV-1) Tax protein. In vitro and in vivo GST-Tax pull-down and coimmunoprecipitation experiments demonstrate that there is a direct interaction between Tax and PCAF, independent of p300/CBP. PCAF can be recruited to the HTLV-1 Tax responsive element in the presence of Tax, and PCAF cooperates with Tax in vivo to activate transcription from the HTLV-1 LTR over 10-fold. Point mutations at Tax amino acid 318 (TaxS318A) or 319 to 320 (Tax M47), which have decreased or no activity on the HTLV-1 promoter, are defective for PCAF binding. Strikingly, the ability of PCAF to stimulate Tax transactivation is not solely dependent on the PCAF HAT domain. Two independent PCAF HAT mutants, which knock out acetyltransferase enzyme activity, activate Tax transactivation to approximately the same level as wild-type PCAF. In contrast, p300 stimulation of Tax transactivation is HAT dependent. These studies provide experimental evidence that PCAF contains a coactivator transcription function independent of the HAT activity on the viral long terminal repeat. PMID:10567539

Allele compensation in tip60+/- mice rescues white adipose tissue function in vivo.

PubMed

Gao, Yuan; Hamers, Nicole; Rakhshandehroo, Maryam; Berger, Ruud; Lough, John; Kalkhoven, Eric

2014-01-01

Adipose tissue is a key regulator of energy homestasis. The amount of adipose tissue is largely determined by adipocyte differentiation (adipogenesis), a process that is regulated by the concerted actions of multiple transcription factors and cofactors. Based on in vitro studies in murine 3T3-L1 preadipocytes and human primary preadipocytes, the transcriptional cofactor and acetyltransferase Tip60 was recently identified as an essential adipogenic factor. We therefore investigated the role of Tip60 on adipocyte differentiation and function, and possible consequences on energy homeostasis, in vivo. Because homozygous inactivation results in early embryonic lethality, Tip60+/- mice were used. Heterozygous inactivation of Tip60 had no effect on body weight, despite slightly higher food intake by Tip60+/- mice. No major effects of heterozygous inactivation of Tip60 were observed on adipose tissue and liver, and Tip60+/- displayed normal glucose tolerance, both on a low fat and a high fat diet. While Tip60 mRNA was reduced to 50% in adipose tissue, the protein levels were unaltered, suggesting compensation by the intact allele. These findings indicate that the in vivo role of Tip60 in adipocyte differentiation and function cannot be properly addressed in Tip60+/- mice, but requires the generation of adipose tissue-specific knock out animals or specific knock-in mice.

Screening North American plant extracts in vitro against Trypanosoma brucei for discovery of new antitrypanosomal drug leads.

PubMed

Jain, Surendra; Jacob, Melissa; Walker, Larry; Tekwani, Babu

2016-05-18

Human African Trypanosomiasis (HAT) is a protozoan parasitic disease caused by Trypanosoma brucei. The disease is endemic in regions of sub-Saharan Africa, covering 36 countries and more than 60 million people at the risk. Only few drugs are available for the treatment of HAT. Current drugs suffer from severe toxicities and require intramuscular or intravenous administrations. The situation is further aggravated due to the emergence of drug resistance. There is an urgent need of new drugs that are effective orally against both stages of HAT. Natural products offer an unmatched source for bioactive molecules with new chemotypes. The extracts prepared from 522 plants collected from various parts of the North America were screened in vitro against blood stage trypamastigote forms of T. brucei. Active extracts were further screened at concentrations ranging from 10 to 0.4 μg/mL. Active extracts were also investigated for toxicity in Differentiated THP1 cells at 10 μg/mL concentration. The results were computed for dose-response analysis and determination of IC50/IC90 values. A significant number (150) of extracts showed >90 % inhibition of growth of trypomastigote blood forms of T. brucei in primary screening at 20 μg/mL concentration. The active extracts were further investigated for dose-response inhibition of T. brucei growth. The antitrypansomal activity of 125 plant extracts was confirmed with IC50 < 10 μg/mL. None of these active extracts showed toxicity against differentiated THP1 cells. Eight plants extracts namely, Alnus rubra, Hoita macrostachya, Sabal minor, Syzygium aqueum, Hamamelis virginiana, Coccoloba pubescens, Rhus integrifolia and Nuphar luteum were identified as highly potent antitrypanosomal extracts with IC50 values <1 μg/mL. Limited phytochemical and pharmacological reports are available for the lead plant extracts with potent antitrypanosomal activity. Follow up evaluation of these plant extracts is likely to yield new antitrypanosomal drug-leads or alternate medicines for treatment of HAT.

Transcription factor HAT1 is a substrate of SnRK2.3 kinase and negatively regulates ABA synthesis and signaling in Arabidopsis responding to drought.

PubMed

Tan, Wenrong; Zhang, Dawei; Zhou, Huapeng; Zheng, Ting; Yin, Yanhai; Lin, Honghui

2018-04-01

Drought is a major threat to plant growth and crop productivity. The phytohormone abscisic acid (ABA) plays a critical role in plant response to drought stress. Although ABA signaling-mediated drought tolerance has been widely investigated in Arabidopsis thaliana, the feedback mechanism and components negatively regulating this pathway are less well understood. Here we identified a member of Arabidopsis HD-ZIP transcription factors HAT1 which can interacts with and be phosphorylated by SnRK2s. hat1hat3, loss-of-function mutant of HAT1 and its homolog HAT3, was hypersensitive to ABA in primary root inhibition, ABA-responsive genes expression, and displayed enhanced drought tolerance, whereas HAT1 overexpressing lines were hyposensitive to ABA and less tolerant to drought stress, suggesting that HAT1 functions as a negative regulator in ABA signaling-mediated drought response. Furthermore, expression levels of ABA biosynthesis genes ABA3 and NCED3 were repressed by HAT1 directly binding to their promoters, resulting in the ABA level was increased in hat1hat3 and reduced in HAT1OX lines. Further evidence showed that both protein stability and binding activity of HAT1 was repressed by SnRK2.3 phosphorylation. Overexpressing SnRK2.3 in HAT1OX transgenic plant made a reduced HAT1 protein level and suppressed the HAT1OX phenotypes in ABA and drought response. Our results thus establish a new negative regulation mechanism of HAT1 which helps plants fine-tune their drought responses.

Allele Compensation in Tip60+/− Mice Rescues White Adipose Tissue Function In Vivo

PubMed Central

Gao, Yuan; Hamers, Nicole; Rakhshandehroo, Maryam; Berger, Ruud; Lough, John; Kalkhoven, Eric

2014-01-01

Adipose tissue is a key regulator of energy homestasis. The amount of adipose tissue is largely determined by adipocyte differentiation (adipogenesis), a process that is regulated by the concerted actions of multiple transcription factors and cofactors. Based on in vitro studies in murine 3T3-L1 preadipocytes and human primary preadipocytes, the transcriptional cofactor and acetyltransferase Tip60 was recently identified as an essential adipogenic factor. We therefore investigated the role of Tip60 on adipocyte differentiation and function, and possible consequences on energy homeostasis, in vivo. Because homozygous inactivation results in early embryonic lethality, Tip60+/− mice were used. Heterozygous inactivation of Tip60 had no effect on body weight, despite slightly higher food intake by Tip60+/− mice. No major effects of heterozygous inactivation of Tip60 were observed on adipose tissue and liver, and Tip60+/− displayed normal glucose tolerance, both on a low fat and a high fat diet. While Tip60 mRNA was reduced to 50% in adipose tissue, the protein levels were unaltered, suggesting compensation by the intact allele. These findings indicate that the in vivo role of Tip60 in adipocyte differentiation and function cannot be properly addressed in Tip60+/− mice, but requires the generation of adipose tissue-specific knock out animals or specific knock-in mice. PMID:24870614

The Active Latitudes of HAT-P-11

NASA Astrophysics Data System (ADS)

Morris, Brett; Hebb, Leslie; Davenport, James R. A.; Hawley, Suzanne L.

2017-01-01

Transiting planets map the brightness of their host stars, as the flux lost during exoplanet transits is proportional to the integrated flux occulted by the planet. We analyze four years of Kepler short-cadence photometry of HAT-P-11 - an active K4 dwarf with a 29 day rotation period, orbited by a hot-Neptune. Due to its highly-misaligned orbit, the planet occults most stellar latitudes during each transit, and the latitude distribution of spots is encoded in the transit light curves. We model each spot occultation in transit to create a spot map of HAT-P-11, which reveals two active latitudes near ±17 degrees. We investigate whether the spot distribution changes in time, and we compare the spot latitude distributions of HAT-P-11 and the Sun throughout the solar activity cycle.

Headgear Accessories Classification Using an Overhead Depth Sensor

PubMed Central

Luna, Carlos A.; Marron-Romera, Marta; Mazo, Manuel; Luengo-Sanchez, Sara; Macho-Pedroso, Roberto

2017-01-01

In this paper, we address the generation of semantic labels describing the headgear accessories carried out by people in a scene under surveillance, only using depth information obtained from a Time-of-Flight (ToF) camera placed in an overhead position. We propose a new method for headgear accessories classification based on the design of a robust processing strategy that includes the estimation of a meaningful feature vector that provides the relevant information about the people’s head and shoulder areas. This paper includes a detailed description of the proposed algorithmic approach, and the results obtained in tests with persons with and without headgear accessories, and with different types of hats and caps. In order to evaluate the proposal, a wide experimental validation has been carried out on a fully labeled database (that has been made available to the scientific community), including a broad variety of people and headgear accessories. For the validation, three different levels of detail have been defined, considering a different number of classes: the first level only includes two classes (hat/cap, and no hat/cap), the second one considers three classes (hat, cap and no hat/cap), and the last one includes the full class set with the five classes (no hat/cap, cap, small size hat, medium size hat, and large size hat). The achieved performance is satisfactory in every case: the average classification rates for the first level reaches 95.25%, for the second one is 92.34%, and for the full class set equals 84.60%. In addition, the online stage processing time is 5.75 ms per frame in a standard PC, thus allowing for real-time operation. PMID:28796177

Novel histone deacetylase inhibitor N25 exerts anti-tumor effects and induces autophagy in human glioma cells by inhibiting HDAC3

PubMed Central

Sun, Xin-Yuan; Qu, Yue; Ni, An-Ran; Wang, Gui-Xiang; Huang, Wei-Bin; Chen, Zhong-Ping; Lv, Zhu-Fen; Zhang, Song; Lindsay, Holly; Zhao, Sibo; Li, Xiao-Nan; Feng, Bing-Hong

2017-01-01

N25, a novel histone deacetylase inhibitor, was created through structural modification of suberoylanilide hydroxamic acid. To evaluate the anti-tumor activity of N25 and clarify its molecular mechanism of inducing autophagy in glioma cells, we investigated its in vitro anti-proliferative effect and in vivo anticancer effect. Moreover, we detected whether N25 induces autophagy in glioma cells by transmission electron microscope and analyzed the protein expression level of HDAC3, Tip60, LC3 in glioma samples by western blot. We additionally analyzed the protein expression level of HDAC3, Tip60, ULK1 (Atg1), and Beclin-1 (Atg6) after treatment with N25 in glioma cells. Our results showed that the anti-tumor activity of N25 in glioma cells is slightly stronger than SAHA both in vitro and in vivo. We found that N25 induced autophagy, and HDAC3 was significantly elevated and Tip60 and LC3 significantly decreased in glioma samples compared with normal brain tissues. Nevertheless, N25 inhibited HDAC3 and up-regulated the protein expression of Tip60, ULK1 (Atg1), and Beclin-1 (Atg6) after treatment of glioma cells with N25. In conclusion, these data suggest that N25 has striking anti-tumor activity in part due to inhibition of HDAC3. Additionally, N25 may induce autophagy through inhibiting HDAC3. PMID:29088860

ATM Mediates pRB Function To Control DNMT1 Protein Stability and DNA Methylation

PubMed Central

Suzuki, Misa; Hayashi, Naoyuki; Kobayashi, Masahiko; Sasaki, Nobunari; Nishiuchi, Takumi; Doki, Yuichiro; Okamoto, Takahiro; Kohno, Susumu; Muranaka, Hayato; Kitajima, Shunsuke; Yamamoto, Ken-ichi

2013-01-01

The retinoblastoma tumor suppressor gene (RB) product has been implicated in epigenetic control of gene expression owing to its ability to physically bind to many chromatin modifiers. However, the biological and clinical significance of this activity was not well elucidated. To address this, we performed genetic and epigenetic analyses in an Rb-deficient mouse thyroid C cell tumor model. Here we report that the genetic interaction of Rb and ATM regulates DNMT1 protein stability and hence controls the DNA methylation status in the promoters of at least the Ink4a, Shc2, FoxO6, and Noggin genes. Furthermore, we demonstrate that inactivation of pRB promotes Tip60 (acetyltransferase)-dependent ATM activation; allows activated ATM to physically bind to DNMT1, forming a complex with Tip60 and UHRF1 (E3 ligase); and consequently accelerates DNMT1 ubiquitination driven by Tip60-dependent acetylation. Our results indicate that inactivation of the pRB pathway in coordination with aberration in the DNA damage response deregulates DNMT1 stability, leading to an abnormal DNA methylation pattern and malignant progression. PMID:23754744

Impact of the Ebola outbreak on Trypanosoma brucei gambiense infection medical activities in coastal Guinea, 2014-2015: A retrospective analysis from the Guinean national Human African Trypanosomiasis control program.

PubMed

Camara, Mariame; Ouattara, Eric; Duvignaud, Alexandre; Migliani, René; Camara, Oumou; Leno, Mamadou; Solano, Philippe; Bucheton, Bruno; Camara, Mamadou; Malvy, Denis

2017-11-01

The 2014-2015 Ebola outbreak massively hit Guinea. The coastal districts of Boffa, Dubreka and Forecariah, three major foci of Human African Trypanosomiasis (HAT), were particularly affected. We aimed to assess the impact of this epidemic on sleeping sickness screening and caring activities. We used preexisting data from the Guinean sleeping sickness control program, collected between 2012 and 2015. We described monthly: the number of persons (i) screened actively; (ii) or passively; (iii) treated for HAT; (iv) attending post-treatment follow-up visits. We compared clinical data, treatment characteristics and Disability Adjusted Life-Years (DALYs) before (February 2012 to December 2013) and during (January 2014 to October 2015) the Ebola outbreak period according to available data. Whereas 32,221 persons were actively screened from February 2012 to December 2013, before the official declaration of the first Ebola case in Guinea, no active screening campaigns could be performed during the Ebola outbreak. Following the reinforcement and extension of HAT passive surveillance system early in 2014, the number of persons tested passively by month increased from 7 to 286 between April and September 2014 and then abruptly decreased to 180 until January 2015 and to none after March 2015. 213 patients initiated HAT treatment, 154 (72%) before Ebola and 59 (28%) during the Ebola outbreak. Those initiating HAT therapy during Ebola outbreak were recruited through passive screening and diagnosed at a later stage 2 of the disease (96% vs. 55% before Ebola, p<0.0001). The proportion of patients attending the 3 months and 6 months post-treatment follow-up visits decreased from 44% to 10% (p <0.0001) and from 16% to 3% (p = 0.017) respectively. The DALYs generated before the Ebola outbreak were estimated to 48.7 (46.7-51.5) and increased up to 168.7 (162.7-174.7), 284.9 (277.1-292.8) and 466.3 (455.7-477.0) during Ebola assuming case fatality rates of 2%, 5% and 10% respectively among under-reported HAT cases. The 2014-2015 Ebola outbreak deeply impacted HAT screening activities in Guinea. Active screening campaigns were stopped. Passive screening dramatically decreased during the Ebola period, but trends could not be compared with pre-Ebola period (data not available). Few patients were diagnosed with more advanced HAT during the Ebola period and retention rates in follow-up were lowered. The drop in newly diagnosed HAT cases during Ebola epidemic is unlikely due to a fall in HAT incidence. Even if we were unable to demonstrate it directly, it is much more probably the consequence of hampered screening activities and of the fear of the population on subsequent confirmation and linkage to care. Reinforced program monitoring, alternative control strategies and sustainable financial and human resources allocation are mandatory during post Ebola period to reduce HAT burden in Guinea.

The HAT TRICK programme for improving physical activity, healthy eating and connectedness among overweight, inactive men: study protocol of a pragmatic feasibility trial.

PubMed

Caperchione, Cristina M; Bottorff, Joan L; Oliffe, John L; Johnson, Steven T; Hunt, Kate; Sharp, Paul; Fitzpatrick, Kayla M; Price, Ryley; Goldenberg, S Larry

2017-09-06

Physical activity, healthy eating and maintaining a healthy weight are associated with reduced risk of cardiovascular disease, type 2 diabetes and cancer and with improved mental health. Despite these benefits, many men do not meet recommended physical activity guidelines and have poor eating behaviours. Many health promotion programmes hold little appeal to men and consequently fail to influence men's health practices. HAT TRICK was designed as a 12-week face-to-face, gender-sensitised intervention for overweight and inactive men focusing on physical activity, healthy eating and social connectedness and was delivered in collaboration with a major junior Canadian ice hockey team (age range 16-20 years). The programme was implemented and evaluated to assess its feasibility. This article describes the intervention design and study protocol of HAT TRICK. HAT TRICK participants (n=60) were men age 35 years, residing in the Okanagan Region of British Columbia, who accumulate 150 min of moderate to vigorous physical activity a week, with a body mass index of >25 kg/m 2 and a pant waist size of >38'. Each 90 min weekly session included targeted health education and theory-guided behavioural change techniques, as well as a progressive (ie, an increase in duration and intensity) group physical activity component. Outcome measures were collected at baseline, 12 weeks and 9 months and included the following: objectively measured anthropometrics, blood pressure, heart rate, physical activity and sedentary behaviour, as well as self-reported physical activity, sedentary behaviour, diet, smoking, alcohol consumption, sleep habits, risk of depression, health-related quality of life and social connectedness. Programme feasibility data (eg, recruitment, satisfaction, adherence, content delivery) were assessed at 12 weeks via interviews and self-report. Ethical approval was obtained from the University of British Columbia Okanagan Behavioural Research Ethics Board (reference no H1600736). Study findings will be disseminated through academic meetings, peer-reviewed publication, web-based podcasts, social media, plain language summaries and co-delivered community presentations. ISRCTN43361357,Pre results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Regulation of Nitrate Transport in Citrus Rootstocks Depending on Nitrogen Availability

PubMed Central

Cerezo, Miguel; Camañes, Gemma; Flors, Víctor; Primo-Millo, Eduardo

2007-01-01

Previously, we reported that in Citrus plants, nitrate influx through the plasmalemma of roots cells follows a biphasic pattern, suggesting the existence of at least two different uptake systems, a high and low affinity transport system (HATS and LATS, respectively). Here, we describe a novel inducible high affinity transport system (iHATS). This new nitrate transport system has a high capacity to uptake nitrate in two different Citrus rootstocks (Cleopatra mandarin and Troyer citrange). The iHATS was saturable, showing higher affinity than constitutive high affinity transport system (cHATS) to the substrate NO3−. The Vmax for this saturable component iHATS was higher than cHATS, reaching similar values in both rootstocks. Additionally, we studied the regulation of root NO3− uptake mediated by both HATS (iHATS and cHATS) and LATS. In both rootstocks, cHATS is constitutive and independent of N-status. Concerning the regulation of iHATS, this system is upregulated by NO3− and down-regulated by the N status and by NO3− itself when plants are exposed to it for a longer period of time. LATS in Cleopatra mandarin and Troyer citrange rootstocks is repressed by the N-status. The use of various metabolic uncouplers or inhibitors indicated that NO3− net uptake mediated by iHATS and LATS was an active transport system in both rootstocks. PMID:19516998

Heparin-associated thrombocytopenia: antibody binding specificity to platelet antigens.

PubMed

Lynch, D M; Howe, S E

1985-11-01

Sera from four patients with heparin-associated thrombocytopenia (HAT) were evaluated by a quantitative enzyme-linked immunosorbent assay (ELISA) to detect heparin-dependent serum platelet-bindable immunoglobulin (S-PBIg) and by Western blotting and immunoprecipitation to investigate the specificity of the antibody binding. All HAT sera showed mildly increased S-PBIg (mean, 7.8 fg per platelet; normal, less than 6.0 fg per platelet) to intact target platelets in the ELISA, which was markedly increased in the presence of heparin (mean, 20.9 fg per platelet). This increase was 20-fold greater than normal control sera, which showed a mean differential increase of only 0.5 fg per platelet. Immunoglobulin binding specificity to platelet antigens was investigated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis of platelet lysate with transfer of the platelet fractions onto nitrocellulose strips (Western blotting) and subsequent immunoassay using HAT and normal sera. In the presence of heparin, the four HAT patients demonstrated increased binding of immunoglobulin to platelet antigens of apparent molecular weights of 180, 124, and 82 kd. Radiolabeled heparin when incubated with HAT sera, normal sera, or albumin blanks bound to platelet proteins of the same apparent molecular weights. These observations are consistent with current hypotheses suggesting that HAT antibody is directed to heparin-platelet complexes or, alternatively, that heparin induces conformational change of antigenic sites on the platelet membrane.

The Starspots of HAT-P-11: Evidence for a Solar-like Dynamo

NASA Astrophysics Data System (ADS)

Morris, Brett M.; Hebb, Leslie; Davenport, James R. A.; Rohn, Graeme; Hawley, Suzanne L.

2017-09-01

We measure the starspot radii and latitude distribution on the K4 dwarf HAT-P-11 from Kepler short-cadence photometry. We take advantage of starspot occultations by HAT-P-11’s highly misaligned planet to compare the spot size and latitude distributions to those of sunspots. We find that HAT-P-11’s spots are distributed in latitude much like sunspots near the solar activity maximum, with a mean spot latitude of ≈16° ± 1°. The majority of HAT-P-11’s starspots have physical sizes that closely resemble the sizes of sunspots at solar maximum. We estimate the mean spotted area coverage on HAT-P-11 to be {3}-1+6 % , roughly two orders of magnitude greater than the typical solar spotted area.

VizieR Online Data Catalog: Spectroscopy and photometry for HAT-P-50--HAT-P-53 (Hartman+, 2015)

NASA Astrophysics Data System (ADS)

Hartman, J. D.; Bhatti, W.; Bakos, G. A.; Bieryla, A.; Kovacs, G.; Latham, D. W.; Csubry, Z.; de Val-Borro, M.; Penev, K.; Buchhave, L. A.; Torres, G.; Howard, A. W.; Marcy, G. W.; Johnson, J. A.; Isaacson, H.; Sato, B.; Boisse, I.; Falco, E.; Everett, M. E.; Szklenar, T.; Fulton, B. J.; Shporer, A.; Kovacs, T.; Hansen, T.; Beky, B.; Noyes, R. W.; Lazar, J.; Papp, I.; Sari, P.

2016-04-01

The HATNet network consists of six identical fully automated instruments, with four at Fred Lawrence Whipple Observatory (FLWO) in AZ, and two on the roof of the Submillimeter Array Hangar Building at Mauna Kea Observatory (MKO) in HI. The light-gathering elements of each instrument include an 11cm diameter telephoto lens, a Sloan r filter, and a 4K*4K front-side-illuminated CCD camera. Observations made in 2007 and early 2008 were carried out using a Cousins R filter. The instruments have a field of view of 10.6°*10.6° and a pixel scale of 9"/pixel at the center of an image. Additional time-series photometric measurements were obtained for all four of the systems using Keplercam on the FLWO 1.2m telescope. For HAT-P-50 we also obtained follow-up photometry with the CCD imager on the Byrne Observatory at Sedgwick (BOS) 0.8m telescope, located at Sedgwick Reserve in Santa Ynez Valley, CA, and operated by the Las Cumbres Observatory Global Telescope institute (LCOGT). HAT-P-50 was observed with HAT-10/G316 on 2008 Nov-2009 May, with HAT-5/G364 on 2009 May, with HAT-9/G364 on 2008 Dec-2009 May, with BOS on 2012 Feb 15, on 2012 Feb 21 and on 2012 Apr 08, and with Keplercam on 2012 Feb 18, on 2012 Nov 28, on 2012 Dec 23, on 2013 Jan 14, and on 2013 Jan 17. HAT-P-51 was observed with HAT-6/G164 on 2007 Sep-2008 Feb, with HAT-9/G164 on 2007 Sep-2008 Feb, with HAT-10/G165 on 2010 Sep-2011 Jan, with HAT-5/G165 on 2010 Nov-2011 Feb, with HAT-8/G165 on 2010 Nov-2011 Feb, with HAT-6/G209 on 2010 Nov-2011 Feb, with HAT-9/G209 on 2010 Nov-2011 Feb, with HAT-7/G210 on 2010 Nov-2011 Jan, and with Keplercam on 2011 Oct 21, on 2012 Jan 05, on 2012 Oct 05, on 2012 Oct 26, and on 2012 Nov 12. HAT-P-52 was observed with HAT-5/G212 on 2010 Sep-Nov, with HAT-8/G212 on 2010 Aug-Nov, and with Keplercam on 2010 Dec 23, on 2011 Sep 05, on 2011 Sep 27, on 2011 Nov 21, and on 2012 Jan 07. HAT-P-53 was observed with HAT-6/G164 on 2007 Sep-2008 Feb, with HAT-9/G164 on 2007 Sep-2008 Feb, with HAT-10/G165 on 2010 Sep-2011 Jan, with HAT-5/G165 on 2010 Nov-2011 Feb, with HAT-8/G165 on 2010 Nov-2011 Feb, and with Keplercam on 2011 Oct 19 and on 2011 Oct 27. The facilities used for each system include the Tillinghast Reflector Echelle Spectrograph (TRES; Resolution Δλ/λ/1000=44) on the 1.5m Tillinghast Reflector at FLWO (used on 2010 Dec-2012 Feb for HAT-P-50, on 2011 Sep 21 for HAT-P-51, on 2010 Dec-2011 Jan for HAT-P-52, and on 2011 Sep 18-19 for HAT-P-53); the Astrophysical Research Consortium Echelle Spectrometer (ARCES; Resolution Δλ/λ/1000=31.5) on the ARC 3.5m telescope at Apache Point Observatory (APO) in New Mexico (used on 2011 Sep 19 for HAT-P-51, and on 2011 Sep 19-20 for HAT-P-53); the FIbre-fed Echelle Spectrograph (FIES) at the 2.5m Nordic Optical Telescope (NOT) at La Palma, Spain (used on 2012 Mar 13-17 with Δλ/λ/1000=67 for HAT-P-50, and on 2011 Aug 4 with Δλ/λ/1000=46 for HAT-P-51); the SOPHIE Spectrograph (Resolution Δλ/λ/1000=39) on the 1.93m telescope at OHP in France (used for HAT-P-51 on 2011 Dec 4-12; the HIgh Resolution Echelle Spectrometer (HIRES; Resolution Δλ/λ/1000=55) on the Keck-I telescope in Hawaii together with the I2 absorption cell (used on 2011 Oct-2012 Feb for HAT-P-51, on 2011 Oct 19 and 2011 Feb-2012 Jul for HAT-P-52, and on 2011 Nov 14 and 2011 Nov-2012 Feb for HAT-P-53); and the High-Dispersion Spectrograph (HDS; Resolution Δλ/λ/1000=60) with the I2 absorption cell on the Subaru telescope in Hawaii (used on 2012 Feb 7 and 2012 Feb-Sep for HAT-P-50, and on 2012 Feb 9 and 2012 Feb 7-10 for HAT-P-51). The high-precision radial velocity measurements for all objects are seen to vary in phase with the transit ephemerides. The data are listed in Table4. All photometric measurements made for the four objects are available in Table5. (3 data files).

Knowledge and prevalence of Human African Trypanosomiasis among residents of Kachia grazing reserve, Kachia local government area, Kaduna state, Nigeria, 2012

PubMed Central

Uba, Belinda Vernyuy; Aliyu, Ahmad; Abubakar, Aisha; Uba, Sabo Ado; Gidado, Saheed; Edukugho, Aboyowa; Anagbogu, Ifeoma; Kalejaiye, John; Nguku, Patrick

2016-01-01

Introduction Human African Trypanosomiasis (HAT) is a vector borne parasitic disease transmitted to humans by infected tse-tse flies cause morbidity including delayed child mental development. Reports of nuisance and bites from tse-tse flies by residents of Kachia grazing led to the study to determine the knowledge, practices and prevalence of HAT among residents of the grazing reserve. Methods We conducted active case search in a cross-sectional study using multi-stage sampling with probability proportionate to size. We administered structured questionnaire on Knowledge, practices relating to HAT prevention and screened for HAT using card agglutination test for Trypanosomiasis (CATT). Knowledge of HAT was scored 0-5 and categorized good (3-5) and poor (0-2) based on score, predisposition to risk of HAT as exposure to ≥two risk factors and, a case of HAT as any respondent that tested positive on CATT. We analysed data using Epi-info and MS-excel. Results Of the 300 respondents, mean age 39(±17years) interviewed, 56.3% were males, 12.0% had good knowledge of HAT and 76.3% were exposed to HAT risk factors. Prevention practices included clearing of overgrown bushes around houses (99%), use of insecticidal treated nets (75.7%) and protective clothing (41.0%). Males {Odds Ratio [OR] 5.0; 95% Confidence Interval (CI) 1.8 - 13.6}, age above 40 years {OR 5.0; 95% CI 1.1 - 24.4} and family history of HAT {OR 8.7; 95% CI 2.4 - 32.1} were significantly associated with HAT knowledge. None tested positive on CATT. Conclusion Despite poor knowledge of HAT, residents practiced HAT preventive measures and zero HAT prevalence was recorded. PMID:27222686

A randomized phase 2 study exploring the role of bevacizumab and a chemotherapy-free approach in HER2-positive metastatic breast cancer: The HAT study (BOOG 2008-2003), a Dutch Breast Cancer Research Group trial.

PubMed

Drooger, Jan C; van Tinteren, Harm; de Groot, Steffen M; Ten Tije, Albert J; de Graaf, Hiltje; Portielje, Johanneke E A; Jager, Agnes; Honkoop, Aafke; Linn, Sabine C; Kroep, Judith R; Erdkamp, Frans L G; Hamberg, Paul; Imholz, Alex L T; van Rossum-Schornagel, Quirine C; Heijns, Joan B; van Leeuwen-Stok, A Elise; Sleijfer, Stefan

2016-10-01

To explore the role of bevacizumab and a chemotherapy-free approach, the authors evaluated the combination of bevacizumab, trastuzumab, and paclitaxel (HAT) and the regimen of trastuzumab and bevacizumab (HA) with the addition of paclitaxel after progression (HA-HAT) as first-line treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. In a noncomparative phase 2 trial, patients were randomized between HAT and HA-HAT. The primary endpoint was the progression-free rate at 1 year (1-year PFR). In the HA-HAT group, progression-free survival (PFS) was separately established for HA (PFS1) and HAT (PFS2). Eighty-four patients received HAT (n = 39) or HA-HAT (n = 45). The 1-year PFR was 74.4% (95% confidence interval [CI], 61.8%-89.4%) and 62.2% (95% CI, 49.6%-89.4%) in the HAT and HA-HAT arms, respectively. The median PFS was 19.8 months (95% CI, 14.9-25.6 months) in the HAT arm and 19.6 months (95% CI, 12.0-32.0 months) in the HA-HAT arm. In the HA-HAT arm, the median PFS1 was 10.4 months (95% CI, 6.2-15.0 months), and the median PFS2 was 8.2 months (95% CI, 7.0-12.6 months). The number and severity of adverse events were comparable between the arms. Both HAT and HA-HAT have promising activity in patients with HER2-positive metastatic breast cancer. In particular, starting with only targeted agents and delaying chemotherapy is worth further exploration. Cancer 2016;122:2961-2970. © 2016 American Cancer Society. © 2016 American Cancer Society.

Effect of tip radius on the incipient plasticity of chromium studied by nanoindentation

DOE PAGES

Wu, Dong; Morris, James R.; Nieh, T. G.

2014-10-01

The onset of plasticity in Cr was investigated by nanoindentation using indenters with tip radii ranging from 60 to 759 nm. The stress for incipient plasticity was found to increase with decreasing tip radius. We find that the cumulative pop-in probability on load could be described successfully by a combined model over the full range of tip radius, indicating that the incipient plasticity might be triggered either by the homogeneous nucleation of dislocation or by the activation of existing dislocations underneath the indenter.

Evaluating long-term effectiveness of sleeping sickness control measures in Guinea.

PubMed

Pandey, Abhishek; Atkins, Katherine E; Bucheton, Bruno; Camara, Mamadou; Aksoy, Serap; Galvani, Alison P; Ndeffo-Mbah, Martial L

2015-10-22

Human African Trypanosomiasis threatens human health across Africa. The subspecies T.b. gambiense is responsible for the vast majority of reported HAT cases. Over the past decade, expanded control efforts accomplished a substantial reduction in HAT transmission, spurring the WHO to include Gambian HAT on its roadmap for 2020 elimination. To inform the implementation of this elimination goal, we evaluated the likelihood that current control interventions will achieve the 2020 target in Boffa prefecture in Guinea, which has one of the highest prevalences for HAT in the country, and where vector control measures have been implemented in combination with the traditional screen and treat strategy. We developed a three-species mathematical model of HAT and used a Bayesian melding approach to calibrate the model to epidemiological and entomological data from Boffa. From the calibrated model, we generated the probabilistic predictions regarding the likelihood that the current HAT control programs could achieve elimination by 2020 in Boffa. Our model projections indicate that if annual vector control is implemented in combination with annual or biennial active case detection and treatment, the probability of eliminating HAT as public health problem in Boffa by 2020 is over 90%. Annual implementation of vector control alone has a significant impact but a decreased chance of reaching the objective (77%). However, if the ongoing control efforts are interrupted, HAT will continue to remain a public health problem. In the presence of a non-human animal transmission reservoir, intervention strategies must be maintained at high coverage, even after 2020 elimination, to prevent HAT reemerging as a public health problem. Complementing active screening and treatment with vector control has the potential to achieve the elimination target before 2020 in the Boffa focus. However, surveillance must continue after elimination to prevent reemergence.

Phosphorylation regulates the water channel activity of the seed-specific aquaporin alpha-TIP.

PubMed

Maurel, C; Kado, R T; Guern, J; Chrispeels, M J

1995-07-03

The vacuolar membrane protein alpha-TIP is a seed-specific protein of the Major Intrinsic Protein family. Expression of alpha-TIP in Xenopus oocytes conferred a 4- to 8-fold increase in the osmotic water permeability (Pf) of the oocyte plasma membrane, showing that alpha-TIP forms water channels and is thus a new aquaporin. alpha-TIP has three putative phosphorylation sites on the cytoplasmic side of the membrane (Ser7, Ser23 and Ser99), one of which (Ser7) has been shown to be phosphorylated. We present several lines of evidence that the activity of this aquaporin is regulated by phosphorylation. First, mutation of the putative phosphorylation sites in alpha-TIP (Ser7Ala, Ser23Ala and Ser99Ala) reduced the apparent water transport activity of alpha-TIP in oocytes, suggesting that phosphorylation of alpha-TIP occurs in the oocytes and participates in the control of water channel activity. Second, exposure of oocytes to the cAMP agonists 8-bromoadenosine 3',5'-cyclic monophosphate, forskolin and 3-isobutyl-1-methylxanthine, which stimulate endogenous protein kinase A (PKA), increased the water transport activity of alpha-TIP by 80-100% after 60 min. That the protein can be phosphorylated by PKA was demonstrated by phosphorylating alpha-TIP in isolated oocyte membranes with the bovine PKA catalytic subunit. Third, the integrity of the three sites at positions 7, 23 and 99 was necessary for the cAMP-dependent increase in the Pf of oocytes expressing alpha-TIP, as well as for in vitro phosphorylation of alpha-TIP. These findings demonstrate that the alpha-TIP water channel can be modulated via phosphorylation of Ser7, Ser23 and Ser99.(ABSTRACT TRUNCATED AT 250 WORDS)

75 FR 28475 - Airworthiness Directives; Airbus Model A330-200 and -300 Series Airplanes, and Model A340-300...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-21

... unsafe condition as: In the door 2 area, the hat-racks are supplied with a basic wire harness which includes ``Oxygen Masks'' activation. In case of a monument installation, the respective non-used hat- rack... door 2 area, the hat-racks are supplied with a basic wire harness which includes ``Oxygen Masks...

Involvement of H2O2 in fluazifop-P-butyl-induced cell death in bristly starbur seedlings.

PubMed

Luo, Xiaoyong; Liu, Zhihang; Sunohara, Yukari; Matsumoto, Hiroshi; Li, Pingliang

2017-11-01

In order to understand the action mechanism of fluazifop-P-butyl (FB) in bristly starbur (Acanthospermum hispidum D.C.), a susceptible plant, the role of active oxygen species (ROS) in herbicide-induced cell death in shoots was investigated. FB-induced phytotoxicity was not reduced by the antioxidants, 1,4-diazabicyclooctane (dabaco), sodium azide, l-tryptophan, d-tryptophan, hydroquinone and dimethyl pyridine N-oxide (DMPO). The activities of superoxide dismutase (SOD) and catalase (CAT), in bristly starbur seedlings were significantly increased by FB at 12 HAT and 24 HAT, while ascorbate peroxidase (APX) and glutathione reductase (GR) activities increased only at 12 HAT. The contents of H 2 O 2 in FB-treated bristly starbur seedlings were significantly higher to that of control between 8 and 24 HAT. According to the analysis of potassium iodide - starch or 3,3-diaminobenzidine, the accumulation of hydrogen peroxide was observed in the apical growing point, stem, petiole and veins of FB-treated bristly starbur seedlings at 24 HAT. The cell viability of bristly starbur seedlings treated by 10μM FB decreased at 18 HAT. These results suggested that FB-induced cell death in bristly starbur shoots may be caused by ROS (O 2 - and H 2 O 2 ) generation and lipid peroxidation. Copyright © 2016 Elsevier Inc. All rights reserved.

[Quality of life of pregnant women infected with the human immunodeficiency virus (HIV) in the city of São Paulo].

PubMed

Tirado, Maria do Carmo Braga do Amaral; Bortoletti, Fátima Ferrreira; Nakamura, Mary Uchiyama; Souza, Eduardo de; Soárez, Patrícia Coelho de; Castelo Filho, Adauto; Amed, Abês Mahmed

2014-05-01

It was to assess the quality of life (QOL) of HIV-infected pregnant women using the HIV/AIDS - Targeted Quality of Life (HAT-QoL) questionnaire. A descriptive study of 60 pregnant women attended at the Multidisciplinary Nucleus of Infectious Diseases During Pregnancy (NUPAIG) - UNIFESP/EPM and in the referral network of the Municipal Office of São Paulo, conducted from February 2011 to October 2012. Sociodemographic and clinical variables were collected from 60 HIV-infected pregnant women who answered the HAT-QoL questionnaire, which included 34 questions about quality of life. The average age was 30 years and the average period of HIV infection was 5.7 years. Only 8.3% of patients had a CD4 cell score of ≤200 cells/mm³ and 45% showed undetectable viral load. The average domain scores ranged from 47.5 to 83.7. The domains with the lowest scores were financial concerns and concerns about secrecy. The domains with the highest scores and lower impact on quality of life were concerns about medication and confidence in the professional. In this initial study with 60 pregnant women, we concluded that the HAT-QOL can contribute to the assessment of quality of life in the population of HIV-infected pregnant women in Brazil.

A nanoparticle-based epigenetic modulator for efficient gene modulation

NASA Astrophysics Data System (ADS)

Pongkulapa, Thanapat

Modulation of gene expression through chromatin remodeling involves epigenetic mechanisms, such as histone acetylation. Acetylation is tightly regulated by two classes of enzymes, histone acetyltransferases (HATs) and histone deacetylases (HDACs). Molecules that can regulate these enzymes by altering (activating or inhibiting) their functions have become a valuable tool for understanding cell development and diseases. HAT activators, i.e. N-(4-Chloro-(3-trifluoromethyl)phenyl)-2-ethoxybenzamide (CTB), have shown a therapeutic potential for many diseases, including cancer and neurodegeneration. However, these compounds encounter a solubility and a membrane permeability issue, which restricts their full potential for practical usage, especially for in vivo applications. To address this issue, in this work, we developed a nanoparticle-based HAT activator CTB, named Au-CTB, by incorporating a new CTB analogue onto gold nanoparticles (AuNPs) along with a poly(ethylene glycol) moiety and a nuclear localization signal (NLS) peptide to assist with solubility and membrane permeability. We found that our new CTB analogue and Au-CTB could activate HAT activity. Significantly, an increase in potency to activate HAT activity by Au-CTB proved the effectiveness of using the nanoparticle delivery platform. In addition, the versatility of Au-CTB platform permits the attachment of multiple ligands with tunable ratios on the nanoparticle surface via facile surface functionalization of gold nanoparticles. Due to its high delivery efficiency and versatility, Au-CTB can be a powerful platform for applications in epigenetic regulation of gene expression.

Irradiation with heavy-ion particles changes the cellular distribution of human histone acetyltransferase HAT1.

PubMed

Lebel, Emily A; Boukamp, Petra; Tafrov, Stefan T

2010-06-01

Hat1 was the first histone acetyltransferase identified; however, its biological function is still unclear. In this report, it is shown for the first time that human Hat1 has two isoforms. Isoform a has 418 amino acids (aa) and is localized exclusively in the nuclear matrix of normal human keratinocytes (NHKs). Isoform b has 334 aa and is located in the cytoplasm, the nucleoplasm, attached to the chromatin and to the nuclear matrix. Immunohistochemical analyses revealed that the bulk of Hat1 is confined to the nucleus, with much lesser amounts in the cytoplasm. Cells undergoing mitotic division have an elevated amount of Hat1 compared to those that are non-mitotic. Senescent cells, however, exhibit a higher concentration of Hat1 in the cytoplasm compare to proliferating cells and the amount of Hat1 in the nucleus decreases with the progression of senescence. NHKs exposed to hydrogen peroxide (H(2)O(2)) or to a beam of high mass and energy ion particles displayed bright nuclear staining for Hat1, a phenotype that was not observed in NHKs exposed to gamma-rays. We established that the enhanced nuclear staining for Hat1 in response to these treatments is regulated by the PI3K and the mitogen-activated protein kinase signaling pathways. Our observations clearly implicate Hat1 in the cellular response assuring the survival of the treated cells.

THE CLINICAL, FUNCTIONAL AND BIOMECHANICAL PRESENTATION OF PATIENTS WITH SYMPTOMATIC HIP ABDUCTOR TENDON TEARS.

PubMed

Ebert, Jay R; Retheesh, Theertha; Mutreja, Rinky; Janes, Gregory C

2016-10-01

Hip abductor tendon (HAT) tearing is commonly implicated in greater trochanteric pain syndrome (GTPS), though limited information exists on the disability associated with this condition and specific presentation of these patients. To describe the clinical, functional and biomechanical presentation of patients with symptomatic HAT tears. Secondary purposes were to investigate the association between these clinical and functional measures, and to compare the pain and disability reported by HAT tear patients to those with end-stage hip osteoarthritis (OA). Prospective case series. One hundred forty-nine consecutive patients with symptomatic HAT tears were evaluated using the Harris (HHS) and Oxford (OHS) Hip Scores, SF-12, an additional series of 10 questions more pertinent to those with lateral hip pain, active hip range of motion (ROM), maximal isometric hip abduction strength, six-minute walk capacity and 30-second single limb stance (SLS) test. The presence of a Trendelenburg sign and pelvis-on-femur (POF) angle were determined via 2D video analysis. An age matched comparative sample of patients with end-stage hip OA was recruited for comparison of all patient-reported outcome scores. Independent t-tests investigated group and limb differences, while analysis of variance evaluated pain changes during the functional tests. Pearson's correlation coefficients investigated the correlation between clinical measures in the HAT tear group. No differences existed in patient demographics and patient-reported outcome scores between HAT tear and hip OA cohorts, apart from significantly worse SF-12 mental subscale scores (p = 0.032) in the HAT tear group. Patients with HAT tears demonstrated significantly lower (p < 0.05) hip abduction strength and active ROM in all planes of motion on their affected limb. Pain significantly increased throughout the 30-second SLS test for the HAT tear group, with 57% of HAT tear patients demonstrating a positive Trendelenburg sign. POF angle during the test was not significantly associated with pain. Patients with symptomatic HAT tears demonstrate poor function, and report pain and disability similar to or worse than those with end-stage hip OA. This information better defines and differentiates the presentation of these patients. Level 3 case-controlled study, with matched comparison.

HST/STIS Transmission Spectral Survey: Probing the Atmospheres of HAT-P-1b and WASP-6b

NASA Astrophysics Data System (ADS)

Nikolov, N.; Sing, D. K.; Pont, F.; Burrows, A. S.; Fortney, J. J.; Ballester, G. E.; Evans, T. M.; Huitson, C. M.; Wakeford, H. R.; Wilson, P. A.; A. D., S.; Gibson, N. P.; Henry, G. W.; Knutson, H.; Etangs, A. L. d.; Showman, A. P.; Vidal-Madjar, A.; Zahnle, K.

2014-03-01

We present optical to near-infrared transmission spectra of HAT-P-1b and WASP-6b, part of a Large HST/STIS hot Jupiter transmission spectral survey (P.I. David Sing). The spectra for each target cover the regimes 2900-5700Å and 5240-10270Å, with resolving power of R = 500. The HAT-P-1b data is coupled with a recent HST/WFC3 transit, spanning the wavelength range 1.087-1.687microns (R=130), acquired in spatial scan mode. The WASP-6b data is complemented with Spritzer/IRAC 3.6 and 4.5 micron transit observations, part of a comparative exoplanetology program (P.I. Jean-Michel Desert). The transmission spectrum of HAT-P-1b shows a strong absorption signature shortward of 5500Å, with a strong blueward slope into the near-UV. We detect atmospheric sodium absorption at a 3.3s significance level, but see no evidence for the potassium feature. The red data implies a marginally flat spectrum with a tentative absorption enhancement at wavelength longer than ~8500Å. The combined STIS and WFC3 optical to NIR spectra differ significantly in absolute radius level (4.3+/-1.6 pressure scale heights), implying strong optical absorption in the atmosphere of HAT-P-1b. The optical to nearinfrared difference cannot be explained by stellar activity, as simultaneous stellar activity monitoring of the G0V HAT-P-1b host star and its identical companion show no significant activity that could explain the result. The red transmission spectrum of WASP-6b is flat with tentative detection of sodium and potassium. We compare both spectra with theoretical atmospheric models, which include haze, sodium and an extra optical absorber in the case of HAT-P-1b. We find that both an optical absorber and a super-solar sodium to water abundance ratio might be a scenario explaining the HAT-P-1b observations.

Efficacy of four different irrigation techniques combined with 60 °C 3% sodium hypochlorite and 17% EDTA in smear layer removal.

PubMed

Guo, Xiangjun; Miao, Hui; Li, Lei; Zhang, Shasha; Zhou, Dongyan; Lu, Yan; Wu, Ligeng

2014-09-08

Efforts to improve the efficacy of smear layer removal by applying irrigant activation at the final irrigation or by elevating the temperature of the irrigant have been reported. However, the combination of such activation protocols with 60 °C 3% sodium hypochlorite (NaOCl) has seldom been mentioned. The aim of this study was to compare the efficacy in smear layer removal of four different irrigation techniques combined with 60 °C 3% NaOCl and 17% EDTA. Fifty single-rooted teeth were randomly divided into five groups (n = 10) according to the irrigant agitation protocols used during chemomechanical preparation(Dentsply Maillefer, Ballaigues, Switzerland): a side-vented needle group, a ultrasonic irrigation (UI) group, a NaviTip FX group, an EndoActivator group, and a control group (no agitation). After each instrumentation, the root canals were irrigated with 1 mL of 3% NaOCl at 60 °C for 1 minute, and after the whole instrumentation, the root canals were rinsed with 1 mL of 17% EDTA for 1 minute. Both NaOCl and EDTA were activated with one of the five irrigation protocols. The efficacy of smear layer removal was scored at the apical, middle and coronal thirds. The Data were statistically analyzed using SAS version 9.2 for Windows (rank sum test for a randomised block design and ANOVA). No significant differences among the NaviTip FX group, EndoActivator group and control groups, and each of these groups showed a lower score than that of UI group (P < 0.05). Within each group, all three thirds were ranked in the following order: coronal > middle > apical (P < 0.05). In the coronal third, the NaviTip FX group was better than UI group. In the middle and apical third, the differences were not significant among any of the groups. Even without any activation, the combination of 60 °C 3% NaOCl and 17% EDTA could remove the smear layer effectively, similar to NaviTip FX or EndoActivator, and these three protocols were more effective than UI. However, regardless of different types of irrigation technique applied, complete removal of the smear layer was not achieved, particularly in the apical third.

A Synthetic DNA-Binding Domain Guides Distinct Chromatin-Modifying Small Molecules to Activate an Identical Gene Network.

PubMed

Han, Le; Pandian, Ganesh N; Chandran, Anandhakumar; Sato, Shinsuke; Taniguchi, Junichi; Kashiwazaki, Gengo; Sawatani, Yoshito; Hashiya, Kaori; Bando, Toshikazu; Xu, Yufang; Qian, Xuhong; Sugiyama, Hiroshi

2015-07-20

Synthetic dual-function ligands targeting specific DNA sequences and histone-modifying enzymes were applied to achieve regulatory control over multi-gene networks in living cells. Unlike the broad array of targeting small molecules for histone deacetylases (HDACs), few modulators are known for histone acetyltransferases (HATs), which play a central role in transcriptional control. As a novel chemical approach to induce selective HAT-regulated genes, we conjugated a DNA-binding domain (DBD) "I" to N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-benzamide (CTB), an artificial HAT activator. In vitro enzyme activity assays and microarray studies were used to demonstrate that distinct functional small molecules could be transformed to have identical bioactivity when conjugated with a targeting DBD. This proof-of-concept synthetic strategy validates the switchable functions of HDACs and HATs in gene regulation and provides a molecular basis for developing versatile bioactive ligands. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Beyond Pilgrim Hats and Turkey Hands: Using Thanksgiving to Promote Citizenship and Activism

ERIC Educational Resources Information Center

Christie, Erica M.; Montgomery, Sarah E.

2010-01-01

In many elementary classrooms, Thanksgiving is celebrated by donning homemade Pilgrim hats, grocery bag vests, and colorful construction-paper headdresses, as students join together to reenact the "first" Thanksgiving with a mock feast. Students compose journal entries on the topic, "what I am thankful for." These typical Thanksgiving activities,…

THE CLINICAL, FUNCTIONAL AND BIOMECHANICAL PRESENTATION OF PATIENTS WITH SYMPTOMATIC HIP ABDUCTOR TENDON TEARS

PubMed Central

Retheesh, Theertha; Mutreja, Rinky; Janes, Gregory C.

2016-01-01

Background Hip abductor tendon (HAT) tearing is commonly implicated in greater trochanteric pain syndrome (GTPS), though limited information exists on the disability associated with this condition and specific presentation of these patients. Purpose To describe the clinical, functional and biomechanical presentation of patients with symptomatic HAT tears. Secondary purposes were to investigate the association between these clinical and functional measures, and to compare the pain and disability reported by HAT tear patients to those with end-stage hip osteoarthritis (OA). Study Design Prospective case series. Methods One hundred forty-nine consecutive patients with symptomatic HAT tears were evaluated using the Harris (HHS) and Oxford (OHS) Hip Scores, SF-12, an additional series of 10 questions more pertinent to those with lateral hip pain, active hip range of motion (ROM), maximal isometric hip abduction strength, six-minute walk capacity and 30-second single limb stance (SLS) test. The presence of a Trendelenburg sign and pelvis-on-femur (POF) angle were determined via 2D video analysis. An age matched comparative sample of patients with end-stage hip OA was recruited for comparison of all patient-reported outcome scores. Independent t-tests investigated group and limb differences, while analysis of variance evaluated pain changes during the functional tests. Pearson's correlation coefficients investigated the correlation between clinical measures in the HAT tear group. Results No differences existed in patient demographics and patient-reported outcome scores between HAT tear and hip OA cohorts, apart from significantly worse SF-12 mental subscale scores (p = 0.032) in the HAT tear group. Patients with HAT tears demonstrated significantly lower (p < 0.05) hip abduction strength and active ROM in all planes of motion on their affected limb. Pain significantly increased throughout the 30-second SLS test for the HAT tear group, with 57% of HAT tear patients demonstrating a positive Trendelenburg sign. POF angle during the test was not significantly associated with pain. Conclusion Patients with symptomatic HAT tears demonstrate poor function, and report pain and disability similar to or worse than those with end-stage hip OA. This information better defines and differentiates the presentation of these patients. Level of Evidence Level 3 case-controlled study, with matched comparison PMID:27757285

Histone deacetylase inhibitors, valproic acid and trichostatin-A induce apoptosis and affect acetylation status of p53 in ERG-positive prostate cancer cells

PubMed Central

FORTSON, WENDELL S.; KAYARTHODI, SHUBHALAXMI; FUJIMURA, YASUO; XU, HUALI; MATTHEWS, ROLAND; GRIZZLE, WILLIAM E.; RAO, VEENA N.; BHAT, GANAPATHY K.; REDDY, E. SHYAM P.

2012-01-01

An ETS family member, ETS Related Gene (ERG) is involved in the Ewing family of tumors as well as leukemias. Rearrangement of the ERG gene with the TMPRSS2 gene has been identified in the majority of prostate cancer patients. Additionally, overexpression of ERG is associated with un- favorable prognosis in prostate cancer patients similar to leukemia patients. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate transcription as well as epigenetic status of genes through acetylation of both histones and transcription factors. Deregulation of HATs and HDACs is frequently seen in various cancers, including prostate cancer. Many cellular oncogenes as well as tumor viral proteins are known to target either or both HATs and HDACs. Several studies have demonstrated that there are alterations of HDAC activity in prostate cancer cells. Recently, we found that ERG binds and inhibits HATs, which suggests that ERG is involved in deregulation of protein acetylation. Additionally, it has been shown that ERG is associated with a higher expression of HDACs. In this study, we tested the effect of the HDAC inhibitors valproic acid (VPA) and trichostatin-A (TSA) on ERG-positive prostate cancer cells (VCaP). We found that VPA and TSA induce apoptosis, upregulate p21/Waf1/CIP1, repress TMPRSS2-ERG expression and affect acetylation status of p53 in VCaP cells. These results suggest that HDAC inhibitors might restore HAT activity through two different ways: by inhibiting HDAC activity and by repressing HAT targeting oncoproteins such as ERG. PMID:21519790

Monitoring the elimination of human African trypanosomiasis: Update to 2014

PubMed Central

Priotto, Gerardo; Paone, Massimo; Diarra, Abdoulaye; Grout, Lise; Mattioli, Raffaele C.; Argaw, Daniel

2017-01-01

Background The World Health Organization (WHO) has targeted the elimination of Human African trypanosomiasis (HAT) ‘as a public health problem’ by 2020. The selected indicators of elimination should be monitored every two years, and we provide here a comprehensive update to 2014. The monitoring system is underpinned by the Atlas of HAT. Results With 3,797 reported cases in 2014, the corresponding milestone (5,000 cases) was surpassed, and the 2020 global target of ‘fewer than 2,000 reported cases per year’ seems within reach. The areas where HAT is still a public health problem (i.e. > 1 HAT reported case per 10,000 people per year) have halved in less than a decade, and in 2014 they corresponded to 350 thousand km2. The number and potential coverage of fixed health facilities offering diagnosis and treatment for HAT has expanded, and approximately 1,000 are now operating in 23 endemic countries. The observed trends are supported by sustained surveillance and improved reporting. Discussion HAT elimination appears to be on track. For gambiense HAT, still accounting for the vast majority of reported cases, progress continues unabated in a context of sustained intensity of screening activities. For rhodesiense HAT, a slow-down was observed in the last few years. Looking beyond the 2020 target, innovative tools and approaches will be increasingly needed. Coordination, through the WHO network for HAT elimination, will remain crucial to overcome the foreseeable and unforeseeable challenges that an elimination process will inevitably pose. PMID:28531222

HAT-P-31b,c: A TRANSITING, ECCENTRIC, HOT JUPITER AND A LONG-PERIOD, MASSIVE THIRD BODY

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

Kipping, D. M.; Hartman, J.; Bakos, G. A.

2011-09-15

We report the discovery of HAT-P-31b, a transiting exoplanet orbiting the V = 11.660 dwarf star GSC 2099-00908. HAT-P-31b is the first planet discovered with the Hungarian-made Automated Telescope (HAT) without any follow-up photometry, demonstrating the feasibility of a new mode of operation for the HATNet project. The 2.17 M{sub J} , 1.1 R{sub J} planet has a period of P{sub b} = 5.0054 days and maintains an unusually high eccentricity of e{sub b} = 0.2450 {+-} 0.0045, determined through Keck, FIbr-fed Echelle Spectrograph, and Subaru high-precision radial velocities (RVs). Detailed modeling of the RVs indicates an additional quadratic residualmore » trend in the data detected to very high confidence. We interpret this trend as a long-period outer companion, HAT-P-31c, of minimum mass 3.4 M{sub J} and period {>=}2.8 years. Since current RVs span less than half an orbital period, we are unable to determine the properties of HAT-P-31c to high confidence. However, dynamical simulations of two possible configurations show that orbital stability is to be expected. Further, if HAT-P-31c has non-zero eccentricity, our simulations show that the eccentricity of HAT-P-31b is actively driven by the presence of c, making HAT-P-31 a potentially intriguing dynamical laboratory.« less

Factors influencing passive surveillance for T. b. rhodesiense human african trypanosomiasis in Uganda.

PubMed

Acup, Christine; Bardosh, Kevin Louis; Picozzi, Kim; Waiswa, Charles; Welburn, Susan Christina

2017-01-01

Sleeping sickness or Human African Trypanosomiasis (HAT) is a neglected tropical disease of public health importance across much of Sub-Saharan Africa. In Uganda, chronic T. b. gambiense HAT (gHAT) and acute T. b. rhodesiense HAT (rHAT) occur in two large but discrete geographical foci. Both forms are difficult to diagnose, expensive to treat and ultimately fatal in the absence of treatment. The area affected by zoonotic rHAT has been steadily expanding, placing a high burden on local health systems. HAT is a disease of neglected populations and is notorious for being under-reported. Here we examine the factors that influence passive rHAT surveillance within the district health system in four Ugandan districts into which the disease had recently been introduced, focusing on staff knowledge, infrastructure and data management. A mixed methods study was undertaken between 2011 and 2013 in Dokolo, Kaberamaido, Soroti and Serere districts to explore health facility capacity and clinical service provision, diagnostic capacity, HAT knowledge and case reporting. Structured interviews were undertaken with 86 medical personnel, including clinicians, nurses, midwives and technicians across 65 HC-II and HC-III medical facilities, where the health infrastructure was also directly observed. Eleven semi-structured interviews were undertaken with medical staff in each of the three designated HAT treatment facilities (Dokolo, Lwala and Serere HC-IV) in the area. HAT treatment centre case records, collected between 2009 and 2012, were analyzed. Most medical staff in HC-II and HC-III facilities had been made aware of HAT from radio broadcasts, newspapers and by word of mouth, suggestive of a lack of formal training. Key knowledge as regards the causative agent, clinical signs and that HAT drugs are provided free of charge was lower amongst HC-II than HC-III staff. Many respondents did not know whether HAT was endemic in their district. In rHAT specialist treatment centres, staff were knowledgeable of HAT and were confident in their ability to diagnose and manage cases. Between 2009-2012, 342 people were diagnosed in the area, 54% in the late stage of the disease. Over the period of this study the proportion of rHAT cases identified in early stage fell and by 2012 the majority of cases identified were diagnosed in the late stage. This study illustrates the critical role of the district health system in HAT management. The increasing proportion of cases identified at a late stage in this study indicates a major gap in lower tier levels in patient referral, diagnosis and reporting that urgently needs to be addressed. Integrating HAT diagnosis into national primary healthcare programs and providing training to medical workers at all levels is central to the new 2030 WHO HAT elimination goal. Given the zoonotic nature of rHAT, joined up active surveillance in human and animal populations in Uganda is also needed. The role of the Coordinating Office for Control of Trypanosomiasis in Uganda in implementing a One Health approach will be key to sustainable management of zoonotic HAT. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Measurement of pressure changes during laser-activated irrigant by an erbium, chromium: yttrium, scandium, gallium, garnet laser.

PubMed

Peeters, Harry Huiz; De Moor, Roeland J G

2015-07-01

The use of Er,Cr:YSGG laser to activate irrigants results in the creation of vapour bubbles and shockwaves. The present study evaluated the magnitude of pressure changes in the root canal during laser-activated irrigation. The root canal of a single extracted maxillary canine was enlarged to a size 40/0.06 file. A pressure sensor was inserted apically into the root canal. The tooth was processed as follows. In the EDTA condition, the tooth was irrigated with 17 % EDTA; in the NaOCl condition, the tooth was irrigated with 3 % NaOCl. In all conditions, the irrigants were activated at 0.75 and 1.75 W for 60 s using RFT2 and MZ2 tips; to analyse the effect of tip placement, the tip was activated at the orifice and after inserting the tip 5 mm deeper than the orifice. Data showed no significant difference between irrigation regimens (p > 0.05). There were no significant differences of the pressure between RFT2 and MZ2 tips (p > 0.05). The placement of tips closer to the apex resulted in significantly higher pressure than at the orifice (p < 0.001). The use of 1.75 W power resulted in a significantly higher increase of pressure compared to 0.75 W (p < 0.001), regardless either the type of solutions or tips used. The magnitude of the pressure changes in the root canal at 0.75 W was significantly lower than 1.75 W regardless of either type of tips or solutions used. The closer the insertion of the tip to the apex, the higher the pressure.

Predictors of successful acceptance of home telemanagement in veterans with Multiple Sclerosis.

PubMed

Finkelstein, Joseph; Cha, Eunme; Wood, Jeffrey; Wallin, Mitchell T

2013-01-01

Modern telehealth technologies may be instrumental in overcoming the barriers of optimal care delivery for patients with MS. However, the significant potential of telemedicine approaches in improving MS care has not yet been fully explored. The Multiple Sclerosis Centers of Excellence of the Department of Veterans Affairs (VA) has been actively promoting the use of telemedicine in helping veterans with MS. Particular attention was given to the development of cost-effective care coordination solutions which can be easily delivered directly to each veteran home via internet and accessed via a regular computer or a mobile device. In this article, the design of the MS HAT system is introduced and results of the initial feasibility evaluation are presented. The feasibility of the MS HAT system was assessed by (1) analyzing attitudinal surveys of veterans with MS who used the MS HAT system at home for over a month; (2) identifying factors affecting acceptance of the MS HAT system; (3) reviewing adherence of MS HAT users to self-testing regimen; (4) analyzing veteran feedback on MS HAT functionality using semi-structured qualitative interviews.

Electronic Effects on Room-Temperature, Gas-Phase C-H Bond Activations by Cluster Oxides and Metal Carbides: The Methane Challenge.

PubMed

Schwarz, Helmut; Shaik, Sason; Li, Jilai

2017-12-06

This Perspective discusses a story of one molecule (methane), a few metal-oxide cationic clusters (MOCCs), dopants, metal-carbide cations, oriented-electric fields (OEFs), and a dizzying mechanistic landscape of methane activation! One mechanism is hydrogen atom transfer (HAT), which occurs whenever the MOCC possesses a localized oxyl radical (M-O • ). Whenever the radical is delocalized, e.g., in [MgO] n •+ the HAT barrier increases due to the penalty of radical localization. Adding a dopant (Ga 2 O 3 ) to [MgO] 2 •+ localizes the radical and HAT transpires. Whenever the radical is located on the metal centers as in [Al 2 O 2 ] •+ the mechanism crosses over to proton-coupled electron transfer (PCET), wherein the positive Al center acts as a Lewis acid that coordinates the methane molecule, while one of the bridging oxygen atoms abstracts a proton, and the negatively charged CH 3 moiety relocates to the metal fragment. We provide a diagnostic plot of barriers vs reactants' distortion energies, which allows the chemist to distinguish HAT from PCET. Thus, doping of [MgO] 2 •+ by Al 2 O 3 enables HAT and PCET to compete. Similarly, [ZnO] •+ activates methane by PCET generating many products. Adding a CH 3 CN ligand to form [(CH 3 CN)ZnO] •+ leads to a single HAT product. The CH 3 CN dipole acts as an OEF that switches off PCET. [MC] + cations (M = Au, Cu) act by different mechanisms, dictated by the M + -C bond covalence. For example, Cu + , which bonds the carbon atom mostly electrostatically, performs coupling of C to methane to yield ethylene, in a single almost barrier-free step, with an unprecedented atomic choreography catalyzed by the OEF of Cu + .

An objective and cross-sectional examination of sun-safe behaviours in New South Wales primary schools.

PubMed

Dudley, Dean A; Cotton, Wayne G; Winslade, Matthew J; Wright, Bradley J; Jackson, Kirsten S; Brown, Alexandra M; Rock, Vanessa

2017-01-05

Previous evaluations have supported the link between sun protection policies and improved sun protection behaviours. However these evaluations have relied on self-reported data. A cross-sectional design as part of an ongoing 18-month cluster-controlled trial in primary schools (n = 20) was used. Researchers conducted direct observations to record students' hat use and teachers' use of sun protective measures during recess and lunch. Researchers also recorded the volume of sunscreen consumed in each school. Only 60% of primary school children wear a sun-safe hat during their breaks when observed using objective measures. Weak correlations were observed between the wearing of a sun-safe hat and a school's socio-economic status (r = 0.26). All other independent variables measured had only very weak correlations (r < 0.19) with sun-safe hat wearing behaviour of students. Sunscreen consumption by school students during the school day is negligible. A large percentage of NSW primary schools in this study wear sun-safe hats during the school day but this is well below what has been reported in previous national surveys. Given the finite resources of schools and the correlation, though small, with SES status for these behaviours, it behoves researchers to investigate low-cost solutions to these problems. Further qualitative data will also be needed to inform the enablers and barriers for sun-safe behaviour interventions to be adopted in NSW primary schools.

Human-Autonomy Teaming in a Flight Following Task

NASA Technical Reports Server (NTRS)

Shively, Robert J.

2017-01-01

The NATO HFM-247 Working Group is creating a summary report of the group's activities on human-autonomy teaming. This chapter is a summary of our at NASA Ames work toward developing a framework for human-autonomy teaming (HAT) in aviation. The purpose of this project was to demonstrate and evaluate proposed tenets of HAT. The HAT features were derived from three tenets and were built into an automated recommender system on a ground station. These tenets include bi-directional communication, automation transparency, and operator directed interface. This study focused primarily on interactions with one piece of automation, the Autonomous Constrained Flight Planner (ACFP). The ACFP is designed to support rapid diversion decisions for commercial pilots in off-nominal situations. Much effort has gone into enhancing this tool not only in capability but also in transparency. In this study, participants used the ACFP at a ground station designed to aid dispatchers in a flight following role to reroute aircraft in situations such as inclement weather, system failures and medical emergencies. Participants performed this task both with HAT features enabled and without and provided feedback. We examined subjective and behavioral indicators of HAT collaborations using a proof-of-concept demonstration of HAT tenets. The data collected suggest potential advantages and disadvantages of HAT.

WARM SPITZER OBSERVATIONS OF THREE HOT EXOPLANETS: XO-4b, HAT-P-6b, AND HAT-P-8b

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

Todorov, Kamen O.; Deming, Drake; Knutson, Heather A.

2012-02-10

We analyze Warm Spitzer/Infrared Array Camera observations of the secondary eclipses of three planets, XO-4b, HAT-P-6b, and HAT-P-8b. We measure secondary eclipse amplitudes at 3.6 {mu}m and 4.5 {mu}m for each target. XO-4b exhibits a stronger eclipse depth at 4.5 {mu}m than at 3.6 {mu}m, which is consistent with the presence of a temperature inversion. HAT-P-8b shows a stronger eclipse amplitude at 3.6 {mu}m and is best described by models without a temperature inversion. The eclipse depths of HAT-P-6b can be fitted with models with a small or no temperature inversion. We consider our results in the context of amore » postulated relationship between stellar activity and temperature inversion and a relationship between irradiation level and planet dayside temperature, as discussed by Knutson et al. and Cowan and Agol, respectively. Our results are consistent with these hypotheses, but do not significantly strengthen them. To measure accurate secondary eclipse central phases, we require accurate ephemerides. We obtain primary transit observations and supplement them with publicly available observations to update the orbital ephemerides of the three planets. Based on the secondary eclipse timing, we set upper boundaries for ecos ({omega}) for HAT-P-6b, HAT-P-8b, and XO-4b and find that the values are consistent with circular orbits.« less

Autoacetylation of the MYST Lysine Acetyltransferase MOF Protein*

PubMed Central

Yang, Chao; Wu, Jiang; Sinha, Sarmistha H.; Neveu, John M.; Zheng, Yujun George

2012-01-01

The MYST family of histone acetyltransferases (HATs) plays critical roles in diverse cellular processes, such as the epigenetic regulation of gene expression. Lysine autoacetylation of the MYST HATs has recently received considerable attention. Nonetheless, the mechanism and function of the autoacetylation process are not well defined. To better understand the biochemical mechanism of MYST autoacetylation and the impact of autoacetylation on the cognate histone acetylation, we carried out detailed analyses of males-absent-on-the-first (MOF), a key member of the MYST family. A number of mutant MOF proteins were produced with point mutations at several key residues near the active site of the enzyme. Autoradiography and immunoblotting data showed that mutation of these residues affects the autoacetylation activity and HAT activity of MOF by various degrees demonstrating that MOF activity is highly sensitive to the chemical changes in those residues. We produced MOF protein in the deacetylated form by using a nonspecific lysine deacetylase. Interestingly, both the autoacetylation activity and the histone acetylation activity of the deacetylated MOF were found to be very close to that of wild-type MOF, suggesting that autoacetylation of MOF only marginally modulates the enzymatic activity. Also, we found that the autoacetylation rates of MOF and deacetylated MOF were much slower than the cognate substrate acetylation. Thus, autoacetylation does not seem to contribute to the intrinsic enzymatic activity in a significant manner. These data provide new insights into the mechanism and function of MYST HAT autoacetylation. PMID:22918831

Fe65 is required for Tip60-directed histone H4 acetylation at DNA strand breaks

PubMed Central

Stante, Maria; Minopoli, Giuseppina; Passaro, Fabiana; Raia, Maddalena; Vecchio, Luigi Del; Russo, Tommaso

2009-01-01

Fe65 is a binding partner of the Alzheimer's β-amyloid precursor protein APP. The possible involvement of this protein in the cellular response to DNA damage was suggested by the observation that Fe65 null mice are more sensitive to genotoxic stress than WT counterpart. Fe65 associated with chromatin under basal conditions and its involvement in DNA damage repair requires this association. A known partner of Fe65 is the histone acetyltransferase Tip60. Considering the crucial role of Tip60 in DNA repair, we explored the hypothesis that the phenotype of Fe65 null cells depended on its interaction with Tip60. We demonstrated that Fe65 knockdown impaired recruitment of Tip60-TRRAP complex to DNA double strand breaks and decreased histone H4 acetylation. Accordingly, the efficiency of DNA repair was decreased upon Fe65 suppression. To explore whether APP has a role in this mechanism, we analyzed a Fe65 mutant unable to bind to APP. This mutant failed to rescue the phenotypes of Fe65 null cells; furthermore, APP/APLP2 suppression results in the impairment of recruitment of Tip60-TRRAP complex to DNA double strand breaks, decreased histone H4 acetylation and repair efficiency. On these bases, we propose that Fe65 and its interaction with APP play an important role in the response to DNA damage by assisting the recruitment of Tip60-TRRAP to DNA damage sites. PMID:19282473

Catalytic Reactor For Oxidizing Mercury Vapor

DOEpatents

Helfritch, Dennis J.

1998-07-28

A catalytic reactor (10) for oxidizing elemental mercury contained in flue gas is provided. The catalyst reactor (10) comprises within a flue gas conduit a perforated corona discharge plate (30a, b) having a plurality of through openings (33) and a plurality of projecting corona discharge electrodes (31); a perforated electrode plate (40a, b, c) having a plurality of through openings (43) axially aligned with the through openings (33) of the perforated corona discharge plate (30a, b) displaced from and opposing the tips of the corona discharge electrodes (31); and a catalyst member (60a, b, c, d) overlaying that face of the perforated electrode plate (40a, b, c) opposing the tips of the corona discharge electrodes (31). A uniformly distributed corona discharge plasma (1000) is intermittently generated between the plurality of corona discharge electrode tips (31) and the catalyst member (60a, b, c, d) when a stream of flue gas is passed through the conduit. During those periods when corona discharge (1000) is not being generated, the catalyst molecules of the catalyst member (60a, b, c, d) adsorb mercury vapor contained in the passing flue gas. During those periods when corona discharge (1000) is being generated, ions and active radicals contained in the generated corona discharge plasma (1000) desorb the mercury from the catalyst molecules of the catalyst member (60a, b, c, d), oxidizing the mercury in virtually simultaneous manner. The desorption process regenerates and activates the catalyst member molecules.

Substance use disorder treatment retention and completion: a prospective study of horse-assisted therapy (HAT) for young adults.

PubMed

Kern-Godal, Ann; Arnevik, Espen Ajo; Walderhaug, Espen; Ravndal, Edle

2015-10-14

Keeping substance use disorder patients actively engaged in treatment is a challenge. Horse-assisted therapy (HAT) is increasingly used as a complementary therapy, with claimed motivational and other benefits to physical and psychological health. This naturalistic study aimed to assess HAT's impact on the duration and completion of treatment for young substance users at Oslo University Hospital. Discharge and other data were derived from the Youth Addiction Treatment Evaluation Project (YATEP) database for patients (n = 108) admitted during an 18-month period. An intention-to-treat design, and univariate and multivariate analyses were used to compare those receiving treatment as usual (n = 43) with those who received treatment as usual plus HAT (n = 65). Despite a lack of randomization, the baseline characteristics of the two groups were similar. However, more HAT participants completed treatment (56.9 vs 14 %, p < 0.001), remained in treatment for longer (mean 141 vs 70 days, p < 0.001) and had a significantly higher chance of completing their treatment than those not given the HAT program. Excluding time in treatment, and after controlling for the potentially confounding influence of age, sex, education, number and severity of substances used, psychological distress and number of temporary exits, the adjusted odds ratio for treatment completion was 8.4 in the HAT group compared with those not participating in HAT (95 % CI 2.7-26.4, p < 0.001). The study found a statistically significant association between HAT participation and time in treatment, and between HAT participation and completion of treatment. This association does not infer causality. However, it adds supporting evidence for the development of an innovative therapy, and warrants investment in further research in relation to its inclusion in substance use disorder treatment.

Precise Orientation of a Single C60 Molecule on the Tip of a Scanning Probe Microscope

NASA Astrophysics Data System (ADS)

Chiutu, C.; Sweetman, A. M.; Lakin, A. J.; Stannard, A.; Jarvis, S.; Kantorovich, L.; Dunn, J. L.; Moriarty, P.

2012-06-01

We show that the precise orientation of a C60 molecule which terminates the tip of a scanning probe microscope can be determined with atomic precision from submolecular contrast images of the fullerene cage. A comparison of experimental scanning tunneling microscopy data with images simulated using computationally inexpensive Hückel theory provides a robust method of identifying molecular rotation and tilt at the end of the probe microscope tip. Noncontact atomic force microscopy resolves the atoms of the C60 cage closest to the surface for a range of molecular orientations at tip-sample separations where the molecule-substrate interaction potential is weakly attractive. Measurements of the C60C60 pair potential acquired using a fullerene-terminated tip are in excellent agreement with theoretical predictions based on a pairwise summation of the van der Waals interactions between C atoms in each cage, i.e., the Girifalco potential [L. Girifalco, J. Phys. Chem. 95, 5370 (1991)JPCHAX0022-365410.1021/j100167a002].

[Hypoglycaemia in patients with type 1 and type 2 diabetes mellitus on insulin therapy. Results of the global HAT study in Argentina].

PubMed

Costa Gil, José E; Linari, María A; Pugnaloni, Natalia; Zambon, Fabio G; Pérez Manghi, Federico; Rezzónico, Mariana

2017-01-01

We describe the results of the HAT study in 433 Argentinean patients with type 1 diabetes (T1D) and 823 with type 2 diabetes (T2D). HAT was an international non-interventional study assessing severe and non-severe hypoglycaemia in patients with T1D and T2D under insulin treatment through a two-part self-assessment questionnaire (retrospective and prospective). The annual incidence of at least one hypoglycaemic episode was 46 episode/patient/year in T1D and 14.2 in T2D (retrospective), 96.5 and 24.6 episode/patient/year in T1D and T2D, respectively (prospective). Hypoglycaemia affected quality of life (on a scale of 0-10 for fear of hypoglycaemia: 60% in T1D and 37.6% in T2D scored 5 to 10), daily life, occupational or academic performance (2.1% with T1D and 3.2% with T2D did not attend to their work after hypoglycaemia), and induced an increased use of health resources (T1D: 66.1% increased glucose monitoring, 60.5% food intake, 51% consultations, 3.5% hospital admissions; 60.5% reduced insulin and 20.9% exercises; T2D increased 46.2% glucose monitoring, 43.8% consultations, 38.6% food intake, 24.1% reduced and 13.9% skipped the insulin dose and 14.3% suspended exercises). Greater numbers of episodes were recorded in the prospective period. An instrument to assess hypoglycaemia in clinical practice and strategies to reduce their risk are required. It is also important to ask about the episodes and reinforce the education of patients and close relatives on hypoglycaemia prevention and treatment.

3.6 and 4.5 μm Spitzer Phase Curves of the Highly Irradiated Hot Jupiters WASP-19b and HAT-P-7b

NASA Astrophysics Data System (ADS)

Wong, Ian; Knutson, Heather A.; Kataria, Tiffany; Lewis, Nikole K.; Burrows, Adam; Fortney, Jonathan J.; Schwartz, Joel; Shporer, Avi; Agol, Eric; Cowan, Nicolas B.; Deming, Drake; Désert, Jean-Michel; Fulton, Benjamin J.; Howard, Andrew W.; Langton, Jonathan; Laughlin, Gregory; Showman, Adam P.; Todorov, Kamen

2016-06-01

We analyze full-orbit phase curve observations of the transiting hot Jupiters WASP-19b and HAT-P-7b at 3.6 and 4.5 μm, obtained using the Spitzer Space Telescope. For WASP-19b, we measure secondary eclipse depths of 0.485%+/- 0.024% and 0.584%+/- 0.029% at 3.6 and 4.5 μm, which are consistent with a single blackbody with effective temperature 2372 ± 60 K. The measured 3.6 and 4.5 μm secondary eclipse depths for HAT-P-7b are 0.156%+/- 0.009% and 0.190%+/- 0.006%, which are well described by a single blackbody with effective temperature 2667 ± 57 K. Comparing the phase curves to the predictions of one-dimensional and three-dimensional atmospheric models, we find that WASP-19b’s dayside emission is consistent with a model atmosphere with no dayside thermal inversion and moderately efficient day-night circulation. We also detect an eastward-shifted hotspot, which suggests the presence of a superrotating equatorial jet. In contrast, HAT-P-7b’s dayside emission suggests a dayside thermal inversion and relatively inefficient day-night circulation; no hotspot shift is detected. For both planets, these same models do not agree with the measured nightside emission. The discrepancies in the model-data comparisons for WASP-19b might be explained by high-altitude silicate clouds on the nightside and/or high atmospheric metallicity, while the very low 3.6 μm nightside planetary brightness for HAT-P-7b may be indicative of an enhanced global C/O ratio. We compute Bond albedos of 0.38 ± 0.06 and 0 (\\lt 0.08 at 1σ ) for WASP-19b and HAT-P-7b, respectively. In the context of other planets with thermal phase curve measurements, we show that WASP-19b and HAT-P-7b fit the general trend of decreasing day-night heat recirculation with increasing irradiation.

Hats Off to Kids! Wisconsin Summer Library Program Manual, 1984. Bulletin No. 4225.

ERIC Educational Resources Information Center

Kennelly, Patti, Ed.

This guide offers suggestions for in-library, community, and school program promotion and activities, including specific ideas for the 1984 theme, "Hats Off to Children." It is intended for libraries participating in the Wisconsin Summer Library Program, which promotes summer use of the library by children, familiarizes them with public…

Syndromic Algorithms for Detection of Gambiense Human African Trypanosomiasis in South Sudan

PubMed Central

Palmer, Jennifer J.; Surur, Elizeous I.; Goch, Garang W.; Mayen, Mangar A.; Lindner, Andreas K.; Pittet, Anne; Kasparian, Serena; Checchi, Francesco; Whitty, Christopher J. M.

2013-01-01

Background Active screening by mobile teams is considered the best method for detecting human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense but the current funding context in many post-conflict countries limits this approach. As an alternative, non-specialist health care workers (HCWs) in peripheral health facilities could be trained to identify potential cases who need testing based on their symptoms. We explored the predictive value of syndromic referral algorithms to identify symptomatic cases of HAT among a treatment-seeking population in Nimule, South Sudan. Methodology/Principal Findings Symptom data from 462 patients (27 cases) presenting for a HAT test via passive screening over a 7 month period were collected to construct and evaluate over 14,000 four item syndromic algorithms considered simple enough to be used by peripheral HCWs. For comparison, algorithms developed in other settings were also tested on our data, and a panel of expert HAT clinicians were asked to make referral decisions based on the symptom dataset. The best performing algorithms consisted of three core symptoms (sleep problems, neurological problems and weight loss), with or without a history of oedema, cervical adenopathy or proximity to livestock. They had a sensitivity of 88.9–92.6%, a negative predictive value of up to 98.8% and a positive predictive value in this context of 8.4–8.7%. In terms of sensitivity, these out-performed more complex algorithms identified in other studies, as well as the expert panel. The best-performing algorithm is predicted to identify about 9/10 treatment-seeking HAT cases, though only 1/10 patients referred would test positive. Conclusions/Significance In the absence of regular active screening, improving referrals of HAT patients through other means is essential. Systematic use of syndromic algorithms by peripheral HCWs has the potential to increase case detection and would increase their participation in HAT programmes. The algorithms proposed here, though promising, should be validated elsewhere. PMID:23350005

Actigraphy in Human African Trypanosomiasis as a Tool for Objective Clinical Evaluation and Monitoring: A Pilot Study

PubMed Central

Njamnshi, Alfred K.; Seke Etet, Paul F.; Perrig, Stephen; Acho, Alphonse; Funsah, Julius Y.; Mumba, Dieudonné; Muyembe, Jean-Jacques; Kristensson, Krister; Bentivoglio, Marina

2012-01-01

Background Human African trypanosomiasis (HAT) or sleeping sickness leads to a complex neuropsychiatric syndrome with characteristic sleep alterations. Current division into a first, hemolymphatic stage and second, meningoencephalitic stage is primarily based on the detection of white blood cells and/or trypanosomes in the cerebrospinal fluid. The validity of this criterion is, however, debated, and novel laboratory biomarkers are under study. Objective clinical HAT evaluation and monitoring is therefore needed. Polysomnography has effectively documented sleep-wake disturbances during HAT, but could be difficult to apply as routine technology in field work. The non-invasive, cost-effective technique of actigraphy has been widely validated as a tool for the ambulatory evaluation of sleep disturbances. In this pilot study, actigraphy was applied to the clinical assessment of HAT patients. Methods/Principal Findings Actigraphy was recorded in patients infected by Trypanosoma brucei gambiense, and age- and sex-matched control subjects. Simultaneous nocturnal polysomnography was also performed in the patients. Nine patients, including one child, were analyzed at admission and two of them also during specific treatment. Parameters, analyzed with user-friendly software, included sleep time evaluated from rest-activity signals, rest-activity rhythm waveform and characteristics. The findings showed sleep-wake alterations of various degrees of severity, which in some patients did not parallel white blood cell counts in the cerebrospinal fluid. Actigraphic recording also showed improvement of the analyzed parameters after treatment initiation. Nocturnal polysomnography showed alterations of sleep time closely corresponding to those derived from actigraphy. Conclusions/Significance The data indicate that actigraphy can be an interesting tool for HAT evaluation, providing valuable clinical information through simple technology, well suited also for long-term follow-up. Actigraphy could therefore objectively contribute to the clinical assessment of HAT patients. This method could be incorporated into a clinical scoring system adapted to HAT to be used in the evaluation of novel treatments and laboratory biomarkers. PMID:22348168

Pneumocystis jirovecii Rtt109, a Novel Drug Target for Pneumocystis Pneumonia in Immunosuppressed Humans

PubMed Central

Dahlin, Jayme L.; Kottom, Theodore; Han, Junhong; Zhou, Hui; Walters, Michael A.; Zhang, Zhiguo

2014-01-01

Pneumocystis pneumonia (PcP) is a significant cause of morbidity and mortality in immunocompromised patients. In humans, PcP is caused by the opportunistic fungal species Pneumocystis jirovecii. Progress in Pneumocystis research has been hampered by a lack of viable in vitro culture methods, which limits laboratory access to human-derived organisms for drug testing. Consequently, most basic drug discovery research for P. jirovecii is performed using related surrogate organisms such as Pneumocystis carinii, which is derived from immunosuppressed rodents. While these studies provide useful insights, important questions arise about interspecies variations and the relative utility of identified anti-Pneumocystis agents against human P. jirovecii. Our recent work has identified the histone acetyltransferase (HAT) Rtt109 in P. carinii (i.e., PcRtt109) as a potential therapeutic target for PcP, since Rtt109 HATs are widely conserved in fungi but are absent in humans. To further address the potential utility of this target in human disease, we now demonstrate the presence of a functional Rtt109 orthologue in the clinically relevant fungal pathogen P. jirovecii (i.e., PjRtt109). In a fashion similar to that of Pcrtt109, Pjrtt109 restores H3K56 acetylation and genotoxic resistance in rtt109-null yeast. Recombinant PjRtt109 is an active HAT in vitro, with activity comparable to that of PcRtt109 and yeast Rtt109. PjRtt109 HAT activity is also enhanced by the histone chaperone Asf1 in vitro. PjRtt109 and PcRtt109 showed similar low micromolar sensitivities to two reported small-molecule HAT inhibitors in vitro. Together, these results demonstrate that PjRtt109 is a functional Rtt109 HAT, and they support the development of anti-Pneumocystis agents directed at Rtt109-catalyzed histone acetylation as a novel therapeutic target for human PcP. PMID:24733475

Pneumocystis jirovecii Rtt109, a novel drug target for Pneumocystis pneumonia in immunosuppressed humans.

PubMed

Dahlin, Jayme L; Kottom, Theodore; Han, Junhong; Zhou, Hui; Walters, Michael A; Zhang, Zhiguo; Limper, Andrew H

2014-07-01

Pneumocystis pneumonia (PcP) is a significant cause of morbidity and mortality in immunocompromised patients. In humans, PcP is caused by the opportunistic fungal species Pneumocystis jirovecii. Progress in Pneumocystis research has been hampered by a lack of viable in vitro culture methods, which limits laboratory access to human-derived organisms for drug testing. Consequently, most basic drug discovery research for P. jirovecii is performed using related surrogate organisms such as Pneumocystis carinii, which is derived from immunosuppressed rodents. While these studies provide useful insights, important questions arise about interspecies variations and the relative utility of identified anti-Pneumocystis agents against human P. jirovecii. Our recent work has identified the histone acetyltransferase (HAT) Rtt109 in P. carinii (i.e., PcRtt109) as a potential therapeutic target for PcP, since Rtt109 HATs are widely conserved in fungi but are absent in humans. To further address the potential utility of this target in human disease, we now demonstrate the presence of a functional Rtt109 orthologue in the clinically relevant fungal pathogen P. jirovecii (i.e., PjRtt109). In a fashion similar to that of Pcrtt109, Pjrtt109 restores H3K56 acetylation and genotoxic resistance in rtt109-null yeast. Recombinant PjRtt109 is an active HAT in vitro, with activity comparable to that of PcRtt109 and yeast Rtt109. PjRtt109 HAT activity is also enhanced by the histone chaperone Asf1 in vitro. PjRtt109 and PcRtt109 showed similar low micromolar sensitivities to two reported small-molecule HAT inhibitors in vitro. Together, these results demonstrate that PjRtt109 is a functional Rtt109 HAT, and they support the development of anti-Pneumocystis agents directed at Rtt109-catalyzed histone acetylation as a novel therapeutic target for human PcP. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

VizieR Online Data Catalog: Photometry for HATS-31 through HATS-35 (de Val-Borro+, 2016)

NASA Astrophysics Data System (ADS)

de Val-Borro, M.; Bakos, G. A.; Brahm, R.; Hartman, J. D.; Espinoza, N.; Penev, K.; Ciceri, S.; Jordan, A.; Bhatti, W.; Csubry, Z.; Bayliss, D.; Bento, J.; Zhou, G.; Rabus, M.; Mancini, L.; Henning, T.; Schmidt, B.; Tan, T. G.; Tinney, C. G.; Wright, D. J.; Kedziora-Chudczer, L.; Bailey, J.; Suc, V.; Durkan, S.; Lazar, J.; Papp, I.; Sari, P.

2017-05-01

The HATSouth survey is a global network of homogeneous, completely automated wide-field telescopes located at three sites in the Southern Hemisphere: HS-1 and -2 are located at Las Campanas Observatory (LCO) in Chile, HS-3 and -4 are located at the High Energy Stereoscopic Survey (H.E.S.S.) site in Namibia, and HS-5 and -6 are located at Siding Spring Observatory (SSO) in Australia. Observations are performed using a Sloan-r filter with four-minute exposures. The HATSouth network was commissioned in 2009 and since then has proved to be a robust system for the monitoring of time-variable phenomena. Each HATSouth unit consists of four Takahashi E180 astrographs with an aperture of 18cm and an f/2.8 focal ratio on a common mount, equipped with Apogee 4096*4096 U16M ALTA cameras. HATS-31 was observed with the HS-1.4/G565 on 2012 Dec-2013 Jun, with the HS-3.4/G565 on 2012 Dec-2013 Jul, and with the HS-5.4/G565 on 2012 Dec-2013 Jul. HATS-32 was observed with the HS-2.3/G586 on 2010 Aug-2011 Nov, with the HS-4.3/G586 on 2010 Aug-2011 Nov, and with the HS-6.3/G586 on 2010 Aug-2011 Nov. HATS-33 was observed with the HS-1.4/G747 on 2013 Mar-2013 Oct, with the HS-2.4/G747 on 2013 Sep-2013 Oct, with the HS-3.4/G747 on 2013 Apr-2013 Nov, with the HS-4.4/G747 on 2013 Sep-2013 Nov, with the HS-5.4/G747 on 2013 Mar-2013 Nov, and with the HS-6.4/G747 on 2013 Sep-2013 Nov. HATS-34 was observed with the HS-2.4/G754 on 2012 Sep-2012 Dec, with the HS-4.4/G754 on 2012 Sep-2013 Jan, and with the HS-6.4/G754 on 2012 Sep-2012 Dec. HATS-35 was observed with the HS-2.4/G778 on 2011 May-2012 Nov, with the HS-4.4/G778 on 2011 Jul-2012 Nov, with the HS-6.4/G778 on 2011 Apr-2012 Oct. The egress of HATS-31b was observed on 2015 February 28 and 2015 April 02 with the Las Cumbres Observatory Global Telescope (LCOGT) 1m+Cerro Tololo Inter-American Observatory (CTIO) telescope network and the Swope 1m telescopes, respectively. Additionally, an almost full transit of HATS-31b was observed with LCOGT 1m+South African Astronomical Observatory/Santa Barbara Instrument Group (LCOGT 1 m+SAAO/SBIG) on 2015 March 6. Another three partial transits of HATS-32b were observed with the Perth Exoplanet Survey Telescope (PEST) 0.3m, DK 1.54m, and the Swope 1m telescopes on 2014 Jul 09, 2014 Nov 04, and 2015 May 28, respectively. The egress of HATS-33 was measured with the 1m LCOGT at CTIO on 2015 May 20. Both ingress and egress of HATS-34b were observed by the PEST 0.3m on 2014 Oct 26 and by the Danish Faint Object Spectrograph and Camera (DFOSC) on the DK 1.54m telescope on 2014 Nov 03. HATS-34b was also observed using Anglo-Australian Telescope 3.9m/InfraRed Imaging Spectrograph 2 (AAT 3.9m/IRIS2) on 2015 Sep 25 but This light curve covers a predicted secondary eclipse event, it is not included in the analysis carried out to determine the system parameters for HATS-34 (however, it is included in the analysis carried out to exclude blend scenarios). Finally, five partial transit events of HATS-35b were obtained between 2015 June 12 and 2015 July 24 using the LCOGT network at CTIO on 2015 Jun 12, 2015 Jul 15 and 2015 Jul 24, at SAAO on 2015 Jul 14, and at SSO on 2015 Jul 18. Reconnaissance spectroscopy was carried out using the Wide Field Spectrograph (WiFeS) on the Australian National University (ANU) 2.3m telescope at SSO on 2014 Dec 30-31 and 2015 Jan 1 for HATS-31, on 2014 Jun 3-5 and 2014 Jun 4 for HATS-32, on 2014 Dec-2015 Mar and 2015 Mar 4 for HATS-33, on 2014 Oct 4 and 2014 Oct 4-10 for HATS-34, and on 2014 Oct 5 and 2014 Oct 11 for HATS-35. Medium-resolution WiFeS observations spectral resolution was R=λ/Δλ=7000. We obtained 11 spectra using CYCLOPS2+University College London Echelle Spectrograph (CYCLOPS2+UCLES; Δλ/λ/1000=70) at the 3.9m AAT on 2015 May 7-13 for HATS-33, 11 spectra using the High-Accuracy Radial velocity Planetary Searcher (HARPS; Δλ/λ/1000=115) on the European Southern Observatory (ESO) 3.6m telescope (6 spectra on 2015 Feb 14-19 for HATS-31; 3 spectra on 2015 Apr 6-8 for HATS-33; 2 spectra on 2015 Apr 7-8 for HATS-35), 10 spectra using CORALIE (Δλ/λ/1000=60) on the Euler 1.2m telescope (5 spectra on 2015 Mar-Jun for HATS-33; 5 spectra on 2014 Nov-2015 Jun for HATS-35), and 32 spectra with Fiber-fed Extended Range Optical Spectrograph (FEROS; Δλ/λ/1000=48) at the Max Planck Gesellschaft (MPG) 2.2m telescope (8 spectra on 2014 Jul-2015 Jun for HATS-32; 4 spectra on 2015 May-Jul for HATS-33; 10 spectra on 2015 Jun-Jul for HATS-34; 10 spectra on 2015 Jun-Jul for HATS-35). The photometric data are available in Table3. The high-resolution spectroscopic data are provided in Table8. (3 data files).

Automatic Semantic Activation of Embedded Words: Is There a ''Hat'' in ''That''

ERIC Educational Resources Information Center

Bowers, J.S.; Davis, C.J.; Hanley, D.A.

2005-01-01

Participants semantically categorized target words that contain subsets (Experiment 1; e.g., target=hatch, subset=hat) or that are parts of supersets (Experiment 2; e.g., target=bee, superset=beer). In both experiments, the targets were categorized in a congruent condition (in which the subset-superset was associated with the same response, e.g.,…

Children's Conception of Thermal Conduction--Or the Story of a Woollen Hat.

ERIC Educational Resources Information Center

Newell, Andrew; Ross, Keith

1996-01-01

Reports on discussions with a year 10-group, following their first lesson on heat energy transfer, that revealed they still had not realized that insulation acted as a barrier; instead they saw it as an active warming agent. Describes a teaching method based on a woollen hat that challenges their naive ideas. (Author/JRH)

Acceptability of a theory-based sedentary behaviour reduction intervention for older adults ('On Your Feet to Earn Your Seat').

PubMed

Matei, Raluca; Thuné-Boyle, Ingela; Hamer, Mark; Iliffe, Steve; Fox, Kenneth R; Jefferis, Barbara J; Gardner, Benjamin

2015-07-02

Adults aged 60 years and over spend most time sedentary and are the least physically active of all age groups. This early-phase study explored acceptability of a theory-based intervention to reduce sitting time and increase activity in older adults, as part of the intervention development process. An 8-week uncontrolled trial was run among two independent samples of UK adults aged 60-75 years. Sample 1, recruited from sheltered housing on the assumption that they were sedentary and insufficiently active, participated between December 2013 and March 2014. Sample 2, recruited through community and faith centres and a newsletter, on the basis of self-reported inactivity (<150 weekly minutes of moderate-to-vigorous activity) and sedentary behaviour (≥ 6 h mean daily sitting), participated between March and August 2014. Participants received a booklet offering 16 tips for displacing sitting with light-intensity activity and forming activity habits, and self-monitoring 'tick-sheets'. At baseline, 4-week, and 8-week follow-ups, quantitative measures were taken of physical activity, sedentary behaviour, and habit. At 8 weeks, tick-sheets were collected and a semi-structured interview conducted. Acceptability was assessed for each sample separately, through attrition and adherence to tips, ANOVAs for behaviour and habit changes, and, for both samples combined, thematic analysis of interviews. In Sample 1, 12 of 16 intervention recipients completed the study (25% attrition), mean adherence was 40% (per-tip range: 15-61%), and there were no clear patterns of changes in sedentary or physical activity behaviour or habit. In Sample 2, 23 of 27 intervention recipients completed (15% attrition), and mean adherence was 58% (per-tip range: 39-82%). Sample 2 decreased mean sitting time and sitting habit, and increased walking, moderate activity, and activity habit. Qualitative data indicated that both samples viewed the intervention positively, found the tips easy to follow, and reported health and wellbeing gains. Low attrition, moderate adherence, and favourability in both samples, and positive changes in Sample 2, indicate the intervention was acceptable. Higher attrition, lower adherence, and no apparent behavioural impact among Sample 1 could perhaps be attributable to seasonal influences. The intervention has been refined to address emergent acceptability problems. An exploratory controlled trial is underway.

Sensitivity and specificity of HAT Sero-K-SeT, a rapid diagnostic test for serodiagnosis of sleeping sickness caused by Trypanosoma brucei gambiense: a case-control study.

PubMed

Büscher, Philippe; Mertens, Pascal; Leclipteux, Thierry; Gilleman, Quentin; Jacquet, Diane; Mumba-Ngoyi, Dieudonné; Pyana, Patient Pati; Boelaert, Marleen; Lejon, Veerle

2014-06-01

Human African trypanosomiasis (HAT) is a life-threatening infection affecting rural populations in sub-Saharan Africa. Large-scale population screening by antibody detection with the Card Agglutination Test for Trypanosomiasis (CATT)/Trypanosoma brucei (T b) gambiense helped reduce the number of reported cases of gambiense HAT to fewer than 10 000 in 2011. Because low case numbers lead to decreased cost-effectiveness of such active screening, we aimed to assess diagnostic accuracy of a rapid serodiagnostic test (HAT Sero-K-SeT) applicable in primary health-care centres. In our case-control study, we assessed participants older than 11 years who presented for HAT Sero-K-SeT and CATT/T b gambiense at primary care centres or to mobile teams (and existing patients with confirmed disease status at these centres) in Bandundu Province, DR Congo. We defined cases as patients with trypanosomes that had been identified in lymph node aspirate, blood, or cerebrospinal fluid. During screening, we recruited controls without previous history of HAT or detectable trypanosomes in blood or lymph who resided in the same area as the cases. We assessed diagnostic accuracy of three antibody detection tests for gambiense HAT: HAT Sero-K-SeT and CATT/T b gambiense (done with venous blood at the primary care centres) and immune trypanolysis (done with plasma at the Institute of Tropical Medicine, Antwerp, Belgium). Between June 6, 2012, and Feb 25, 2013, we included 134 cases and 356 controls. HAT Sero-K-SeT had a sensitivity of 0·985 (132 true positives, 95% CI 0·947-0·996) and a specificity of 0·986 (351 true negatives, 0·968-0·994), which did not differ significantly from CATT/T b gambiense (sensitivity 95% CI 0·955, 95% CI 0·906-0·979 [128 true positives] and specificity 0·972, 0·949-0·985 [346 true negatives]) or immune trypanolysis (sensitivity 0·985, 0·947-0·996 [132 true positives] and specificity 0·980, 0·960-0·990 [349 true negatives]). The diagnostic accuracy of HAT Sero-K-SeT is adequate for T b gambiense antibody detection in local health centres and could be used for active screening whenever a cold chain and electricity supply are unavailable and CATT/T b gambiense cannot be done. Copyright © 2014 Büscher et al. Open Access article distributed under the terms of CC BY-NC-ND. Published by .. All rights reserved.

Loss of GCN5 leads to increased neuronal apoptosis by upregulating E2F1- and Egr-1-dependent BH3-only protein Bim.

PubMed

Wu, Yanna; Ma, Shanshan; Xia, Yong; Lu, Yangpeng; Xiao, Shiyin; Cao, Yali; Zhuang, Sidian; Tan, Xiangpeng; Fu, Qiang; Xie, Longchang; Li, Zhiming; Yuan, Zhongmin

2017-01-26

Cellular acetylation homeostasis is a kinetic balance precisely controlled by histone acetyl-transferase (HAT) and histone deacetylase (HDAC) activities. The loss of the counterbalancing function of basal HAT activity alters the precious HAT:HDAC balance towards enhanced histone deacetylation, resulting in a loss of acetylation homeostasis, which is closely associated with neuronal apoptosis. However, the critical HAT member whose activity loss contributes to neuronal apoptosis remains to be identified. In this study, we found that inactivation of GCN5 by either pharmacological inhibitors, such as CPTH2 and MB-3, or by inactivation with siRNAs leads to a typical apoptosis in cultured cerebellar granule neurons. Mechanistically, the BH3-only protein Bim is transcriptionally upregulated by activated Egr-1 and E2F1 and mediates apoptosis following GCN5 inhibition. Furthermore, in the activity withdrawal- or glutamate-evoked neuronal apoptosis models, GCN5 loses its activity, in contrast to Bim induction. Adenovirus-mediated overexpression of GCN5 suppresses Bim induction and apoptosis. Interestingly, the loss of GCN5 activity and the induction of Egr-1, E2F1 and Bim are involved in the early brain injury (EBI) following subarachnoid haemorrhage (SAH) in rats. HDAC inhibition not only significantly rescues Bim expression and apoptosis induced by either potassium deprivation or GCN5 inactivation but also ameliorates these events and EBI in SAH rats. Taken together, our results highlight a new mechanism by which the loss of GCN5 activity promotes neuronal apoptosis through the transcriptional upregulation of Bim, which is probably a critical event in triggering neuronal death when cellular acetylation homeostasis is impaired.

Towards understanding the presence/absence of Human African Trypanosomosis in a focus of Côte d'Ivoire: a spatial analysis of the pathogenic system

PubMed Central

Courtin, Fabrice; Jamonneau, Vincent; Oké, Emmanuel; Coulibaly, Bamoro; Oswald, Yohan; Dupont, Sophie; Cuny, Gérard; Doumenge, Jean-Pierre; Solano, Philippe

2005-01-01

Background This study aimed at identifying factors influencing the development of Human African Trypanosomosis (HAT, or sleeping sickness) in the focus of Bonon, located in the mesophile forest of Côte d'Ivoire. A previous study mapping the main daytime activity sites of 96 patients revealed an important disparity between the area south of the town- where all the patients lived- and the area north of the town, apparently free of disease. In order to explain this disparity, we carried out a spatial analysis of the key components of the pathogenic system, i.e. the human host, the tsetse vector and the trypanosomes in their environment using a geographic information system (GIS). Results This approach at the scale of a HAT focus enabled us to identify spatial patterns which linked to the transmission and the dissemination of this disease. The history of human settlement (with the rural northern area exploited much earlier than the southern one) appears to be a major factor which determines the land use pattern, which itself may account for differences found in vector densities (tsetse were found six times more abundant in the southern rural area than in the northern). Vector density, according to the human and environmental context in which it is found (here an intense mobility between the town of Bonon and the rural areas), may explain the observed spatial differences in HAT prevalence. Conclusion This work demonstrates the role of GIS analyses of key components of the pathogenic system in providing a better understanding of transmission and dissemination of HAT. Moreover, following the identification of the most active transmission areas, and of an area unfavourable to HAT transmission, this study more precisely delineates the boundaries of the Bonon focus. As a follow-up, targeted tsetse control activities starting north of Bonon (with few chances of reinvasion due to very low densities) going south, and additional medical surveys in the south will be proposed to the Ivoirian HAT control program to enhance the control of the disease in this focus. This work also shows the evolution of HAT regarding time and environment, and the methodology used may be able to predict possible sleeping sickness development/extinction in areas with similar history and space organization. PMID:16269078

Pliant Micro Membrane-Wing Tip Vorticity Estimation Using Strain Sensitive Active Materials

DTIC Science & Technology

2012-02-01

AFOSR/ RSA Flow Interactions & Control, Program Manager Air Force Office of Scientific Research 875 N Randolph St, Suite 325, Room 3112 Arlington, VA...678 363< -67< 363< 386- 765; 768 ; 36ɟ 768 < 36ɡ 3-65 :639 36ɝ 56ɜ 36ɝ 56ɜ 3463 :63: 76-< 36:4 7673 36:4 3865 :63< 465< -649 4639 -64; 3-65 ឱ...36-7 -698 36-9 3865 7633 7689 36<- 768 : 36ɟ 3-65 :65; 36ɜ 56ɠ 36<: 56ɠ 396< :635 767- 36:: 7679 36:; 3865 :637 46-5 -6:5 46-4 -6:- 3-63  -69

Changing landscapes, changing practice: negotiating access to sleeping sickness services in a post-conflict society.

PubMed

Palmer, Jennifer J; Kelly, Ann H; Surur, Elizeous I; Checchi, Francesco; Jones, Caroline

2014-11-01

For several decades, control programmes for human African trypanosomiasis (HAT, or sleeping sickness) in South Sudan have been delivered almost entirely as humanitarian interventions: large, well-organised, externally-funded but short-term programmes with a strategic focus on active screening. When attempts to hand over these programmes to local partners fail, resident populations must actively seek and negotiate access to tests at hospitals via passive screening. However, little is known about the social impact of such humanitarian interventions or the consequences of withdrawal on access to and utilisation of remaining services by local populations. Based on qualitative and quantitative fieldwork in Nimule, South Sudan (2008-2010), where passive screening necessarily became the predominant strategy, this paper investigates the reasons why, among two ethnic groups (Madi returnees and Dinka displaced populations), service uptake was so much higher among the latter. HAT tests were the only form of clinical care for which displaced Dinka populations could self-refer; access to all other services was negotiated through indigenous area workers. Because of the long history of conflict, these encounters were often morally and politically fraught. An open-door policy to screening supported Dinka people to 'try' HAT tests in the normal course of treatment-seeking, thereby empowering them to use HAT services more actively. This paper argues that in a context like South Sudan, where HAT control increasingly depends upon patient-led approaches to case-detection, it is imperative to understand the cultural values and political histories associated with the practice of testing and how medical humanitarian programmes shape this landscape of care, even after they have been scaled down. Copyright © 2014 Elsevier Ltd. All rights reserved.

Validation of mercury tip-switch and accelerometer activity sensors for identifying resting and active behavior in bears

USGS Publications Warehouse

Jasmine Ware,; Rode, Karyn D.; Pagano, Anthony M.; Bromaghin, Jeffrey F.; Robbins, Charles T.; Joy Erlenbach,; Shannon Jensen,; Amy Cutting,; Nicole Nicassio-Hiskey,; Amy Hash,; Owen, Megan A.; Heiko Jansen,

2015-01-01

Activity sensors are often included in wildlife transmitters and can provide information on the behavior and activity patterns of animals remotely. However, interpreting activity-sensor data relative to animal behavior can be difficult if animals cannot be continuously observed. In this study, we examined the performance of a mercury tip-switch and a tri-axial accelerometer housed in collars to determine whether sensor data can be accurately classified as resting and active behaviors and whether data are comparable for the 2 sensor types. Five captive bears (3 polar [Ursus maritimus] and 2 brown [U. arctos horribilis]) were fitted with a collar specially designed to internally house the sensors. The bears’ behaviors were recorded, classified, and then compared with sensor readings. A separate tri-axial accelerometer that sampled continuously at a higher frequency and provided raw acceleration values from 3 axes was also mounted on the collar to compare with the lower resolution sensors. Both accelerometers more accurately identified resting and active behaviors at time intervals ranging from 1 minute to 1 hour (≥91.1% accuracy) compared with the mercury tip-switch (range = 75.5–86.3%). However, mercury tip-switch accuracy improved when sampled at longer intervals (e.g., 30–60 min). Data from the lower resolution accelerometer, but not the mercury tip-switch, accurately predicted the percentage of time spent resting during an hour. Although the number of bears available for this study was small, our results suggest that these activity sensors can remotely identify resting versus active behaviors across most time intervals. We recommend that investigators consider both study objectives and the variation in accuracy of classifying resting and active behaviors reported here when determining sampling interval.

NASA Human Spaceflight Architecture Team Lunar Destination Activities

NASA Technical Reports Server (NTRS)

Connolly, J. F.; Mueller, R. P.; Whitley, R. J.

2012-01-01

NASA's Human Spaceflight Architecture Team (HAT) Lunar Destination Team has been developing a number of "Design Reference Missions" (DRM) to inform exploration architecture development, transportation approaches, and destination elements and operations. There are four destinations being considered in the HAT studies: Cis-Lunar, Lunar, Near Earth Asteroids and Mars. The lunar destination includes all activities that occur on the moon itself, but not low lunar orbit operations or Earth Moon LaGrange points which are the responsibility of the HAT Cis-Lunar Team. This paper will review the various surface DRMs developed as representative scenarios that could occur in a human lunar return. The approaches have been divided into two broad categories: a seven day short stay mission with global capabilities and a longer extended duration stay of 28 days which is limited to the lunar poles as a landing zone. The surface elements, trade studies, traverses, concept of operations and other relevant issues and methodologies will be presented and discussed in the context and framework of the HAT ground rules and assumptions which are constrained by NASA's available transportation systems. An international collaborative effort based on the 2011 Global Exploration Roadmap (GER) will also be examined and evaluated.

The histone acetyltransferases CBP and Chameau integrate developmental and DNA replication programs in Drosophila ovarian follicle cells

PubMed Central

McConnell, Kristopher H.; Dixon, Michael; Calvi, Brian R.

2012-01-01

DNA replication origin activity changes during development. Chromatin modifications are known to influence the genomic location of origins and the time during S phase that they initiate replication in different cells. However, how chromatin regulates origins in concert with cell differentiation remains poorly understood. Here, we use developmental gene amplification in Drosophila ovarian follicle cells as a model to investigate how chromatin modifiers regulate origins in a developmental context. We find that the histone acetyltransferase (HAT) Chameau (Chm) binds to amplicon origins and is partially required for their function. Depletion of Chm had relatively mild effects on origins during gene amplification and genomic replication compared with previous knockdown of its ortholog HBO1 in human cells, which has severe effects on origin function. We show that another HAT, CBP (Nejire), also binds amplicon origins and is partially required for amplification. Knockdown of Chm and CBP together had a more severe effect on nucleosome acetylation and amplicon origin activity than knockdown of either HAT alone, suggesting that these HATs collaborate in origin regulation. In addition to their local function at the origin, we show that Chm and CBP also globally regulate the developmental transition of follicle cells into the amplification stages of oogenesis. Our results reveal a complexity of origin epigenetic regulation by multiple HATs during development and suggest that chromatin modifiers are a nexus that integrates differentiation and DNA replication programs. PMID:22951641

"SALOME gave my dignity back": the role of randomized heroin trials in transforming lives in the Downtown Eastside of Vancouver, Canada.

PubMed

Jozaghi, Ehsan

2014-01-01

Although numerous studies on heroin-assisted treatment (HAT) have been published in leading international journals, little attention has been given to HAT's clients, their stories, and what constitutes the most influential factor in the treatment process. The present study investigates the role of HAT in transforming the lives of injection drug users (IDUs) in Vancouver, Canada. This study is qualitative focusing on 16 in-depth interviews with patients from the randomized trials of HAT. Interviews were transcribed verbatim and analyzed thematically using NVivo 10 software. The findings revealed a positive change in many respects: the randomized trials reduce criminal activity, sex work, and illicit drug use. In addition, the trials improved the health and social functioning of its clients, with some participants acquiring work or volunteer positions. Many of the participants have been able to reconnect with their family members, which was not possible before the program. Furthermore, the relationship between the staff and patients at the project appears to have transformed the behavior of participants. Attending HAT in Vancouver has been particularly effective in creating a unique microenvironment where IDUs who have attended HAT have been able to form a collective identity advocating for their rights. The result of this research points to the need for continuation of the project beyond the current study, leading toward a permanent program.

The Bromodomain of Gcn5 Regulates Site Specificity of Lysine Acetylation on Histone H3*

PubMed Central

Cieniewicz, Anne M.; Moreland, Linley; Ringel, Alison E.; Mackintosh, Samuel G.; Raman, Ana; Gilbert, Tonya M.; Wolberger, Cynthia; Tackett, Alan J.; Taverna, Sean D.

2014-01-01

In yeast, the conserved histone acetyltransferase (HAT) Gcn5 associates with Ada2 and Ada3 to form the catalytic module of the ADA and SAGA transcriptional coactivator complexes. Gcn5 also contains an acetyl-lysine binding bromodomain that has been implicated in regulating nucleosomal acetylation in vitro, as well as at gene promoters in cells. However, the contribution of the Gcn5 bromodomain in regulating site specificity of HAT activity remains unclear. Here, we used a combined acid-urea gel and quantitative mass spectrometry approach to compare the HAT activity of wild-type and Gcn5 bromodomain-mutant ADA subcomplexes (Gcn5-Ada2-Ada3). Wild-type ADA subcomplex acetylated H3 lysines with the following specificity; H3K14 > H3K23 > H3K9 ≈ H3K18 > H3K27 > H3K36. However, when the Gcn5 bromodomain was defective in acetyl-lysine binding, the ADA subcomplex demonstrated altered site-specific acetylation on free and nucleosomal H3, with H3K18ac being the most severely diminished. H3K18ac was also severely diminished on H3K14R, but not H3K23R, substrates in wild-type HAT reactions, further suggesting that Gcn5-catalyzed acetylation of H3K14 and bromodomain binding to H3K14ac are important steps preceding H3K18ac. In sum, this work details a previously uncharacterized cross-talk between the Gcn5 bromodomain “reader” function and enzymatic HAT activity that might ultimately affect gene expression. Future studies of how mutations in bromodomains or other histone post-translational modification readers can affect chromatin-templated enzymatic activities will yield unprecedented insight into a potential “histone/epigenetic code.” MS data are available via ProteomeXchange with identifier PXD001167. PMID:25106422

The Atlas of human African trypanosomiasis: a contribution to global mapping of neglected tropical diseases

PubMed Central

2010-01-01

Background Following World Health Assembly resolutions 50.36 in 1997 and 56.7 in 2003, the World Health Organization (WHO) committed itself to supporting human African trypanosomiasis (HAT)-endemic countries in their efforts to remove the disease as a public health problem. Mapping the distribution of HAT in time and space has a pivotal role to play if this objective is to be met. For this reason WHO launched the HAT Atlas initiative, jointly implemented with the Food and Agriculture Organization of the United Nations, in the framework of the Programme Against African Trypanosomosis. Results The distribution of HAT is presented for 23 out of 25 sub-Saharan countries having reported on the status of sleeping sickness in the period 2000 - 2009. For the two remaining countries, i.e. Angola and the Democratic Republic of the Congo, data processing is ongoing. Reports by National Sleeping Sickness Control Programmes (NSSCPs), Non-Governmental Organizations (NGOs) and Research Institutes were collated and the relevant epidemiological data were entered in a database, thus incorporating (i) the results of active screening of over 2.2 million people, and (ii) cases detected in health care facilities engaged in passive surveillance. A total of over 42 000 cases of HAT and 6 000 different localities were included in the database. Various sources of geographic coordinates were used to locate the villages of epidemiological interest. The resulting average mapping accuracy is estimated at 900 m. Conclusions Full involvement of NSSCPs, NGOs and Research Institutes in building the Atlas of HAT contributes to the efficiency of the mapping process and it assures both the quality of the collated information and the accuracy of the outputs. Although efforts are still needed to reduce the number of undetected and unreported cases, the comprehensive, village-level mapping of HAT control activities over a ten-year period ensures a detailed and reliable representation of the known geographic distribution of the disease. Not only does the Atlas serve research and advocacy, but, more importantly, it provides crucial evidence and a valuable tool for making informed decisions to plan and monitor the control of sleeping sickness. PMID:21040555

Common Eigenvectors of N Particles' Compatible Observables and its Squeezing Operator

NASA Astrophysics Data System (ADS)

Xu, Shi-Min; Xu, Xing-Lei; Li, Hong-Qi

We construct 2N operators for a N-particle system, namely one center-of-mass coordinate operator, N-1 relative coordinate operators, one total momentum operator and N-1 mass-weighted relative momentum operators, and give common eigenvectors of N compatible observables \\{∑ Ni=1hat {p}i,hat {x}1-hat {x}2,hat {x}2-hat {x}3,hat {x}3-hat {x}4,...; ,hat {x}N-1-hat {x}N\\}, which are composed of N particles' coordinate hat {x}i and momentum hat {p}i. By compatible, we mean such observables can be simultaneously determined. Using the technique of integration within an ordered product of operators (IWOP), we prove that the common eigenvectors are complete and orthonormal, and hereby qualified for making up a representation. This new representation can be applied to solving some dynamic problems in quantum mechanics.

Candidate gene polymorphisms study between human African trypanosomiasis clinical phenotypes in Guinea.

PubMed

Kaboré, Justin Windingoudi; Ilboudo, Hamidou; Noyes, Harry; Camara, Oumou; Kaboré, Jacques; Camara, Mamadou; Koffi, Mathurin; Lejon, Veerle; Jamonneau, Vincent; MacLeod, Annette; Hertz-Fowler, Christiane; Belem, Adrien Marie Gaston; Matovu, Enock; Bucheton, Bruno; Sidibe, Issa

2017-08-01

Human African trypanosomiasis (HAT), a lethal disease induced by Trypanosoma brucei gambiense, has a range of clinical outcomes in its human host in West Africa: an acute form progressing rapidly to second stage, spontaneous self-cure and individuals able to regulate parasitaemia at very low levels, have all been reported from endemic foci. In order to test if this clinical diversity is influenced by host genetic determinants, the association between candidate gene polymorphisms and HAT outcome was investigated in populations from HAT active foci in Guinea. Samples were collected from 425 individuals; comprising of 232 HAT cases, 79 subjects with long lasting positive and specific serology but negative parasitology and 114 endemic controls. Genotypes of 28 SNPs in eight genes passed quality control and were used for an association analysis. IL6 rs1818879 allele A (p = 0.0001, OR = 0.39, CI95 = [0.24-0.63], BONF = 0.0034) was associated with a lower risk of progressing from latent infection to active disease. MIF rs36086171 allele G seemed to be associated with an increased risk (p = 0.0239, OR = 1.65, CI95 = [1.07-2.53], BONF = 0.6697) but did not remain significant after Bonferroni correction. Similarly MIF rs12483859 C allele seems be associated with latent infections (p = 0.0077, OR = 1.86, CI95 = [1.18-2.95], BONF = 0.2157). We confirmed earlier observations that APOL1 G2 allele (DEL) (p = 0.0011, OR = 2.70, CI95 = [1.49-4.91], BONF = 0.0301) is associated with a higher risk and APOL1 G1 polymorphism (p = 0.0005, OR = 0.45, CI95 = [0.29-0.70], BONF = 0.0129) with a lower risk of developing HAT. No associations were found with other candidate genes. Our data show that host genes are involved in modulating Trypanosoma brucei gambiense infection outcome in infected individuals from Guinea with IL6 rs1818879 being associated with a lower risk of progressing to active HAT. These results enhance our understanding of host-parasite interactions and, ultimately, may lead to the development of new control tools.

Acetylation mediates Cx43 reduction caused by electrical stimulation

PubMed Central

Meraviglia, Viviana; Azzimato, Valerio; Colussi, Claudia; Florio, Maria Cristina; Binda, Anna; Panariti, Alice; Qanud, Khaled; Suffredini, Silvia; Gennaccaro, Laura; Miragoli, Michele; Barbuti, Andrea; Lampe, Paul D.; Gaetano, Carlo; Pramstaller, Peter P.; Capogrossi, Maurizio C.; Recchia, Fabio A.; Pompilio, Giulio; Rivolta, Ilaria; Rossini, Alessandra

2015-01-01

Communication between cardiomyocytes depends upon Gap Junctions (GJ). Previous studies have demonstrated that electrical stimulation induces GJ remodeling and modifies histone acetylases (HAT) and deacetylases (HDAC) activities, although these two results have not been linked. The aim of this work was to establish whether electrical stimulation modulates GJ-mediated cardiac cell-cell communication by acetylation-dependent mechanisms. Field stimulation of HL-1 cardiomyocytes at 0.5 Hz for 24 hours significantly reduced Connexin43 (Cx43) expression and cell-cell communication. HDAC activity was down-regulated whereas HAT activity was not modified resulting in increased acetylation of Cx43. Consistent with a post-translational mechanism, we did not observe a reduction in Cx43 mRNA in electrically stimulated cells, while the proteasomal inhibitor MG132 maintained Cx43 expression. Further, the treatment of paced cells with the HAT inhibitor Anacardic Acid maintained both the levels of Cx43 and cell-cell communication. Finally, we observed increased acetylation of Cx43 in the left ventricles of dogs subjected to chronic tachypacing as a model of abnormal ventricular activation. In conclusion, our findings suggest that altered electrical activity can regulate cardiomyocyte communication by influencing the acetylation status of Cx43. PMID:26264759

Measurements of the UVR protection provided by hats used at school.

PubMed

Gies, Peter; Javorniczky, John; Roy, Colin; Henderson, Stuart

2006-01-01

The importance of protection against solar ultraviolet radiation (UVR) in childhood has lead to SunSmart policies at Australian schools, in particular primary schools, where children are encouraged and in many cases required to wear hats at school. Hat styles change regularly and the UVR protection provided by some of the hat types currently used and recommended for sun protection by the various Australian state cancer councils had not been previously evaluated. The UVR protection of the hats was measured using UVR sensitive polysulphone film badges attached to different facial sites on rotating headforms. The sun protection type hats included in this study were broad-brimmed hats, "bucket hats" and legionnaires hats. Baseball caps, which are very popular, were also included. The broad-brimmed hats and bucket hats provided the most UVR protection for the six different sites about the face and head. Legionnaires hats also provided satisfactory UVR protection, but the caps did not provide UVR protection to many of the facial sites. The highest measured UVR protection factors for facial sites other than the forehead were 8 to 10, indicating that, while some hats can be effective, they need to be used in combination with other forms of UVR protection.

The risk of capsular breakage from phacoemulsification needle contact with the lens capsule: a laboratory study.

PubMed

Meyer, Jay J; Kuo, Annie F; Olson, Randall J

2010-06-01

To determine capsular breakage risk from contact by phacoemulsification needles by machine and tip type. Experimental laboratory investigation. Infiniti (Alcon, Inc.) with Intrepid cartridges and Signature (Abbott Medical Optics, Inc.) phacoemulsification machines were tested using 19- and 20-gauge sharp and rounded tips. Actual and unoccluded flow vacuum were determined at 550 mm Hg, bottle height of 75 cm, and machine-indicated flow rate of 60 mL/minute. Breakage from brief tip contact with a capsular surrogate and human cadaveric lenses was calculated. Nineteen-gauge tips had more flow and less unoccluded flow vacuum than 20-gauge tips for both machines, with highest unoccluded flow vacuum in the Infiniti. The 19-gauge sharp tip was more likely than the 20-gauge sharp tip to cause surrogate breakage for Signature with micropulse and Ellips (Abbott Medical Optics, Inc.) ultrasound at 100% power. For Infiniti using OZil (Alcon, Inc.) ultrasound, 20-gauge sharp tips were more likely than 19-gauge sharp tips to break the membrane. For cadaveric lenses, using rounded 20-gauge tips at 100% power, breakage rates were micropulse (2.3%), Ellips (2.3%), OZil (5.3%). Breakage rates for sharp 20-gauge Ellips tips were higher than for rounded tips. Factors influencing capsular breakage may include active vacuum at the tip, flow rate, needle gauge, and sharpness. Nineteen-gauge sharp tips were more likely than 20-gauge tips to cause breakage in lower vacuum methods. For higher-vacuum methods, breakage is more likely with 20-gauge than with 19-gauge tips. Rounded-edge tips are less likely than sharp-edged tips to cause breakage. Copyright 2010 Elsevier Inc. All rights reserved.

Transfection using hydroxyapatite nanoparticles in the inner ear via an intact round window membrane in chinchilla

NASA Astrophysics Data System (ADS)

Wu, Xuewen; Ding, Dalian; Jiang, Haiyan; Xing, Xiaowei; Huang, Suping; Liu, Hong; Chen, Zhedong; Sun, Hong

2012-01-01

Hydroxyapatite nanoparticles (nHAT) are known to have excellent biocompatibility, and have attracted increasing attention as new candidates of non-viral vectors for gene therapy. In our previous studies, nHAT carrying a therapeutic gene and a reporter gene were successfully transfected into the spiral ganglion neurons in the inner ear of guinea pigs in vivo as well as in the cultured cell lines, although the transfection efficiencies were never higher than 30%. In this study, the surface modification of nHAT with polyethylenimine (PEI) was made (PEI-nHAT, diameter = 73.09 ± 27.32 nm) and a recombinant plasmid carrying enhanced green fluorescent protein (EGFP) gene and neurotrophin-3 (NT-3) gene was constructed as pEGFPC2-NT3. The PEI modified nHAT and the recombinant plasmid was then connected to form the nHAT-based vector-gene complex (PEI-nHAT-pEGFPC2-NT3). This complex was then placed onto the intact round window membranes of the chinchillas for inner ear transfection. Auditory brainstem response (ABR) was tested to evaluate auditory function. Green fluorescence of EGFP was observed using confocal microscopy 48 h after administering vector-gene complexes. There was no significant threshold shift in tone burst-evoked ABR at any tested frequency. Abundant, condensed green fluorescence was found in dark cells on both sides of the crista and around the macula of the utricle. Scattered EGFP signals were also detected in vestibular hair cells, some Schwann cells in the cochlear spiral ganglion region, some outer pillar cells in the organ of Corti, and a few cells in the stria vascularis. The density of green fluorescence-marked cells was obviously higher in the vestibular dark cell area than in other areas of the inner ear, suggesting that vestibular dark cells may have the ability to actively engulf the nHAT-based vector-gene complexes. Considering the high transfection efficiency in the vestibular system, PEI-nHAT may be a potential vector for gene therapy of inner ear diseases, especially vestibular disorders, and deserves further study.

Tsetse Control and Gambian Sleeping Sickness; Implications for Control Strategy.

PubMed

Tirados, Inaki; Esterhuizen, Johan; Kovacic, Vanja; Mangwiro, T N Clement; Vale, Glyn A; Hastings, Ian; Solano, Philippe; Lehane, Michael J; Torr, Steve J

2015-01-01

Gambian sleeping sickness (human African trypanosomiasis, HAT) outbreaks are brought under control by case detection and treatment although it is recognised that this typically only reaches about 75% of the population. Vector control is capable of completely interrupting HAT transmission but is not used because it is considered too expensive and difficult to organise in resource-poor settings. We conducted a full scale field trial of a refined vector control technology to determine its utility in control of Gambian HAT. The major vector of Gambian HAT is the tsetse fly Glossina fuscipes which lives in the humid zone immediately adjacent to water bodies. From a series of preliminary trials we determined the number of tiny targets required to reduce G. fuscipes populations by more than 90%. Using these data for model calibration we predicted we needed a target density of 20 per linear km of river in riverine savannah to achieve >90% tsetse control. We then carried out a full scale, 500 km2 field trial covering two HAT foci in Northern Uganda to determine the efficacy of tiny targets (overall target density 5.7/km2). In 12 months, tsetse populations declined by more than 90%. As a guide we used a published HAT transmission model and calculated that a 72% reduction in tsetse population is required to stop transmission in those settings. The Ugandan census suggests population density in the HAT foci is approximately 500 per km2. The estimated cost for a single round of active case detection (excluding treatment), covering 80% of the population, is US$433,333 (WHO figures). One year of vector control organised within the country, which can completely stop HAT transmission, would cost US$42,700. The case for adding this method of vector control to case detection and treatment is strong. We outline how such a component could be organised.

Tsetse Control and Gambian Sleeping Sickness; Implications for Control Strategy

PubMed Central

Kovacic, Vanja; Mangwiro, T. N. Clement; Vale, Glyn A.; Hastings, Ian; Solano, Philippe; Lehane, Michael J.; Torr, Steve J.

2015-01-01

Background Gambian sleeping sickness (human African trypanosomiasis, HAT) outbreaks are brought under control by case detection and treatment although it is recognised that this typically only reaches about 75% of the population. Vector control is capable of completely interrupting HAT transmission but is not used because it is considered too expensive and difficult to organise in resource-poor settings. We conducted a full scale field trial of a refined vector control technology to determine its utility in control of Gambian HAT. Methods and Findings The major vector of Gambian HAT is the tsetse fly Glossina fuscipes which lives in the humid zone immediately adjacent to water bodies. From a series of preliminary trials we determined the number of tiny targets required to reduce G. fuscipes populations by more than 90%. Using these data for model calibration we predicted we needed a target density of 20 per linear km of river in riverine savannah to achieve >90% tsetse control. We then carried out a full scale, 500 km2 field trial covering two HAT foci in Northern Uganda to determine the efficacy of tiny targets (overall target density 5.7/km2). In 12 months, tsetse populations declined by more than 90%. As a guide we used a published HAT transmission model and calculated that a 72% reduction in tsetse population is required to stop transmission in those settings. Interpretation The Ugandan census suggests population density in the HAT foci is approximately 500 per km2. The estimated cost for a single round of active case detection (excluding treatment), covering 80% of the population, is US$433,333 (WHO figures). One year of vector control organised within the country, which can completely stop HAT transmission, would cost US$42,700. The case for adding this method of vector control to case detection and treatment is strong. We outline how such a component could be organised. PMID:26267814

Radiologic characterization of the Mexican Hat, Utah, uranium mill tailings remedial action site: Appendix D, Addenda D1--D7

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

Ludlam, J.R.

1985-01-01

This radiologic characterization of the inactive uranium millsite at Mexican Hat, Utah, was conducted by Bendix Field Engineering Corporation foe the US Department of Energy (DOE), Grand Junction Project Office, in response to and in accord with a Statement of Work prepared by the DOE Uranium Mill tailings Remedial Action Project (UMTRAP) Technical Assistance Contractor, Jacobs Engineering Group, Inc. the objective of this project was to determine the horizontal and vertical extent of contamination that exceeds the US Environmental Protection Agency (EPA) standards at the Mexican Hat site. The data presented in this report are required for characterization of themore » areas adjacent to the Mexican Hat tailings piles and for the subsequent design of cleanup activities. Some on-pile sampling was required to determine the depth of the 15-pCi/g Ra-226 interface in an area where wind and water erosion has taken place.« less

More Than Just a Break from Treatment: How Substance Use Disorder Patients Experience the Stable Environment in Horse-Assisted Therapy.

PubMed

Kern-Godal, Ann; Brenna, Ida Halvorsen; Arnevik, Espen Ajo; Ravndal, Edle

2016-01-01

Inclusion of horse-assisted therapy (HAT) in substance use disorder (SUD) treatment is rarely reported. Our previous studies show improved treatment retention and the importance of the patient-horse relationship. This qualitative study used thematic analysis, within a social constructionist framework, to explore how eight patients experienced contextual aspects of HAT's contribution to their SUD treatment. Participants described HAT as a "break from usual treatment". However, four interrelated aspects of this experience, namely "change of focus", "activity", "identity", and "motivation," suggest HAT is more than just a break from usual SUD treatment. The stable environment is portrayed as a context where participants could construct a positive self: one which is useful, responsible, and accepted; more fundamentally, a different self from the "patient/self" receiving treatment for a problem. The implications extend well beyond animal-assisted or other adjunct therapies. Their relevance to broader SUD policy and treatment practices warrants further study.

Conductance manipulation at the molecular level

NASA Astrophysics Data System (ADS)

Paulsson, Magnus; Stafström, Sven

1999-05-01

Using a tight-binding model we have studied the electronic transmission through a C60 molecule sandwiched between a metal surface and a metal (scanning tunnelling microscope) tip. By simulating compression of C60 we have interpreted an experimental study of the variation of the conductance through a C60 molecule with an applied external pressure. We found that the observed increase in conductance cannot be explained in terms of the changes in the electronic structure of the C60 molecule alone. Effects related to the metal/molecule contact, i.e. the strength of the metal/C60 interaction and the shape of the molecular orbitals in the tip, are in fact more important for the conductance. In view of this we discuss the importance of interference effects in the tip/molecule coupling.

Analysis of Activity Patterns and Performance in Polio Survivors

DTIC Science & Technology

2006-10-01

variable were inspected for asymmetry and long-tailedness and normality. When appropriate, transformations (e.g. log function) were made. Data were...thighs and a combined pelvis -HAT segment was used for our analyses. The ankles were modeled as universal joints, the knees as revolutes, and the...segment, lumped pelvis + HAT, universal ankle, revolute knee, spherical hip; pin at CP entire stance Stance sagittal knee and frontal hip

Inhibition of PCAF histone acetyltransferase, cytotoxicity and cell permeability of 2-acylamino-1-(3- or 4-carboxy-phenyl)benzamides.

PubMed

Park, Woong Jae; Ma, Eunsook

2012-11-05

Small molecule HAT inhibitors are useful tools to unravel the role of histone acetyltransferases (HATs) in the cell and they also have relevance in oncology. We synthesized a series of 2-acylamino-1-(3- or 4-carboxyphenyl)benzamides 8–19 bearing C6, C8, C10, C12, C14, and C16 acyl chains at the 2-amino position of 2-aminobenzoic acid. Enzyme inhibition of these compounds was investigated using in vitro PCAF HAT assays. The inhibitory activities of compounds 8–10, 16, and 19 were similar to that of anacardic acid, and 17 was found to be more active than anacardic acid at 100 μM. Compounds 11–15 showed the low inhibitory activity on PCAF HAT. The cytotoxicity of the synthesized compounds was evaluated by SRB (sulforhodamine B) assay against seven human cancer cell lines: HT-29 (colon), HCT-116 (colon), MDA-231 (breast), A549 (lung), Hep3B (hepatoma), HeLa (cervical) and Caki (kidney) and one normal cell line (HSF). Compound 17 was more active than anacardic acid against human colon cancer (HCT 116, IC(50): 29.17 μM), human lung cancer (A549, IC₅₀: 32.09 μM) cell lines. 18 was more active than anacardic acid against human colon cancer (HT-29, IC₅₀: 35.49 μM and HCT 116, IC₅₀: 27.56 μM), human lung cancer (A549, IC₅₀: 30.69 μM), and human cervical cancer (HeLa, IC₅₀: 34.41 μM) cell lines. The apparent permeability coefficient (P(app), cm/s) values of two compounds (16 and 17) were evaluated as 68.21 and 71.48 × 10⁻⁶ cm/s by Caco-2 cell permeability assay.

Home Team: Over 60 Home Learning Tips from the American Federation of Teachers [and] El Equipo del Hogar: La American Federation of Teachers Presenta Mas de 60 Consejos para el Aprendizaje.

ERIC Educational Resources Information Center

Whitman, Ruth

Suggestions directed to parents and family members for turning everyday home activities into opportunities for learning are based on three principles: reading and researching; reinforcement and reward; and review and reapplication. It is proposed that establishing a good home learning environment includes setting regular, daily times to work with…

40 CFR 60.101a - Definitions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... tip to prevent oxygen infiltration (backflow) into the flare tip. For flares with no water seals, the... function of preventing oxygen infiltration (backflow) into the flare tip. [73 FR 35867, June 24, 2008, as...

Insights into intermolecular interactions, electrostatic properties and the stability of C646 in the binding pocket of p300 histone acetyltransferase enzyme: a combined molecular dynamics and charge density study.

PubMed

Sivanandam, Magudeeswaran; Saravanan, Kandasamy; Kumaradhas, Poomani

2017-10-30

Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are enzymes that exhibit an important transcription activity. Dysfunction of these enzymes may lead to different diseases including cancer, cardiovascular, and other diseases. Therefore, these enzymes are the potential target for the generation of new therapeutics. C646 is a synthetic p300 HAT inhibitor; its structural and the electrostatic properties are the paradigm to understand its activity in the active site of p300 HAT enzyme. The docked C646 molecule in the active site forms expected key intermolecular interactions with the amino acid residues Trp1436, Tyr1467, and one water molecule (W1861); and these interactions are important for acetylation reaction. When compare the active site structure of C646 with the gas-phase structure, it is confirmed that the electron density distribution of polar bonds are highly altered, when the molecule present in the active site. In the gas-phase structure of C646, a large negative regions of electrostatic potential is found at the vicinity of O(4), O(5), and O(6) atoms; whereas, the negative region of these atoms are reduced in the active site. The molecular dynamics (MD) simulation also performed, it reveals the conformational stability and the intermolecular interactions of C646 molecule in the active site of p300.

Changes in extracellular calcium activity during gravity sensing in maize roots

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

Bjoerkman, T.; Cleland, R.E.

1990-05-01

A redistribution of calcium downward across the root cap has been proposed as an essential part of gravitropism in roots. Exogenous {sup 45}Ca moves preferentially downward across gravistimulated maize root tips. However, because of the many calcium-binding sites in the apoplast, this might not result in a physiologically effect change in the apoplasmic calcium activity. To test whether there is such a change, we measured the effect of gravistimulation on the calcium activity with calcium-specific microelectrodes. Decapped maize roots (Zea mays L. cv. Golden Cross Bantam) were grown for 31 h to regenerate gravitropic sensitivity, but not root caps. Themore » calcium activity in the apoplasm surrounding the gravity-sensing cells could then be measured. The initial pCa was 2.60 {plus minus} 0.28 (approx 2.5 mM). The calcium activity on the upper side of the root tip remained constant for about five minutes after gravistimulation, then decreased by about one half. On the lower side, after a similar lag the calcium activity doubled. Control roots, which were decapped but measured before recovering gravisensitivity (19 h), showed no change in calcium activity. We have found a distinct and rapid differential in the apoplasmic calcium activity between the upper and lower sides of gravistimulated maize root tips.« less

The GTC exoplanet transit spectroscopy survey. IV. Confirmation of the flat transmission spectrum of HAT-P-32b

NASA Astrophysics Data System (ADS)

Nortmann, L.; Pallé, E.; Murgas, F.; Dreizler, S.; Iro, N.; Cabrera-Lavers, A.

2016-10-01

We observed the hot Jupiter HAT-P-32b (also known as HAT-P-32Ab) to determine its optical transmission spectrum by measuring the wavelength-dependent, planet-to-star radius ratios in the region between 518-918 nm. We used the OSIRIS instrument at the Gran Telescopio CANARIAS (GTC) in long-slit spectroscopy mode, placing HAT-P-32 and a reference star in the same slit and obtaining a time series of spectra covering two transit events. Using the best quality data set, we were able to yield 20 narrowband transit light curves, with each passband spanning a 20 nm wide interval. After removal of all systematic noise signals and light curve modeling, the uncertainties for the resulting radius ratios lie between 337 and 972 ppm. The radius ratios show little variation with wavelength, suggesting a high altitude cloud layer masking any atmospheric features. Alternatively, a strong depletion in alkali metals or a much smaller than expected planetary atmospheric scale height could be responsible for the lack of atmospheric features. Our result of a flat transmission spectrum is consistent with a previous ground-based study of the optical spectrum of this planet. This agreement between independent results demonstrates that ground-based measurements of exoplanet atmospheres can give reliable and reproducible results despite the fact that the data often is heavily affected by systematic noise as long as the noise source is well understood and properly corrected. We also extract an optical spectrum of the M-dwarf companion HAT-P-32B. Using PHOENIX stellar atmosphere models we determine an effective temperature of Teff = 3187+60-71 K, which is slightly colder than previous studies relying only on broadband infrared data. The 20 narrowband and white light curves are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/594/A65

Hippocampal histone acetylation regulates object recognition and the estradiol-induced enhancement of object recognition

PubMed Central

Zhao, Zaorui; Fan, Lu; Fortress, Ashley M.; Boulware, Marissa I.; Frick, Karyn M.

2012-01-01

Histone acetylation has recently been implicated in learning and memory processes, yet necessity of histone acetylation for such processes has not been demonstrated using pharmacological inhibitors of histone acetyltransferases (HATs). As such, the present study tested whether garcinol, a potent HAT inhibitor in vitro, could impair hippocampal memory consolidation and block the memory-enhancing effects of the modulatory hormone 17β-estradiol (E2). We first showed that bilateral infusion of garcinol (0.1, 1, or 10 μg/side) into the dorsal hippocampus (DH) immediately after training impaired object recognition memory consolidation in ovariectomized female mice. A behaviorally effective dose of garcinol (10 μg/side) also significantly decreased DH HAT activity. We next examined whether DH infusion of a behaviorally subeffective dose of garcinol (1 ng/side) could block the effects of DH E2 infusion on object recognition and epigenetic processes. Immediately after training, ovariectomized female mice received bilateral DH infusions of vehicle, E2 (5 μg/side), garcinol (1 ng/side), or E2 plus garcinol. Forty-eight hours later, garcinol blocked the memory-enhancing effects of E2. Garcinol also reversed the E2-induced increase in DH histone H3 acetylation, HAT activity, and levels of the de novo methyltransferase DNMT3B, as well as the E2-induced decrease in levels of the memory repressor protein histone deacetylase 2 (HDAC2). Collectively, these findings suggest that histone acetylation is critical for object recognition memory consolidation and the beneficial effects of E2 on object recognition. Importantly, this work demonstrates that the role of histone acetylation in memory processes can be studied using a HAT inhibitor. PMID:22396409

Sensitivity and Specificity of a Prototype Rapid Diagnostic Test for the Detection of Trypanosoma brucei gambiense Infection: A Multi-centric Prospective Study.

PubMed

Bisser, Sylvie; Lumbala, Crispin; Nguertoum, Etienne; Kande, Victor; Flevaud, Laurence; Vatunga, Gedeao; Boelaert, Marleen; Büscher, Philippe; Josenando, Theophile; Bessell, Paul R; Biéler, Sylvain; Ndung'u, Joseph M

2016-04-01

A major challenge in the control of human African trypanosomiasis (HAT) is lack of reliable diagnostic tests that are rapid and easy to use in remote areas where the disease occurs. In Trypanosoma brucei gambiense HAT, the Card Agglutination Test for Trypanosomiasis (CATT) has been the reference screening test since 1978, usually on whole blood, but also in a 1/8 dilution (CATT 1/8) to enhance specificity. However, the CATT is not available in a single format, requires a cold chain for storage, and uses equipment that requires electricity. A solution to these challenges has been provided by rapid diagnostic tests (RDT), which have recently become available. A prototype immunochromatographic test, the SD BIOLINE HAT, based on two native trypanosomal antigens (VSG LiTat 1.3 and VSG LiTat 1.5) has been developed. We carried out a non-inferiority study comparing this prototype to the CATT 1/8 in field settings. The prototype SD BIOLINE HAT, the CATT Whole Blood and CATT 1/8 were systematically applied on fresh blood samples obtained from 14,818 subjects, who were prospectively enrolled through active and passive screening in clinical studies in three endemic countries of central Africa: Angola, the Democratic Republic of the Congo and the Central African Republic. One hundred and forty nine HAT cases were confirmed by parasitology. The sensitivity and specificity of the prototype SD BIOLINE HAT was 89.26% (95% confidence interval (CI) = 83.27-93.28) and 94.58% (95% CI = 94.20-94.94) respectively. The sensitivity and specificity of the CATT on whole blood were 93.96% (95% CI = 88.92-96.79) and 95.91% (95% CI = 95.58-96.22), and of the CATT 1/8 were 89.26% (95% CI = 83.27-93.28) and 98.88% (95% CI = 98.70-99.04) respectively. After further optimization, the prototype SD BIOLINE HAT could become an alternative to current screening methods in primary healthcare settings in remote, resource-limited regions where HAT typically occurs.

HATS-39b, HATS-40b, HATS-41b, and HATS-42b: three inflated hot Jupiters and a super-Jupiter transiting F stars

NASA Astrophysics Data System (ADS)

Bento, J.; Hartman, J. D.; Bakos, G. Á.; Bhatti, W.; Csubry, Z.; Penev, K.; Bayliss, D.; de Val-Borro, M.; Zhou, G.; Brahm, R.; Espinoza, N.; Rabus, M.; Jordán, A.; Suc, V.; Ciceri, S.; Sarkis, P.; Henning, T.; Mancini, L.; Tinney, C. G.; Wright, D. J.; Durkan, S.; Tan, T. G.; Lázár, J.; Papp, I.; Sári, P.

2018-07-01

We report the discovery of four transiting hot Jupiters from the HATSouth survey: HATS-39b, HATS-40b, HATS-41b, and HATS-42b. These discoveries add to the growing number of transiting planets orbiting moderately bright (12.5 ≲ V ≲ 13.7) F dwarf stars on short (2-5 d) periods. The planets have similar radii, ranging from 1.33^{+0.29}_{-0.20} RJ for HATS-41b to 1.58^{+0.16}_{-0.12} RJ for HATS-40b. Their masses and bulk densities, however, span more than an order of magnitude. HATS-39b has a mass of 0.63 ± 0.13 MJ, and an inflated radius of 1.57 ± 0.12 RJ, making it a good target for future transmission spectroscopic studies. HATS-41b is a very massive 9.7 ± 1.6 MJ planet and one of only a few hot Jupiters found to date with a mass over 5 MJ. This planet orbits the highest metallicity star ([Fe/H] = 0.470 ± 0.010) known to host a transiting planet and is also likely on an eccentric orbit. The high mass, coupled with a relatively young age (1.34^{+0.31}_{-0.51} Gyr) for the host star, is a factor that may explain why this planet's orbit has not yet circularized.

Differential Effects of Histone Acetyltransferase GCN5 or PCAF Knockdown on Urothelial Carcinoma Cells

PubMed Central

Koutsogiannouli, Evangelia A.; Hader, Christiane; Pinkerneil, Maria; Hoffmann, Michèle J.; Schulz, Wolfgang A.

2017-01-01

Disturbances in histone acetyltransferases (HATs) are common in cancers. In urothelial carcinoma (UC), p300 and CBP are often mutated, whereas the GNAT family HATs GCN5 and PCAF (General Control Nonderepressible 5, p300/CBP-Associated Factor) are often upregulated. Here, we explored the effects of specific siRNA-mediated knockdown of GCN5, PCAF or both in four UC cell lines (UCCs). Expression of various HATs and marker proteins was measured by qRT-PCR and western blot. Cellular effects of knockdowns were analyzed by flow cytometry and ATP-, caspase-, and colony forming-assays. GCN5 was regularly upregulated in UCCs, whereas PCAF was variable. Knockdown of GCN5 or both GNATs, but not of PCAF alone, diminished viability and inhibited clonogenic growth in 2/4 UCCs, inducing cell cycle changes and caspase-3/7 activity. PCAF knockdown elicited GCN5 mRNA upregulation. Double knockdown increased c-MYC and MDM2 (Mouse Double Minute 2) in most cell lines. In conclusion, GCN5 upregulation is especially common in UCCs. GCN5 knockdown impeded growth of specific UCCs, whereas PCAF knockdown elicited minor effects. The limited sensitivity towards GNAT knockdown and its variation between the cell lines might be due to compensatory effects including HAT, c-MYC and MDM2 upregulation. Our results predict that developing drugs targeting individual HATs for UC treatment may be challenging. PMID:28678170

Acetylation of Mammalian ADA3 Is Required for Its Functional Roles in Histone Acetylation and Cell Proliferation.

PubMed

Mohibi, Shakur; Srivastava, Shashank; Bele, Aditya; Mirza, Sameer; Band, Hamid; Band, Vimla

2016-10-01

Alteration/deficiency in activation 3 (ADA3) is an essential component of specific histone acetyltransferase (HAT) complexes. We have previously shown that ADA3 is required for establishing global histone acetylation patterns and for normal cell cycle progression (S. Mohibi et al., J Biol Chem 287:29442-29456, 2012, http://dx.doi.org/10.1074/jbc.M112.378901). Here, we report that these functional roles of ADA3 require its acetylation. We show that ADA3 acetylation, which is dynamically regulated in a cell cycle-dependent manner, reflects a balance of coordinated actions of its associated HATs, GCN5, PCAF, and p300, and a new partner that we define, the deacetylase SIRT1. We use mass spectrometry and site-directed mutagenesis to identify major sites of ADA3 acetylated by GCN5 and p300. Acetylation-defective mutants are capable of interacting with HATs and other components of HAT complexes but are deficient in their ability to restore ADA3-dependent global or locus-specific histone acetylation marks and cell proliferation in Ada3-deleted murine embryonic fibroblasts (MEFs). Given the key importance of ADA3-containing HAT complexes in the regulation of various biological processes, including the cell cycle, our study presents a novel mechanism to regulate the function of these complexes through dynamic ADA3 acetylation. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Acetylation of Mammalian ADA3 Is Required for Its Functional Roles in Histone Acetylation and Cell Proliferation

PubMed Central

Mohibi, Shakur; Srivastava, Shashank; Bele, Aditya; Mirza, Sameer; Band, Hamid

2016-01-01

Alteration/deficiency in activation 3 (ADA3) is an essential component of specific histone acetyltransferase (HAT) complexes. We have previously shown that ADA3 is required for establishing global histone acetylation patterns and for normal cell cycle progression (S. Mohibi et al., J Biol Chem 287:29442–29456, 2012, http://dx.doi.org/10.1074/jbc.M112.378901). Here, we report that these functional roles of ADA3 require its acetylation. We show that ADA3 acetylation, which is dynamically regulated in a cell cycle-dependent manner, reflects a balance of coordinated actions of its associated HATs, GCN5, PCAF, and p300, and a new partner that we define, the deacetylase SIRT1. We use mass spectrometry and site-directed mutagenesis to identify major sites of ADA3 acetylated by GCN5 and p300. Acetylation-defective mutants are capable of interacting with HATs and other components of HAT complexes but are deficient in their ability to restore ADA3-dependent global or locus-specific histone acetylation marks and cell proliferation in Ada3-deleted murine embryonic fibroblasts (MEFs). Given the key importance of ADA3-containing HAT complexes in the regulation of various biological processes, including the cell cycle, our study presents a novel mechanism to regulate the function of these complexes through dynamic ADA3 acetylation. PMID:27402865

“SALOME gave my dignity back”: The role of randomized heroin trials in transforming lives in the Downtown Eastside of Vancouver, Canada

PubMed Central

Jozaghi, Ehsan

2014-01-01

Although numerous studies on heroin-assisted treatment (HAT) have been published in leading international journals, little attention has been given to HAT’s clients, their stories, and what constitutes the most influential factor in the treatment process. The present study investigates the role of HAT in transforming the lives of injection drug users (IDUs) in Vancouver, Canada. This study is qualitative focusing on 16 in-depth interviews with patients from the randomized trials of HAT. Interviews were transcribed verbatim and analyzed thematically using NVivo 10 software. The findings revealed a positive change in many respects: the randomized trials reduce criminal activity, sex work, and illicit drug use. In addition, the trials improved the health and social functioning of its clients, with some participants acquiring work or volunteer positions. Many of the participants have been able to reconnect with their family members, which was not possible before the program. Furthermore, the relationship between the staff and patients at the project appears to have transformed the behavior of participants. Attending HAT in Vancouver has been particularly effective in creating a unique microenvironment where IDUs who have attended HAT have been able to form a collective identity advocating for their rights. The result of this research points to the need for continuation of the project beyond the current study, leading toward a permanent program. PMID:24646474

A Human-Autonomy Teaming Approach for a Flight-Following Task

NASA Technical Reports Server (NTRS)

Brandt, Summer L.; Russell, Ricky; Lachter, Joel; Shively, Robert

2017-01-01

Managing aircraft is becoming more complex with increasingly sophisticated automation responsible for more flight tasks. With this increased complexity, it is becoming more difficult for operators to understand what the automation is doing and why. Human involvement with increasingly autonomous systems must adjust to allow for a more dynamic relationship involving cooperation and teamwork. As part of an ongoing project to develop a framework for human-autonomy teaming (HAT) in aviation, a part-task study was conducted to demonstrate, evaluate and refine proposed critical aspects of HAT. These features were built into an automated recommender system on a ground station available from previous studies. Participants performed a flight-following task once with the original ground station (i.e., No HAT condition) and once with the HAT features enabled (i.e., HAT condition). Behavioral and subjective measures were collected; subjective measures are presented here. Overall, participants preferred the ground station with HAT features enabled compared to the station without the HAT features. Participants reported that the HAT displays and automation were preferred for keeping up with operationally important issues. Additionally, participants reported that the HAT displays and automation provided enough situation awareness to complete the task and reduced workload relative to the No HAT baseline.

Human T-cell leukemia virus type-1-encoded protein HBZ represses p53 function by inhibiting the acetyltransferase activity of p300/CBP and HBO1

PubMed Central

Hoang, Kimson; Ankney, John A.; Nguyen, Stephanie T.; Rushing, Amanda W.; Polakowski, Nicholas; Miotto, Benoit; Lemasson, Isabelle

2016-01-01

Adult T-cell leukemia (ATL) is an often fatal malignancy caused by infection with the complex retrovirus, human T-cell Leukemia Virus, type 1 (HTLV-1). In ATL patient samples, the tumor suppressor, p53, is infrequently mutated; however, it has been shown to be inactivated by the viral protein, Tax. Here, we show that another HTLV-1 protein, HBZ, represses p53 activity. In HCT116 p53+/+ cells treated with the DNA-damaging agent, etoposide, HBZ reduced p53-mediated activation of p21/CDKN1A and GADD45A expression, which was associated with a delay in G2 phase-arrest. These effects were attributed to direct inhibition of the histone acetyltransferase (HAT) activity of p300/CBP by HBZ, causing a reduction in p53 acetylation, which has be linked to decreased p53 activity. In addition, HBZ bound to, and inhibited the HAT activity of HBO1. Although HBO1 did not acetylate p53, it acted as a coactivator for p53 at the p21/CDKN1A promoter. Therefore, through interactions with two separate HAT proteins, HBZ impairs the ability of p53 to activate transcription. This mechanism may explain how p53 activity is restricted in ATL cells that do not express Tax due to modifications of the HTLV-1 provirus, which accounts for a majority of patient samples. PMID:26625199

Distribution of acetylated histones resulting from Gal4-VP16 recruitment of SAGA and NuA4 complexes

PubMed Central

Vignali, Marissa; Steger, David J.; Neely, Kristen E.; Workman, Jerry L.

2000-01-01

We analyzed the targeting of histone acetyltransferase (HAT) complexes by DNA-binding activators during transcriptional activation and the resulting distribution of acetylated histones. An in vitro competition assay was developed to acetylate and transcribe a nucleosomal array template in the presence of excess non-specific chromatin, which mimics in vivo conditions. Stimulation of transcription from the nucleosomal array template under competitive conditions by the SAGA and NuA4 HAT complexes depended on the presence of the Gal4-VP16 activator, which recognizes sites in the promoter and directly interacts with these HATs. Importantly, the stimulation of transcription by SAGA and NuA4 depended on the presence of Gal4-VP16 during histone acetylation, and Gal4-VP16-bound nucleosomal templates were acetylated preferentially by SAGA and NuA4 relative to the competitor chromatin. While targeting of the SAGA complex led to H3 acetylation of promoter-proximal nucleosomes, targeting of the NuA4 complex led to a broader domain of H4 acetylation of >3 kbp. Thus, either promoter-proximal H3 acetylation by SAGA or broadly distributed acetylation of H4 by NuA4 activated transcription from chromatin templates. PMID:10835360

QSAR modeling for anti-human African trypanosomiasis activity of substituted 2-Phenylimidazopyridines

NASA Astrophysics Data System (ADS)

Masand, Vijay H.; El-Sayed, Nahed N. E.; Mahajan, Devidas T.; Mercader, Andrew G.; Alafeefy, Ahmed M.; Shibi, I. G.

2017-02-01

In the present work, sixty substituted 2-Phenylimidazopyridines previously reported with potent anti-human African trypanosomiasis (HAT) activity were selected to build genetic algorithm (GA) based QSAR models to determine the structural features that have significant correlation with the activity. Multiple QSAR models were built using easily interpretable descriptors that are directly associated with the presence or the absence of a structural scaffold, or a specific atom. All the QSAR models have been thoroughly validated according to the OECD principles. All the QSAR models are statistically very robust (R2 = 0.80-0.87) with high external predictive ability (CCCex = 0.81-0.92). The QSAR analysis reveals that the HAT activity has good correlation with the presence of five membered rings in the molecule.

A Human-Autonomy Teaming Approach for a Flight-Following Task

NASA Technical Reports Server (NTRS)

Brandt, Summer L.; Lachter, Joel; Russell, Ricky; Shively, R. Jay

2017-01-01

Human involvement with increasingly autonomous systems must adjust to allow for a more dynamic relationship involving cooperation and teamwork. As part of an ongoing project to develop a framework for human autonomy teaming (HAT) in aviation, a study was conducted to evaluate proposed tenets of HAT. Participants performed a flight-following task at a ground station both with and without HAT features enabled. Overall, participants preferred the ground station with HAT features enabled over the station without the HAT features. Participants reported that the HAT displays and automation were preferred for keeping up with operationally important issues. Additionally, participants reported that the HAT displays and automation provided enough situation awareness to complete the task, reduced the necessary workload and were efficient. Overall, there was general agreement that HAT features supported teaming with the automation. These results will be used to refine and expand our proposed framework for human-autonomy teaming.

Inner Core Anisotropy: Can Seismic Observations be Reconciled with Ab Initio Calculations of Elasticity?

NASA Astrophysics Data System (ADS)

Song, X.; Jordan, T. H.

2016-12-01

Body-wave and normal-mode observations have revealed an inner-core structure that is radially layered, axially anisotropic, and hemispherically asymmetric. Previous theoretical studies have examined the consistency of these features with the elasticity of iron crystals thought to dominate inner-core composition, but a fully consistent model has been elusive. Here we compare the seismic observation with effective-medium models derived from ab initio calculations of the elasticity tensors for hcp-Fe and bcc-Fe. Our estimates are based on Jordan's (GJI, 2015) effective medium theory, which is derived from a self-consistent, second-order Born approximation. The theory provides closed-form expressions for the effective elastic parameters of 3D anisotropic, heterogeneous media in which the local anisotropy is a constant hexagonal stiffness tensor C stochastically oriented about a constant symmetry axis \\hat{s} and the statistics of the small-scale heterogeneities are transversely isotropic in the plane perpendicular to \\hat{s}. The stochastic model is then described by a dimensionless "aspect ratio of the heterogeneity", 0 ≤ η < ∞, and a dimensionless "orientation ratio of the anisotropy", 0 ≤ ξ < ∞. The latter determines the degree to which the axis of C is aligned with \\hat{s}. We compute the loci of models with \\hat{s} oriented along the Earth's rotational axis ( \\hat{s} = north) by varying ξ and η for various ab initio estimates of C. We show that a lot of widely used estimates of C are inconsistent with most published normal-mode models of inner-core anisotropy. In particular, if the P-wave fast axis aligns with the rotational axis, which is required to satisfy the body-wave observations, then these hcp-Fe models predict that the fast polarization of the S waves is in the plane perpendicular to \\hat{s}, which disagrees with most normal-mode models. We have attempted to resolve this discrepancy by examining alternative hcp-Fe models, including radially anisotropic distributions of stochastic anisotropy and heterogeneity (i.e., where \\hat{s} = \\hat{r}), as well as bcc-Fe models. Our calculations constrain the form of C needed to satisfy the seismological inferences.

WARM SPITZER PHOTOMETRY OF THREE HOT JUPITERS: HAT-P-3b, HAT-P-4b AND HAT-P-12b

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

Todorov, Kamen O.; Deming, Drake; Knutson, Heather A.

2013-06-20

We present Warm Spitzer/IRAC secondary eclipse time series photometry of three short-period transiting exoplanets, HAT-P-3b, HAT-P-4b and HAT-P-12b, in both the available 3.6 and 4.5 {mu}m bands. HAT-P-3b and HAT-P-4b are Jupiter-mass objects orbiting an early K and an early G dwarf star, respectively. For HAT-P-3b we find eclipse depths of 0.112%+0.015%-0.030% (3.6 micron) and 0.094%+0.016%-0.009% (4.5 {mu}m). The HAT-P-4b values are 0.142%+0.014%-0.016% (3.6 micron) and 0.122%+0.012%-0.014% 4.5 {mu}m). The two planets' photometry is consistent with inefficient heat redistribution from their day to night sides (and low albedos), but it is inconclusive about possible temperature inversions in their atmospheres. HAT-P-12bmore » is a Saturn-mass planet and is one of the coolest planets ever observed during secondary eclipse, along with the hot Neptune GJ 436b and the hot Saturn WASP-29b. We are able to place 3{sigma} upper limits on the secondary eclipse depth of HAT-P-12b in both wavelengths: <0.042% (3.6 {mu}m) and <0.085% (4.5 {mu}m). We discuss these results in the context of the Spitzer secondary eclipse measurements of GJ 436b and WASP-29b. It is possible that we do not detect the eclipses of HAT-P-12b due to high eccentricity, but find that weak planetary emission in these wavelengths is a more likely explanation. We place 3{sigma} upper limits on the |e cos {omega}| quantity (where e is eccentricity and {omega} is the argument of periapsis) for HAT-P-3b (<0.0081) and HAT-P-4b (<0.0042), based on the secondary eclipse timings.« less

NIHSeniorHealth Celebrating 10 Years of online health and wellness information! | NIH MedlinePlus the Magazine

MedlinePlus

... information Open captioned videos Easy-to-read language Research-based Content Over 60 health topics 150 health videos Over 200 quizzes Frequently asked questions Bi-weekly healthy aging tips Most Popular Health Topics Exercise and Physical Activity * Eating Well as You Get Older * Shingles * ...

Direct Blood Dry LAMP: A Rapid, Stable, and Easy Diagnostic Tool for Human African Trypanosomiasis

PubMed Central

Hayashida, Kyoko; Kajino, Kiichi; Hachaambwa, Lottie; Namangala, Boniface; Sugimoto, Chihiro

2015-01-01

Loop-mediated isothermal amplification (LAMP) is a rapid and sensitive tool used for the diagnosis of a variety of infectious diseases. One of the advantages of this method over the polymerase chain reaction is that DNA amplification occurs at a constant temperature, usually between 60–65°C; therefore, expensive devices are unnecessary for this step. However, LAMP still requires complicated sample preparation steps and a well-equipped laboratory to produce reliable and reproducible results, which limits its use in resource-poor laboratories in most developing countries. In this study, we made several substantial modifications to the technique to carry out on-site diagnosis of Human African Trypanosomiasis (HAT) in remote areas using LAMP. The first essential improvement was that LAMP reagents were dried and stabilized in a single tube by incorporating trehalose as a cryoprotectant to prolong shelf life at ambient temperature. The second technical improvement was achieved by simplifying the sample preparation step so that DNA or RNA could be amplified directly from detergent-lysed blood samples. With these modifications, diagnosis of HAT in local clinics or villages in endemic areas becomes a reality, which could greatly impact on the application of diagnosis not only for HAT but also for other tropical diseases. PMID:25769046

Temperature dependence of exciton and charge carrier dynamics in organic thin films

NASA Astrophysics Data System (ADS)

Platt, A. D.; Kendrick, M. J.; Loth, M.; Anthony, J. E.; Ostroverkhova, O.

2011-12-01

We report on physical mechanisms behind the temperature-dependent optical absorption, photoluminescence (PL), and photoconductivity in spin-coated films of a functionalized anthradithiophene (ADT) derivative, ADT-triethylsilylethynyl (TES)-F, and its composites with C60 and another ADT derivative, ADT-TIPS-CN. Measurements of absorption and PL spectra, PL lifetimes, and transient photocurrent were performed at temperatures between 98 and 300 K as a function of applied electric field. In pristine ADT-TES-F films, absorptive and emissive species were identified to be disordered H aggregates whose properties are affected by static and dynamic disorder. The exciton bandwidths were ≤0.06 and ˜0.115 eV for absorptive and emissive aggregates, respectively, indicative of higher disorder in the emissive species. The exciton in the latter was found to be delocalized over approximately four to five molecules. The PL properties were significantly modified upon adding a guest molecule to the ADT-TES-F host. In ADT-TES-F/C60 composites, the PL was considerably quenched due to photoinduced electron transfer from ADT-TES-F to C60, while in ADT-TES-F/ADT-TIPS-CN blends, the PL was dominated by emission from an exciplex formed between ADT-TES-F and ADT-TIPS-CN molecules. In all materials, the PL quantum yield dramatically decreased as the temperature increased due to thermally activated nonradiative recombination. Considerable electric-field-induced PL quenching was observed at low temperatures at electric fields above ˜105 V/cm due to tunneling into dark states. No significant contribution of ADT-TES-F emissive exciton dissociation to transient photocurrent was observed. In all materials, charge carriers were photogenerated at sub-500-ps time scales, limited by the laser pulse width, with temperature- and electric-field-independent photogeneration efficiency. In ADT-TES-F/C60 (2%) composites, the photogeneration efficiency was a factor of 2-3 higher than that in pristine ADT-TES-F films. In ADT-TES-F/ADT-TIPS-CN (2%) blends, an additional charge carrier photogeneration component was observed at room temperature at time scales of ˜20 ns due to exciplex dissociation. At ˜0.5-5 ns after photoexcitation, the carriers propagated via thermally and electric-field-activated hopping with an activation energy of ˜0.025 eV. At time scales longer than ˜5 ns, charge transport of carriers that are not frozen in traps proceeded through tunneling via isoenergetic sites.

Spatial predictions of Rhodesian Human African Trypanosomiasis (sleeping sickness) prevalence in Kaberamaido and Dokolo, two newly affected districts of Uganda.

PubMed

Batchelor, Nicola A; Atkinson, Peter M; Gething, Peter W; Picozzi, Kim; Fèvre, Eric M; Kakembo, Abbas S L; Welburn, Susan C

2009-12-15

The continued northwards spread of Rhodesian sleeping sickness or Human African Trypanosomiasis (HAT) within Uganda is raising concerns of overlap with the Gambian form of the disease. Disease convergence would result in compromised diagnosis and treatment for HAT. Spatial determinants for HAT are poorly understood across small areas. This study examines the relationships between Rhodesian HAT and several environmental, climatic and social factors in two newly affected districts, Kaberamaido and Dokolo. A one-step logistic regression analysis of HAT prevalence and a two-step logistic regression method permitted separate analysis of both HAT occurrence and HAT prevalence. Both the occurrence and prevalence of HAT were negatively correlated with distance to the closest livestock market in all models. The significance of distance to the closest livestock market strongly indicates that HAT may have been introduced to this previously unaffected area via the movement of infected, untreated livestock from endemic areas. This illustrates the importance of the animal reservoir in disease transmission, and highlights the need for trypanosomiasis control in livestock and the stringent implementation of regulations requiring the treatment of cattle prior to sale at livestock markets to prevent any further spread of Rhodesian HAT within Uganda.

GPS-PAIL: prediction of lysine acetyltransferase-specific modification sites from protein sequences.

PubMed

Deng, Wankun; Wang, Chenwei; Zhang, Ying; Xu, Yang; Zhang, Shuang; Liu, Zexian; Xue, Yu

2016-12-22

Protein acetylation catalyzed by specific histone acetyltransferases (HATs) is an essential post-translational modification (PTM) and involved in the regulation a broad spectrum of biological processes in eukaryotes. Although several ten thousands of acetylation sites have been experimentally identified, the upstream HATs for most of the sites are unclear. Thus, the identification of HAT-specific acetylation sites is fundamental for understanding the regulatory mechanisms of protein acetylation. In this work, we first collected 702 known HAT-specific acetylation sites of 205 proteins from the literature and public data resources, and a motif-based analysis demonstrated that different types of HATs exhibit similar but considerably distinct sequence preferences for substrate recognition. Using 544 human HAT-specific sites for training, we constructed a highly useful tool of GPS-PAIL for the prediction of HAT-specific sites for up to seven HATs, including CREBBP, EP300, HAT1, KAT2A, KAT2B, KAT5 and KAT8. The prediction accuracy of GPS-PAIL was critically evaluated, with a satisfying performance. Using GPS-PAIL, we also performed a large-scale prediction of potential HATs for known acetylation sites identified from high-throughput experiments in nine eukaryotes. Both online service and local packages were implemented, and GPS-PAIL is freely available at: http://pail.biocuckoo.org.

GPS-PAIL: prediction of lysine acetyltransferase-specific modification sites from protein sequences

PubMed Central

Deng, Wankun; Wang, Chenwei; Zhang, Ying; Xu, Yang; Zhang, Shuang; Liu, Zexian; Xue, Yu

2016-01-01

Protein acetylation catalyzed by specific histone acetyltransferases (HATs) is an essential post-translational modification (PTM) and involved in the regulation a broad spectrum of biological processes in eukaryotes. Although several ten thousands of acetylation sites have been experimentally identified, the upstream HATs for most of the sites are unclear. Thus, the identification of HAT-specific acetylation sites is fundamental for understanding the regulatory mechanisms of protein acetylation. In this work, we first collected 702 known HAT-specific acetylation sites of 205 proteins from the literature and public data resources, and a motif-based analysis demonstrated that different types of HATs exhibit similar but considerably distinct sequence preferences for substrate recognition. Using 544 human HAT-specific sites for training, we constructed a highly useful tool of GPS-PAIL for the prediction of HAT-specific sites for up to seven HATs, including CREBBP, EP300, HAT1, KAT2A, KAT2B, KAT5 and KAT8. The prediction accuracy of GPS-PAIL was critically evaluated, with a satisfying performance. Using GPS-PAIL, we also performed a large-scale prediction of potential HATs for known acetylation sites identified from high-throughput experiments in nine eukaryotes. Both online service and local packages were implemented, and GPS-PAIL is freely available at: http://pail.biocuckoo.org. PMID:28004786

P300 inhibition enhances gemcitabine-induced apoptosis of pancreatic cancer

PubMed Central

Ono, Hiroaki; Basson, Marc D.; Ito, Hiromichi

2016-01-01

The transcriptional cofactor p300 has histone acetyltransferase activity (HAT) and has been reported to participate in chromatin remodeling and DNA repair. We hypothesized that targeting p300 can enhance the cytotoxicity of gemcitabine, which induces pancreatic cancer cell apoptosis by damaging DNA. Expression of p300 was confirmed in pancreatic cancer cell lines and human pancreatic adenocarcinoma tissues by western blotting and immunohistochemistry. When pancreatic cancer cells were treated with gemcitabine, p300 was recruited to chromatin within 24 hours, indicating the role in response to DNA damage. When p300 was gene-silenced with siRNA, histone acetylation was substantially reduced and pancreatic cancer cells were sensitized to gemcitabine. The selective p300 HAT inhibitor C646 similarly decreased histone acetylation, increased gemcitabine-induced apoptosis and thus enhanced the cytotoxicity of gemcitabine on pancreatic cancer cells. These findings indicate that p300 contributes to chemo-resistance of pancreatic cancer against gemcitabine and suggest that p300 and its HAT activity may be a potential therapeutic target to improve outcomes in patients with pancreatic cancer. PMID:27322077

Architecture of the Saccharomyces cerevisiae SAGA transcription coactivator complex

PubMed Central

Han, Yan; Luo, Jie; Ranish, Jeffrey; Hahn, Steven

2014-01-01

The conserved transcription coactivator SAGA is comprised of several modules that are involved in activator binding, TBP binding, histone acetylation (HAT) and deubiquitination (DUB). Crosslinking and mass spectrometry, together with genetic and biochemical analyses, were used to determine the molecular architecture of the SAGA-TBP complex. We find that the SAGA Taf and Taf-like subunits form a TFIID-like core complex at the center of SAGA that makes extensive interactions with all other SAGA modules. SAGA-TBP binding involves a network of interactions between subunits Spt3, Spt8, Spt20, and Spt7. The HAT and DUB modules are in close proximity, and the DUB module modestly stimulates HAT function. The large activator-binding subunit Tra1 primarily connects to the TFIID-like core via its FAT domain. These combined results were used to derive a model for the arrangement of the SAGA subunits and its interactions with TBP. Our results provide new insight into SAGA function in gene regulation, its structural similarity with TFIID, and functional interactions between the SAGA modules. PMID:25216679

Molecular identification of PpHDAC1, the first histone deacetylase fron the slime mold Physarum polycephalum.

PubMed

Brandtner, Eva-Maria; Lechner, Thomas; Loidl, Peter; Lusser, Alexandra

2002-01-01

The dynamic state of post-translational acetylation of eukaryotic histones is maintained by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HATs and HDACs have been shown to be components of various regulatory protein complexes in the cell. Their enzymatic activities, intracellular localization and substrate specificities are regulated in a complex, cell cycle related manner. In the myxomycete Physarum polycephalum multiple HATs and HDACs can be distinguished in biochemical terms and they exhibit dynamic activity patterns depending on the cell cycle stage. Here we report on the cloning of the first P. polycephalum HDAC (PpHDAC1) related to the S. cerevisiae Rpd3 protein. The expression pattern of PpHDAC1 mRNA was analysed at different time points of the cell cycle and found to be largely constant. Treatment of macroplasmodia with the HDAC inhibitor trichostatin A at several cell cycle stages resulted in a significant delay in entry into mitosis of treated versus untreated plasmodia. No effect of TSA treatment could be observed on PpHDAC1 expression itself.

The Effectiveness Evaluation of Helicopter Ambulance Transport among Neurotrauma Patients in Korea

PubMed Central

Park, Kyoung Duck; Seo, Sook Jin; Oh, Chang Hyun; Kim, Se Hyuk

2014-01-01

Objective Helicopter ambulance transport (HAT) is a highly resource-intensive facility that is a well-established part of the trauma transport system in many developed countries. Here, we review the benefit of HAT for neurosurgical patients in Korea. Methods This retrospective study followed neurotrauma patients who were transferred by HAT to a single emergency trauma center over a period of 2 years. The clinical benefits of HAT were measured according to the necessity of emergency surgical intervention and the differences in the time taken to transport patients by ground ambulance transport (GAT) and HAT. Results Ninety-nine patients were transferred to a single university hospital using HAT, of whom 32 were taken to the neurosurgery department. Of these 32 patients, 10 (31.3%) needed neurosurgical intervention, 14 (43.8%) needed non-neurosurgical intervention, 3 (9.4%) required both, and 11 (34.4%) did not require any intervention. The transfer time was faster using HAT than the estimated time needed for GAT, although for a relatively close distance (<50 km) without ground obstacles (mountain or sea) HAT did not improve transfer time. The cost comparison showed that HAT was more expensive than GAT (3,292,000 vs. 84,000 KRW, p<0.001). Conclusion In this Korean-based study, we found that HAT has a clinical benefit for neurotrauma cases involving a transfer from a distant site or an isolated area. A more precise triage for using HAT should be considered to prevent overuse of this expensive transport method. PMID:25289124

The Effectiveness Evaluation of Helicopter Ambulance Transport among Neurotrauma Patients in Korea.

PubMed

Park, Kyoung Duck; Seo, Sook Jin; Oh, Chang Hyun; Kim, Se Hyuk; Cho, Jin Mo

2014-07-01

Helicopter ambulance transport (HAT) is a highly resource-intensive facility that is a well-established part of the trauma transport system in many developed countries. Here, we review the benefit of HAT for neurosurgical patients in Korea. This retrospective study followed neurotrauma patients who were transferred by HAT to a single emergency trauma center over a period of 2 years. The clinical benefits of HAT were measured according to the necessity of emergency surgical intervention and the differences in the time taken to transport patients by ground ambulance transport (GAT) and HAT. Ninety-nine patients were transferred to a single university hospital using HAT, of whom 32 were taken to the neurosurgery department. Of these 32 patients, 10 (31.3%) needed neurosurgical intervention, 14 (43.8%) needed non-neurosurgical intervention, 3 (9.4%) required both, and 11 (34.4%) did not require any intervention. The transfer time was faster using HAT than the estimated time needed for GAT, although for a relatively close distance (<50 km) without ground obstacles (mountain or sea) HAT did not improve transfer time. The cost comparison showed that HAT was more expensive than GAT (3,292,000 vs. 84,000 KRW, p<0.001). In this Korean-based study, we found that HAT has a clinical benefit for neurotrauma cases involving a transfer from a distant site or an isolated area. A more precise triage for using HAT should be considered to prevent overuse of this expensive transport method.

HAT-P-39b-HAT-P-41b: Three Highly Inflated Transiting Hot Jupiters

NASA Astrophysics Data System (ADS)

Hartman, J. D.; Bakos, G. Á.; Béky, B.; Torres, G.; Latham, D. W.; Csubry, Z.; Penev, K.; Shporer, A.; Fulton, B. J.; Buchhave, L. A.; Johnson, J. A.; Howard, A. W.; Marcy, G. W.; Fischer, D. A.; Kovács, G.; Noyes, R. W.; Esquerdo, G. A.; Everett, M.; Szklenár, T.; Quinn, S. N.; Bieryla, A.; Knox, R. P.; Hinz, P.; Sasselov, D. D.; Fűrész, G.; Stefanik, R. P.; Lázár, J.; Papp, I.; Sári, P.

2012-11-01

We report the discovery of three new transiting extrasolar planets orbiting moderately bright (V = 11.1, 11.7, and 12.4) F stars. The planets HAT-P-39b through HAT-P-41b have periods of P = 3.5439 days, 4.4572 days, and 2.6940 days, masses of 0.60 M J, 0.62 M J, and 0.80 M J, and radii of 1.57 R J, 1.73 R J, and 1.68 R J, respectively. They orbit stars with masses of 1.40 M ⊙, 1.51 M ⊙, and 1.51 M ⊙, respectively. The three planets are members of an emerging population of highly inflated Jupiters with 0.4 M J < M < 1.5 M J and R > 1.5 R J. Based in part on observations obtained at the W. M. Keck Observatory, which is operated by the University of California and the California Institute of Technology. Keck time has been granted by NOAO (A201Hr, A289Hr, and A284Hr), NASA (N049Hr, N018Hr, N167Hr, N029Hr, N108Hr, and N154Hr), and the NOAO Gemini/Keck time-exchange program (G329Hr). Based in part on observations made with the Nordic Optical Telescope, operated on the island of La Palma jointly by Denmark, Finland, Iceland, Norway, and Sweden, in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias. Based in part on observations obtained with facilities of the Las Cumbres Observatory Global Telescope. Observations reported here were obtained at the MMT Observatory, a joint facility of the Smithsonian Institution and the University of Arizona.

EPC1/TIP60-Mediated Histone Acetylation Facilitates Spermiogenesis in Mice.

PubMed

Dong, Yixin; Isono, Kyo-Ichi; Ohbo, Kazuyuki; Endo, Takaho A; Ohara, Osamu; Maekawa, Mamiko; Toyama, Yoshiro; Ito, Chizuru; Toshimori, Kiyotaka; Helin, Kristian; Ogonuki, Narumi; Inoue, Kimiko; Ogura, Atsuo; Yamagata, Kazutsune; Kitabayashi, Issay; Koseki, Haruhiko

2017-10-01

Global histone hyperacetylation is suggested to play a critical role for replacement of histones by transition proteins and protamines to compact the genome during spermiogenesis. However, the underlying mechanisms for hyperacetylation-mediated histone replacement remains poorly understood. Here, we report that EPC1 and TIP60, two critical components of the mammalian nucleosome acetyltransferase of H4 (NuA4) complexes, are coexpressed in male germ cells. Strikingly, genetic ablation of either Epc1 or Tip60 disrupts hyperacetylation and impairs histone replacement, in turn causing aberrant spermatid development. Taking these observations together, we reveal an essential role of the NuA4 complexes for histone hyperacetylation and subsequent compaction of the spermatid genome. Copyright © 2017 American Society for Microbiology.

Retransplantation in Late Hepatic Artery Thrombosis: Graft Access and Transplant Outcome.

PubMed

Buchholz, Bettina M; Khan, Shakeeb; David, Miruna D; Gunson, Bridget K; Isaac, John R; Roberts, Keith J; Muiesan, Paolo; Mirza, Darius F; Tripathi, Dhiraj; Perera, M Thamara P R

2017-08-01

Definitive treatment for late hepatic artery thrombosis (L-HAT) is retransplantation (re-LT); however, the L-HAT-associated disease burden is poorly represented in allocation models. Graft access and transplant outcome of the re-LT experience between 2005 and 2016 was reviewed with specific focus on the L-HAT cohort in this single-center retrospective study. Ninety-nine (5.7%) of 1725 liver transplantations were re-LT with HAT as the main indication (n = 43; 43%) distributed into early (n = 25) and late (n = 18) episodes. Model for end-stage liver disease as well as United Kingdom model for end-stage liver disease did not accurately reflect high disease burden of graft failure associated infections such as hepatic abscesses and biliary sepsis in L-HAT. Hence, re-LT candidates with L-HAT received low prioritization and waited longest until the allocation of an acceptable graft (median, 103 days; interquartile range, 28-291 days), allowing for progression of biliary sepsis. Balance of risk score and 3-month mortality score prognosticated good transplant outcome in L-HAT but, contrary to the prediction, the factual 1-year patient survival after re-LT was significantly inferior in L-HAT compared to early HAT, early non-HAT and late non-HAT (65% vs 82%, 92% and 95%) which was mainly caused by sepsis and multiorgan failure driving 3-month mortality (28% vs 11%, 16% and 0%). Access to a second graft after a median waitlist time of 6 weeks achieved the best short- and long-term outcome in re-LT for L-HAT (3-month mortality, 13%; 1-year survival, 77%). Inequity in graft access and peritransplant sepsis are fundamental obstacles for successful re-LT in L-HAT. Offering a graft for those in need at the best window of opportunity could facilitate earlier engrafting with improved outcomes.

Acetylation of nucleosomal histones by p300 facilitates transcription from tax-responsive human T-cell leukemia virus type 1 chromatin template.

PubMed

Lu, Hanxin; Pise-Masison, Cynthia A; Fletcher, Terace M; Schiltz, R Louis; Nagaich, Akhilesh K; Radonovich, Michael; Hager, Gordon; Cole, Philip A; Brady, John N

2002-07-01

Expression of human T-cell leukemia virus type 1 (HTLV-1) is regulated by the viral transcriptional activator Tax. Tax activates viral transcription through interaction with the cellular transcription factor CREB and the coactivators CBP/p300. One key property of the coactivators is the presence of histone acetyltransferase (HAT) activity, which enables p300/CBP to modify nucleosome structure. The data presented in this manuscript demonstrate that full-length p300 and CBP facilitate transcription of a reconstituted chromatin template in the presence of Tax and CREB. The ability of p300 and CBP to activate transcription from the chromatin template is dependent upon the HAT activity. Moreover, the coactivator HAT activity must be tethered to the template by Tax and CREB, since a p300 mutant that fails to interact with Tax did not facilitate transcription or acetylate histones. p300 acetylates histones H3 and H4 within nucleosomes located in the promoter and 5' proximal regions of the template. Nucleosome acetylation is accompanied by an increase in the level of binding of RNA polymerase II transcription factor TFIID and RNA polymerase II to the promoter. Interestingly, we found distinct transcriptional activities between CBP and p300. CBP, but not p300, possesses an N-terminal activation domain which directly activates Tax-mediated HTLV-1 transcription from a naked DNA template. Finally, using the chromatin immunoprecipitation assay, we provide the first direct experimental evidence that p300 and CBP are associated with the HTLV-1 long terminal repeat in vivo.

Proceedings of the Annual Meeting (21st), Aquatic Plant Control Research Program Held in Mobile, Alabama on 17-21 November 1986

DTIC Science & Technology

1987-11-01

triploid grass carl) (ca. 13 kg/ vegetated ha). A subsequent 123 50. 40 . \\A 30 B Figure 1. Percent composition of aquatic 0- \\macrophytes in Devils Lake...10 Tips (L&S)t KLB 38 2.50 1.74 0 to 7 Tips (I&S4 RRD 40 2.03 1.54 0Oto 6 Hydrillat Tips (L&S)t SQL 30 3.70 2.14 0 to 9 Tips (L&S4t KLB 32 4.60 1.98 0...perfoliatus P. tricarinatus I ercsm10 20 30 40 50 60 70 8 Number of individuals Figure 5. Bar graph depicting average number of eggs and adults of

Regulation of H+ Extrusion and Cytoplasmic pH in Maize Root Tips Acclimated to a Low-Oxygen Environment.

PubMed

Xia, J. H.; Roberts, JKM.

1996-05-01

We tested the hypothesis that H+ extrusion contributes to cytoplasmic pH regulation and tolerance of anoxia in maize (Zea mays) root tips. We studied root tips of whole seedlings that were acclimated to a low-oxygen environment by pretreatment in 3% (v/v) O2. Acclimated root tips characteristically regulate cytoplasmic pH near neutrality and survive prolonged anoxia, whereas nonacclimated tips undergo severe cytoplasmic acidosis and die much more quickly. We show that the plasma membrane H+-ATPase can operate under anoxia and that net H+ extrusion increases when cytoplasmic pH falls. However, at an external pH near 6.0, H+ extrusion contributes little to cytoplasmic pH regulation. At more acidic external pH values, net H+ flux into root tips increases dramatically, leading to a decrease in cytoplasmic pH and reduced tolerance of anoxia. We present evidence that, under these conditions, H+ pumps are activated to partly offset acidosis due to H+ influx and, thereby, contribute to cytoplasmic pH regulation and tolerance of anoxia. The regulation of H+ extrusion under anoxia is discussed with respect to the acclimation response and mechanisms of intracellular pH regulation in aerobic plant cells.

Intrinsic Antioxidant Potential of the Aminoindole Structure: A Computational Kinetics Study of Tryptamine.

PubMed

Bentz, Erika N; Lobayan, Rosana M; Martínez, Henar; Redondo, Pilar; Largo, Antonio

2018-06-21

A computational kinetics study of the antioxidant activity of tryptamine toward HO • and HOO • radicals in water at 298 K has been carried out. Density functional methods have been employed for the quantum chemical calculations, and the conventional transition state theory was used for rate constant evaluation. Different mechanisms have been considered: radical adduct formation (RAF), single electron transfer (SET), and hydrogen atom transfer (HAT). For the reaction of tryptamine with the hydroxyl radical, nearly all channels are diffusion-controlled, and the overall rate constant is very high, 6.29 × 10 10 M -1 s -1 . The RAF mechanism has a branching ratio of 55%, followed by the HAT mechanism (31%), whereas the SET mechanism accounts just for 13% of the products. The less hindered carbon atom neighboring to the nitrogen of the indole ring seems to be the preferred site for the RAF mechanism, with a branching ratio of 16%. The overall rate constant for the reaction of tryptamine with the HOO • radical is 3.71 × 10 4 M -1 s -1 , suggesting that it could be a competitive process with other reactions of hydroperoxyl radicals in biological environments. For this reaction only the HAT mechanism seems viable. Furthermore, only two centers may contribute to the HAT mechanism, the nitrogen atom of the indole ring and a carbon atom of the aminoethyl chain, the former accounting for more than 91% of the total products. Our results suggest that tryptamine could have a noticeable scavenging activity toward radicals, and that this activity is mainly related to the nitrogen atom of the indole ring, thus showing the relevance of their behavior in the study of aminoindoles.

Dynamics of quiet human stance: computer simulations of a triple inverted pendulum model.

PubMed

Günther, Michael; Wagner, Heiko

2016-01-01

For decades, the biomechanical description of quiet human stance has been dominated by the single inverted pendulum (SIP) paradigm. However, in the past few years, the SIP model family has been falsified as an explanatory approach. Double inverted pendulum models have recently proven to be inappropriate. Human topology with three major leg joints suggests in a natural way to examine triple inverted pendulum (TIP) models as an appropriate approach. In this study, we focused on formulating a TIP model that can synthesise stable balancing attractors based on minimalistic sensor information and actuation complexity. The simulated TIP oscillation amplitudes are realistic in vertical direction. Along with the horizontal ankle, knee and hip positions, though, all simulated joint angle amplitudes still exceed the measured ones about threefold. It is likely that they could be eventually brought down to the physiological range by using more sensor information. The TIP systems' eigenfrequency spectra come out as another major result. The eigenfrequencies spread across about 0.1 Hz...20 Hz. Our main result is that joint stiffnesses can be reduced even below statically required values by using an active hip torque balancing strategy. When reducing mono- and bi-articular stiffnesses further down to levels threatening dynamic stability, the spectra indicate a change from torus-like (stable) to strange (chaotic) attractors. Spectra of measured ground reaction forces appear to be strange-attractor-like. We would conclude that TIP models are a suitable starting point to examine more deeply the dynamic character of and the essential structural properties behind quiet human stance. Abbreviations and technical terms Inverted pendulum body exposed to gravity and pivoting in a joint around position of unstable equilibrium (operating point) SIP single inverted pendulum: one rigid body pivoting around fixation to the ground (external joint) DIP double inverted pendulum: two bodies; external and internal joint operate around instability TIP triple inverted pendulum: three bodies; external and both internal joints operate around instability QIP quadruple inverted pendulum: four bodies, foot replaces external joint; all three internal joints operate around instability Eigenfrequency characteristic frequency that a physical system is oscillating at when externally excited at a limited energy level DOF degree of freedom; in mechanics: linear displacement or angle or combination thereof Mono-articular stiffness: coefficient of proportionality between mechanical displacement of a DOF and restoring force/torque component in the respective DOF Bi-articular stiffness coefficient of proportionality between mechanical displacement of a DOF and restoring force/torque component in another DOF GRF ground reaction force HAT segment including head, arms and trunk COM centre of mass COP centre of pressure in the plane of the force platform surface.

Effect of light dispersion of LED curing lights on resin composite polymerization.

PubMed

Vandewalle, Kraig S; Roberts, Howard W; Andrus, Jeffrey L; Dunn, William J

2005-01-01

This study evaluated the effect of light dispersion of halogen and LED curing lights on resin composite polymerization. One halogen (Optilux 501, SDS/Kerr, Orange, CA, USA) and five light-emitting diode (LED) curing lights (SmartLite iQ, Dentsply Caulk, Milford, DE, USA; LEDemetron 1, SDS/Kerr; FLASHlite 1001, Discus Dental, Culver City, CA, USA; UltraLume LED 5, Ultradent Products, South Jordan, UT, USA; Allegro, Den-Mat, Santa Maria, CA, USA) were used in this study. Specimens (8 mm diameter by 2 mm thick) were made in polytetrafluoroethylene molds using hybrid (Z100, 3M ESPE, St. Paul, MN, USA) and microfill (A110, 3M ESPE) composite resins. The top surface was polymerized for 5 seconds with the curing light guide tip positioned at a distance of 1 and 5 mm. Degree of conversion (DC) of the composite specimens was analyzed on the bottom surface using micro-Fourier Transform Infrared (FTIR) spectroscopy (Perkin-Elmer FTIR Spectrometer, Wellesley, PA, USA) 10 minutes after light activation. DC at the bottom of the 2 mm specimen was expressed as a percentage of the mean maximum DC. Five specimens were created per curing light and composite type (n=5). Percent mean DC ratios and SDs were calculated for each light under each testing condition. Data were analyzed by analysis of variance (ANOVA)/Tukey's test (alpha = .05). A beam analyzer (LBA-700, Spiricon, Logan, UT, USA) was used to record the emitted light from the curing lights at 0 and 5 mm distances (n=5). A Top Hat factor was used to compare the quality of the emitted beam profile (LBA/PC, Spiricon). The divergence angle from vertical was also determined in the x- and y-axes (LBA/PC). Mean values and SDs were calculated for each light under each testing condition (0 and 5 mm, x- and y-axes) and analyzed by a two-way ANOVA/Tukey's test (alpha = .05). For DC ratios, significant differences were found based on curing light and curing distance (p < .05). At 1 mm, Optilux 501 and FLASHlite 1001 produced significantly higher DC ratios with the hybrid resin composite. No differences were found among lights with the microfill at 1 mm. At 5 mm, SmartLite iQ, FLASHlite 1001, LEDemetron 1, and UltraLume LED 5 produced significantly higher DC ratios with the hybrid resin composite, whereas LEDemetron 1 and SmartLite iQ produced significantly higher DC ratios with the microfill resin composite. The UltraLume LED 5, Allegro, and Optilux 501 had significant reductions in mean DC ratios at curing distances of 1 and 5 mm with both resin composite types. For dispersion of light, significant differences were found in Top Hat factor and divergence angle (p < .001). SmartLite iQ had overall the highest Top Hat factor and lowest divergence angle of tested lights. A linear regression analysis relating pooled DC with pooled Top Hat factors and divergence angles found a very good correlation (r2 = .86) between dispersion of light over distance and the ability to polymerize resin composite. The latest generation of LED curing lights provides DC ratios similar to or better than the halogen curing light at a curing distance of 5 mm. Dispersion of light plays a significant role in the DC of resin composite. To maximize curing effectiveness, light guides should be maintained in close proximity to the surface of the light-activated restorative material.

Ectopic expression of different cytokinin-regulated transcription factor genes of Arabidopsis thaliana alters plant growth and development.

PubMed

Köllmer, Ireen; Werner, Tomáš; Schmülling, Thomas

2011-08-15

The plant hormone cytokinin rapidly alters the steady state transcript levels of a number of transcription factor genes suggesting that these might have a function in mediating cytokinin effects. Here we report the analysis of Arabidopsis thaliana plants with an altered expression level of four different cytokinin-regulated transcription factor genes. These include GATA22 (also known as CGA1/GNL), two genes coding for members of the homeodomain zip (HD zip) class II transcription factor family (HAT4, HAT22), and bHLH64. Ectopic expression of the GATA22 gene induced the development of chloroplasts in root tissue where it is normally suppressed and led to the formation of shorter and less branched roots. Overexpression of HAT22 lowered the seedlings chlorophyll content and caused an earlier onset of leaf senescence. Enhanced expression of the HAT4 gene led to severe defects in inflorescence stem development and to a decrease in root growth and branching, while hat4 insertional mutants developed a larger root system. 35S:bHLH64 transgenic plants showed a pleiotropic phenotype, consisting of larger rosettes, reduced chlorophyll content and an elongated and thickened hypocotyl. Flower development was strongly disturbed leading to sterile plants. The results are consistent with specific functions of these transcription factor genes in regulating part of the cytokinin activities and suggest their action as convergence point with other signalling pathways, particularly those of gibberellin and light. Copyright © 2011 Elsevier GmbH. All rights reserved.

Engineering negative differential conductance with the Cu(111) surface state.

PubMed

Heinrich, B W; Rastei, M V; Choi, D-J; Frederiksen, T; Limot, L

2011-12-09

Low-temperature scanning tunneling microscopy and spectroscopy are employed to investigate electron tunneling from a C60-terminated tip into a Cu(111) surface. Tunneling between a C60 orbital and the Shockley surface states of copper is shown to produce negative differential conductance (NDC) contrary to conventional expectations. NDC can be tuned through barrier thickness or C60 orientation up to complete extinction. The orientation dependence of NDC is a result of a symmetry matching between the molecular tip and the surface states.

VizieR Online Data Catalog: iz follow-up photometry of HAT-P-65 and HAT-P-66 (Hartman+, 2016)

NASA Astrophysics Data System (ADS)

Hartman, J. D.; Bakos, G. A.; Bhatti, W.; Penev, K.; Bieryla, A.; Latham, D. W.; Kovacs, G.; Torres, G.; Csubry, Z.; de Val-Borro, M.; Buchhave, L.; Kovacs, T.; Quinn, S.; Howard, A. W.; Isaacson, H.; Fulton, B. J.; Everett, M. E.; Esquerdo, G.; Beky, B.; Szklenar, T.; Falco, E.; Santerne, A.; Boisse, I.; Hebrard, G.; Burrows, A.; Lazar, J.; Papp, I.; Sari, P.

2017-05-01

Both HAT-P-65 and Both HAT-P-66 were selected as candidate transiting planet systems based on Sloan r-band photometric time series observations carried out with the HATNet telescope network. HATNet consists of six 11cm aperture telephoto lenses, each coupled to an APOGEE front-side-illuminated CCD camera, and each placed on a fully automated telescope mount. Four of the instruments are located at Fred Lawrence Whipple Observatory (FLWO) in Arizona, USA, while two are located on the roof of the Submillimeter Array hangar building at Mauna Kea Observatory (MKO) on the island of Hawaii, USA. Each instrument observes a 10.6°*10.6° field of view. We conducted follow-up photometric time series observations of each object using KeplerCam on the 1.2m telescope at FLWO. HAT-P-65 was observed on 2009 Sep-Dec with a r-band filter using the HAT-6/G342 (located at FLWO) and the HAT-8/G342 (located on the roof of the Smithsonian Astrophysical Observatory Submillimeter Array hangar building at Mauna Kea Observatory in Hawaii), and on 2011 Jun 10 (i filter), 2011 Jun 26 (i filter), 2011 Jul 14 (i filter), 2011 Sep 20 (i filter), 2013 Sep 16 (z filter), 2013 Sep 29 (i filter), and 2013 Oct 04 (i filter) using the FLWO 1.2m/KeplerCam. HAT-P-66 was observed on 2011 Feb-2012 Mar using the HAT-10/G101 (located at FLWO) with a r-band filter, using the HAT-6/G101 (located at FLWO) with a r-band filter, and using the HAT-7/G101 (located at FLWO) with a r-band filter, on 2011 Feb-2012 Apr using the HAT-5/G101 (located at FLWO) with a r-band filter, on 2011 May-2012 Jun using the HAT-8/G101 (located on the roof of the Smithsonian Astrophysical Observatory Submillimeter Array hangar building at Mauna Kea Observatory in Hawaii) with a r-band filter, on 2011 Oct-2012 Jan using the HAT-9/G101 (located at FLWO) with a r-band filter, and on 2015 Apr 29 (i filter), 2015 Nov 26 (z filter), 2015 Dec 08 (i filter) using the FLWO 1.2m/KeplerCam. Spectroscopic observations of both HAT-P-65 and HAT-P-66 were carried out using the Tillinghast Reflector Echelle Spectrograph (TRES) on the 1.5m Tillinghast Reflector at FLWO (on 2010 Oct 27 for HAT-P-65, and 2014 Nov-2015 Jun for HAT-P-66), and the HIgh-Resolution Echelle Spectrometer (HIRES) on the Keck I 10m at Mauna Kea Observatory (MKO) on the island of Hawaii, USA (on 2010 Dec 14 and 2010 Dec-2013 Aug for HAT-P-65, and on 2016 Feb 3 and 2015 Dec-2016 Jan for HAT-P-66). For HAT-P-65 we also obtained observations on 2010 Aug 21-22 and 2011 Oct 8 using the Fibre-fed Echelle Spectrograph (FIES) on the 2.5m Nordic Optical Telescope (NOT) at the Observatorio del Roque de los Muchachos on the Spanish island of La Palma. For HAT-P-66 spectroscopic observations were also collected on 2015 Mar-2016 Jan using the SOPHIE spectrograph on the 1.93m telescope at the Observatoire de Haute-Provence (OHP) in France. The light curve measurements are available in Table2. The individual radial velocity and bisector span measurements are made available in Table4. (5 data files).

Poisson sampling - The adjusted and unadjusted estimator revisited

Treesearch

Michael S. Williams; Hans T. Schreuder; Gerardo H. Terrazas

1998-01-01

The prevailing assumption, that for Poisson sampling the adjusted estimator "Y-hat a" is always substantially more efficient than the unadjusted estimator "Y-hat u" , is shown to be incorrect. Some well known theoretical results are applicable since "Y-hat a" is a ratio-of-means estimator and "Y-hat u" a simple unbiased estimator...

30 CFR 56.15002 - Hard hats.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Hard hats. 56.15002 Section 56.15002 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Personal Protection § 56.15002 Hard hats. All persons shall wear suitable hard hats when in or around a mine or plant where falling objects...

30 CFR 56.15002 - Hard hats.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Hard hats. 56.15002 Section 56.15002 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Personal Protection § 56.15002 Hard hats. All persons shall wear suitable hard hats when in or around a mine or plant where falling objects...

30 CFR 57.15002 - Hard hats.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Hard hats. 57.15002 Section 57.15002 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Underground § 57.15002 Hard hats. All persons shall wear suitable hard hats when in or around a mine or plant...

30 CFR 57.15002 - Hard hats.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Hard hats. 57.15002 Section 57.15002 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Underground § 57.15002 Hard hats. All persons shall wear suitable hard hats when in or around a mine or plant...

30 CFR 56.15002 - Hard hats.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Hard hats. 56.15002 Section 56.15002 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Personal Protection § 56.15002 Hard hats. All persons shall wear suitable hard hats when in or around a mine or plant where falling objects...

30 CFR 56.15002 - Hard hats.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Hard hats. 56.15002 Section 56.15002 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Personal Protection § 56.15002 Hard hats. All persons shall wear suitable hard hats when in or around a mine or plant where falling objects...

30 CFR 56.15002 - Hard hats.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Hard hats. 56.15002 Section 56.15002 Mineral... HEALTH SAFETY AND HEALTH STANDARDS-SURFACE METAL AND NONMETAL MINES Personal Protection § 56.15002 Hard hats. All persons shall wear suitable hard hats when in or around a mine or plant where falling objects...

30 CFR 57.15002 - Hard hats.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Hard hats. 57.15002 Section 57.15002 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Underground § 57.15002 Hard hats. All persons shall wear suitable hard hats when in or around a mine or plant...

30 CFR 57.15002 - Hard hats.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Hard hats. 57.15002 Section 57.15002 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Underground § 57.15002 Hard hats. All persons shall wear suitable hard hats when in or around a mine or plant...

30 CFR 57.15002 - Hard hats.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Hard hats. 57.15002 Section 57.15002 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR METAL AND NONMETAL MINE SAFETY AND... Underground § 57.15002 Hard hats. All persons shall wear suitable hard hats when in or around a mine or plant...

Efficacy of cocaine contingency management in heroin-assisted treatment: Results of a randomized controlled trial.

PubMed

Blanken, Peter; Hendriks, Vincent M; Huijsman, Ineke A; van Ree, Jan M; van den Brink, Wim

2016-07-01

To determine the efficacy of contingency management (CM), targeting cocaine use, as an add-on intervention for heroin dependent patients in supervised heroin-assisted treatment (HAT) with frequent cocaine use. Multi-center, open-label, parallel group, randomized controlled trial. Twelve specialized addiction treatment centers for HAT in The Netherlands; April 2006-January 2011. 214 chronic, treatment-refractory heroin dependent patients in HAT, with frequent cocaine use. Routine, daily supervised diacetylmorphine treatment, co-prescribed with oral methadone (HAT), with and without 6 months contingency management for cocaine use as an add-on intervention; HAT+CM and HAT-only, respectively. Primary outcome was the longest, uninterrupted duration of cocaine abstinence, based upon laboratory urinalysis. Secondary outcome measures included other cocaine-related measures, treatment retention in HAT, and multi-domain health-related treatment response. In an intention-to-treat analysis, HAT+CM was more effective than HAT-only in promoting longer, uninterrupted duration of cocaine abstinence (3.7 weeks versus 1.6 weeks; negative binomial regression: Exp(B)=2.34, 95%-CI: 1.70-3.23; p<0.001). This result remained significant in sensitivity analyses and was supported by all secondary, cocaine-related outcome measures. Treatment retention in HAT was high (91.6%) with no difference between the groups. The improvement in multi-domain health-related treatment response during the trial was numerically higher in HAT+CM (from 37.4% to 53.1%; +15.7%) than in HAT-only (from 44.5% to 46.5%; +2.0%), but this difference was statistically not significant. Contingency management is an effective add-on intervention to promote longer, uninterrupted periods of cocaine abstinence in chronic, treatment-refractory heroin dependent patients in heroin-assisted treatment with frequent cocaine use. The trial has been registered in The Netherlands National Trial Register under clinical trial registration number NTR4728. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Identification of Compounds with Anti-Proliferative Activity against Trypanosoma brucei brucei Strain 427 by a Whole Cell Viability Based HTS Campaign

PubMed Central

Kaiser, Marcel; Chatelain, Eric; Moawad, Sarah R.; Ganame, Danny; Ioset, Jean-Robert; Avery, Vicky M.

2012-01-01

Human African Trypanosomiasis (HAT) is caused by two trypanosome sub-species, Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense. Drugs available for the treatment of HAT have significant issues related to difficult administration regimes and limited efficacy across species and disease stages. Hence, there is considerable need to find new alternative and less toxic drugs. An approach to identify starting points for new drug candidates is high throughput screening (HTS) of large compound library collections. We describe the application of an Alamar Blue based, 384-well HTS assay to screen a library of 87,296 compounds against the related trypanosome subspecies, Trypanosoma brucei brucei bloodstream form lister 427. Primary hits identified against T.b. brucei were retested and the IC50 value compounds were estimated for T.b. brucei and a mammalian cell line HEK293, to determine a selectivity index for each compound. The screening campaign identified 205 compounds with greater than 10 times selectivity against T.b. brucei. Cluster analysis of these compounds, taking into account chemical and structural properties required for drug-like compounds, afforded a panel of eight compounds for further biological analysis. These compounds had IC50 values ranging from 0.22 µM to 4 µM with associated selectivity indices ranging from 19 to greater than 345. Further testing against T.b. rhodesiense led to the selection of 6 compounds from 5 new chemical classes with activity against the causative species of HAT, which can be considered potential candidates for HAT early drug discovery. Structure activity relationship (SAR) mining revealed components of those hit compound structures that may be important for biological activity. Four of these compounds have undergone further testing to 1) determine whether they are cidal or static in vitro at the minimum inhibitory concentration (MIC), and 2) estimate the time to kill. PMID:23209849

Piceatannol and resveratrol share inhibitory effects on hydrogen peroxide release, monoamine oxidase and lipogenic activities in adipose tissue, but differ in their antilipolytic properties.

PubMed

Les, Francisco; Deleruyelle, Simon; Cassagnes, Laure-Estelle; Boutin, Jean A; Balogh, Balázs; Arbones-Mainar, José M; Biron, Simon; Marceau, Picard; Richard, Denis; Nepveu, Françoise; Mauriège, Pascale; Carpéné, Christian

2016-10-25

Piceatannol is a hydroxylated derivative of resveratrol. While both dietary polyphenols coexist in edible plants and fruits, and share equivalent concentrations in several wines, the influence of piceatannol on adiposity has been less studied than that of resveratrol. Though resveratrol is now recognized to limit fat deposition in various obesity models, the benefit of its dietary supplementation remains under debate regarding human obesity treatment or prevention. The research for more potent resveratrol analogs is therefore still undergoing. This prompted us to compare various effects of piceatannol and resveratrol directly on human adipose tissue (hAT). Hydrogen peroxide release was measured by Amplex Red-based fluorescence in subcutaneous hAT samples from obese patients. Interactions of stilbenes with human amine oxidases and quinone reductase were assessed by radiometric methods, computational docking and electron paramagnetic resonance. Influences on lipogenic and lipolytic activities were compared in mouse adipocytes. Resveratrol and piceatannol inhibited monoamine oxidase (MAO) with respective IC50 of 18.5 and 133.7 μM, but not semicarbazide-sensitive amine oxidase (SSAO) in hAT. For both stilbenes, the docking scores were better for MAO than for SSAO. Piceatannol and resveratrol similarly hampered hydrogen peroxide detection in assays with and without hAT, while they shared pro-oxidant activities when incubated with purified quinone reductase. They exhibited similar dose-dependent inhibition of adipocyte lipogenic activity. Only piceatannol inhibited basal and stimulated lipolysis when incubated at a dose ≥100 μM. Thus, piceatannol exerted on fat cells dose-dependent effects similar to those of resveratrol, except for a stronger antilipolytic action. In this regard, piceatannol should be useful in limiting the lipotoxicity related to obesity when ingested or administered alone - or might hamper the fat mobilization induced by resveratrol when simultaneously administered with it. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Functional Analysis of Histone Acetyltransferase MOF in Tumorigenesis

PubMed Central

Su, Jiaming; Wang, Fei; Cai, Yong; Jin, Jingji

2016-01-01

Changes in chromatin structure and heritably regulating the gene expression by epigenetic mechanisms, such as histone post-translational modification, are involved in most cellular biological processes. Thus, abnormal regulation of epigenetics is implicated in the occurrence of various diseases, including cancer. Human MOF (males absent on the first) is a member of the MYST (Moz-Ybf2/Sas3-Sas2-Tip60) family of histone acetyltransferases (HATs). As a catalytic subunit, MOF can form at least two distinct multiprotein complexes (MSL and NSL) in human cells. Both complexes can acetylate histone H4 at lysine 16 (H4K16); however, the NSL complex possesses broader substrate specificity and can also acetylate histone H4 at lysines 5 and 8 (H4K5 and H4K8), suggesting the complexity of the intracellular functions of MOF. Silencing of MOF in cells leads to genomic instability, inactivation of gene transcription, defective DNA damage repair and early embryonic lethality. Unbalanced MOF expression and its corresponding acetylation of H4K16 have been found in certain primary cancer tissues, including breast cancer, medulloblastoma, ovarian cancer, renal cell carcinoma, colorectal carcinoma, gastric cancer, as well as non-small cell lung cancer. In this review, we provide a brief overview of MOF and its corresponding histone acetylation, introduce recent research findings that link MOF functions to tumorigenesis and speculate on the potential role that may be relevant to tumorigenic pathways. PMID:26784169

The Functional Analysis of Histone Acetyltransferase MOF in Tumorigenesis.

PubMed

Su, Jiaming; Wang, Fei; Cai, Yong; Jin, Jingji

2016-01-14

Changes in chromatin structure and heritably regulating the gene expression by epigenetic mechanisms, such as histone post-translational modification, are involved in most cellular biological processes. Thus, abnormal regulation of epigenetics is implicated in the occurrence of various diseases, including cancer. Human MOF (males absent on the first) is a member of the MYST (Moz-Ybf2/Sas3-Sas2-Tip60) family of histone acetyltransferases (HATs). As a catalytic subunit, MOF can form at least two distinct multiprotein complexes (MSL and NSL) in human cells. Both complexes can acetylate histone H4 at lysine 16 (H4K16); however, the NSL complex possesses broader substrate specificity and can also acetylate histone H4 at lysines 5 and 8 (H4K5 and H4K8), suggesting the complexity of the intracellular functions of MOF. Silencing of MOF in cells leads to genomic instability, inactivation of gene transcription, defective DNA damage repair and early embryonic lethality. Unbalanced MOF expression and its corresponding acetylation of H4K16 have been found in certain primary cancer tissues, including breast cancer, medulloblastoma, ovarian cancer, renal cell carcinoma, colorectal carcinoma, gastric cancer, as well as non-small cell lung cancer. In this review, we provide a brief overview of MOF and its corresponding histone acetylation, introduce recent research findings that link MOF functions to tumorigenesis and speculate on the potential role that may be relevant to tumorigenic pathways.

30 CFR 75.1720-1 - Distinctively colored hard hats, or hard caps; identification for newly employed, inexperienced...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Distinctively colored hard hats, or hard caps... STANDARDS-UNDERGROUND COAL MINES Miscellaneous § 75.1720-1 Distinctively colored hard hats, or hard caps; identification for newly employed, inexperienced miners. Hard hats or hard caps distinctively different in color...

30 CFR 77.1710-1 - Distinctively colored hard hats or hard caps; identification for newly employed, inexperienced...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Distinctively colored hard hats or hard caps... Distinctively colored hard hats or hard caps; identification for newly employed, inexperienced miners. Hard hats or hard caps distinctively different in color from those worn by experienced miners shall be worn at...

30 CFR 77.1710-1 - Distinctively colored hard hats or hard caps; identification for newly employed, inexperienced...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Distinctively colored hard hats or hard caps... Distinctively colored hard hats or hard caps; identification for newly employed, inexperienced miners. Hard hats or hard caps distinctively different in color from those worn by experienced miners shall be worn at...

30 CFR 77.1710-1 - Distinctively colored hard hats or hard caps; identification for newly employed, inexperienced...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Distinctively colored hard hats or hard caps... Distinctively colored hard hats or hard caps; identification for newly employed, inexperienced miners. Hard hats or hard caps distinctively different in color from those worn by experienced miners shall be worn at...

30 CFR 75.1720-1 - Distinctively colored hard hats, or hard caps; identification for newly employed, inexperienced...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Distinctively colored hard hats, or hard caps... STANDARDS-UNDERGROUND COAL MINES Miscellaneous § 75.1720-1 Distinctively colored hard hats, or hard caps; identification for newly employed, inexperienced miners. Hard hats or hard caps distinctively different in color...

30 CFR 75.1720-1 - Distinctively colored hard hats, or hard caps; identification for newly employed, inexperienced...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Distinctively colored hard hats, or hard caps... STANDARDS-UNDERGROUND COAL MINES Miscellaneous § 75.1720-1 Distinctively colored hard hats, or hard caps; identification for newly employed, inexperienced miners. Hard hats or hard caps distinctively different in color...

30 CFR 75.1720-1 - Distinctively colored hard hats, or hard caps; identification for newly employed, inexperienced...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Distinctively colored hard hats, or hard caps... STANDARDS-UNDERGROUND COAL MINES Miscellaneous § 75.1720-1 Distinctively colored hard hats, or hard caps; identification for newly employed, inexperienced miners. Hard hats or hard caps distinctively different in color...

30 CFR 77.1710-1 - Distinctively colored hard hats or hard caps; identification for newly employed, inexperienced...

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Distinctively colored hard hats or hard caps... Distinctively colored hard hats or hard caps; identification for newly employed, inexperienced miners. Hard hats or hard caps distinctively different in color from those worn by experienced miners shall be worn at...

30 CFR 75.1720-1 - Distinctively colored hard hats, or hard caps; identification for newly employed, inexperienced...

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Distinctively colored hard hats, or hard caps... STANDARDS-UNDERGROUND COAL MINES Miscellaneous § 75.1720-1 Distinctively colored hard hats, or hard caps; identification for newly employed, inexperienced miners. Hard hats or hard caps distinctively different in color...

30 CFR 77.1710-1 - Distinctively colored hard hats or hard caps; identification for newly employed, inexperienced...

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Distinctively colored hard hats or hard caps... Distinctively colored hard hats or hard caps; identification for newly employed, inexperienced miners. Hard hats or hard caps distinctively different in color from those worn by experienced miners shall be worn at...

Entanglement Potential Versus Negativity of Wigner Function for SUP-Operated Quantum States

NASA Astrophysics Data System (ADS)

Chatterjee, Arpita

2018-02-01

We construct a distinct category of nonclassical quantum states by applying a superposition of products (SUP) of field annihilation (\\hat {a}) and creation (\\hat {a}^{\\dagger }) operators of the type (s\\hat {a}\\hat {a}^{\\dagger }+t\\hat {a}^{\\dagger }\\hat {a}), with s2+t2=1, upon thermal and even coherent states. We allow these SUP operated states to undergo a decoherence process and then describe the nonclassical features of the resulted field by using the entanglement potential (EP) and the negativity of the Wigner distribution function. Our analysis reveals that both the measures are reduced in the linear loss process. The partial negativity of the Wigner function disappears when losses exceed 50% but EP exists always.

Treating Head Lice

MedlinePlus

... contact during play and other activities at home, school, and elsewhere (sports activities, playgrounds, slumber parties, and camps). Teach children not to share clothing and supplies, such as hats, scarves, helmets, sports uniforms, towels, combs, brushes, bandanas, hair ties, and headphones. ...

Assessment of Elementary School Students’ Sun Protection Behaviors

PubMed Central

Hunter, Seft; Wells, Kristen J.; Jacobsen, Paul B.; Lee, Ji-Hyun; Boulware, David; Love-Jackson, Kymia; Abdulla, Rania; Roetzheim, Richard G.

2013-01-01

Introduction Emerging studies suggest that excessive sun exposure in childhood contributes to the development of skin cancer later in life. Children rarely wear a wide-brimmed hat when outside although these hats offer the best protection to the areas on the face where children are most likely to be sunburned. The current study explores 4th grade student assessment of their sun protection behaviors outside at school and at times other than when they are at school. Method This study utilized baseline data collected in the Fall of 2006 for the Sun Protection for Florida’s Children (SPF) project. In brief, the SPF project is a group randomized trial to test the effectiveness of a school based intervention promoting sun protection in general, and hat use in particular. The project targets all 4th grade students in Hillsborough County Schools, FL. The data reported in this study were collected at baseline before any intervention activities was initiated. Approximately 2,086 4th grade students completed self-report surveys evaluating sun protection behaviors. Trained research assistants carried out 99 direct observations of physical education classes over a five week period during Fall 2006 in Tampa, Florida. Results In general, the self-reported use of various methods of sun protection was low. Approximately one third of students reported that they wore sunscreen (32.8%) or sunglasses (32.3%) before leaving home for school. Only a small percentage of students wore long sleeves (15.0%) or a hat with a brim (16.4%) before leaving for school. In addition, few students wore a hat with a wide brim when outside but not at school (16.4%). Students spent an average of 59.1 minutes per week outdoors while attending school and 35.5 minutes during peak sun exposure. In general, female students and Hispanic, African American, and students of other racial and ethnic groups were more likely to practice sun protection behaviors at school than white or male students. Students who attended schools with a mandatory uniform policy were less likely to wear hats with brims. Discussion A single sunburn heightens a child’s risk of developing skin cancer later on in life. Sun exposure at school poses a significant risk to student health and more needs to be done to promote the use of a wide-brimmed hat and limiting student sun exposure. A wide brimmed hat shows the most promise in helping students to protect the face at neck areas where sunburns are most likely to develop. More needs to be done to promote hat use and limiting sun exposure while children are at school. PMID:19686304

VizieR Online Data Catalog: i filter photometry for HATS-25 through HATS-30 (Espinoza+, 2016)

NASA Astrophysics Data System (ADS)

Espinoza, N.; Bayliss, D.; Hartman, J. D.; Bakos, G. A.; Jordan, A.; Zhou, G.; Mancini, L.; Brahm, R.; Ciceri, S.; Bhatti, W.; Csubry, Z.; Rabus, M.; Penev, K.; Bento, J.; de Val-Borro, M.; Henning, T.; Schmidt, B.; Suc, V.; Wright, D. J.; Tinney, C. G.; Tan, T. G.; Noyes, R.

2017-05-01

The photometric detection data of the six exoplanets come from the three HATSouth sites, namely, the site at Las Campanas Observatory in Chile (LCO, whose stations are designated HS-1 and HS-2), the site at of the High Energy Spectroscopic Survey (HESS) in Namibia (whose stations are designated HS-3 and HS-4) and the site at the Siding Spring Observatory (SSO) in Australia whose stations are designated HS-5 and HS-6). HATS-25 was observed with an r SDSS filter on 2011 Mar-2011 Aug using HS-2.1, on 2011 Jul-2011 Aug using HS-4.1, and on 2011 May with HS-6.1. HATS-26 was observed with an r SDSS filter on 2012 Feb-2012 Jun using HS-2.3, HS-4.3, and HS-6.3. HATS-27 was observed with an r SDSS filter on 2011 Apr-2012 Jul using HS-2.1, on 2011 Jul-2012 Jul using HS-4.1, and on 2011 May-2012 Jul using HS-6.1. HATS-28 was observed with an r SDSS filter on 2013 Mar-2013 Oct using HS-1.2, on 2013 Sep-2013 Oct using HS-2.2, on 2013 Apr-2013 Nov using HS-3.2, on 2013 Sep-2013 Nov using HS-4.2 and HS-6.2, and 2013 Mar-2013 Nov using HS-5.2. HATS-29 was observed with an r SDSS filter on 2013 Apr-2013 May using HS-1.1, on 2013 Sep-2013 Oct using HS-2.1, on 2013 Apr-2013 Nov using HS-3.1, on 2013 Sep-2013 Nov using HS-4.1 and HS-6.1, and on 2013 Mar-2013 Nov using HS-5.1. HATS-30 was observed using an r SDSS filter on 2012 Sep-2012 Dec using HS-2.3, HS-6.3 and HS-2.4, on 2012 Sep-2013 Jan using HS-4.4, on 2012 Sep-2012 Dec using HS-6.4, and on 2011 Jul-2012 Oct using HS-1.1, HS-3.1 and HS-5.1. Photometric follow-up for the six systems was obtained mainly from 1m-class telescopes at different sites of the Las Cumbres Observatory Global Telescope (LCOGT) network, using the i filter. In particular, one partial transit and a full transit was observed for HATS-25b on 2015 February 23 at Cerro Tololo Inter-American Observatory (CTIO) and 2015 March 16 at SSO, respectively; three partial transits were observed for HATS-26b on 2015 April 19 and 2015 May 21 at CTIO, and 2015 June 04 at SSO; one full transit was observed for HATS-27b on 2015 April 09 at SSO; two partial transits were observed for HATS-28b on 2015 August 31 and 2015 September 03 at CTIO; one full transit and a partial transit were observed for HATS-29b on 2015 and 2014 June, respectively, at CTIO; and two partial transits were observed for HATS-30b on 2014 October 19 at South African Astronomical Observatory (SAAO) and on 2014 Oct 23 at CTIO. In addition, one full transit of HATS-27b was observed using the 0.3m Perth Exoplanet Survey Telescope (PEST) on 2015 March 12 using a RC filter. The reconnaissance spectroscopy of our candidates was made using the Wide Field Spectrograph (WiFeS), located on the Australian National University (ANU) 2.3m telescope. The observing strategy usually consists of taking data with two resolutions: R=λ/Δλ=7000 (medium) and R=3000 (low). For HATS-25, four medium resolution spectra (2014 Jun-Aug) and one low resolution spectrum (2014 Aug 5) were obtained. For HATS-26, two medium resolution spectra (2014 Jun 3-5) and one low resolution spectrum (2014 Jun 4) were obtained. For HATS-27, three medium resolution (2014 Jun 3-5) and one low resolution (2014 Jun 2) spectra were obtained. For HATS-28, only one low resolution spectrum (2015 Jun 1) was obtained. For HATS-29, four medium resolution spectra (2014 Dec-2015 Mar) and one low resolution spectrum (2015 Mar 2) were obtained. For HATS-30, three medium resolution spectra (2014 Oct 4-10) and one low resolution spectrum (2014 Oct 4) were obtained. High-precision spectroscopy was obtained for our targets with different instruments. Several R=115000 spectra were taken with the High Accuracy Radial Velocity Planet Searcher (HARPS) on the ESO 3.6m telescope at La Silla Observatory (LSO) between 2015 February and 2016 March in order to obtain high-precision radial velocities for HATS-25, HATS-26, HATS-27, and HATS-29. Spectra with R=48000 were also taken with the Fiber-fed Extended Range Optical Spectrograph (FEROS) mounted on the Max Planck Gesellschaft (MPG) 2.2m telescope at La Silla Observatory (LSO) between 2014 July and 2015 July in order to both extract precise spectroscopic parameters of the host stars and obtain precise radial velocities for all of our targets. In addition, R=60000 spectra were also taken with the CORALIE spectrograph mounted on the 1.2m Euler telescope at LSO between 2014 June and November for HATS-26, HATS-27, HATS-29, and HATS-30. Finally, eight R=70000 spectra were obtained for HATS-29 on 2015 May to measure radial velocities, using the CYCLOPS2 fiber feed with the University College London Echelle Spectrograph (UCLES) on the 3.9m Anglo-Australian Telescope (AAT). (3 data files).

Listen Up, Everyone! Conquering Students' Inattentiveness When You're the Guest Lecturer. Tips from the Experts

ERIC Educational Resources Information Center

Badia, Giovanna

2015-01-01

How does an instructor capture students' attention in a guest lecture or one-shot class? In this article, the author presents some strategies to attract and maintain students' interest in a 60-90 minute session, which explore methods for understanding students' needs, obtaining buy-in, showing enthusiasm, and incorporating in-class activities. A…

James J. Gallagher: Man in the White Hat

ERIC Educational Resources Information Center

Jolly, Jennifer L.; Robinson, Ann

2014-01-01

In classic Western movies, the good guy could be frequently identified by his trademark white Stetson hat, whereas the bad guy always wore black. James J. Gallagher wore many hats during his career that spanned over six decades; he too would be known as the "man in the white hat,"--trusted to do the right thing. From 1967 to 1970,…

Spin Triplet Nematic Pairing Symmetry and Superconducting Double Transition in U1-xThxBe13

NASA Astrophysics Data System (ADS)

Machida, Kazushige

2018-03-01

Motivated by a recent experiment on U1-xThxBe13 with x = 3%, we develop a theory to narrow down the possible pair symmetry to consistently describe the double transition utilizing various theoretical tools, including group theory and Ginzburg-Landau theory. It is explained in terms of the two-dimensional representation Eu with spin triplet. Symmetry breaking causes the degenerate Tc to split into two. The low-temperature phase is identified as the cyclic p wave: d(k) = \\hat{x}kx + ɛ \\hat{y}ky + ɛ 2\\hat{z}kz with ɛ3 = 1, whereas the biaxial nematic phase: d(k) = √{3} (\\hat{x}kx - \\hat{y}ky) is the high-temperature one. This allows us to simultaneously identify the uniaxial nematic phase: d(k) = 2\\hat{z}kz - \\hat{x}kx - \\hat{y}ky for UBe13, which spontaneously breaks the cubic symmetry of the system. Those pair functions are fully consistent with this description and existing data. We comment on the accidental scenario in addition to this degeneracy scenario and the intriguing topological nature hidden in this long-known material.

A polymorphism in the haptoglobin, haptoglobin related protein locus is associated with risk of human sleeping sickness within Cameroonian populations.

PubMed

Ofon, Elvis; Noyes, Harry; Mulindwa, Julius; Ilboudo, Hamidou; Simuunza, Martin; Ebo'o, Vincent; Njiokou, Flobert; Koffi, Mathurin; Bucheton, Bruno; Fogue, Pythagore; Hertz-Fowler, Christiane; MacLeod, Annette; Simo, Gustave

2017-10-01

Human African Trypanosomiasis (HAT) is a neglected disease targeted for elimination as a public health problem by 2020. Elimination requires a better understanding of the epidemiology and clinical evolution of HAT. In addition to the classical clinical evolution of HAT, asymptomatic carriers and spontaneous cure have been reported in West Africa. A genetic component to human susceptibility to HAT has been suggested to explain these newly observed responses to infection. In order to test for genetic associations with infection response, genetic polymorphism in 17 genes were tested (APOL1, IL1B, IL4, IL4R, IL6, IL8, IL12B, IL12RB1, IL10, TNFA, INFG, MIF, HLA-G, HLA-A, HP, HPR and CFH). A case-control study was performed on 180 blood samples collected from 56 cases and 124 controls from Cameroon. DNA was extracted from blood samples. After quality control, 25 samples (24 controls and 1 case) were eliminated. The genotyping undertaken on 155 individuals including 55 cases and 100 controls were investigated at 96 loci (88 SNPs and 8 indels) located on 17 genes. Associations between these loci and HAT were estimated via a case-control association test. Analyses of 64 SNPs and 4 indels out of 96 identified in the selected genes reveal that the minor allele (T) of rs8062041 in haptoglobin (HP) appeared to be protective against HAT (p = 0.0002395, OR 0.359 (CI95 [0.204-0.6319])); indicating higher frequency in cases compared to controls. This minor allele with adjusted p value of 0.0163 is associated with a lower risk (protective effect) of developing sleeping sickness. The haptoglobin related protein HPR and HP are tightly linked and both are duplicated in some people and may lead to higher activity. This increased production could be responsible of the protection associated with rs8062041 even though this SNP is within HP.

A polymorphism in the haptoglobin, haptoglobin related protein locus is associated with risk of human sleeping sickness within Cameroonian populations

PubMed Central

Ofon, Elvis; Noyes, Harry; Mulindwa, Julius; Ilboudo, Hamidou; Simuunza, Martin; Ebo’o, Vincent; Njiokou, Flobert; Koffi, Mathurin; Bucheton, Bruno; Fogue, Pythagore; Hertz-Fowler, Christiane; MacLeod, Annette

2017-01-01

Background Human African Trypanosomiasis (HAT) is a neglected disease targeted for elimination as a public health problem by 2020. Elimination requires a better understanding of the epidemiology and clinical evolution of HAT. In addition to the classical clinical evolution of HAT, asymptomatic carriers and spontaneous cure have been reported in West Africa. A genetic component to human susceptibility to HAT has been suggested to explain these newly observed responses to infection. In order to test for genetic associations with infection response, genetic polymorphism in 17 genes were tested (APOL1, IL1B, IL4, IL4R, IL6, IL8, IL12B, IL12RB1, IL10, TNFA, INFG, MIF, HLA-G, HLA-A, HP, HPR and CFH). Methodology A case-control study was performed on 180 blood samples collected from 56 cases and 124 controls from Cameroon. DNA was extracted from blood samples. After quality control, 25 samples (24 controls and 1 case) were eliminated. The genotyping undertaken on 155 individuals including 55 cases and 100 controls were investigated at 96 loci (88 SNPs and 8 indels) located on 17 genes. Associations between these loci and HAT were estimated via a case-control association test. Results Analyses of 64 SNPs and 4 indels out of 96 identified in the selected genes reveal that the minor allele (T) of rs8062041 in haptoglobin (HP) appeared to be protective against HAT (p = 0.0002395, OR 0.359 (CI95 [0.204–0.6319])); indicating higher frequency in cases compared to controls. This minor allele with adjusted p value of 0.0163 is associated with a lower risk (protective effect) of developing sleeping sickness. Conclusion The haptoglobin related protein HPR and HP are tightly linked and both are duplicated in some people and may lead to higher activity. This increased production could be responsible of the protection associated with rs8062041 even though this SNP is within HP. PMID:29077717

Hit-to-lead development of the chamigrane endoperoxide merulin A for the treatment of African sleeping sickness.

PubMed

Navarro, Gabriel; Chokpaiboon, Supchar; De Muylder, Geraldine; Bray, Walter M; Nisam, Sean C; McKerrow, James H; Pudhom, Khanitha; Linington, Roger G

2012-01-01

Human African trypanosomiasis (HAT) is an infectious disease with a large global health burden occurring primarily in Central and Eastern Africa. Most current treatments have poor blood brain barrier (BBB) penetration, which prevent them from targeting the most lethal stage of the infection. In addition, current therapeutics suffer from a variety of limitations ranging from serious side effects to difficulties with treatment administration. Therefore it is of crucial importance to find new treatments that are safe, affordable, and effective against both sub-species of Trypanosoma brucei. Semi-synthetic derivatization of the fungally-derived natural product merulin A (1) has led to the discovery of new development candidates for the protozoan parasite T. brucei, the causative agent of HAT. Creation of an initial SAR library based around the merulin scaffold revealed several key features required for activity, including the endoperoxide bridge, as well as one position suitable for further derivatization. Subsequent synthesis of a 20-membered analogue library, guided by the addition of acyl groups that improve the drug-like properties of the merulin A core, resulted in the development of compound 12 with an IC(50) of 60 nM against T. brucei, and a selectivity index greater than 300-fold against HeLa and immortalized glial cells. We report the semi-synthetic optimization of the merulin class of endoperoxide natural products as development candidates against T. brucei. We have identified compounds with low nM antiparasitic activities and high selectivity indices against HeLa cells. These compounds can be produced economically in large quantities via a one step derivatization from the microbial fermentation broth isolate, making them encouraging lead candidates for further development.

Tapered plug foam spray apparatus

NASA Technical Reports Server (NTRS)

Allen, Peter B. (Inventor)

1996-01-01

A two-component foam spray gun is readily disassembled for cleaning. It includes a body (1) with reactant (12, 14) and purge gas (16) inlet ports. A moldable valve packing (32) inside the body has a tapered conical interior surface (142), and apertures which match the reactant ports. A valve/tip (40) has a conical outer surface (48) which mates with the valve packing (32). The valve/tip (40) is held in place by a moldable packing washer (34), held at non-constant pressure by a screw (36, 38). The interior of the valve/tip (40) houses a removable mixing chamber (50). The mixing chamber (50) has direct flow orifices (60) and an auxiliary flow path (58, 60) which ameliorate pressure surges. The spray gun can be disassembled for cleaning without disturbing the seal, by removing the valve/tip (40) to the rear, thereby breaking it free of the conical packing. Rotation of the valve/tip (40) relative to the body (1) shuts off the reactant flow, and starts the purge gas flow.

40 CFR 60.101a - Definitions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... infiltration (backflow) into the flare tip. For flares with no water seals, the function of purge gas is... of preventing oxygen infiltration (backflow) into the flare tip. [73 FR 35867, June 24, 2008, as...

Application of Human-Autonomy Teaming to an Advanced Ground Station for Reduced Crew Operations

NASA Technical Reports Server (NTRS)

Ho, Nhut; Johnson, Walter; Panesar, Karanvir; Wakeland, Kenny; Sadler, Garrett; Wilson, Nathan; Nguyen, Bao; Lachter, Joel; Stallmann, Summer

2017-01-01

Within human factors there is burgeoning interest in the "human-autonomy teaming" (HAT) concept as a way to address the challenges of interacting with complex, increasingly autonomous systems. The HAT concept comes out of an aspiration to interact with increasingly autonomous systems as a team member, rather than simply use automation as a tool. The authors, and others, have proposed core tenets for HAT that include bi-directional communication, automation and system transparency, and advanced coordination between human and automated teammates via predefined, dynamic task sequences known as "plays." It is believed that, with proper implementation, HAT should foster appropriate teamwork, thus increasing trust and reliance on the system, which in turn will reduce workload, increase situation awareness, and improve performance. To this end, HAT has been demonstrated and/or studied in multiple applications including search and rescue operations, healthcare and medicine, autonomous vehicles, photography, and aviation. The current paper presents one such effort to apply HAT. It details the design of a HAT agent, developed by Human Automation Teaming Solutions, Inc., to facilitate teamwork between the automation and the human operator of an advanced ground dispatch station. This dispatch station was developed to support a NASA project investigating a concept called Reduced Crew Operations (RCO); consequently, we have named the agent R-HATS. Part of the RCO concept involves a ground operator providing enhanced support to a large number of aircraft with a single pilot on the flight deck. When assisted by R-HATS, operators can monitor and support or manage a large number of aircraft and use plays to respond in real-time to complicated, workload-intensive events (e.g., an airport closure). A play is a plan that encapsulates goals, tasks, and a task allocation strategy appropriate for a particular situation. In the current implementation, when a play is initiated by a user, R-HATS determines what tasks need to be completed and has the ability to autonomously execute them (e.g., determining diversion options and uplinking new routes to aircraft) when it is safe and appropriate. R-HATS has been designed to both support end users and researchers in RCO and HAT. Additionally, R-HATS and its underlying architecture were developed with generalizability in mind as a modular software applicable outside of RCO/aviation domains. This paper will also discuss future further development and testing of RHATS.

HAT-P-18b AND HAT-P-19b: TWO LOW-DENSITY SATURN-MASS PLANETS TRANSITING METAL-RICH K STARS

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

Hartman, J. D.; Bakos, G. A.; Torres, G.

2011-01-01

We report the discovery of two new transiting extrasolar planets. HAT-P-18b orbits the V = 12.759 K2 dwarf star GSC 2594-00646, with a period P = 5.508023 {+-} 0.000006 days, transit epoch T{sub c} = 2454715.02174 {+-} 0.00020 (BJD), and transit duration 0.1131 {+-} 0.0009 days. The host star has a mass of 0.77 {+-} 0.03 M{sub sun}, radius of 0.75 {+-} 0.04 R{sub sun}, effective temperature 4803 {+-} 80 K, and metallicity [Fe/H] = +0.10 {+-} 0.08. The planetary companion has a mass of 0.197 {+-} 0.013 M{sub J} and radius of 0.995 {+-} 0.052 R{sub J}, yielding amore » mean density of 0.25 {+-} 0.04 g cm{sup -3}. HAT-P-19b orbits the V = 12.901 K1 dwarf star GSC 2283-00589, with a period P = 4.008778 {+-} 0.000006 days, transit epoch T{sub c} = 2455091.53417 {+-} 0.00034 (BJD), and transit duration 0.1182 {+-} 0.0014 days. The host star has a mass of 0.84 {+-} 0.04 M{sub sun}, radius of 0.82 {+-} 0.05 R{sub sun}, effective temperature 4990 {+-} 130 K, and metallicity [Fe/H] = +0.23 {+-} 0.08. The planetary companion has a mass of 0.292 {+-} 0.018 M{sub J} and radius of 1.132 {+-} 0.072 R{sub J}, yielding a mean density of 0.25 {+-} 0.04 g cm{sup -3}. The radial velocity residuals for HAT-P-19 exhibit a linear trend in time, which indicates the presence of a third body in the system. Comparing these observations with theoretical models, we find that HAT-P-18b and HAT-P-19b are each consistent with a hydrogen-helium-dominated gas giant planet with negligible core mass. HAT-P-18b and HAT-P-19b join HAT-P-12b and WASP-21b in an emerging group of low-density Saturn-mass planets, with negligible inferred core masses. However, unlike HAT-P-12b and WASP-21b, both HAT-P-18b and HAT-P-19b orbit stars with super-solar metallicity. This calls into question the heretofore suggestive correlation between the inferred core mass and host star metallicity for Saturn-mass planets.« less

Baselining Fugitive and Vented Emissions Across Canadian Energy Developments

NASA Astrophysics Data System (ADS)

O'Connell, L.; Risk, D. A.; Fougère, C. R.; Atherton, E.; Baillie, J.; Marshall, A. D.

2017-12-01

Nearly half of Alberta's oil and gas related methane emissions are due to fugitives and leaks, which pose significant potential for mitigation. Accurate and spatially-extensive emissions data can help operators and regulators meet reduction targets, and highlight which infrastructure requires immediate attention. This study used a vehicle-based gas monitoring system to detect and quantify methane emissions across large geographic areas in real-time. Our objectives were to quantify methane mixing ratios, determine the drivers of emission variation across several developments, and to evaluate emissions frequency and severity from several thousand wells and facilities. We measured fugitive, un-combusted flaring, and vented emissions within Lloydminster (heavy oil), Peace River (heavy oil), and Medicine Hat (conventional gas), Alberta during fall 2016. During this time, CO2, CH4, H2S, C2H6, and δ13CH4 (Picarro 2210 and Teledyne T101) were recorded from public roads at 1 Hz intervals, collecting over 6.7 million unique measurements in total. Methane anomalies were generally mild (0.2-0.5 ppm) in Peace River and Medicine Hat, but in Lloydminster, CH4 mixing ratios were elevated, and at their worst exceeded 6 ppm over 60 km of driving. We classified oil and gas related plumes based on geochemical emission signatures, and attributed the plumes based on wind direction and proximity to one of the >3200 infrastructural sources we surveyed during the triplicated campaign routes. The relative gas ratios (C1:C2, CO2:CH4) and isotopic signatures of plumes were within expected ranges for each development. Emission frequencies differed amongst developments, but were highest in Lloydminster, where 56% of wells were emitting methane-rich gas above our minimum detection limits. In Medicine Hat and Peace River, 28% and 29% of active wells were tagged as potential emission sources, respectively. Although active wells were the predominant source of emissions, other classes of infrastructure were also tagged as sources. We observed both episodic and persistent emissions in each development, owing to the sporadic and unpredictable nature of oilfield emissions. This study demonstrates the practicality of mobile surveying as both a regional-scale and wellpad-scale screening tool to help manage methane emissions in Alberta.

Exposure to the Tips From Former Smokers Campaign Among Adolescents in the United States.

PubMed

Zhao, Xiaoquan; Cai, Xiaomei

2016-05-01

Evaluation of the Tips from Former Smokers (Tips) campaign in the United States so far has focused exclusively on adult smokers. This study provides evidence on the level of exposure to Tips among adolescents in the United States, an important secondary audience for the campaign. Data came from the 2013 National Youth Tobacco Survey (N = 18 406). Exposure to Tips was measured by ad recall. Characteristics of adolescents reporting exposure versus no exposure were examined through a series of bivariate analysis linking exposure to smoking status, demographics, and important risk factors. Most adolescents in the United States (63%, 95% confidence interval [CI] = 60.6%, 65.3%) were exposed to at least one Tips ad. Current smokers (70.6%, 95% CI = 67.7%, 73.4%), noncurrent smokers (67.7%, 95% CI = 65.5%, 69.7%), and high-risk never-smokers (63.8%, 95% CI = 60.2%, 67.2%) reported greater exposure than low-risk never-smokers (60.7%, 95% CI = 57.8%, 63.5%; all P < .05). Those who reported exposure were more likely to be female; be older in age; be white (vs. Hispanic); live with a smoker; have less firm smoking rules in the family; have one or more friends using tobacco or are not sure; have been exposed to tobacco advertising from one or more sources; and have skipped classes in the past 30 days. Tips has significant reach among adolescents in the United States, particularly among those with smoking experience and those whose life environments include more pro-smoking influences. Close monitoring of the Tips' impact on this important population is needed. This study shows substantial adolescent awareness of the Tips campaign in the United States. This evidence has important implications for the comprehensive evaluation of the public health impact of Tips. So far research on Tips has focused almost entirely on adult smokers. Findings of this study suggest that the potential impact of Tips on adolescents, particularly those at high risk of smoking, should become an integral part of the evaluation research agenda. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Does being a "SunSmart School" influence hat-wearing compliance? An ecological study of hat-wearing rates at Australian primary schools in a region of high sun exposure.

PubMed

Turner, Denise; Harrison, Simone L; Buettner, Petra; Nowak, Madeleine

2014-03-01

Childhood sun exposure is an important risk factor for skin cancer. Anecdotal evidence suggests that hats are under-utilized by Australian primary school students. The proportion of students and adult role-models wearing hats was observed at 36 primary schools (63.9% SunSmart schools [SSS]) in Townsville (latitude 19.3°S; high to extreme maximum daily UV-index year round), Queensland, Australia, from 2009 to 2011. Overall, 52.2% of 28,775 students and 47.9% of 2954 adults were observed wearing a hat. Hat use (all styles) among SSS and non-SunSmart school (NSSS) students was similar before (24.2% vs 20.5%; p=0.701), after (25.4% vs 21.7%; p=0.775) and during school-hours (93.0% vs 89.2%; p=0.649) except SSS students wore gold-standard (broad-brim/bucket/legionnaire) hats during school play-breaks more often in the warmer months (October-March) than NSSS students (54.7% vs 37.4%; p=0.02). Although the proportion of adults who wore hats (all styles) was similar at SSS and NSSS (48.2% vs 46.8%; p=0.974), fewer adults at SSS wore them before school (3.7% vs 10.2%; p=0.035). SunSmart status is not consistently associated with better hat-wearing behavior. The protective nature of hats and the proportion of school students and adult role-models wearing them could be improved, possibly by offering incentives to schools that promote sun-safety. Copyright © 2013 Elsevier Inc. All rights reserved.

How a Hat May Affect 3-Month-Olds' Recognition of a Face: An Eye-Tracking Study

PubMed Central

Bulf, Hermann; Valenza, Eloisa; Turati, Chiara

2013-01-01

Recent studies have shown that infants’ face recognition rests on a robust face representation that is resilient to a variety of facial transformations such as rotations in depth, motion, occlusion or deprivation of inner/outer features. Here, we investigated whether 3-month-old infants’ ability to represent the invariant aspects of a face is affected by the presence of an external add-on element, i.e. a hat. Using a visual habituation task, three experiments were carried out in which face recognition was investigated by manipulating the presence/absence of a hat during face encoding (i.e. habituation phase) and face recognition (i.e. test phase). An eye-tracker system was used to record the time infants spent looking at face-relevant information compared to the hat. The results showed that infants’ face recognition was not affected by the presence of the external element when the type of the hat did not vary between the habituation and test phases, and when both the novel and the familiar face wore the same hat during the test phase (Experiment 1). Infants’ ability to recognize the invariant aspects of a face was preserved also when the hat was absent in the habituation phase and the same hat was shown only during the test phase (Experiment 2). Conversely, when the novel face identity competed with a novel hat, the hat triggered the infants’ attention, interfering with the recognition process and preventing the infants’ preference for the novel face during the test phase (Experiment 3). Findings from the current study shed light on how faces and objects are processed when they are simultaneously presented in the same visual scene, contributing to an understanding of how infants respond to the multiple and composite information available in their surrounding environment. PMID:24349378

How a hat may affect 3-month-olds' recognition of a face: an eye-tracking study.

PubMed

Bulf, Hermann; Valenza, Eloisa; Turati, Chiara

2013-01-01

Recent studies have shown that infants' face recognition rests on a robust face representation that is resilient to a variety of facial transformations such as rotations in depth, motion, occlusion or deprivation of inner/outer features. Here, we investigated whether 3-month-old infants' ability to represent the invariant aspects of a face is affected by the presence of an external add-on element, i.e. a hat. Using a visual habituation task, three experiments were carried out in which face recognition was investigated by manipulating the presence/absence of a hat during face encoding (i.e. habituation phase) and face recognition (i.e. test phase). An eye-tracker system was used to record the time infants spent looking at face-relevant information compared to the hat. The results showed that infants' face recognition was not affected by the presence of the external element when the type of the hat did not vary between the habituation and test phases, and when both the novel and the familiar face wore the same hat during the test phase (Experiment 1). Infants' ability to recognize the invariant aspects of a face was preserved also when the hat was absent in the habituation phase and the same hat was shown only during the test phase (Experiment 2). Conversely, when the novel face identity competed with a novel hat, the hat triggered the infants' attention, interfering with the recognition process and preventing the infants' preference for the novel face during the test phase (Experiment 3). Findings from the current study shed light on how faces and objects are processed when they are simultaneously presented in the same visual scene, contributing to an understanding of how infants respond to the multiple and composite information available in their surrounding environment.

False Positivity of Non-Targeted Infections in Malaria Rapid Diagnostic Tests: The Case of Human African Trypanosomiasis

PubMed Central

Gillet, Philippe; Mumba Ngoyi, Dieudonné; Lukuka, Albert; Kande, Viktor; Atua, Benjamin; van Griensven, Johan; Muyembe, Jean-Jacques; Jacobs, Jan; Lejon, Veerle

2013-01-01

Background In endemic settings, diagnosis of malaria increasingly relies on the use of rapid diagnostic tests (RDTs). False positivity of such RDTs is poorly documented, although it is especially relevant in those infections that resemble malaria, such as human African trypanosomiasis (HAT). We therefore examined specificity of malaria RDT products among patients infected with Trypanosoma brucei gambiense. Methodology/Principal Findings Blood samples of 117 HAT patients and 117 matched non-HAT controls were prospectively collected in the Democratic Republic of the Congo. Reference malaria diagnosis was based on real-time PCR. Ten commonly used malaria RDT products were assessed including three two-band and seven three-band products, targeting HRP-2, Pf-pLDH and/or pan-pLDH antigens. Rheumatoid factor was determined in PCR negative subjects. Specificity of the 10 malaria RDT products varied between 79.5 and 100% in HAT-negative controls and between 11.3 and 98.8% in HAT patients. For seven RDT products, specificity was significantly lower in HAT patients compared to controls. False positive reactions in HAT were mainly observed for pan-pLDH test lines (specificities between 13.8 and 97.5%), but also occurred frequently for the HRP-2 test line (specificities between 67.9 and 98.8%). The Pf-pLDH test line was not affected by false-positive lines in HAT patients (specificities between 97.5 and 100%). False positivity was not associated to rheumatoid factor, detected in 7.6% of controls and 1.2% of HAT patients. Conclusions/Significance Specificity of some malaria RDT products in HAT was surprisingly low, and constitutes a risk for misdiagnosis of a fatal but treatable infection. Our results show the importance to assess RDT specificity in non-targeted infections when evaluating diagnostic tests. PMID:23638201

ING3 promotes prostate cancer growth by activating the androgen receptor.

PubMed

Nabbi, Arash; McClurg, Urszula L; Thalappilly, Subhash; Almami, Amal; Mobahat, Mahsa; Bismar, Tarek A; Binda, Olivier; Riabowol, Karl T

2017-05-16

The androgen receptor (AR) is a major driver of prostate cancer, and increased AR levels and co-activators of the receptor promote the development of prostate cancer. INhibitor of Growth (ING) proteins target lysine acetyltransferase or lysine deacetylase complexes to the histone H3K4Me3 mark of active transcription, to affect chromatin structure and gene expression. ING3 is a stoichiometric member of the TIP60 lysine acetyltransferase complex implicated in prostate cancer development. Biopsies of 265 patients with prostate cancer were stained for ING3, pan-cytokeratin, and DNA. LNCaP and C4-2 androgen-responsive cells were used for in vitro assays including immunoprecipitation, western blotting, Luciferase reporter assay and quantitative polymerase chain reaction. Cell viability and migration assays were performed in prostate cancer cell lines using scrambled siRNA or siRNA targeting ING3. We find that ING3 levels and AR activity positively correlate in prostate cancer. ING3 potentiates androgen effects, increasing expression of androgen-regulated genes and androgen response element-driven reporters to promote growth and anchorage-independent growth. Conversely, ING3 knockdown inhibits prostate cancer cell growth and invasion. ING3 activates the AR by serving as a scaffold to increase interaction between TIP60 and the AR in the cytoplasm, enhancing receptor acetylation and translocation to the nucleus. Activation is independent of ING3's ability to target the TIP60 complex to H3K4Me3, identifying a previously unknown chromatin-independent cytoplasmic activity for ING3. In agreement with in vitro observations, analysis of The Cancer Genome Atlas (TCGA) data (n = 498) and a prostate cancer tissue microarray (n = 256) show that ING3 levels are higher in aggressive prostate cancers, with high levels of ING3 predicting shorter patient survival in a low AR subgroup. Including ING3 levels with currently used indicators such as the Gleason score provides more accurate prognosis in primary prostate cancer. In contrast to the majority of previous reports suggesting tumor suppressive functions in other cancers, our observations identify a clear oncogenic role for ING3, which acts as a co-activator of AR in prostate cancer. Data from TCGA and our previous and current tissue microarrays suggest that ING3 levels correlate with AR levels and that in patients with low levels of the receptor, ING3 level could serve as a useful prognostic biomarker.

The GAPS Programme with HARPS-N at TNG. VIII. Observations of the Rossiter-McLaughlin effect and characterisation of the transiting planetary systems HAT-P-36 and WASP-11/HAT-P-10

NASA Astrophysics Data System (ADS)

Mancini, L.; Esposito, M.; Covino, E.; Raia, G.; Southworth, J.; Tregloan-Reed, J.; Biazzo, K.; Bonomo, A. S.; Desidera, S.; Lanza, A. F.; Maciejewski, G.; Poretti, E.; Sozzetti, A.; Borsa, F.; Bruni, I.; Ciceri, S.; Claudi, R.; Cosentino, R.; Gratton, R.; Martinez Fiorenzano, A. F.; Lodato, G.; Lorenzi, V.; Marzari, F.; Murabito, S.; Affer, L.; Bignamini, A.; Bedin, L. R.; Boccato, C.; Damasso, M.; Henning, Th.; Maggio, A.; Micela, G.; Molinari, E.; Pagano, I.; Piotto, G.; Rainer, M.; Scandariato, G.; Smareglia, R.; Zanmar Sanchez, R.

2015-07-01

Context. Orbital obliquity is thought to be a fundamental parameter in tracing the physical mechanisms that cause the migration of giant planets from the snow line down to roughly 10-2 au from their host stars. We are carrying out a large programme to estimate the spin-orbit alignment of a sample of transiting planetary systems to study what the possible configurations of orbital obliquity are and whether they correlate with other stellar or planetary properties. Aims: We determine the true and the projected obliquity of HAT-P-36 and WASP-11/HAT-P-10 systems, respectively, which are both composed of a relatively cool star (with effective temperature Teff< 6100 K) and a hot-Jupiter planet. Methods: Thanks to the high-resolution spectrograph HARPS-N, we observed the Rossiter-McLaughlin effect for both systems by acquiring precise (3-8 m s-1) radial-velocity measurements during planetary transit events. We also present photometric observations comprising six light curves that cover five transit events, which were obtained using three medium-class telescopes. One transit of WASP-11/HAT-P-10 was followed simultaneously from two observatories. The three transit light curves of HAT-P-36 b show anomalies that are attributable to starspot complexes on the surface of the parent star, in agreement with the analysis of its spectra that indicates moderate activity ( log R'HK = -4.65 dex). By analysing the complete HATNet data set of HAT-P-36, we estimated the stellar rotation period by detecting a periodic photometric modulation in the light curve caused by star spots, obtaining Prot = 15.3 ± 0.4 days, which implies that the inclination of the stellar rotational axis with respect to the line of sight is i⋆ = 65° ± 34°. Results: We used the new spectroscopic and photometric data to revise the main physical parameters and measure the sky-projected misalignment angle of the two systems. We found λ = -14° ± 18° for HAT-P-36 and λ = 7° ± 5° for WASP-11/HAT-P-10, indicating in both cases a good spin-orbit alignment. In the case of HAT-P-36, we were also able to estimate an upper limit of its real obliquity, which turned out to be ψ< 63 degrees. Based on observations made with (i) the Italian 3.58 m Telescopio Nazionale Galileo at the Observatory of Roque de los Muchachos; (ii) the Cassini 1.52 m telescope at the Astronomical Observatory of Bologna; (iii) the Zeiss 1.23 m telescope at the Observatory of Calar Alto, and the IAC 80 cm telescope at the Teide Observatory.Table 1 and Appendix A are available in electronic form at http://www.aanda.orgData of the light curves are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/579/A136

A B-type histone acetyltransferase Hat1 regulates secondary metabolism, conidiation, and cell wall integrity in the taxol-producing fungus Pestalotiopsis microspora.

PubMed

Zhang, Qian; Chen, Longfei; Yu, Xi; Liu, Heng; Akhberdi, Oren; Pan, Jiao; Zhu, Xudong

2016-12-01

In filamentous fungi, many gene clusters for the biosynthesis of secondary metabolites often stay silent under laboratory culture conditions because of the absence of communication with its natural environment. Epigenetic processes have been demonstrated to be critical in the expression of the genes or gene clusters. Here, we report the identification of a B-type histone acetyltransferase, Hat1, and demonstrate its significant roles in secondary metabolism, conidiation, and the cell wall integrity in the fungus Pestalotiopsis microspora. An hat1 deletion strain shows a dramatic decrease of SMs in this fungus, suggesting hat1 functions as a global regulator on secondary metabolism. Moreover, the mutant strain hat1Δ delays to produce conidia with significantly decreased number of conidia, while shows little effect on vegetative growth, suggesting that it plays a critical role in conidiation. The hypersensitivity of hat1Δ to Congo red demonstrates that disruption of hat1 impairs the integrity of cell wall. Overexpression of the wild-type hat1 allele enhances conidiation by boosting the number of conidia. This is the first report on the role of a B-type histone acetyltransferase in fungal secondary metabolism and cell wall integrity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

'On Your Feet to Earn Your Seat', a habit-based intervention to reduce sedentary behaviour in older adults: study protocol for a randomized controlled trial.

PubMed

Gardner, Benjamin; Thuné-Boyle, Ingela; Iliffe, Steve; Fox, Kenneth R; Jefferis, Barbara J; Hamer, Mark; Tyler, Nick; Wardle, Jane

2014-09-20

Many older adults are both highly sedentary (that is, spend considerable amounts of time sitting) and physically inactive (that is, do little physical activity). This protocol describes an exploratory trial of a theory-based behaviour change intervention in the form of a booklet outlining simple activities ('tips') designed both to reduce sedentary behaviour and to increase physical activity in older adults. The intervention is based on the 'habit formation' model, which proposes that consistent repetition leads to behaviour becoming automatic, sustaining activity gains over time. The intervention is being developed iteratively, in line with Medical Research Council complex intervention guidelines. Selection of activity tips was informed by semi-structured interviews and focus groups with older adults, and input from a multidisciplinary expert panel. An ongoing preliminary field test of acceptability among 25 older adults will inform further refinement. An exploratory randomized controlled trial will be conducted within a primary care setting, comparing the tips booklet with a control fact sheet. Retired, inactive and sedentary adults (n = 120) aged 60 to 74 years, with no physical impairments precluding light physical activity, will be recruited from general practices in north London, UK. The primary outcomes are recruitment and attrition rates. Secondary outcomes are changes in behaviour, habit, health and wellbeing over 12 weeks. Data will be used to inform study procedures for a future, larger-scale definitive randomized controlled trial. Current Controlled Trials ISRCTN47901994.

General survey of hAT transposon superfamily with highlight on hobo element in Drosophila.

PubMed

Ladevèze, Véronique; Chaminade, Nicole; Lemeunier, Françoise; Periquet, Georges; Aulard, Sylvie

2012-09-01

The hAT transposons, very abundant in all kingdoms, have a common evolutionary origin probably predating the plant-fungi-animal divergence. In this paper we present their general characteristics. Members of this superfamily belong to Class II transposable elements. hAT elements share transposase, short terminal inverted repeats and eight base-pairs duplication of genomic target. We focus on hAT elements in Drosophila, especially hobo. Its distribution, dynamics and impact on genome restructuring in laboratory strains as well as in natural populations are reported. Finally, the evolutionary history of hAT elements, their domestication and use as transgenic tools are discussed.

DNA-binding activity of TNF-{alpha} inducing protein from Helicobacter pylori

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

Kuzuhara, T.; Suganuma, M.; Oka, K.

2007-11-03

Tumor necrosis factor-{alpha} (TNF-{alpha}) inducing protein (Tip{alpha}) is a carcinogenic factor secreted from Helicobacter pylori (H. pylori), mediated through both enhanced expression of TNF-{alpha} and chemokine genes and activation of nuclear factor-{kappa}B. Since Tip{alpha} enters gastric cancer cells, the Tip{alpha} binding molecules in the cells should be investigated. The direct DNA-binding activity of Tip{alpha} was observed by pull down assay using single- and double-stranded genomic DNA cellulose. The surface plasmon resonance assay, indicating an association between Tip{alpha} and DNA, revealed that the affinity of Tip{alpha} for (dGdC)10 is 2400 times stronger than that of del-Tip{alpha}, an inactive Tip{alpha}. This suggestsmore » a strong correlation between DNA-binding activity and carcinogenic activity of Tip{alpha}. And the DNA-binding activity of Tip{alpha} was first demonstrated with a molecule secreted from H. pylori.« less

Rationale, design, samples, and baseline sun protection in a randomized trial on a skin cancer prevention intervention in resort environments.

PubMed

Buller, David B; Andersen, Peter A; Walkosz, Barbara J; Scott, Michael D; Beck, Larry; Cutter, Gary R

2016-01-01

Exposure to solar ultraviolet radiation during recreation is a risk factor for skin cancer. A trial evaluated an intervention to promote advanced sun protection (sunscreen pre-application/reapplication; protective hats and clothing; use of shade) during vacations. Adult visitors to hotels/resorts with outdoor recreation (i.e., vacationers) participated in a group-randomized pretest-posttest controlled quasi-experimental design in 2012-14. Hotels/resorts were pair-matched and randomly assigned to the intervention or untreated control group. Sun. protection (e.g., clothing, hats, shade and sunscreen) was measured in cross-sectional samples by observation and a face-to-face intercept survey during two-day visits. Initially, 41 hotel/resorts (11%) participated but 4 dropped out before posttest. Hotel/resorts were diverse (employees=30 to 900; latitude=24° 78' N to 50° 52' N; elevation=2ft. to 9726ft. above sea level), and had a variety of outdoor venues (beaches/pools, court/lawn games, golf courses, common areas, and chairlifts). At pretest, 4347 vacationers were observed and 3531 surveyed. More females were surveyed (61%) than observed (50%). Vacationers were mostly 35-60years old, highly educated (college education=68%) and non-Hispanic white (93%), with high-risk skin types (22%). Vacationers reported covering 60% of their skin with clothing. Also, 40% of vacationers used shade; 60% applied sunscreen; and 42% had been sunburned. The trial faced challenges recruiting resorts but result showed that the large, multi-state sample of vacationers were at high risk for solar UV exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

New anti-trypanosomal active tetracyclic iridoid isolated from Morinda lucida Benth.

PubMed

Suzuki, Mitsuko; Tung, Nguyen Huu; Kwofie, Kofi D; Adegle, Richard; Amoa-Bosompem, Michael; Sakyiamah, Maxwell; Ayertey, Frederick; Owusu, Kofi Baffour-Awuah; Tuffour, Isaac; Atchoglo, Philip; Frempong, Kwadwo Kyereme; Anyan, William K; Uto, Takuhiro; Morinaga, Osamu; Yamashita, Taizo; Aboagye, Frederic; Appiah, Alfred Ampomah; Appiah-Opong, Regina; Nyarko, Alexander K; Yamaoka, Shoji; Yamaguchi, Yasuchika; Edoh, Dominic; Koram, Kwadwo; Ohta, Nobuo; Boakye, Daniel A; Ayi, Irene; Shoyama, Yukihiro

2015-08-01

Human African trypanosomiasis (HAT), commonly known as sleeping sickness has remained a serious health problem in many African countries with thousands of new infected cases annually. Chemotherapy, which is the main form of control against HAT has been characterized lately by the viewpoints of toxicity and drug resistance issues. Recently, there have been a lot of emphases on the use of medicinal plants world-wide. Morinda lucida Benth. is one of the most popular medicinal plants widely distributed in Africa and several groups have reported on its anti-protozoa activities. In this study, we have isolated one novel tetracyclic iridoid, named as molucidin, from the CHCl3 fraction of the M. lucida leaves by bioassay-guided fractionation and purification. Molucidin was structurally elucidated by (1)H and (13)C NMR including HMQC, HMBC, H-H COSY and NOESY resulting in tetracyclic iridoid skeleton, and its absolute configuration was determined. We have further demonstrated that molucidin presented a strong anti-trypanosomal activity, indicating an IC50 value of 1.27 μM. The cytotoxicity study using human normal and cancer cell lines indicated that molucidin exhibited selectivity index (SI) against two normal fibroblasts greater than 4.73. Furthermore, structure-activity relationship (SAR) study was undertaken with molucidin and oregonin, which is identical to anti-trypanosomal active components of Alnus japonica. Overlapping analysis of the lowest energy conformation of molucidin with oregonin suggested a certain similarities of aromatic rings of both oregonin and molucidin. These results contribute to the future drug design studies for HAT. Copyright © 2015 Elsevier Ltd. All rights reserved.

Optimization and Prediction of Ultimate Tensile Strength in Metal Active Gas Welding.

PubMed

Ampaiboon, Anusit; Lasunon, On-Uma; Bubphachot, Bopit

2015-01-01

We investigated the effect of welding parameters on ultimate tensile strength of structural steel, ST37-2, welded by Metal Active Gas welding. A fractional factorial design was used for determining the significance of six parameters: wire feed rate, welding voltage, welding speed, travel angle, tip-to-work distance, and shielded gas flow rate. A regression model to predict ultimate tensile strength was developed. Finally, we verified optimization of the process parameters experimentally. We achieved an optimum tensile strength (558 MPa) and wire feed rate, 19 m/min, had the greatest effect, followed by tip-to-work distance, 7 mm, welding speed, 200 mm/min, welding voltage, 30 V, and travel angle, 60°. Shield gas flow rate, 10 L/min, was slightly better but had little effect in the 10-20 L/min range. Tests showed that our regression model was able to predict the ultimate tensile strength within 4%.

Impact of Aging and Cognition on Hearing Assistive Technology Use

PubMed Central

Jorgensen, Lindsey E.; Messersmith, Jessica J.

2015-01-01

Many factors go into appropriate recommendation and use of hearing assistive technology (HAT). The aging auditory system presents with its own complications and intricacies; there are many types of age-related hearing loss, and it is possible that the underlying cause of hearing loss can significantly impact the recommendations and performance with HATs. The audiologist should take into consideration peripheral and central auditory function when selecting HATs for the aging adult population as well as when selecting appropriate types of technology including personal sound amplification products, hearing aids, cochlear implants, and other assistive technology. The cognitive ability of the patient plays a central role in the recommendations of HAT. It is possible that the use of HATs could mitigate some of the effects of cognitive decline and thus should be considered as early as possible. Assessment of ability and appropriate recommendations are crucial to consistent use of HAT devices. PMID:27516716

Linear entropy and collapse–revival phenomenon for a general formalism N-type four-level atom interacting with a single-mode field

NASA Astrophysics Data System (ADS)

Eied, A. A.

2018-05-01

In this paper, the linear entropy and collapse-revival phenomenon through the relation (< {\\hat{a}}+{\\hat{a}} > -{\\bar{n}}) in a system of N-configuration four-level atom interacting with a single-mode field with additional forms of nonlinearities of both the field and the intensity-dependent atom-field coupling functional are investigated. A factorization of the initial density operator is assumed, considering the field to be initially in a squeezed coherent states and the atom initially in its most upper excited state. The dynamical behavior of the linear entropy and the time evolution of (< {\\hat{a}}+ {\\hat{a}} > -{\\bar{n}}) are analyzed. In particular, the effects of the mean photon number, detuning, Kerr-like medium and the intensity-dependent coupling functional on the entropy and the evolution of (< {\\hat{a}}+ {\\hat{a}} > -{\\bar{n}}) are examined.

Ground-based transit observations of the HAT-P-18, HAT-P-19, HAT-P-27/WASP40 and WASP-21 systems

NASA Astrophysics Data System (ADS)

Seeliger, M.; Kitze, M.; Errmann, R.; Richter, S.; Ohlert, J. M.; Chen, W. P.; Guo, J. K.; Göğüş, E.; Güver, T.; Aydın, B.; Mottola, S.; Hellmich, S.; Fernandez, M.; Aceituno, F. J.; Dimitrov, D.; Kjurkchieva, D.; Jensen, E.; Cohen, D.; Kundra, E.; Pribulla, T.; Vaňko, M.; Budaj, J.; Mallonn, M.; Wu, Z.-Y.; Zhou, X.; Raetz, St.; Adam, C.; Schmidt, T. O. B.; Ide, A.; Mugrauer, M.; Marschall, L.; Hackstein, M.; Chini, R.; Haas, M.; Ak, T.; Güzel, E.; Özdönmez, A.; Ginski, C.; Marka, C.; Schmidt, J. G.; Dincel, B.; Werner, K.; Dathe, A.; Greif, J.; Wolf, V.; Buder, S.; Pannicke, A.; Puchalski, D.; Neuhäuser, R.

2015-08-01

As part of our ongoing effort to investigate transit timing variations (TTVs) of known exoplanets, we monitored transits of the four exoplanets HAT-P-18b, HAT-P-19b, HAT-P-27b/WASP-40b and WASP-21b. All of them are suspected to show TTVs due to the known properties of their host systems based on the respective discovery papers. During the past three years 46 transit observations were carried out, mostly using telescopes of the Young Exoplanet Transit Initiative. The analyses are used to refine the systems' orbital parameters. In all cases we found no hints for significant TTVs, or changes in the system parameters inclination, fractional stellar radius and planet-to-star radius ratio. However, comparing our results with those available in the literature shows that we can confirm the already published values.

The human airway trypsin-like protease modulates the urokinase receptor (uPAR, CD87) structure and functions.

PubMed

Beaufort, Nathalie; Leduc, Dominique; Eguchi, Hiroshi; Mengele, Karin; Hellmann, Daniela; Masegi, Tsukio; Kamimura, Takashi; Yasuoka, Susumu; Fend, Falko; Chignard, Michel; Pidard, Dominique

2007-05-01

The human airway trypsin-like protease (HAT) is a respiratory epithelium-associated, type II transmembrane serine protease, which is also detected as an extracellular enzyme in lung fluids during airway inflammatory disorders. We have evaluated its capacity to affect the urokinase-type plasminogen activator receptor (uPAR), a membrane glycolipid-anchored, three-domain (D1D2D3) glycoprotein that plays a crucial role in innate immunity and inflammation by supporting cell migration and matrix degradation, with structure and biological properties that can be regulated via limited endoproteolysis. With the use of immunoblotting, flow immunocytometry, and ELISA analyses applied to a recombinant uPAR protein and to uPAR-expressing monocytic and human bronchial epithelial cells, it was shown that exposure of uPAR to soluble HAT in the range of 10-500 nM resulted in the proteolytic processing of the full-length (D1D2D3) into the truncated (D2D3) species, with cleavage occurring in the D1 to D2 linker sequence after arginine residues at position 83 and 89. Using immunohistochemistry, we found that both HAT and uPAR were expressed in the human bronchial epithelium. Moreover, transient cotransfection in epithelial cells showed that membrane coexpression of the two partners produced a constitutive and extensive shedding of the D1 domain, occurring for membrane-associated HAT concentrations in the nanomolar range. Because the truncated receptor was found to be unable to bind two of the major uPAR ligands, the adhesive matrix protein vitronectin and the serine protease urokinase, it thus appears that proteolytic regulation of uPAR by HAT is likely to modulate cell adherence and motility, as well as tissue remodeling during the inflammatory response in the airways.

HATS-22b, HATS-23b and HATS-24b: three new transiting super-Jupiters from the HATSouth project

NASA Astrophysics Data System (ADS)

Bento, J.; Schmidt, B.; Hartman, J. D.; Bakos, G. Á.; Ciceri, S.; Brahm, R.; Bayliss, D.; Espinoza, N.; Zhou, G.; Rabus, M.; Bhatti, W.; Penev, K.; Csubry, Z.; Jordán, A.; Mancini, L.; Henning, T.; de Val-Borro, M.; Tinney, C. G.; Wright, D. J.; Durkan, S.; Suc, V.; Noyes, R.; Lázár, J.; Papp, I.; Sári, P.

2017-06-01

We report the discovery of three moderately high-mass transiting hot Jupiters from the HATSouth survey: HATS-22b, HATS-23b and HATS-24b. These planets add to the number of known planets in the ˜2MJ regime. HATS-22b is a 2.74 ± 0.11 MJ mass and 0.953_{-0.029}^{+0.048} R_J radius planet orbiting a V = 13.455 ± 0.040 sub-solar mass (M* = 0.759 ± 0.019 M⊙; R* = 0.759 ± 0.019 R⊙) K-dwarf host star on an eccentric (e = 0.079 ± 0.026) orbit. This planet's high planet-to-stellar mass ratio is further evidence that migration mechanisms for hot Jupiters may rely on exciting orbital eccentricities that bring the planets closer to their parent stars followed by tidal circularization. HATS-23b is a 1.478 ± 0.080 MJ mass and 1.69 ± 0.24 RJ radius planet on a grazing orbit around a V = 13.901 ± 0.010 G-dwarf with properties very similar to those of the Sun (M* = 1.115 ± 0.054; R* = 1.145 ± 0.070). HATS-24b orbits a moderately bright V = 12.830 ± 0.010 F-dwarf star (M* = 1.218 ± 0.036 M⊙; R_\\star = 1.194_{-0.041}^{+0.066} R_{⊙}). This planet has a mass of 2.39_{-0.12}^{+0.21} M_J and an inflated radius of 1.516_{-0.065}^{+0.085} R_J.

Estimating the burden of rhodesiense sleeping sickness during an outbreak in Serere, eastern Uganda

PubMed Central

Fèvre, Eric M; Odiit, Martin; Coleman, Paul G; Woolhouse, Mark EJ; Welburn, Susan C

2008-01-01

Background Zoonotic sleeping sickness, or HAT (Human African Trypanosomiasis), caused by infection with Trypanosoma brucei rhodesiense, is an under-reported and neglected tropical disease. Previous assessments of the disease burden expressed as Disability-Adjusted Life Years (DALYs) for this infection have not distinguished T.b. rhodesiense from infection with the related, but clinically distinct Trypanosoma brucei gambiense form. T.b. rhodesiense occurs focally, and it is important to assess the burden at the scale at which resource-allocation decisions are made. Methods The burden of T.b. rhodesiense was estimated during an outbreak of HAT in Serere, Uganda. We identified the unique characteristics affecting the burden of rhodesiense HAT such as age, severity, level of under-reporting and duration of hospitalisation, and use field data and empirical estimates of these to model the burden imposed by this and other important diseases in this study population. While we modelled DALYs using standard methods, we also modelled uncertainty of our parameter estimates through a simulation approach. We distinguish between early and late stage HAT morbidity, and used disability weightings appropriate for the T.b. rhodesiense form of HAT. We also use a model of under-reporting of HAT to estimate the contribution of un-reported mortality to the overall disease burden in this community, and estimate the cost-effectiveness of hospital-based HAT control. Results Under-reporting accounts for 93% of the DALY estimate of rhodesiense HAT. The ratio of reported malaria cases to reported HAT cases in the same health unit was 133:1, however, the ratio of DALYs was 3:1. The age productive function curve had a close correspondence with the HAT case distribution, and HAT cases occupied more patient admission time in Serere during 1999 than all other infectious diseases other than malaria. The DALY estimate for HAT in Serere shows that the burden is much greater than might be expected from its relative incidence. Hospital based control in this setting appears to be highly cost-effective, highlighting the value of increasing coverage of therapy and reducing under-reporting. Conclusion We show the utility of calculating DALYs for neglected diseases at the local decision making level, and emphasise the importance of improved reporting systems for acquiring a better understanding of the burden of neglected zoonotic diseases. PMID:18366755

Application of Human-Autonomy Teaming (HAT) Patterns to Reduce Crew Operations (RCO)

NASA Technical Reports Server (NTRS)

Shively, R. Jay; Brandt, Summer L.; Lachter, Joel; Matessa, Mike; Sadler, Garrett; Battiste, Henri

2011-01-01

Unmanned aerial systems, advanced cockpits, and air traffic management are all seeing dramatic increases in automation. However, while automation may take on some tasks previously performed by humans, humans will still be required to remain in the system for the foreseeable future. The collaboration between humans and these increasingly autonomous systems will begin to resemble cooperation between teammates, rather than simple task allocation. It is critical to understand this human-autonomy teaming (HAT) to optimize these systems in the future. One methodology to understand HAT is by identifying recurring patterns of HAT that have similar characteristics and solutions. This paper applies a methodology for identifying HAT patterns to an advanced cockpit project.

Flowfield analysis of modern helicopter rotors in hover by Navier-Stokes method

NASA Technical Reports Server (NTRS)

Srinivasan, G. R.; Raghavan, V.; Duque, E. P. N.

1991-01-01

The viscous, three-dimensional, flowfields of UH60 and BERP rotors are calculated for lifting hover configurations using a Navier-Stokes computational fluid dynamics method with a view to understand the importance of planform effects on the airloads. In this method, the induced effects of the wake, including the interaction of tip vortices with successive blades, are captured as a part of the overall flowfield solution without prescribing any wake models. Numerical results in the form of surface pressures, hover performance parameters, surface skin friction and tip vortex patterns, and vortex wake trajectory are presented at two thrust conditions for UH60 and BERP rotors. Comparison of results for the UH60 model rotor show good agreement with experiments at moderate thrust conditions. Comparison of results with equivalent rectangular UH60 blade and BERP blade indicates that the BERP blade, with an unconventional planform, gives more thrust at the cost of more power and a reduced figure of merit. The high thrust conditions considered produce severe shock-induced flow separation for UH60 blade, while the BERP blade develops more thrust and minimal separation. The BERP blade produces a tighter tip vortex structure compared with the UH60 blade. These results and the discussion presented bring out the similarities and differences between the two rotors.

Defeating the United States with Radiological Weapons in Fourth Generation Warfare

DTIC Science & Technology

2003-04-01

wearing their hats. First graders tend to lose things like hats, and the statistics show that is likely that in the first two days, half the...only those who still have hats. Statistics then predict that in the next two days, half of these 16 will lose their hats, and only 8 will still...the number of “hits” on human tissue. It is theoretically possible, although statistically unfathomable; that a person could sleep inside the

Spitzer Secondary Eclipses of HAT-P-13b

NASA Astrophysics Data System (ADS)

Hardy, Ryan A.; Harrington, J.; Hardin, M. R.; Madhusudhan, N.; Cubillos, P.; Blecic, J.; Bakos, G.; Hartman, J. D.

2013-10-01

HAT-P-13 b is a transiting hot Jupiter with a slightly eccentric orbit (e = 0.010) inhabiting a two-planet system. The two-planet arrangement provides an opportunity to probe the interior structure of HAT-P-13b. Under equilibrium-tide theory and confirmation that the apsides of planets b and c are in alignment, a measurement of the planet's eccentricity can be related to the planet's tidal Love number k2, which describes the central condensation of the planet's mass and its deformation under tidal effects. A measurement of k2 could constrain interior models of HAT-P-13b. HAT-P-13b's orbit is configured favorably for refinement of the eccentricity by secondary eclipse timing observations, which provide direct measurements of ecosω. In 2010, Spitzer observed two secondary eclipses of HAT-P-13b in the 3.6- and 4.5-μm IRAC bandpasses. We present secondary eclipse times and depths; joint models of the HAT-P-13 system that incorporate transit photometry and radial velocity data; and constraints on the atmospheric chemistry of HAT-P-13b that suggest solar-abundance composition without a thermal inversion. Spitzer is operated by the Jet Propulsion Laboratory, California Institute of Technology, under a contract with NASA, which provided support for this work. This work was supported in part by NASA Planetary Atmospheres Grant NNX13AF38G.

55. Mayfield (Imper 1991b)

Treesearch

Sheauchi Cheng

2004-01-01

This candidate RNA is on the Lassen National Forest in Siskiyou County. It is approximately 37 air miles (60 km) due E. of Mount Shasta and about 27 miles (43 km) N. of Fall River Mills. The cRNA lies within the Hat Creek Ranger District. Its boundaries include parts of sections 10, 11, 12, 14, and 15 of T40N, R3E MDM (41°19'N., 122°36'W.), USGS Hambone quad...

Power law inflation with electromagnetism

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

Luo, Xianghui; Isenberg, James, E-mail: isenberg@uoregon.edu

2013-07-15

We generalize Ringström’s global future causal stability results (Ringström 2009) [11] for certain expanding cosmological solutions of the Einstein-scalar field equations to solutions of the Einstein–Maxwell-scalar field system. In particular, after noting that the power law inflationary spacetimes (M{sup n+1},g{sup -hat}, ϕ{sup -hat}) considered by Ringström (2009) in [11] are solutions of the Einstein–Maxwell-scalar field system (with exponential potential) as well as of the Einstein-scalar field system (with the same exponential potential), we consider (nonlinear) perturbations of initial data sets of these spacetimes which include electromagnetic perturbations as well as gravitational and scalar perturbations. We show that if (as inmore » Ringström (2009) [11]) we focus on pairs of relatively scaled open sets U{sub R{sub 0}}⊂U{sub 4R{sub 0}} on an initial slice of (M{sup n+1},g{sup -hat}), and if we choose a set of perturbed data which on U{sub 4R{sub 0}} is sufficiently close to that of (M{sup n+1},g{sup -hat},ϕ{sup -hat}, A{sup -hat} = 0), then in the maximal globally hyperbolic spacetime development (M{sup n+1},g,ϕ,A) of this data via the Einstein–Maxwell-scalar field equations, all causal geodesics emanating from U{sub R{sub 0}} are future complete (just as in (M{sup n+1},g{sup -hat})). We also verify that, in a certain sense, the future asymptotic behavior of the fields in the spacetime developments of the perturbed data sets does not differ significantly from the future asymptotic behavior of (M{sup n+1},g{sup -hat}, ϕ{sup -hat}, A{sup -hat} = 0). -- Highlights: •We prove stability of expanding solutions of the Einstein–Maxwell-scalar field equations. •All nearby solutions are geodesically complete. •The topology of the initial slice is irrelevant to our stability results.« less

Sun protection at elementary schools: a cluster randomized trial.

PubMed

Hunter, Seft; Love-Jackson, Kymia; Abdulla, Rania; Zhu, Weiwei; Lee, Ji-Hyun; Wells, Kristen J; Roetzheim, Richard

2010-04-07

Elementary schools represent both a source of childhood sun exposure and a setting for educational interventions. Sun Protection of Florida's Children was a cluster randomized trial promoting hat use at (primary outcome) and outside of schools among fourth-grade students during August 8, 2006, through May 22, 2007. Twenty-two schools were randomly assigned to the intervention (1115 students) or control group (1376 students). Intervention schools received classroom sessions targeting sun protection attitudes and social norms. Each student attending an intervention school received two free wide-brimmed hats. Hat use at school was measured by direct observation and hat use outside of school was measured by self-report. A subgroup of 378 students (178 in the intervention group and 200 in the control group) underwent serial measurements of skin pigmentation to explore potential physiological effects of the intervention. Generalized linear mixed models were used to evaluate the intervention effect by accounting for the cluster randomized trial design. All P values were two-sided and were claimed as statistically significant at a level of .05. The percentage of students observed wearing hats at control schools remained essentially unchanged during the school year (baseline = 2%, fall = 0%, and spring = 1%) but increased statistically significantly at intervention schools (baseline = 2%, fall = 30%, and spring = 41%) (P < .001 for intervention effect comparing the change in rate of hat use over time at intervention vs control schools). Self-reported use of hats outside of school did not change statistically significantly during the study (control: baseline = 14%, fall = 14%, and spring = 11%; intervention: baseline = 24%, fall = 24%, and spring = 23%) nor did measures of skin pigmentation. The intervention increased use of hats among fourth-grade students at school but had no effect on self-reported wide-brimmed hat use outside of school or on measures of skin pigmentation.

Facial exposure to ultraviolet radiation: Predicted sun protection effectiveness of various hat styles.

PubMed

Backes, C; Religi, A; Moccozet, L; Vuilleumier, L; Vernez, D; Bulliard, J-L

2018-04-23

Solar ultraviolet radiation (UVR) doses received by individuals are highly influenced by behavioural and environmental factors. This study aimed at quantifying hats' sun protection effectiveness in various exposure conditions, by predicting UVR exposure doses and their anatomical distributions. A well-defined three-dimensional head morphology and four hat styles (a cap, a helmet, a middle- and a wide-brimmed hat) were added to a previously published model. Midday (12:00-14:00) and daily (08:00 - 17:00) seasonal UVR doses were estimated at various facial skin zones, with and without hat-wear, accounting for each UVR component. Protection effectiveness was calculated by the relative reduction of predicted UVR dose, expressed as a predictive protection factor (PPF). The unprotected entire face received 2.5 times higher UVR doses during a summer midday compared to a winter midday (3.3 vs. 1.3 SED) with highest doses received at the nose (6.1 SED). During a cloudless summer day, the lowest mean UVR dose is received by the entire face protected by a wide-brimmed hat (1.7 SED). No hat reached 100% protection at any facial skin zone (PPF max : 76%). Hats' sun protection effectiveness varied highly with environmental conditions and were mainly limited by the high contribution of diffuse UVR, irrespective of hat style. Larger brim sizes afforded greater facial protection than smaller brim sizes except around midday when the sun position is high. Consideration of diffuse and reflected UVR in sun educational messages could improve sun protection effectiveness. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Application of Human-Autonomy Teaming (HAT) Patterns to Reduce Crew Operations (RCO)

NASA Technical Reports Server (NTRS)

Shively, R. Jay; Brandt, Summer L.; Lachter, Joel; Matessa, Mike; Sadler, Garrett; Battiste, Henri

2016-01-01

Unmanned aerial systems, robotics, advanced cockpits, and air traffic management are all examples of domains that are seeing dramatic increases in automation. While automation may take on some tasks previously performed by humans, humans will still be required, for the foreseeable future, to remain in the system. The collaboration with humans and these increasingly autonomous systems will begin to resemble cooperation between teammates, rather than simple task allocation. It is critical to understand this human-autonomy teaming (HAT) to optimize these systems in the future. One methodology to understand HAT is by identifying recurring patterns of HAT that have similar characteristics and solutions. This paper applies a methodology for identifying HAT patterns to an advanced cockpit project.

HAT-P-34b-HAT-P-37b: FOUR TRANSITING PLANETS MORE MASSIVE THAN JUPITER ORBITING MODERATELY BRIGHT STARS

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

Bakos, G. A.; Hartman, J. D.; Csubry, Z.

2012-07-15

We report the discovery of four transiting extrasolar planets (HAT-P-34b-HAT-P-37b) with masses ranging from 1.05 to 3.33 M{sub J} and periods from 1.33 to 5.45 days. These planets orbit relatively bright F and G dwarf stars (from V = 10.16 to V = 13.2). Of particular interest is HAT-P-34b which is moderately massive (3.33 M{sub J}), has a high eccentricity of e = 0.441 {+-} 0.032 at a period of P = 5.452654 {+-} 0.000016 days, and shows hints of an outer component. The other three planets have properties that are typical of hot Jupiters.

Transportation systems safety hazard analysis tool (SafetyHAT) user guide (version 1.0)

DOT National Transportation Integrated Search

2014-03-24

This is a user guide for the transportation system Safety Hazard Analysis Tool (SafetyHAT) Version 1.0. SafetyHAT is a software tool that facilitates System Theoretic Process Analysis (STPA.) This user guide provides instructions on how to download, ...

Annual reduction of solar UV exposure to the facial area of outdoor workers in Southeast Queensland by wearing a hat.

PubMed

Wong, J C; Airey, D K; Fleming, R A

1996-06-01

The total annual exposure to erythemally effective UVR was estimated for average work situations in a high exposure environment, viz, farm workers in Southeast Queensland (27.5 degrees S), and the effect of hat usage was examined. If no sun protection is used, the annual erythema exposures for this group of workers at three facial sites forehead, nose and cheek are 40, 57 and 34 J.cm-2 respectively. If a hat is worn throughout the year, the exposures are reduced to 6, 19 and 20 J.cm-2, respectively. The mean ratio of exposure without the hat to that with the hat (mean protection factor, MPF) was found to be 6 for the forehead, 3 for the nose and 2 for the cheek. The risk of non-melanoma skin cancers without the protection of the hat is estimated to increase by up to 100 times for basal cell carcinomas and 13 times for squamous cell carcinomas for a whole year of exposure.

Intermolecular artifacts in probe microscope images of C60 assemblies

NASA Astrophysics Data System (ADS)

Jarvis, Samuel Paul; Rashid, Mohammad Abdur; Sweetman, Adam; Leaf, Jeremy; Taylor, Simon; Moriarty, Philip; Dunn, Janette

2015-12-01

Claims that dynamic force microscopy has the capability to resolve intermolecular bonds in real space continue to be vigorously debated. To date, studies have been restricted to planar molecular assemblies with small separations between neighboring molecules. Here we report the observation of intermolecular artifacts over much larger distances in 2D assemblies of C60 molecules, with compelling evidence that in our case the tip apex is terminated by a C60 molecule (rather than the CO termination typically exploited in ultrahigh resolution force microscopy). The complete absence of directional interactions such as hydrogen or halogen bonding, the nonplanar structure of C60, and the fullerene termination of the tip apex in our case highlight that intermolecular artifacts are ubiquitous in dynamic force microscopy.

HATS-50b through HATS-53b: Four Transiting Hot Jupiters Orbiting G-type Stars Discovered by the HATSouth Survey

NASA Astrophysics Data System (ADS)

Henning, Th.; Mancini, L.; Sarkis, P.; Bakos, G. Á.; Hartman, J. D.; Bayliss, D.; Bento, J.; Bhatti, W.; Brahm, R.; Ciceri, S.; Csubry, Z.; de Val-Borro, M.; Espinoza, N.; Fulton, B. J.; Howard, A. W.; Isaacson, H. T.; Jordán, A.; Marcy, G. W.; Penev, K.; Rabus, M.; Suc, V.; Tan, T. G.; Tinney, C. G.; Wright, D. J.; Zhou, G.; Durkan, S.; Lazar, J.; Papp, I.; Sari, P.

2018-02-01

We report the discovery of four close-in transiting exoplanets (HATS-50b through HATS-53b), discovered using the HATSouth three-continent network of homogeneous and automated telescopes. These new exoplanets belong to the class of hot Jupiters and orbit G-type dwarf stars, with brightness in the range V = 12.5–14.0 mag. While HATS-53 has many physical characteristics similar to the Sun, the other three stars appear to be metal-rich ([{Fe}/{{H}}]=0.2{--}0.3), larger, and more massive. Three of the new exoplanets, namely HATS-50b, HATS-51b, and HATS-53b, have low density (HATS-50b: 0.39+/- 0.10 {M}{{J}}, 1.130+/- 0.075 {R}{{J}}; HATS-51b: 0.768+/- 0.045 {M}{{J}}, 1.41+/- 0.19 {R}{{J}}; HATS-53b: 0.595+/- 0.089 {M}{{J}}, 1.340+/- 0.056 {R}{{J}}) and similar orbital periods (3.8297 days, 3.3489 days, 3.8538 days, respectively). Instead, HATS-52b is more dense (mass 2.24+/- 0.15 {M}{{J}} and radius 1.382+/- 0.086 {R}{{J}}) and has a shorter orbital period (1.3667 days). It also receives an intensive radiation from its parent star and, consequently, presents a high equilibrium temperature ({T}{eq}=1834+/- 73 K). HATS-50 shows a marginal additional transit feature consistent with an ultra-short-period hot super Neptune (upper mass limit 0.16 {M}{{J}}), which will be able to be confirmed with TESS photometry. The HATSouth network is operated by a collaboration consisting of Princeton University (PU), the Max Planck Institute für Astronomie (MPIA), the Australian National University (ANU), and the Pontificia Universidad Católica de Chile (PUC). The station at Las Campanas Observatory (LCO) of the Carnegie Institute is operated by PU in conjunction with PUC, the station at the High Energy Spectroscopic Survey (H.E.S.S.) site is operated in conjunction with MPIA, and the station at Siding Spring Observatory (SSO) is operated jointly with ANU. Based in part on observations made with the ESO 3.6 m, the NTT, the MPG 2.2 m and Euler 1.2 m Telescopes at the ESO Observatory in La Silla. Based in part on observations made with the 3.9 m Anglo-Australian Telescope and the ANU 2.3 m Telescope, both at SSO. Based in part on observations made with the Keck I Telescope at Mauna Kea Observatory in Hawaii. Based in part on observations obtained with the facilities of the Las Cumbres Observatory Global Telescope and with the Perth Exoplanet Survey Telescope.

Histone acetyltransferase activity of MOF is required for MLL-AF9 leukemogenesis

PubMed Central

Valerio, Daria G.; Xu, Haiming; Chen, Chun-Wei; Hoshii, Takayuki; Eisold, Meghan E.; Delaney, Christopher; Cusan, Monica; Deshpande, Aniruddha J.; Huang, Chun-Hao; Lujambio, Amaia; Zheng, George; Zuber, Johannes; Pandita, Tej K.; Lowe, Scott W.; Armstrong, Scott A.

2017-01-01

Chromatin-based mechanisms offer therapeutic targets in acute myeloid leukemia (AML) that are of great current interest. In this study, we conducted an RNAi-based screen to identify druggable chromatin regulator-based targets in leukemias marked by oncogenic rearrangements of the MLL gene. In this manner, we discovered the H4K16 histone acetyltransferase (HAT) MOF to be important for leukemia cell growth. Conditional deletion of Mof in a mouse model of MLL-AF9-driven leukemogenesis reduced tumor burden and prolonged host survival. RNA sequencing showed an expected downregulation of genes within DNA damage repair pathways that are controlled by MOF, as correlated with a significant increase in yH2AX nuclear foci in Mof-deficient MLL-AF9 tumor cells. In parallel, Mof loss also impaired global H4K16 acetylation in the tumor cell genome. Rescue experiments with catalytically inactive mutants of MOF showed that its enzymatic activity was required to maintain cancer pathogenicity. In support of the role of MOF in sustaining H4K16 acetylation, a small molecule inhibitor of the HAT component MYST blocked the growth of both murine and human MLL-AF9 leukemia cell lines. Furthermore Mof inactivation suppressed leukemia development in a NUP98-HOXA9 driven AML model. Taken together, our results establish that the HAT activity of MOF is required to sustain MLL-AF9 leukemia and may be important for multiple AML subtypes. Blocking this activity is sufficient to stimulate DNA damage, offering a rationale to pursue MOF inhibitors as a targeted approach to treat MLL-rearranged leukemias. PMID:28202522

Delphinidin, a specific inhibitor of histone acetyltransferase, suppresses inflammatory signaling via prevention of NF-{kappa}B acetylation in fibroblast-like synoviocyte MH7A cells

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

Seong, Ah-Reum; Yoo, Jung-Yoon; Choi, KyungChul

Highlights: {yields} Delphinidin is a novel inhibitor of p300/CBP histone acetyltransferase. {yields} Delphinidin prevents the hyperacetylation of p65 by inhibiting the HAT activity of p300/CBP. {yields} Delphinidin efficiently suppresses the expression of inflammatory cytokines in MH7A cells via hypoacetylation of NF-{kappa}B. {yields} Delphinidin inhibits cytokine release in the Jurkat T lymphocyte cell line. -- Abstract: Histone acetyltransferase (HAT) inhibitors (HATi) isolated from dietary compounds have been shown to suppress inflammatory signaling, which contributes to rheumatoid arthritis. Here, we identified a novel HATi in Punica granatum L. known as delphinidin (DP). DP did not affect the activity of other epigenetic enzymesmore » (histone deacetylase, histone methyltransferase, or sirtuin1). DP specifically inhibited the HAT activities of p300/CBP. It also inhibited p65 acetylation in MH7A cells, a human rheumatoid arthritis synovial cell line. DP-induced hypoacetylation was accompanied by cytosolic accumulation of p65 and nuclear localization of IKB{alpha}. Accordingly, DP treatment inhibited TNF{alpha}-stimulated increases in NF-{kappa}B function and expression of NF-{kappa}B target genes in these cells. Importantly, DP suppressed lipopolysaccharide-induced pro-inflammatory cytokine expression in Jurkat T lymphocytes, demonstrating that HATi efficiently suppresses cytokine-mediated immune responses. Together, these results show that the HATi activity of DP counters anti-inflammatory signaling by blocking p65 acetylation and that this compound may be useful in preventing inflammatory arthritis.« less

Warm Spitzer and Palomar near-IR secondary eclipse photometry of two hot Jupiters: WASP-48b and HAT-P-23b

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

O'Rourke, Joseph G.; Knutson, Heather A.; Désert, Jean-Michel

2014-02-01

We report secondary eclipse photometry of two hot Jupiters, WASP-48b and HAT-P-23b, at 3.6 and 4.5 μm taken with the InfraRed Array Camera aboard the Spitzer Space Telescope during the warm Spitzer mission and in the H and K{sub S} bands with the Wide Field IR Camera at the Palomar 200 inch Hale Telescope. WASP-48b and HAT-P-23b are Jupiter-mass and twice Jupiter-mass objects orbiting an old, slightly evolved F star and an early G dwarf star, respectively. In the H, K{sub S} , 3.6 μm, and 4.5 μm bands, respectively, we measure secondary eclipse depths of 0.047% ± 0.016%, 0.109%more » ± 0.027%, 0.176% ± 0.013%, and 0.214% ± 0.020% for WASP-48b. In the K{sub S} , 3.6 μm, and 4.5 μm bands, respectively, we measure secondary eclipse depths of 0.234% ± 0.046%, 0.248% ± 0.019%, and 0.309% ± 0.026% for HAT-P-23b. For WASP-48b and HAT-P-23b, respectively, we measure delays of 2.6 ± 3.9 minutes and 4.0 ± 2.4 minutes relative to the predicted times of secondary eclipse for circular orbits, placing 2σ upper limits on |ecos ω| of 0.0053 and 0.0080, both of which are consistent with circular orbits. The dayside emission spectra of these planets are well-described by blackbodies with effective temperatures of 2158 ± 100 K (WASP-48b) and 2154 ± 90 K (HAT-P-23b), corresponding to moderate recirculation in the zero albedo case. Our measured eclipse depths are also consistent with one-dimensional radiative transfer models featuring varying degrees of recirculation and weak thermal inversions or no inversions at all. We discuss how the absence of strong temperature inversions on these planets may be related to the activity levels and metallicities of their host stars.« less

Flight service evaluation of an advanced composite empennage component on commercial transport aircraft. Phase 1: Engineering development

NASA Technical Reports Server (NTRS)

Ary, A.; Axtell, C.; Fogg, L.; Jackson, A.; James, A. M.; Mosesian, B.; Vanderwier, J.; Vanhamersveld, J.

1976-01-01

The empennage component selected for this program is the vertical fin box of the L-1011 aircraft. The box structure extends from the fuselage production joint to the tip rib and includes the front and rear spars. Various design options were evaluated to arrive at a configuration which would offer the highest potential for satisfying program objectives. The preferred configuration selected consists of a hat-stiffened cover with molded integrally stiffened spars, aluminum trussed composite ribs, and composite miniwich web ribs with integrally molded caps. Material screening tests were performed to select an advanced composite material system for the Advanced Composite Vertical Fin (ACFV) that would meet the program requirements from the standpoint of quality, reproducibility, and cost. Preliminary weight and cost analysis were made, targets established, and tracking plans developed. These include FAA certification, ancillary test program, quality control, and structural integrity control plans.

Preliminary Design Study of a Tail Rotor Blade Jettison Concept

DTIC Science & Technology

1978-07-01

mannar licai^infi tha hohtar or any olhar parion or torporatlon, or convaylni any ti«hti or l>armiHlon, to manuUiMura ut«, or »rti m\\ fvii «i\\(<<>l...Twist (from center of rotation to blade tip) deg - 20.0 Outboard Blade Airfoil Section m SC-1095 Tip Loss Factor - 0.97 First Flatwise Frequency...basic elements. The prototype system designed for fabrication and evaluation testing differed from a fully productionized configuration In several

Control of the Water Transport Activity of Barley HvTIP3;1 Specifically Expressed in Seeds.

PubMed

Utsugi, Shigeko; Shibasaka, Mineo; Maekawa, Masahiko; Katsuhara, Maki

2015-09-01

Tonoplast intrinsic proteins (TIPs) are involved in the transport and storage of water, and control intracellular osmotic pressure by transporting material related to the water potential of cells. In the present study, we focused on HvTIP3;1 during the periods of seed development and desiccation in barley. HvTIP3;1 was specifically expressed in seeds. An immunochemical analysis showed that HvTIP3;1 strongly accumulated in the aleurone layers and outer layers of barley seeds. The water transport activities of HvTIP3;1 and HvTIP1;2, which also accumulated in seeds, were measured in the heterologous expression system of Xenopus oocytes. When they were expressed individually, HvTIP1;2 transported water, whereas HvTIP3;1 did not. However, HvTIP3;1 exhibited water transport activity when co-expressed with HvTIP1;2 in oocytes, and this activity was higher than when HvTIP1;2 was expressed alone. This is the first report to demonstrate that the water permeability of a TIP aquaporin was activated when co-expressed with another TIP. The split-yellow fluorescent protein (YFP) system in onion cells revealed that HvTIP3;1 interacted with HvTIP1;2 to form a heterotetramer in plants. These results suggest that HvTIP3;1 functions as an active water channel to regulate water movement through tissues during the periods of seed development and desiccation. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Quercetin induces apoptosis of Trypanosoma brucei gambiense and decreases the proinflammatory response of human macrophages.

PubMed

Mamani-Matsuda, Maria; Rambert, Jérôme; Malvy, Denis; Lejoly-Boisseau, Hélène; Daulouède, Sylvie; Thiolat, Denis; Coves, Sara; Courtois, Pierrette; Vincendeau, Philippe; Mossalayi, M Djavad

2004-03-01

In addition to parasite spread, the severity of disease observed in cases of human African trypanosomiasis (HAT), or sleeping sickness, is associated with increased levels of inflammatory mediators, including tumor necrosis factor (TNF)-alpha and nitric oxide derivatives. In the present study, quercetin (3,3',4',5,7-pentahydroxyflavone), a potent immunomodulating flavonoid, was shown to directly induce the death of Trypanosoma brucei gambiense, the causative agent of HAT, without affecting normal human cell viability. Quercetin directly promoted T. b. gambiense death by apoptosis as shown by Annexin V binding. In addition to microbicidal activity, quercetin induced dose-dependent decreases in the levels of TNF-alpha and nitric oxide produced by activated human macrophages. These results highlight the potential use of quercetin as an antimicrobial and anti-inflammatory agent for the treatment of African trypanomiasis.

P300/CBP acts as a coactivator to cartilage homeoprotein-1 (Cart1), paired-like homeoprotein, through acetylation of the conserved lysine residue adjacent to the homeodomain.

PubMed

Iioka, Takashi; Furukawa, Keizo; Yamaguchi, Akira; Shindo, Hiroyuki; Yamashita, Shunichi; Tsukazaki, Tomoo

2003-08-01

The paired-like homeoprotein, Cart1, is involved in skeletal development. We describe here that the general coactivator p300/CBP controls the transcription activity of Cart1 through acetylation of a lysine residue that is highly conserved in other homeoproteins. Acetylation of this residue increases the interaction between p300/CBP and Cart1 and enhances its transcriptional activation. Cart1 encodes a paired-like homeoprotein expressed selectively in chondrocyte lineage during embryonic development. Although its target gene remains unknown, gene disruption studies have revealed that Cart1 plays an important role for craniofacial bone formation as well as limb development by cooperating with another homeoprotein, Alx4. In this report, we study the functional involvement of p300/CBP, coactivators with intrinsic histone acetyltransferase (HAT) activity, in the transcriptional control of Cart1. To study the transcription activity of Cart1, a reporter construct containing a putative Cart1 binding site was transiently transfected with the expression vectors of each protein. The interaction between p300/CBP and Cart1 was investigated by glutathione S-transferase (GST) pull-down, yeast two-hybrid, and immunoprecipitation assays. In vitro acetylation assay was performed with the recombinant p300-HAT domain and Cart1 in the presence of acetyl-CoA. p300 and CBP stimulate Cart1-dependent transcription activity, and this transactivation is inhibited by E1A and Tax, oncoproteins that suppress the activity of p300/CBP. Cart1 binds to p300 in vivo and in vitro, and this requires the homeodomain of Cart 1 and N-terminal 139 amino acids of p300. Confocal microscopy analysis shows that Cart1 recruits overexpressed and endogenous p300 to a Cart1-specific subnuclear compartment. Cart1 is acetylated in vivo and sodium butyrate and trichostatin A, histone deacetylase inhibitors, markedly enhance the transcription activity of Cart1. Deletion and mutagenesis analysis identifies the 131st lysine that locates immediately adjacent to the homeodomain as a target of p300-HAT, and a point mutation to this residue attenuates the binding affinity to p300 as well as p300-dependent transcription activity. Together, these results indicate that p300/CBP acts as a cotransactivator to Cart1 through a direct interaction and specific lysine acetylation. In addition, because 131st lysine is highly conserved in other types of homeoprotein, this lysine may be a common target for HAT of p300/CBP for these proteins.

A novel technique for micro-hole forming on skull with the assistance of ultrasonic vibration.

PubMed

Li, Zhe; Yang, Daoguo; Hao, Weidong; Wu, Tiecheng; Wu, Song; Li, Xiaoping

2016-04-01

Micro-hole opening on skull is technically challenging and is hard to realize by micro-drilling. Low-stiffness of the drill bit is a serious drawback in micro-drilling. To deal with this problem, a novel ultrasonic vibration assisted micro-hole forming technique has been developed. Tip geometry and vibration amplitude are two key factors affecting the performance of this hole forming technique. To investigate their effects, experiment was carried out with 300μm diameter tools of three different tip geometries at three different vibration amplitudes. Hole forming performance was evaluated by the required thrust force, dimensional accuracy, exit burr and micro-structure of bone tissue around the generated hole. Based on the findings from current study, the 60° conically tipped tool helps generate a micro-hole of better quality at a smaller thrust force, and it is more suitable for hole forming than the 120° conically tipped tool and the blunt tipped tool. As for the vibration amplitude, when a larger amplitude is used, a micro-hole of better quality and higher dimensional accuracy can be formed at a smaller thrust force. Findings from this study would lay a technical foundation for accurately generating a high-quality micro-hole on skull, which enables minimally invasive insertion of a microelectrode into brain for neural activity measuring. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development of a fine thermocouple-needle system for real-time feedback of thermal tumour ablation margin

PubMed Central

Ishizaka, H; Shiraishi, A; Awata, S; Shimizu, A; Hirasawa, S

2011-01-01

Thermal tumour ablation techniques such as radiofrequency (RF) ablation are applied for radical removal of local tumours as an easier, less invasive alternative to surgical resection. A serious drawback of thermal ablation, however, is that the ablation area cannot be accurately assessed during the procedure. To achieve real-time feedback and exact and safe ablation, a superfine thermocouple-needle system (TNS) comprising a 0.25-mm diameter thermocouple embedded in a 22-G, 15-cm-long needle was devised and efficacy was tested in vitro using porcine livers (n = 15) and in vivo using rabbit back muscles (n = 2) and livers (n = 3). A 17-gauge RF electrode with a 2 cm active tip was used for ablation. The TNS was inserted 1 cm from the active tip of the RF electrode and liver temperature around the electrode was measured concurrently. The RF current was cut off when the temperature reached 60°C or after 5 min at ≥50°C. Porcine livers and rabbit back muscles were then cut along a plane passing through the axes of the electrode and the TNS. In rabbit livers, contrast-enhanced CT was performed to evaluate ablation areas. Ablation areas in cut surfaces of porcine livers exhibited well-defined discoloured regions and the TNS tip precisely pinpointed the margin of the ablation area. Contrast-enhanced CT of rabbit livers showed the TNS tip accurately located at the margin of areas without contrast enhancement. These results indicate that the TNS can accurately show ablation margins and that placing the TNS tip at the intended ablation margin permits exact thermal ablation. PMID:21937618

Short communication. Development of a fine thermocouple-needle system for real-time feedback of thermal tumour ablation margin.

PubMed

Ishizaka, H; Shiraishi, A; Awata, S; Shimizu, A; Hirasawa, S

2011-12-01

Thermal tumour ablation techniques such as radiofrequency (RF) ablation are applied for radical removal of local tumours as an easier, less invasive alternative to surgical resection. A serious drawback of thermal ablation, however, is that the ablation area cannot be accurately assessed during the procedure. To achieve real-time feedback and exact and safe ablation, a superfine thermocouple-needle system (TNS) comprising a 0.25-mm diameter thermocouple embedded in a 22-G, 15-cm-long needle was devised and efficacy was tested in vitro using porcine livers (n = 15) and in vivo using rabbit back muscles (n = 2) and livers (n = 3). A 17-gauge RF electrode with a 2 cm active tip was used for ablation. The TNS was inserted 1 cm from the active tip of the RF electrode and liver temperature around the electrode was measured concurrently. The RF current was cut off when the temperature reached 60°C or after 5 min at ≥50°C. Porcine livers and rabbit back muscles were then cut along a plane passing through the axes of the electrode and the TNS. In rabbit livers, contrast-enhanced CT was performed to evaluate ablation areas. Ablation areas in cut surfaces of porcine livers exhibited well-defined discoloured regions and the TNS tip precisely pinpointed the margin of the ablation area. Contrast-enhanced CT of rabbit livers showed the TNS tip accurately located at the margin of areas without contrast enhancement. These results indicate that the TNS can accurately show ablation margins and that placing the TNS tip at the intended ablation margin permits exact thermal ablation.

Investigations of Functional and Structural Interactions Between c-src and HER2: Involvement in Human Breast Tumor Formation

DTIC Science & Technology

1998-07-01

UNCLASSIFIED AD NUMBER ADB239338 NEW LIMITATION CHANGE TO Approved for public release, distribution unlimited FROM Distribution authorized to U.S...OR CORPORATION; OR CONVEY ANY. RIGHTS OR PERMI SION TO MANUFACTURE, USE, OR SELL ANY PATENTED INVENTIC HAT MAY RELATE TO THEM. LIMITED GHTS LEGEND...Contract Number: DAMD17-96-1-60Q8 Contractor: University of Virgi ia Location of Limited Rights Data (Pages): 1-39 Those portions of the technical data

Analysis of a model of gambiense sleeping sickness in humans and cattle.

PubMed

Ndondo, A M; Munganga, J M W; Mwambakana, J N; Saad-Roy, C M; van den Driessche, P; Walo, R O

2016-01-01

Human African Trypanosomiasis (HAT) and Nagana in cattle, commonly called sleeping sickness, is caused by trypanosome protozoa transmitted by bites of infected tsetse flies. We present a deterministic model for the transmission of HAT caused by Trypanosoma brucei gambiense between human hosts, cattle hosts and tsetse flies. The model takes into account the growth of the tsetse fly, from its larval stage to the adult stage. Disease in the tsetse fly population is modeled by three compartments, and both the human and cattle populations are modeled by four compartments incorporating the two stages of HAT. We provide a rigorous derivation of the basic reproduction number R0. For R0 < 1, the disease free equilibrium is globally asymptotically stable, thus HAT dies out; whereas (assuming no return to susceptibility) for R0 >1, HAT persists. Elasticity indices for R0 with respect to different parameters are calculated with baseline parameter values appropriate for HAT in West Africa; indicating parameters that are important for control strategies to bring R0 below 1. Numerical simulations with R0 > 1 show values for the infected populations at the endemic equilibrium, and indicate that with certain parameter values, HAT could not persist in the human population in the absence of cattle.

Rationale, Design, Samples, and Baseline Sun Protection in a Randomized Trial on a Skin Cancer Prevention Intervention in Resort Environments

PubMed Central

Buller, David B.; Andersen, Peter A.; Walkosz, Barbara J.; Scott, Michael D.; Beck, Larry; Cutter, Gary R.

2016-01-01

Introduction Exposure to solar ultraviolet radiation during recreation is a risk factor for skin cancer. A trial evaluating an intervention to promote advanced sun protection (sunscreen pre-application/reapplication; protective hats and clothing; use of shade) during vacations. Materials and Methods Adult visitors to hotels/resorts with outdoor recreation (i.e., vacationers) participated in a group-randomized pretest-posttest controlled quasi-experimental design in 2012–14. Hotels/resorts were pair-matched and randomly assigned to the intervention or untreated control group. Sun protection (e.g., clothing, hats, shade and sunscreen) was measured in cross-sectional samples by observation and a face-to-face intercept survey during two-day visits. Results Initially, 41 hotel/resorts (11%) participated but 4 dropped out before posttest. Hotel/resorts were diverse (employees=30 to 900; latitude=24o 78′ N to 50o 52′ N; elevation=2 ft. to 9,726 ft. above sea level), and had a variety of outdoor venues (beaches/pools, court/lawn games, golf courses, common areas, and chairlifts). At pretest, 4,347 vacationers were observed and 3,531 surveyed. More females were surveyed (61%) than observed (50%). Vacationers were mostly 35–60 years old, highly educated (college education = 68%) and non-Hispanic white (93%), with high-risk skin types (22%). Vacationers reported covering 60% of their skin with clothing. Also, 40% of vacationers used shade; 60% applied sunscreen; and 42% had been sunburned. Conclusions The trial faced challenges recruiting resorts but result show that the large, multi-state sample of vacationers were at high risk for solar UV exposure. PMID:26593781

Nanostar probes for tip-enhanced spectroscopy

NASA Astrophysics Data System (ADS)

Kim, Woong; Kim, Nara; Park, Joon Won; Kim, Zee Hwan

2015-12-01

To overcome the current limit of tip-enhanced spectroscopy that is based on metallic nano-probes, we developed a new scanning probe with a metallic nanostar, a nanoparticle with sharp spikes. A Au nanoparticle of 5 nm was first attached to the end of a tip through DNA-DNA hybridization and mechanical pick-up. The nanoparticle was converted to a nanostar with a core diameter of ~70 nm and spike lengths between 50 nm and 80 nm through the reduction of Au3+ with ascorbic acid in the presence of Ag+. Fabrication yields of such tips exceeded 60%, and more than 80% of such tips showed a mechanical durability sufficient for use in scanning microscopy. Effectiveness of the new probes for tip-enhanced Raman scattering (TERS) and tip-enhanced fluorescence (TEF) was confirmed. The probes exhibited the necessary enhancement for TEF, and the tip-on and tip-off ratios varied between 5 and 100. This large tip-to-tip variability may arise from the uncontrolled orientation of the apexes of the spike with respect to the sample surface, which calls for further fabrication improvement. The result overall supports a new fabrication approach for the probe that is effective for tip-enhanced spectroscopy.To overcome the current limit of tip-enhanced spectroscopy that is based on metallic nano-probes, we developed a new scanning probe with a metallic nanostar, a nanoparticle with sharp spikes. A Au nanoparticle of 5 nm was first attached to the end of a tip through DNA-DNA hybridization and mechanical pick-up. The nanoparticle was converted to a nanostar with a core diameter of ~70 nm and spike lengths between 50 nm and 80 nm through the reduction of Au3+ with ascorbic acid in the presence of Ag+. Fabrication yields of such tips exceeded 60%, and more than 80% of such tips showed a mechanical durability sufficient for use in scanning microscopy. Effectiveness of the new probes for tip-enhanced Raman scattering (TERS) and tip-enhanced fluorescence (TEF) was confirmed. The probes exhibited the necessary enhancement for TEF, and the tip-on and tip-off ratios varied between 5 and 100. This large tip-to-tip variability may arise from the uncontrolled orientation of the apexes of the spike with respect to the sample surface, which calls for further fabrication improvement. The result overall supports a new fabrication approach for the probe that is effective for tip-enhanced spectroscopy. Electronic supplementary information (ESI) available: Illustrations of TERS and TEF experiments, information about the TEM images, scheme of surface preparation and peak assignments of TERS spectra. See DOI: 10.1039/c5nr06657c

High-Mobility 6,13-Bis(triisopropylsilylethynyl) Pentacene Transistors Using Solution-Processed Polysilsesquioxane Gate Dielectric Layers.

PubMed

Matsuda, Yu; Nakahara, Yoshio; Michiura, Daisuke; Uno, Kazuyuki; Tanaka, Ichiro

2016-04-01

Polysilsesquioxane (PSQ) is a low-temperature curable polymer that is compatible with low-cost plastic substrates. We cured PSQ gate dielectric layers by irradiation with ultraviolet light at ~60 °C, and used them for 6,13-bis(triisopropylsilylethynyl) pentacene (TIPS-pentacene) thin film transistors (TFTs). The fabricated TFTs have shown the maximum and average hole mobility of 1.3 and 0.78 ± 0.3 cm2V-1s-1, which are comparable to those of the previously reported transistors using single-crystalline TIPS-pentacene micro-ribbons for their active layers and thermally oxidized SiO2 for their gate dielectric layers. Itis therefore demonstrated that PSQ is a promising polymer gate dielectric material for low-cost organic TFTs.

Abiotic stresses modulate expression of major intrinsic proteins in barley (Hordeum vulgare).

PubMed

Ligaba, Ayalew; Katsuhara, Maki; Shibasaka, Mineo; Djira, Gemechis

2011-02-01

In one of the most important crops, barley (Hordeum vulgare L.), gene expression and physiological roles of most major intrinsic proteins (MIPs) remained to be elucidated. Here we studied expression of five tonoplast intrinsic protein isoforms (HvTIP1;2, HvTIP2;1, HvTIP2;2, HvTIP2;3 and HvTIP4;1), a NOD26-like intrinsic protein (HvNIP2;1) and a plasma membrane intrinsic protein (HvPIP2;1) by using the quantitative real-time RT-PCR. Five-day-old seedlings were exposed to abiotic stresses (salt, heavy metals and nutrient deficiency), abscisic acid (ABA) and gibberellic acid (GA) for 24 h. Treatment with 100 mM NaCl, 0.1 mM ABA and 1 mM GA differentially regulated gene expression in roots and shoots. Nitrogen and prolonged P-deficiency downregulated expression of most MIP genes in roots. Intriguingly, gene expression was restored to the values in the control three days after nutrient supply was resumed. Heavy metals (0.2 mM each of Cd, Cu, Zn and Cr) downregulated the transcript levels by 60-80% in roots, whereas 0.2 mM Hg upregulated expressions of most genes in roots. This was accompanied by a 45% decrease in the rate of transpiration. In order to study the physiological role of the MIPs, cDNA of three genes (HvTIP2;1, HvTIP2;3 and HvNIP2;1) have been cloned and heterologous expression was performed in Xenopus laevis oocytes. Osmotic water permeability was determined by a swelling assay. However, no water uptake activity was observed for the three proteins. Hence, the possible physiological role of the proteins is discussed. Copyright © 2010 Académie des sciences. Published by Elsevier SAS. All rights reserved.

From Health Advice to Taboo: Community Perspectives on the Treatment of Sleeping Sickness in the Democratic Republic of Congo, a Qualitative Study

PubMed Central

Mpanya, Alain; Hendrickx, David; Baloji, Sylvain; Lumbala, Crispin; da Luz, Raquel Inocêncio; Boelaert, Marleen; Lutumba, Pascal

2015-01-01

Background Socio-cultural and economic factors constitute real barriers for uptake of screening and treatment of Human African Trypanosomiasis (HAT) in the Democratic Republic of Congo (DRC). Better understanding and addressing these barriers may enhance the effectiveness of HAT control. Methods We performed a qualitative study consisting of semi-structured interviews and focus group discussions in the Bandundu and Kasaï Oriental provinces, two provinces lagging behind in the HAT elimination effort. Our study population included current and former HAT patients, as well as healthcare providers and program managers of the national HAT control program. All interviews and discussions were voice recorded on a digital device and data were analysed with the ATLAS.ti software. Findings Health workers and community members quoted a number of prohibitions that have to be respected for six months after HAT treatment: no work, no sexual intercourse, no hot food, not walking in the sun. Violating these restrictions is believed to cause serious, and sometimes deadly, complications. These strong prohibitions are well-known by the community and lead some people to avoid HAT screening campaigns, for fear of having to observe such taboos in case of diagnosis. Discussion The restrictions originally aimed to mitigate the severe adverse effects of the melarsoprol regimen, but are not evidence-based and became obsolete with the new safer drugs. Correct health information regarding HAT treatment is essential. Health providers should address the perspective of the community in a constant dialogue to keep abreast of unintended transformations of meaning. PMID:25856578

From health advice to taboo: community perspectives on the treatment of sleeping sickness in the Democratic Republic of Congo, a qualitative study.

PubMed

Mpanya, Alain; Hendrickx, David; Baloji, Sylvain; Lumbala, Crispin; da Luz, Raquel Inocêncio; Boelaert, Marleen; Lutumba, Pascal

2015-04-01

Socio-cultural and economic factors constitute real barriers for uptake of screening and treatment of Human African Trypanosomiasis (HAT) in the Democratic Republic of Congo (DRC). Better understanding and addressing these barriers may enhance the effectiveness of HAT control. We performed a qualitative study consisting of semi-structured interviews and focus group discussions in the Bandundu and Kasaï Oriental provinces, two provinces lagging behind in the HAT elimination effort. Our study population included current and former HAT patients, as well as healthcare providers and program managers of the national HAT control program. All interviews and discussions were voice recorded on a digital device and data were analysed with the ATLAS.ti software. Health workers and community members quoted a number of prohibitions that have to be respected for six months after HAT treatment: no work, no sexual intercourse, no hot food, not walking in the sun. Violating these restrictions is believed to cause serious, and sometimes deadly, complications. These strong prohibitions are well-known by the community and lead some people to avoid HAT screening campaigns, for fear of having to observe such taboos in case of diagnosis. The restrictions originally aimed to mitigate the severe adverse effects of the melarsoprol regimen, but are not evidence-based and became obsolete with the new safer drugs. Correct health information regarding HAT treatment is essential. Health providers should address the perspective of the community in a constant dialogue to keep abreast of unintended transformations of meaning.

Single multivalent vaccination boosted by trickle larval infection confers protection against experimental lymphatic filariasis

PubMed Central

Joseph, SK; Ramaswamy, K

2013-01-01

The multivalent vaccine BmHAT, consisting of the Brugia malayi infective larval (L3) antigens heat shock protein12.6 (HSP12.6), abundant larval transcript-2 (ALT-2) and tetraspanin large extra cellular loop (TSP-LEL), was shown to be protective in rodent models from our laboratory. We hypothesize that since these antigens were identified using protective antibodies from immune endemic normal individuals, the multivalent vaccine can be augmented by natural L3 infections providing protection to the vaccinated host. This hypothesis was tested using single dose of DNA and Protein or Protein alone of the BmHAT vaccination in gerbils followed by live trickle L3 infection as booster dose. Vaccine-induced protection in gerbils was determined by worm establishment, micropore chamber assay and by antibody dependant cell cytotoxicity (ADCC) assay. Results were compared with the traditional prime-boost vaccination regimen. Gerbils vaccinated with BmHAT and boosted with L3 trickle infection were protected 51% (BmHAT DNA-Protein) and 48% (BmHAT Protein) respectively. BmHAT vaccination plus L3 trickle booster generated significant titer of antigen-specific IgG antibodies comparable to the traditional prime boost vaccination approach. BmHAT vaccination plus L3 trickle booster also generated antigen-specific cells in the spleen of vaccinated animals and these cells secreted predominantly IFN-γ and IL-4 in response to the vaccine antigens. These studies thus show that single dose of BmHAT multivalent vaccination followed by L3 trickle booster infection can confer significant protection against lymphatic filariasis. PMID:23735679

A cluster randomized trial of sun protection at elementary schools. Results from year 2.

PubMed

Roetzheim, Richard G; Love-Jackson, Kymia M; Hunter, Seft G; Lee, Ji-Hyun; Chen, Ren; Abdulla, Rania; Wells, Kristen J

2011-12-01

Elementary schools are one potential venue for sun protection interventions that reduce childhood sun exposure. To assess Year-2 results from a cluster randomized trial promoting hat use at schools. Block randomization was used to assign intervention/control status to participating schools. Data were collected from 2006 to 2008 and analyzed in 2007-2010. Of the 24 schools in the School District of Hillsborough County, Florida enrolled, 4th-graders were targeted in the first year and followed through their 5th-grade year. Classroom sessions were conducted to improve sun protection knowledge, foster more positive attitudes about hat use, and change the subjective norm of wearing hats when at school. Year-2 outcomes assessed included hat use at school (measured by direct observation), hat use outside of school (measured by self-report) and skin pigmentation and nevi counts (measured for a subgroup of 439 students). The percentage of students observed wearing hats at control schools remained unchanged during the 2-year period (range 0%-2%) but increased significantly at intervention schools (2% at baseline, 41% at end of Year 1, 19% at end of Year 2; p<0.001 for intervention effect). Measures of skin pigmentation, nevi counts, and self-reported use of hats outside of school did not change during the study period. This intervention increased use of hats at school through Year 2 but had no measurable effect on skin pigmentation or nevi. Whether school-based interventions can ultimately prevent skin cancer is uncertain. Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Volume in moment tensor space in terms of distance

NASA Astrophysics Data System (ADS)

Tape, Walter; Tape, Carl

2017-07-01

Suppose that we want to assess the extent to which some large collection of moment tensors is concentrated near a fixed moment tensor m. We are naturally led to consider the distribution of the distances of the moment tensors from m. This distribution, however, can only be judged in conjunction with the distribution of distances from m for randomly chosen moment tensors. In cumulative form, the latter distribution is the same as the fractional volume \\hat{V}(ω ) of the set of all moment tensors that are within distance ω of m. This definition of \\hat{V}(ω ) assumes that a reasonable universe {M} of moment tensors has been specified at the outset and that it includes the original collection as a subset. Our main goal in this article is to derive a formula for \\hat{V}(ω ) when {M} is the set [Λ]_{U} of all moment tensors having a specified eigenvalue triple Λ. We find that \\hat{V}(ω ) depends strongly on Λ, and we illustrate the dependence by plotting the derivative curves \\hat{V}^' }(ω ) for various seismologically relevant Λs. The exotic and unguessable shapes of these curves underscores the futility of interpreting the distribution of distances for the original moment tensors without knowing \\hat{V}(ω ) or \\hat{V}^' }(ω ). The derivation of the formula for \\hat{V}(ω ) relies on a certain ϕ σz coordinate system for [Λ]_{U}, which we treat in detail. Our underlying motivation for the paper is the estimation of uncertainties in moment tensor inversion.

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

Albrecht, Simon; Winn, Joshua N.; Johnson, John A.

We provide evidence that the obliquities of stars with close-in giant planets were initially nearly random, and that the low obliquities that are often observed are a consequence of star-planet tidal interactions. The evidence is based on 14 new measurements of the Rossiter-McLaughlin effect (for the systems HAT-P-6, HAT-P-7, HAT-P-16, HAT-P-24, HAT-P-32, HAT-P-34, WASP-12, WASP-16, WASP-18, WASP-19, WASP-26, WASP-31, Gl 436, and Kepler-8), as well as a critical review of previous observations. The low-obliquity (well-aligned) systems are those for which the expected tidal timescale is short, and likewise the high-obliquity (misaligned and retrograde) systems are those for which the expectedmore » timescale is long. At face value, this finding indicates that the origin of hot Jupiters involves dynamical interactions like planet-planet interactions or the Kozai effect that tilt their orbits rather than inspiraling due to interaction with a protoplanetary disk. We discuss the status of this hypothesis and the observations that are needed for a more definitive conclusion.« less

Application of Human-Autonomy Teaming (HAT) Patterns to Reduced Crew Operations (RCO)

NASA Technical Reports Server (NTRS)

Shively, R. Jay; Brandt, Summer L.; Lachter, Joel; Matessa, Mike; Sadler, Garrett; Battiste, Henri

2016-01-01

As part of the Air Force - NASA Bi-Annual Research Council Meeting, slides will be presented on recent Reduced Crew Operations (RCO) work. Unmanned aerial systems, robotics, advanced cockpits, and air traffic management are all examples of domains that are seeing dramatic increases in automation. While automation may take on some tasks previously performed by humans, humans will still be required, for the foreseeable future, to remain in the system. The collaboration with humans and these increasingly autonomous systems will begin to resemble cooperation between teammates, rather than simple task allocation. It is critical to understand this human-autonomy teaming (HAT) to optimize these systems in the future. One methodology to understand HAT is by identifying recurring patterns of HAT that have similar characteristics and solutions. A methodology for identifying HAT patterns to an advanced cockpit project is discussed.

Enhanced passive screening and diagnosis for gambiense human African trypanosomiasis in north-western Uganda – Moving towards elimination

PubMed Central

Bessell, Paul Richard; Ndung’u, Joseph Mathu

2017-01-01

Introduction The incidence of gambiense human African trypanosomiasis (gHAT) in Uganda has been declining, from 198 cases in 2008, to only 20 in 2012. Interruption of transmission of the disease by early diagnosis and treatment is core to the control and eventual elimination of gHAT. Until recently, the format of available screening tests had restricted screening and diagnosis to central health facilities (passive screening). We describe a novel strategy that is contributing to elimination of gHAT in Uganda through expansion of passive screening to the entire population at risk. Methodology / Principal findings In this strategy, patients who are clinically suspected of having gHAT at primary health facilities are screened using a rapid diagnostic test (RDT), followed by parasitological confirmation at strategically located microscopy centres. For patients who are positive with the RDT and negative by microscopy, blood samples undergo further testing using loop-mediated isothermal amplification (LAMP), a molecular test that detects parasite DNA. LAMP positive patients are considered strong suspects, and are re-evaluated by microscopy. Location and upgrading of facilities to perform microscopy and LAMP was informed by results of georeferencing and characterization of all public healthcare facilities in the 7 gHAT endemic districts in Uganda. Three facilities were upgraded to perform RDTs, microscopy and LAMP, 9 to perform RDTs and microscopy, and 200 to screen patients with RDTs. This reduced the distance that a sick person must travel to be screened for gHAT to a median distance of 2.5km compared to 23km previously. In this strategy, 9 gHAT cases were diagnosed in 2014, and 4 in 2015. Conclusions This enhanced passive screening strategy for gHAT has enabled full coverage of the population at risk, and is being replicated in other gHAT endemic countries. The improvement in case detection is making elimination of the disease in Uganda an imminent possibility. PMID:29023573

The changing epidemiology of human African trypanosomiasis among patients from nonendemic countries--1902-2012.

PubMed

Neuberger, Ami; Meltzer, Eyal; Leshem, Eyal; Dickstein, Yaakov; Stienlauf, Shmuel; Schwartz, Eli

2014-01-01

Although human African trypanosomiasis (HAT) is uncommon among patients from non-endemic countries (NEC), there has been an increase in the number of cases reported in recent years. A systematic review of the literature was performed. The number of incoming tourists to HAT endemic countries was obtained from the United Nations World Tourism Organization. All HAT cases diagnosed in patients from NEC were included. Immigrants and refugees were excluded. We compared patients during and after the colonial period, and analyzed the relationship between the number of incoming travellers and the number of HAT cases. Between 1902 and 2012, HAT was reported in 244 patients. Most HAT cases were reported before 1920, and after the year 2000. In the colonial era the average age of patients was lower (32.5±7.8 vs. 43.0±16.1 years, P<0.001), the proportion of females was lower (10.0% vs. 23.9%, P<0.01], most cases were diagnosed in expatriates, missionaries and soldiers (74.3%), and Gambian trypanosomiasis accounted for 86/110, (78%) of cases. In the post-colonial era most patients 91/125 (72.8%) were short-term tourists to game parks in Eastern and South-Eastern Africa (mainly in Tanzania); Rhodesian trypanosomiasis accounted for 94/123 (76.4%) of cases. Between 1995 and 2010 there has been a constant linear increase in the number of incoming tourists to Tanzania, and HAT cases occurred in small outbreaks rather than following a similar linear pattern. In recent decades HAT patients from NEC are older, and more likely to be tourists who acquired the disease while visiting game-parks in Eastern and South-Eastern Africa. While Rhodesian trypanosomiasis is relatively uncommon among Africans, it now accounts for most cases reported among patients from NEC. Returning febrile travellers without an alternative diagnosis should be evaluated for HAT. Cases among travellers may serve as sentinels for Rhodesian trypanosomiasis "hot spots" in Africa.

Trends in Ground-State Entropies for Transition Metal Based Hydrogen Atom Transfer Reactions

PubMed Central

Mader, Elizabeth A.; Manner, Virginia W.; Markle, Todd F.; Wu, Adam; Franz, James A.; Mayer, James M.

2009-01-01

Reported herein are thermochemical studies of hydrogen atom transfer (HAT) reactions involving transition metal H-atom donors MIILH and oxyl radicals. [FeII(H2bip)3]2+, [FeII(H2bim)3]2+, [CoII(H2bim)3]2+ and RuII(acac)2(py-imH) [H2bip = 2,2’-bi-1,4,5,6-tetrahydropyrimidine, H2bim = 2,2’-bi-imidazoline, acac = 2,4-pentandionato, py-imH = 2-(2’-pyridyl)-imidazole)] each react with TEMPO (2,2,6,6-tetramethyl-1-piperidinoxyl) or tBu3PhO• (2,4,6-tri-tert-butylphenoxyl) to give the deprotonated, oxidized metal complex MIIIL, and TEMPOH or tBu3PhOH. Solution equilibrium measurements for the reaction of [CoII(H2bim)3]2+ with TEMPO show a large, negative ground-state entropy for hydrogen atom transfer, −41 ± 2 cal mol−1 K−1. This is even more negative than the ΔSoHAT = −30 ± 2 cal mol−1 K−1 for the two iron complexes and the ΔSoHAT for RuII(acac)2(py-imH) + TEMPO, 4.9 ± 1.1 cal mol−1 K−1, as reported earlier. Calorimetric measurements quantitatively confirm the enthalpy of reaction for [FeII(H2bip)3]2+ + TEMPO, thus also confirming ΔSoHAT. Calorimetry on TEMPOH + tBu3PhO• gives ΔHoHAT = −11.2 ± 0.5 kcal mol−1 which matches the enthalpy predicted from the difference in literature solution BDEs. A brief evaluation of the literature thermochemistry of TEMPOH and tBu3PhOH supports the common assumption that ΔSoHAT ≈ 0 for HAT reactions of organic and small gas-phase molecules. However, this assumption does not hold for transition metal based HAT reactions. The trend in magnitude of |ΔSoHAT| for reactions with TEMPO, RuII(acac)2(py-imH) << [FeII(H2bip)3]2+ = [FeII(H2bim)3]2+ < [CoII(H2bim)3]2+, is surprisingly well predicted by the trends for electron transfer half-reaction entropies, ΔSoET, in aprotic solvents. This is because both ΔSoET and ΔSoHAT have substantial contributions from vibrational entropy, which varies significantly with the metal center involved. The close connection between ΔSoHAT and ΔSoET provides an important link between these two fields and provides a starting point from which to predict which HAT systems will have important ground-state entropy effects. PMID:19275235

In Vitro and In Vivo Investigation of High-Intensity Focused Ultrasound (HIFU) Hat-Type Ablation Mode

PubMed Central

Dai, Hongya; Chen, Fei; Yan, Sijing; Ding, Xiaoya; Ma, Dazhao; Wen, Jing; Xu, Die; Zou, Jianzhong

2017-01-01

Background The aim of this study was to investigate the feasibility of the application of high-intensity focused ultrasound (HIFU) hat-type ablation mode in in vitro and in vivo models, and to compare the ablation effects of different parameter combinations. Material/Methods HIFU hat-type ablation was performed in isolated bovine liver tissue and in the liver tissue in living rabbits, and the coagulative necrosis for different parameter combinations (plane angles and irradiation order) was investigated. We also analyzed and compared the ablation effects of traditional ablation and hat-type ablation modes. Coagulative necrosis morphology was detected with TTC staining, and the coagulative necrosis volume and energy efficiency factor (EEF) were calculated and compared. Results Coagulative necrosis was observed in all the ablated groups, and the coagulative necrosis volume was much larger than the irradiation area. The coagulative necrosis induced by the hat-type ablation was more regular and controllable than the traditional ablation. The angles between the ablation planes determined the coagulative necrosis morphology, but did not affect the coagulative necrosis volume. Moreover, the irradiation order significantly influenced the coagulative necrosis. Importantly, under certain conditions, hat-type ablation achieved higher efficiency compared with the traditional ablation mode. Conclusions Compared with the traditional ablation mode, HIFU hat-type ablation effectively shortened the irradiation time, reduced the over-accumulation of energy, and increased the HIFU ablation efficiency. PMID:28699626

In Vitro and In Vivo Investigation of High-Intensity Focused Ultrasound (HIFU) Hat-Type Ablation Mode.

PubMed

Dai, Hongya; Chen, Fei; Yan, Sijing; Ding, Xiaoya; Ma, Dazhao; Wen, Jing; Xu, Die; Zou, Jianzhong

2017-07-12

BACKGROUND The aim of this study was to investigate the feasibility of the application of high-intensity focused ultrasound (HIFU) hat-type ablation mode in in vitro and in vivo models, and to compare the ablation effects of different parameter combinations. MATERIAL AND METHODS HIFU hat-type ablation was performed in isolated bovine liver tissue and in the liver tissue in living rabbits, and the coagulative necrosis for different parameter combinations (plane angles and irradiation order) was investigated. We also analyzed and compared the ablation effects of traditional ablation and hat-type ablation modes. Coagulative necrosis morphology was detected with TTC staining, and the coagulative necrosis volume and energy efficiency factor (EEF) were calculated and compared. RESULTS Coagulative necrosis was observed in all the ablated groups, and the coagulative necrosis volume was much larger than the irradiation area. The coagulative necrosis induced by the hat-type ablation was more regular and controllable than the traditional ablation. The angles between the ablation planes determined the coagulative necrosis morphology, but did not affect the coagulative necrosis volume. Moreover, the irradiation order significantly influenced the coagulative necrosis. Importantly, under certain conditions, hat-type ablation achieved higher efficiency compared with the traditional ablation mode. CONCLUSIONS Compared with the traditional ablation mode, HIFU hat-type ablation effectively shortened the irradiation time, reduced the over-accumulation of energy, and increased the HIFU ablation efficiency.

VizieR Online Data Catalog: Differential photometry of the F-subgiant HAT-P-67 (Zhou+, 2017)

NASA Astrophysics Data System (ADS)

Zhou, G.; Bakos, G. A.; Hartman, J. D.; Latham, D. W.; Torres, G.; Bhatti, W.; Penev, K.; Buchhave, L.; Kovacs, G.; Bieryla, A.; Quinn, S.; Isaacson, H.; Fulton, B. J.; Falco, E.; Csubry, Z.; Everett, M.; Szklenar, T.; Esquerdo, G.; Berlind, P.; Calkins, M. L.; Beky, B.; Knox, R. P.; Hinz, P.; Horch, E. P.; Hirsch, L.; Howell, S. B.; Noyes, R. W.; Marcy, G.; de Val-Borro, M.; Lazar, J.; Papp, I.; Sari, P.

2018-04-01

The transits of HAT-P-67b were first detected with the HATNet survey (Bakos et al. 2004PASP..116..266B). HATNet employs a network of small, wide field telescopes, located at the Fred Lawrence Whipple Observatory (FLWO) in Arizona and at the Mauna Kea Observatory (MKO) in Hawaii, to photometrically monitor selected 8x8° fields of the sky. A total of 4050 I band observations were taken by HAT-5 and HAT-8 from 2005 January to July, and an additional 4518 observations were obtained in the Cousins R band using HAT-5, HAT-7, and HAT-8 telescopes between 2008 February and August. To better characterize the planetary properties, follow-up photometry of the transits were obtained using the KeplerCam on the FWLO 1.2 m telescope. KeplerCam is a 4Kx4K CCD camera with a pixel scale of 0.672"/pixel at 2x2 pixel binning. The photometry was reduced as per Bakos et al. (2010, J/ApJ/710/1724). A full transit was observed in the Sloan-i band on 2012 May 28, and five partial transits were observed on 2011 April 15, May 19, June 07, and 2013 April 25 in the Sloan-i band, and 2013 May 24 in the Sloan-z band. (1 data file).

Thermal and Mechanical Buckling Analysis of Hypersonic Aircraft Hat-Stiffened Panels With Varying Face Sheet Geometry and Fiber Orientation

NASA Technical Reports Server (NTRS)

Ko, William L.

1996-01-01

Mechanical and thermal buckling behavior of monolithic and metal-matrix composite hat-stiffened panels were investigated. The panels have three types of face-sheet geometry: Flat face sheet, microdented face sheet, and microbulged face sheet. The metal-matrix composite panels have three types of face-sheet layups, each of which is combined with various types of hat composite layups. Finite-element method was used in the eigenvalue extractions for both mechanical and thermal buckling. The thermal buckling analysis required both eigenvalue and material property iterations. Graphical methods of the dual iterations are shown. The mechanical and thermal buckling strengths of the hat-stiffened panels with different face-sheet geometry are compared. It was found that by just microdenting or microbulging of the face sheet, the axial, shear, and thermal buckling strengths of both types of hat-stiffened panels could be enhanced considerably. This effect is more conspicuous for the monolithic panels. For the metal-matrix composite panels, the effect of fiber orientations on the panel buckling strengths was investigated in great detail, and various composite layup combinations offering, high panel buckling strengths are presented. The axial buckling strength of the metal-matrix panel was sensitive to the change of hat fiber orientation. However, the lateral, shear, and thermal buckling strengths were insensitive to the change of hat fiber orientation.

Impact of very advanced donor age on hepatic artery thrombosis after liver transplantation.

PubMed

Cescon, Matteo; Zanello, Matteo; Grazi, Gian Luca; Cucchetti, Alessandro; Ravaioli, Matteo; Ercolani, Giorgio; Del Gaudio, Massimo; Lauro, Augusto; Morelli, Maria Cristina; Pinna, Antonio Daniele

2011-08-27

The impact of advanced donor age on hepatic artery thrombosis (HAT) after liver transplantation (LT) is controversial. We analyzed the incidence of and risk factors for HAT in LT with donors aged 70 years or older. Eighty patients were transplanted between 1998 and 2002 (group A) and 132 between 2003 and 2008 (group B). In the more recent approach to hepatic artery (HA) reconstruction, the donor HA was systematically preferred to the Carrel patch/celiac trunk, the reconstruction of donor accessory right HA on the donor gastroduodenal artery significantly increased, and the use of interposition grafts was minimized. Group B showed higher Model for End-stage Liver Disease score, lower ischemia time, and lower use of the folding technique/mesenteric conduits. There were 10 cases of HAT (4.7%): 8 (10%) in group A and 2 (1.5%) in group B (P=0.007). Early HAT occurred in 7 (8.8%) patients in group A and in 2 (1.5%) in group B (P=0.02). Group A (P=0.01), anatomical variations of HA (P=0.005), and the use of interposition grafts (P=0.004) were all factors independently affecting HAT. A low incidence of late HAT was observed in single-center LTs with very old donors. Early HAT decreased over time to largely acceptable rates because of more appropriate technical management.

Histone H3 and the histone acetyltransferase Hat1p contribute to DNA double-strand break repair.

PubMed

Qin, Song; Parthun, Mark R

2002-12-01

The modification of newly synthesized histones H3 and H4 by type B histone acetyltransferases has been proposed to play a role in the process of chromatin assembly. The type B histone acetyltransferase Hat1p and specific lysine residues in the histone H3 NH(2)-terminal tail (primarily lysine 14) are redundantly required for telomeric silencing. As many gene products, including other factors involved in chromatin assembly, have been found to participate in both telomeric silencing and DNA damage repair, we tested whether mutations in HAT1 and the histone H3 tail were also sensitive to DNA-damaging agents. Indeed, mutations both in specific lysine residues in the histone H3 tail and in HAT1 resulted in sensitivity to methyl methanesulfonate. The DNA damage sensitivity of the histone H3 and HAT1 mutants was specific for DNA double-strand breaks, as these mutants were sensitive to the induction of an exogenous restriction endonuclease, EcoRI, but not to UV irradiation. While histone H3 mutations had minor effects on nonhomologous end joining, the primary defect in the histone H3 and HAT1 mutants was in the recombinational repair of DNA double-strand breaks. Epistasis analysis indicates that the histone H3 and HAT1 mutants may influence DNA double-strand break repair through Asf1p-dependent chromatin assembly.

Quercetin Induces Apoptosis of Trypanosoma brucei gambiense and Decreases the Proinflammatory Response of Human Macrophages

PubMed Central

Mamani-Matsuda, Maria; Rambert, Jérôme; Malvy, Denis; Lejoly-Boisseau, Hélène; Daulouède, Sylvie; Thiolat, Denis; Coves, Sara; Courtois, Pierrette; Vincendeau, Philippe; Djavad Mossalayi, M.

2004-01-01

In addition to parasite spread, the severity of disease observed in cases of human African trypanosomiasis (HAT), or sleeping sickness, is associated with increased levels of inflammatory mediators, including tumor necrosis factor (TNF)-α and nitric oxide derivatives. In the present study, quercetin (3,3′,4′,5,7-pentahydroxyflavone), a potent immunomodulating flavonoid, was shown to directly induce the death of Trypanosoma brucei gambiense, the causative agent of HAT, without affecting normal human cell viability. Quercetin directly promoted T. b. gambiense death by apoptosis as shown by Annexin V binding. In addition to microbicidal activity, quercetin induced dose-dependent decreases in the levels of TNF-α and nitric oxide produced by activated human macrophages. These results highlight the potential use of quercetin as an antimicrobial and anti-inflammatory agent for the treatment of African trypanomiasis. PMID:14982785

The Sino-Indian Border Dispute: India’s Current Options

DTIC Science & Technology

1993-06-04

Thus came into being the ’Red Hat’ sect of Lamaism which enjoyed the ruler’s patronage. This, however, had adverse affects and the Red Hats slowly...north, seized power and established the ’Yellow Hat’ sect of Lamaism which purported to follow a refined doctrine. The fourth reincarnation of Tsong Khapa

Subregion-Specific p300 Conditional Knock-Out Mice Exhibit Long-Term Memory Impairments

ERIC Educational Resources Information Center

Oliveira, Ana M. M.; Estevez, Marcel A.; Hawk, Joshua D.; Grimes, Shannon; Brindle, Paul K.; Abel, Ted

2011-01-01

Histone acetylation plays a critical role during long-term memory formation. Several studies have demonstrated that the histone acetyltransferase (HAT) CBP is required during long-term memory formation, but the involvement of other HAT proteins has not been extensively investigated. The HATs CBP and p300 have at least 400 described interacting…

Histone Acetyltransferase Activity of MOF Is Required for MLL-AF9 Leukemogenesis.

PubMed

Valerio, Daria G; Xu, Haiming; Chen, Chun-Wei; Hoshii, Takayuki; Eisold, Meghan E; Delaney, Christopher; Cusan, Monica; Deshpande, Aniruddha J; Huang, Chun-Hao; Lujambio, Amaia; Zheng, YuJun George; Zuber, Johannes; Pandita, Tej K; Lowe, Scott W; Armstrong, Scott A

2017-04-01

Chromatin-based mechanisms offer therapeutic targets in acute myeloid leukemia (AML) that are of great current interest. In this study, we conducted an RNAi-based screen to identify druggable chromatin regulator-based targets in leukemias marked by oncogenic rearrangements of the MLL gene. In this manner, we discovered the H4K16 histone acetyltransferase (HAT) MOF to be important for leukemia cell growth. Conditional deletion of Mof in a mouse model of MLL-AF9 -driven leukemogenesis reduced tumor burden and prolonged host survival. RNA sequencing showed an expected downregulation of genes within DNA damage repair pathways that are controlled by MOF, as correlated with a significant increase in yH2AX nuclear foci in Mof -deficient MLL-AF9 tumor cells. In parallel, Mof loss also impaired global H4K16 acetylation in the tumor cell genome. Rescue experiments with catalytically inactive mutants of MOF showed that its enzymatic activity was required to maintain cancer pathogenicity. In support of the role of MOF in sustaining H4K16 acetylation, a small-molecule inhibitor of the HAT component MYST blocked the growth of both murine and human MLL-AF9 leukemia cell lines. Furthermore, Mof inactivation suppressed leukemia development in an NUP98-HOXA9 -driven AML model. Taken together, our results establish that the HAT activity of MOF is required to sustain MLL-AF9 leukemia and may be important for multiple AML subtypes. Blocking this activity is sufficient to stimulate DNA damage, offering a rationale to pursue MOF inhibitors as a targeted approach to treat MLL -rearranged leukemias. Cancer Res; 77(7); 1753-62. ©2017 AACR . ©2017 American Association for Cancer Research.

Disruption of sheet-like structures in Alfvénic turbulence by magnetic reconnection

NASA Astrophysics Data System (ADS)

Mallet, A.; Schekochihin, A. A.; Chandran, B. D. G.

2017-07-01

We propose a mechanism whereby the intense, sheet-like structures naturally formed by dynamically aligning Alfvénic turbulence are destroyed by magnetic reconnection at a scale \\hat{λ }_D, larger than the dissipation scale predicted by models of intermittent, dynamically aligning turbulence. The reconnection process proceeds in several stages: first, a linear tearing mode with N magnetic islands grows and saturates, and then the X-points between these islands collapse into secondary current sheets, which then reconnect until the original structure is destroyed. This effectively imposes an upper limit on the anisotropy of the structures within the perpendicular plane, which means that at scale \\hat{λ }_D the turbulent dynamics change: at scales larger than \\hat{λ }_D, the turbulence exhibits scale-dependent dynamic alignment and a spectral index approximately equal to -3/2, while at scales smaller than \\hat{λ }_D, the turbulent structures undergo a succession of disruptions due to reconnection, limiting dynamic alignment, steepening the effective spectral index and changing the final dissipation scale. The scaling of \\hat{λ }_D with the Lundquist (magnetic Reynolds) number S_{L_\\perp } depends on the order of the statistics being considered, and on the specific model of intermittency; the transition between the two regimes in the energy spectrum is predicted at approximately \\hat{λ }_D˜ S_{L_\\perp }^{-0.6}. The spectral index below \\hat{λ }_D is bounded between -5/3 and -2.3. The final dissipation scale is at \\hat{λ }_{η ,∞}˜ S_{L_\\perp }^{-3/4}, the same as the Kolmogorov scale arising in theories of turbulence that do not involve scale-dependent dynamic alignment.

Safety, Pharmacokinetic, and Efficacy Studies of Oral DB868 in a First Stage Vervet Monkey Model of Human African Trypanosomiasis

PubMed Central

Thuita, John K.; Wolf, Kristina K.; Murilla, Grace A.; Liu, Qiang; Mutuku, James N.; Chen, Yao; Bridges, Arlene S.; Mdachi, Raymond E.; Ismail, Mohamed A.; Ching, Shelley; Boykin, David W.; Hall, James Edwin; Tidwell, Richard R.; Paine, Mary F.; Brun, Reto; Wang, Michael Zhuo

2013-01-01

There are no oral drugs for human African trypanosomiasis (HAT, sleeping sickness). A successful oral drug would have the potential to reduce or eliminate the need for patient hospitalization, thus reducing healthcare costs of HAT. The development of oral medications is a key objective of the Consortium for Parasitic Drug Development (CPDD). In this study, we investigated the safety, pharmacokinetics, and efficacy of a new orally administered CPDD diamidine prodrug, 2,5-bis[5-(N-methoxyamidino)-2-pyridyl]furan (DB868; CPD-007-10), in the vervet monkey model of first stage HAT. DB868 was well tolerated at a dose up to 30 mg/kg/day for 10 days, a cumulative dose of 300 mg/kg. Mean plasma levels of biomarkers indicative of liver injury (alanine aminotransferase, aspartate aminotransferase) were not significantly altered by drug administration. In addition, no kidney-mediated alterations in creatinine and urea concentrations were detected. Pharmacokinetic analysis of plasma confirmed that DB868 was orally available and was converted to the active compound DB829 in both uninfected and infected monkeys. Treatment of infected monkeys with DB868 began 7 days post-infection. In the infected monkeys, DB829 attained a median Cmax (dosing regimen) that was 12-fold (3 mg/kg/day for 7 days), 15-fold (10 mg/kg/day for 7 days), and 31-fold (20 mg/kg/day for 5 days) greater than the IC50 (14 nmol/L) against T. b. rhodesiense STIB900. DB868 cured all infected monkeys, even at the lowest dose tested. In conclusion, oral DB868 cured monkeys with first stage HAT at a cumulative dose 14-fold lower than the maximum tolerated dose and should be considered a lead preclinical candidate in efforts to develop a safe, short course (5–7 days), oral regimen for first stage HAT. PMID:23755309

Telling our stories: heroin-assisted treatment and SNAP activism in the Downtown Eastside of Vancouver.

PubMed

Boyd, Susan; Murray, Dave; MacPherson, Donald

2017-05-18

This article highlights the experiences of a peer-run group, SALOME/NAOMI Association of Patients (SNAP), that meets weekly in the Downtown Eastside of Vancouver, British Columbia, Canada. SNAP is a unique independent peer- run drug user group that formed in 2011 following Canada's first heroin-assisted treatment trial (HAT), North America Opiate Medication Initiative (NAOMI). SNAP's members are now made up of former research participants who participated in two heroin-assisted trials in Vancouver. This article highlights SNAP members' experiences as research subjects in Canada's second clinical trial conducted in Vancouver, Study to Assess Longer-term Opioid Medication Effectiveness (SALOME), that began recruitment of research participants in 2011. This paper draws on one brainstorming session, three focus groups, and field notes, with the SALOME/NAOMI Association of Patients (SNAP) in late 2013 about their experiences as research subjects in Canada's second clinical trial, SALOME in the DTES of Vancouver, and fieldwork from a 6-year period (March 2011 to February 2017) with SNAP members. SNAP's research draws on research principles developed by drug user groups and critical methodological frameworks on community-based research for social justice. The results illuminate how participating in the SALOME clinical trial impacted the lives of SNAP members. In addition, the findings reveal how SNAP member's advocacy for HAT impacts the group in positive ways. Seven major themes emerged from the analysis of the brainstorming and focus groups: life prior to SALOME, the clinic setting and routine, stability, 6-month transition, support, exiting the trial and ethics, and collective action, including their participation in a constitutional challenge in the Supreme Court of BC to continue receiving HAT once the SALOME trial ended. HAT benefits SNAP members. They argue that permanent HAT programs should be established in Canada because they are an effective harm reduction initiative, one that also reduces opioid overdose deaths.

Heroin-assisted Treatment (HAT) a Decade Later: A Brief Update on Science and Politics

PubMed Central

Oviedo-Joekes, Eugenia; Blanken, Peter; Haasen, Christian; Rehm, Jürgen; Schechter, Martin T.; Strang, John; van den Brink, Wim

2007-01-01

Since the initial Swiss heroin-assisted treatment (HAT) study conducted in the mid-1990s, several other jurisdictions in Europe and North America have implemented HAT trials. All of these studies embrace the same goal—investigating the utility of medical heroin prescribing for problematic opioid users—yet are distinct in various key details. This paper briefly reviews (initiated or completed) studies and their main parameters, including primary research objectives, design, target populations, outcome measures, current status and—where available—key results. We conclude this overview with some final observations on a decade of intensive HAT research in the jurisdictions examined, including the suggestion that there is a mounting onus on the realm of politics to translate the—largely positive—data from completed HAT science into corresponding policy and programming in order to expand effective treatment options for the high-risk population of illicit opioid users. PMID:17562183

VizieR Online Data Catalog: Differential photometry of the EB* HATS551-027 (Zhou+, 2015)

NASA Astrophysics Data System (ADS)

Zhou, G.; Bayliss, D.; Hartman, J. D.; Rabus, M.; Bakos, G. A.; Jordan, A.; Brahm, R.; Penev, K.; Csubry, Z.; Mancini, L.; Espinoza, N.; de Val-Borro, M.; Bhatti, W.; Ciceri, S.; Henning, T.; Schmidt, B.; Murphy, S. J.; Butler, R. P.; Arriagada, P.; Shectman, S.; Crane, J.; Thompson, I.; Suc, V.; Noyes, R. W.

2017-11-01

The eclipses of HATS551-027 were first identified by observations from the HATSouth survey (Bakos et al. 2013PASP..125..154B). HATSouth is a global network of identical, fully robotic telescopes, providing continuous monitoring of selected 128 deg2 fields of the southern sky. A total of 16622 observations of HATS551-027 were obtained from HATSouth units HS-1, HS-2 in Chile, HS-3, HS-4 in Namibia, and HS-6 in Australia from 2009 September to 2010 September. Two secondary eclipses of HATS551-027 were observed by the Merope camera on 2-m Faulkes Telescope South (FTS), at Siding Spring Observatory, on 2012 December 12 and 2013 March 20. A near-complete primary eclipse of HATS551-027 was observed by the SITe#3 camera on the Swope 1 m telescope at Las Campanas Observatory, Chile, on 2013 February 26. (1 data file).

How Do We Community College Activities Professionals Keep Our Many Hats from Making Us as "Mad as a Hatter?"

ERIC Educational Resources Information Center

Bannish, Shelley K.

2001-01-01

Offers recommendations on keeping balance in their working lives for community college activities professionals. Addresses: (1) prioritizing, delegating, and knowing the right people; (2) saying "no"; (3) what to do when saying "yes"; (4) support and guidance; and (5) where family fits in. (EV)

Interactions of Histone Acetyltransferase p300 with the Nuclear Proteins Histone and HMGB1, As Revealed by Single Molecule Atomic Force Spectroscopy.

PubMed

Banerjee, S; Rakshit, T; Sett, S; Mukhopadhyay, R

2015-10-22

One of the important properties of the transcriptional coactivator p300 is histone acetyltransferase (HAT) activity that enables p300 to influence chromatin action via histone modulation. p300 can exert its HAT action upon the other nuclear proteins too--one notable example being the transcription-factor-like protein HMGB1, which functions also as a cytokine, and whose accumulation in the cytoplasm, as a response to tissue damage, is triggered by its acetylation. Hitherto, no information on the structure and stability of the complexes between full-length p300 (p300FL) (300 kDa) and the histone/HMGB1 proteins are available, probably due to the presence of unstructured regions within p300FL that makes it difficult to be crystallized. Herein, we have adopted the high-resolution atomic force microscopy (AFM) approach, which allows molecularly resolved three-dimensional contour mapping of a protein molecule of any size and structure. From the off-rate and activation barrier values, obtained using single molecule dynamic force spectroscopy, the biochemical proposition of preferential binding of p300FL to histone H3, compared to the octameric histone, can be validated. Importantly, from the energy landscape of the dissociation events, a model for the p300-histone and the p300-HMGB1 dynamic complexes that HAT forms, can be proposed. The lower unbinding forces of the complexes observed in acetylating conditions, compared to those observed in non-acetylating conditions, indicate that upon acetylation, p300 tends to weakly associate, probably as an outcome of charge alterations on the histone/HMGB1 surface and/or acetylation-induced conformational changes. To our knowledge, for the first time, a single molecule level treatment of the interactions of HAT, where the full-length protein is considered, is being reported.

Oxoiron(IV) Tetramethylcyclam Complexes with Axial Carboxylate Ligands: Effect of Tethering the Carboxylate on Reactivity.

PubMed

Bigelow, Jennifer O; England, Jason; Klein, Johannes E M N; Farquhar, Erik R; Frisch, Jonathan R; Martinho, Marlène; Mandal, Debasish; Münck, Eckard; Shaik, Sason; Que, Lawrence

2017-03-20

Oxoiron(IV) species are implicated as reactive intermediates in nonheme monoiron oxygenases, often acting as the agent for hydrogen-atom transfer from substrate. A histidine is the most likely ligand trans to the oxo unit in most enzymes characterized thus far but is replaced by a carboxylate in the case of isopenicillin N synthase. As the effect of a trans carboxylate ligand on the properties of the oxoiron(IV) unit has not been systematically studied, we have synthesized and characterized four oxoiron(IV) complexes supported by the tetramethylcyclam (TMC) macrocycle and having a carboxylate ligand trans to the oxo unit. Two complexes have acetate or propionate axial ligands, while the other two have the carboxylate functionality tethered to the macrocyclic ligand framework by one or two methylene units. Interestingly, these four complexes exhibit substrate oxidation rates that differ by more than 100-fold, despite having E p,c values for the reduction of the Fe═O unit that span a range of only 130 mV. Eyring parameters for 1,4-cyclohexadiene oxidation show that reactivity differences originate from differences in activation enthalpy between complexes with tethered carboxylates and those with untethered carboxylates, in agreement with computational results. As noted previously for the initial subset of four complexes, the logarithms of the oxygen atom transfer rates of 11 complexes of the Fe IV (O)TMC(X) series increase linearly with the observed E p,c values, reflecting the electrophilicity of the Fe═O unit. In contrast, no correlation with E p,c values is observed for the corresponding hydrogen atom transfer (HAT) reaction rates; instead, the HAT rates increase as the computed triplet-quintet spin state gap narrows, consistent with Shaik's two-state-reactivity model. In fact, the two complexes with untethered carboxylates are among the most reactive HAT agents in this series, demonstrating that the axial ligand can play a key role in tuning the HAT reactivity in a nonheme iron enzyme active site.

Chemotherapy of Second Stage Human African Trypanosomiasis: Comparison between the Parenteral Diamidine DB829 and Its Oral Prodrug DB868 in Vervet Monkeys

PubMed Central

Thuita, John K.; Wolf, Kristina K.; Murilla, Grace A.; Bridges, Arlene S.; Boykin, David W.; Mutuku, James N.; Liu, Qiang; Jones, Susan K.; Gem, Charles O.; Ching, Shelley; Tidwell, Richard R.; Wang, Michael Z.; Paine, Mary F.; Brun, Reto

2015-01-01

Human African trypanosomiasis (HAT, sleeping sickness) ranks among the most neglected tropical diseases based on limited availability of drugs that are safe and efficacious, particularly against the second stage (central nervous system [CNS]) of infection. In response to this largely unmet need for new treatments, the Consortium for Parasitic Drug Development developed novel parenteral diamidines and corresponding oral prodrugs that have shown cure of a murine model of second stage HAT. As a rationale for selection of one of these compounds for further development, the pharmacokinetics and efficacy of intramuscular (IM) active diamidine 2,5-bis(5-amidino-2-pyridyl)furan (DB829; CPD-0802) and oral prodrug2,5-bis[5-(N-methoxyamidino)-2-pyridyl]furan (DB868) were compared in the vervet monkey model of second stage HAT. Treatment was initiated 28 days post-infection of monkeys with T. b. rhodesiense KETRI 2537. Results showed that IM DB829 at 5 mg/kg/day for 5 consecutive days, 5 mg/kg/day every other day for 5 doses, or 2.5 mg/kg/day for 5 consecutive days cured all monkeys (5/5). Oral DB868 was less successful, with no cures (0/2) at 3 mg/kg/day for 10 days and cure rates of 1/4 at 10 mg/kg/day for 10 days and 20 mg/kg/day for 10 days; in total, only 2/10 monkeys were cured with DB868 dose regimens. The geometric mean plasma Cmax of IM DB829 at 5 mg/kg following the last of 5 doses was 25-fold greater than that after 10 daily oral doses of DB868 at 20 mg/kg. These data suggest that the active diamidine DB829, administered IM, should be considered for further development as a potential new treatment for second stage HAT. PMID:25654243

Spatial and temporal compact equations for water waves

NASA Astrophysics Data System (ADS)

Dyachenko, Alexander; Kachulin, Dmitriy; Zakharov, Vladimir

2016-04-01

A one-dimensional potential flow of an ideal incompressible fluid with a free surface in a gravity field is the Hamiltonian system with the Hamiltonian: H = 1/2intdxint-∞^η |nablaφ|^2dz + g/2ont η^2dxŗφ(x,z,t) - is the potential of the fluid, g - gravity acceleration, η(x,t) - surface profile Hamiltonian can be expanded as infinite series of steepness: {Ham4} H &=& H2 + H3 + H4 + dotsŗH2 &=& 1/2int (gη2 + ψ hat kψ) dx, ŗH3 &=& -1/2int \\{(hat kψ)2 -(ψ_x)^2}η dx,ŗH4 &=&1/2int {ψxx η2 hat kψ + ψ hat k(η hat k(η hat kψ))} dx. where hat k corresponds to the multiplication by |k| in Fourier space, ψ(x,t)= φ(x,η(x,t),t). This truncated Hamiltonian is enough for gravity waves of moderate amplitudes and can not be reduced. We have derived self-consistent compact equations, both spatial and temporal, for unidirectional water waves. Equations are written for normal complex variable c(x,t), not for ψ(x,t) and η(x,t). Hamiltonian for temporal compact equation can be written in x-space as following: {SPACE_C} H = intc^*hat V c dx + 1/2int [ i/4(c2 partial/partial x {c^*}2 - {c^*}2 partial/partial x c2)- |c|2 hat K(|c|^2) ]dx Here operator hat V in K-space is so that Vk = ω_k/k. If along with this to introduce Gardner-Zakharov-Faddeev bracket (for the analytic in the upper half-plane function) {GZF} partial^+x Leftrightarrow ikθk Hamiltonian for spatial compact equation is the following: {H24} &&H=1/gint1/ω|cω|2 dω +ŗ&+&1/2g^3int|c|^2(ddot c^*c + ddot c c^*)dt + i/g^2int |c|^2hatω(dot c c* - cdot c^*)dt. equation of motion is: {t-space} &&partial /partial xc +i/g partial^2/partial t^2c =ŗ&=& 1/2g^3partial^3/partial t3 [ partial^2/partial t^2(|c|^2c) +2 |c|^2ddot c +ddot c^*c2 ]+ŗ&+&i/g3 partial^3/partial t3 [ partial /partial t( chatω |c|^2) + dot c hatω |c|2 + c hatω(dot c c* - cdot c^*) ]. It solves the spatial Cauchy problem for surface gravity wave on the deep water. Main features of the equations are: Equations are written for complex normal variable c(x,t) which is analytic function in the upper half-planeHamiltonians both for temporal and spatial equations are very simple It can be easily implemented for numerical simulation The equations can be generalized for "almost" 2-D waves like KdV is generalized to KP. This work was supported by was Grant "Wave turbulence: theory, numerical simulation, experiment" #14-22-00174 of Russian Science Foundation.

Giant Paperclip Necklaces, Soup-Can Rings and Cherry-Pie Hats

ERIC Educational Resources Information Center

Winters, Laurel A.

2011-01-01

In this article, the author describes an art project inspired by the wearable sculpture art created by artist Marjorie Schick. Students used wallpaper paste and newspapers to create papier-mache for a mountain hat, a cherry-pie mask/hat, a "dress" shoe and a Cubistic mask. Cardboard was used in many of these things, in addition to being used as…

Collaborative care: Using six thinking hats for decision making.

PubMed

Cioffi, Jane Marie

2017-12-01

To apply six thinking hats technique for decision making in collaborative care. In collaborative partnerships, effective communications need to occur in patient, family, and health care professional meetings. The effectiveness of these meetings depends on the engagement of participants and the quality of the meeting process. The use of six thinking hats technique to engage all participants in effective dialogue is proposed. Discussion paper. Electronic databases, CINAHL, Pub Med, and Science Direct, were searched for years 1990 to 2017. Using six thinking hats technique in patient family meetings nurses can guide a process of dialogue that focuses decision making to build equal care partnerships inclusive of all participants. Nurses will need to develop the skills for using six thinking hats technique and provide support to all participants during the meeting process. Collaborative decision making can be augmented by six thinking hat technique to provide patients, families, and health professionals with opportunities to make informed decisions about care that considers key issues for all involved. Nurses who are most often advocates for patients and their families are in a unique position to lead this initiative in meetings as they network with all health professionals. © 2017 John Wiley & Sons Australia, Ltd.

Optimization of an Active Twist Rotor Blade Planform for Improved Active Response and Forward Flight Performance

NASA Technical Reports Server (NTRS)

Sekula, Martin K; Wilbur, Matthew L.

2014-01-01

A study was conducted to identify the optimum blade tip planform for a model-scale active twist rotor. The analysis identified blade tip design traits which simultaneously reduce rotor power of an unactuated rotor while leveraging aeromechanical couplings to tailor the active response of the blade. Optimizing the blade tip planform for minimum rotor power in forward flight provided a 5 percent improvement in performance compared to a rectangular blade tip, but reduced the vibration control authority of active twist actuation by 75 percent. Optimizing for maximum blade twist response increased the vibration control authority by 50 percent compared to the rectangular blade tip, with little effect on performance. Combined response and power optimization resulted in a blade tip design which provided similar vibration control authority to the rectangular blade tip, but with a 3.4 percent improvement in rotor performance in forward flight.

Enhancer of polycomb coordinates multiple signaling pathways to promote both cyst and germline stem cell differentiation in the Drosophila adult testis

PubMed Central

Feng, Lijuan; Shi, Zhen; Chen, Xin

2017-01-01

Stem cells reside in a particular microenvironment known as a niche. The interaction between extrinsic cues originating from the niche and intrinsic factors in stem cells determines their identity and activity. Maintenance of stem cell identity and stem cell self-renewal are known to be controlled by chromatin factors. Herein, we use the Drosophila adult testis which has two adult stem cell lineages, the germline stem cell (GSC) lineage and the cyst stem cell (CySC) lineage, to study how chromatin factors regulate stem cell differentiation. We find that the chromatin factor Enhancer of Polycomb [E(Pc)] acts in the CySC lineage to negatively control transcription of genes associated with multiple signaling pathways, including JAK-STAT and EGF, to promote cellular differentiation in the CySC lineage. E(Pc) also has a non-cell-autonomous role in regulating GSC lineage differentiation. When E(Pc) is specifically inactivated in the CySC lineage, defects occur in both germ cell differentiation and maintenance of germline identity. Furthermore, compromising Tip60 histone acetyltransferase activity in the CySC lineage recapitulates loss-of-function phenotypes of E(Pc), suggesting that Tip60 and E(Pc) act together, consistent with published biochemical data. In summary, our results demonstrate that E(Pc) plays a central role in coordinating differentiation between the two adult stem cell lineages in Drosophila testes. PMID:28196077

Sun-Protective Behaviors of Student Spectators at Inter-school Swimming Carnivals in a Tropical Region Experiencing High Ambient Solar Ultraviolet Radiation

PubMed Central

Turner, Denise; Harrison, Simone Lee; Bates, Nicole

2016-01-01

Skin cancer is the most common cancer in humans and Australia (particularly in Queensland) has the highest incidence globally. Sunlight is a known skin carcinogen and reflects off water, exacerbating the risk of sunburn. In 1988, the “SunSmart Program” was developed to promote sun-protection to Australian children. Within a decade, it evolved to include a voluntary national accreditation program for schools, known as the SunSmart Schools (SSS) Program. Additionally, in 2008, it became compulsory for primary schoolchildren attending Queensland government-funded schools to wear a shirt during all water-based activities, except when competing. We observed the proportion of student spectators from 41 Townsville (latitude 19.3°S) primary schools (65.9% SSS) wearing hats at inter-school swimming carnivals in 2009–2011 and 2015 and the proportion wearing a shirt. Overall, a median of 30.7% student spectators from each school wore a hat [max 46.2% (2009); min 18% (2015)] and 77.3% wore a shirt [max 95.8% (2009); min 74.5% (2015)], suggesting that hats are under-utilized. Students from non-government (private) schools were twice as likely as students from government schools to wear a hat (41 vs. 18.2% p = 0.003). Neither the hat nor the shirt-wearing behaviors of student spectators were significantly influenced by their school’s size (number of students), educational advantage, sun-protection policy score, or SunSmart status, indicating that other socioeconomic factors, not assessed here, may have influenced the results. Our findings suggest that the mandatory swim-shirt policy introduced in 2008 was very effective, especially initially. However, monitoring and feedback of results to schools may be needed to maintain high levels of compliance in the longer-term. Schoolchildren attending swimming carnivals should not rely on sunscreen or shade alone to protect against direct and reflected-sunlight, and need prompting to put a hat and shirt back on immediately after a race. This responsibility could be delegated to either a parent or a student prefect, if teachers are too busy to encourage and monitor sun-safety compliance among the students in their care. PMID:27579300

Composition and Antioxidant Activity of Water-Soluble Polysaccharides from Tuber indicum

PubMed Central

Luo, Qiang; Zhang, Jie; Yan, Liang; Tang, Yuanlin; Ding, Xiang; Yang, Zhirong

2011-01-01

Abstract Crude water-soluble Chinese truffle Tuber indicum polysaccharide (TIP) was extracted from the fruiting bodies with water and then successively purified by DEAE–cellulose 52 and Sephadex G-100 column chromatography, yielding two major polysaccharide fractions: TIP1-1 and TIP2-1. High-performance gel permeation chromatography analysis showed that the average molecular sizes of TIP1-1 and TIP2-1 were approximately 1.75×104 Da and 5.73×103 Da, respectively. Monosaccharide component analysis by gas chromatography indicated that TIP1-1 was composed of mannose, glucose, galactose, and rhamannose in the respective molar ratio of 3.93:1.24:0.75:1.26 and that TIP2-1 contained mannose, glucose, and arabinose in the respective molar ratio of 5.27:1.44:0.43. The antioxidant activity analyses revealed that TIP1-1 and TIP2-1 possessed considerable antioxidant activity. Compared with TIP1-1, which has a higher molecular weight and contains no uronic acid, TIP2-1 exhibited a protective effect on PC12 cells injured by H2O2 and a higher scavenging activity against free radicals. The relative effects of the lower molecular size, the presence of uronic acid, and the antioxidant activity of TIP2-1 appear to be significant. Accordingly, the Chinese truffle T. indicum might serve as an effective antioxidative healthcare food and source of natural antioxidants. PMID:21877953

A new protocol for functional analysis of adipogenesis using reverse transfection technology and time-lapse video microscopy.

PubMed

Grönniger, Elke; Wessel, Sonja; Kühn, Sonja Christin; Söhle, Jörn; Wenck, Horst; Stäb, Franz; Winnefeld, Marc

2010-07-01

Since the worldwide increase in obesity represents a growing challenge for healthcare systems, research focusing on fat cell metabolism has become a focal point of interest. Here, we describe a small interfering RNA (siRNA)-technology-based screening method to study fat cell differentiation in human primary preadipocytes that could be further developed towards an automated middle-throughput screening procedure. First, we established optimal conditions for the reverse transfection of human primary preadipocytes demonstrating that an efficient reverse transfection of preadipocytes is technically feasible. Aligning the processes of reverse transfection and fat cell differentiation utilizing peroxisome proliferator-activated receptor gamma (PPAR gamma)-siRNA, we showed that preadipocyte differentiation was suppressed by knock-down of PPAR gamma, the key regulator of fat cell differentiation. The use of fluorescently labelled fatty acids in combination with fluorescence time-lapse microscopy over a longer period of time enabled us to quantify the PPAR gamma phenotype. Additionally, our data demonstrate that reverse transfection of human cultured preadipocytes with TIP60 (HIV-1 Tat-interacting protein 60)-siRNA lead to a TIP60 knock-down and subsequently inhibits fat cell differentiation, suggesting a role of this protein in human adipogenesis. In conclusion, we established a protocol that allows for an efficient functional and time-dependent analysis by quantitative time-lapse microscopy to identify novel adipogenesis-associated genes.

Not Just Hats Anymore: Binomial Inversion and the Problem of Multiple Coincidences

ERIC Educational Resources Information Center

Hathout, Leith

2007-01-01

The well-known "hats" problem, in which a number of people enter a restaurant and check their hats, and then receive them back at random, is often used to illustrate the concept of derangements, that is, permutations with no fixed points. In this paper, the problem is extended to multiple items of clothing, and a general solution to the problem of…

White Hats Chasing Black Hats: Careers in IT and the Skills Required to Get There. Advisory from Professionals

ERIC Educational Resources Information Center

Fulton, Eric; Lawrence, Cameron; Clouse, Shawn

2013-01-01

The aim of this paper is to illuminate the exciting world in which "white hat crackers" operate and to suggest topics that can help prepare students to enter this high-demand field. While currently there is extraordinary demand for graduates to fill these positions that have relatively high starting salaries, employers find it difficult…

HATS-31b through HATS-35b: Five Transiting Hot Jupiters Discovered By the HATSouth Survey

NASA Astrophysics Data System (ADS)

de Val-Borro, M.; Bakos, G. Á.; Brahm, R.; Hartman, J. D.; Espinoza, N.; Penev, K.; Ciceri, S.; Jordán, A.; Bhatti, W.; Csubry, Z.; Bayliss, D.; Bento, J.; Zhou, G.; Rabus, M.; Mancini, L.; Henning, T.; Schmidt, B.; Tan, T. G.; Tinney, C. G.; Wright, D. J.; Kedziora-Chudczer, L.; Bailey, J.; Suc, V.; Durkan, S.; Lázár, J.; Papp, I.; Sári, P.

2016-12-01

We report the discovery of five new transiting hot-Jupiter planets discovered by the HATSouth survey, HATS-31b through HATS-35b. These planets orbit moderately bright stars with V magnitudes within the range of 11.9-14.4 mag while the planets span a range of masses of 0.88-1.22 {M}{{J}} and have somewhat inflated radii between 1.23 and 1.64 {R}{{J}}. These planets can be classified as typical hot Jupiters, with HATS-31b and HATS-35b being moderately inflated gas giant planets with radii of 1.64+/- 0.22 {R}{{J}} and {1.464}-0.044+0.069 {R}{{J}}, respectively, that can be used to constrain inflation mechanisms. All five systems present a higher Bayesian evidence for a fixed-circular-orbit model than for an eccentric orbit. The orbital periods range from 1.8209993+/- 0.0000016 day for HATS-35b) to 3.377960+/- 0.000012 day for HATS-31b. Additionally, HATS-35b orbits a relatively young F star with an age of 2.13+/- 0.51 Gyr. We discuss the analysis to derive the properties of these systems and compare them in the context of the sample of well-characterized transiting hot Jupiters known to date. The HATSouth network is operated by a collaboration consisting of Princeton University (PU), the Max Planck Institute für Astronomie (MPIA), the Australian National University (ANU), and the Pontificia Universidad Católica de Chile (PUC). The station at Las Campanas Observatory (LCO) of the Carnegie Institute is operated by PU in conjunction with PUC, the station at the High Energy Spectroscopic Survey (H.E.S.S.) site is operated in conjunction with MPIA, and the station at Siding Spring Observatory (SSO) is operated jointly with ANU. Based in part on data collected at the Subaru Telescope, which is operated by the National Astronomical Observatory of Japan. Based in part on observations made with the MPG 2.2 m and Euler1.2 m Telescopes at the ESO Observatory in La Silla. This paper uses observations obtained with facilities of the Las Cumbres Observatory Global Telescope.

Spatial and social factors associated with transportation and recreational physical activity among adults in Hat Yai City, Songkhla,Thailand.

PubMed

Churangsarit, Saowaphan; Chongsuvivatwong, Virasakdi

2011-08-01

Transportation physical activity (TPA) and recreational physical activity (RPA) in an urban area can be sources of physical activity (PA) in addition to working. This study was conducted in Hat Yai City Municipality, the fourth most populous city in Thailand, to describe the magnitude of these physical activities and identify their associated factors. 369 adults were selected from a random sampling of registered households. Based on the Global Physical Activity Questionnaire (GPAQ), subjects were interviewed on their modes of TPA and RPA during the past week. Hurdle regression was used to examine predictors for having PA separately from predictor of intensity of PA among the active. Metabolic equivalent (MET) of TPA and RPA were computed. Prevalence of not having TPA and RPA were 71.3% and 45.8%, respectively. TPA and RPA contributed 1.5% and 9.2% of total PA. Active commuters were more common in females 40 or more years old, less sedentary persons, and those living near shopping places. Persons having RPA were more likely to be less sedentary, whereas the intensity of RPA was higher among single persons and males. TPA and RPA in this study area were uncommon. Further strategies are needed to improve the situation, especially among sedentary persons.

Comparison of Various Supersonic Turbine Tip Designs to Minimize Aerodynamic Loss and Tip Heating

NASA Technical Reports Server (NTRS)

Shyam, Vikram; Ameri, Ali

2012-01-01

The rotor tips of axial turbines experience high heat flux and are the cause of aerodynamic losses due to tip clearance flows, and in the case of supersonic tips, shocks. As stage loadings increase, the flow in the tip gap approaches and exceeds sonic conditions. This introduces effects such as shock-boundary layer interactions and choked flow that are not observed for subsonic tip flows that have been studied extensively in literature. This work simulates the tip clearance flow for a flat tip, a diverging tip gap and several contoured tips to assess the possibility of minimizing tip heat flux while maintaining a constant massflow from the pressure side to the suction side of the rotor, through the tip clearance. The Computational Fluid Dynamics (CFD) code GlennHT was used for the simulations. Due to the strong favorable pressure gradients the simulations assumed laminar conditions in the tip gap. The nominal tip gap width to height ratio for this study is 6.0. The Reynolds number of the flow is 2.4 x 10(exp 5) based on nominal tip width and exit velocity. A wavy wall design was found to reduce heat flux by 5 percent but suffered from an additional 6 percent in aerodynamic loss coefficient. Conventional tip recesses are found to perform far worse than a flat tip due to severe shock heating. Overall, the baseline flat tip was the second best performer. A diverging converging tip gap with a hole was found to be the best choice. Average tip heat flux was reduced by 37 percent and aerodynamic losses were cut by over 6 percent.

HAT-P-18b and HAT-P-19b: Two Low-density Saturn-mass Planets Transiting Metal-rich K Stars

NASA Astrophysics Data System (ADS)

Hartman, J. D.; Bakos, G. Á.; Sato, B.; Torres, G.; Noyes, R. W.; Latham, D. W.; Kovács, G.; Fischer, D. A.; Howard, A. W.; Johnson, J. A.; Marcy, G. W.; Buchhave, L. A.; Füresz, G.; Perumpilly, G.; Béky, B.; Stefanik, R. P.; Sasselov, D. D.; Esquerdo, G. A.; Everett, M.; Csubry, Z.; Lázár, J.; Papp, I.; Sári, P.

2011-01-01

We report the discovery of two new transiting extrasolar planets. HAT-P-18b orbits the V = 12.759 K2 dwarf star GSC 2594-00646, with a period P = 5.508023 ± 0.000006 days, transit epoch Tc = 2454715.02174 ± 0.00020 (BJD), and transit duration 0.1131 ± 0.0009 days. The host star has a mass of 0.77 ± 0.03 M sun, radius of 0.75 ± 0.04 R sun, effective temperature 4803 ± 80 K, and metallicity [Fe/H] = +0.10 ± 0.08. The planetary companion has a mass of 0.197 ± 0.013 M J and radius of 0.995 ± 0.052 R J, yielding a mean density of 0.25 ± 0.04 g cm-3. HAT-P-19b orbits the V = 12.901 K1 dwarf star GSC 2283-00589, with a period P = 4.008778 ± 0.000006 days, transit epoch Tc = 2455091.53417 ± 0.00034 (BJD), and transit duration 0.1182 ± 0.0014 days. The host star has a mass of 0.84 ± 0.04 M sun, radius of 0.82 ± 0.05 R sun, effective temperature 4990 ± 130 K, and metallicity [Fe/H] = +0.23 ± 0.08. The planetary companion has a mass of 0.292 ± 0.018 M J and radius of 1.132 ± 0.072 R J, yielding a mean density of 0.25 ± 0.04 g cm-3. The radial velocity residuals for HAT-P-19 exhibit a linear trend in time, which indicates the presence of a third body in the system. Comparing these observations with theoretical models, we find that HAT-P-18b and HAT-P-19b are each consistent with a hydrogen-helium-dominated gas giant planet with negligible core mass. HAT-P-18b and HAT-P-19b join HAT-P-12b and WASP-21b in an emerging group of low-density Saturn-mass planets, with negligible inferred core masses. However, unlike HAT-P-12b and WASP-21b, both HAT-P-18b and HAT-P-19b orbit stars with super-solar metallicity. This calls into question the heretofore suggestive correlation between the inferred core mass and host star metallicity for Saturn-mass planets. Based in part on observations obtained at the W. M. Keck Observatory, which is operated by the University of California and the California Institute of Technology. Keck time has been granted by NOAO (A146Hr, A201Hr, and A264Hr), NASA (N018Hr, N049Hr, N128Hr, and N167Hr), and by the NOAO Keck-Gemini time exchange program (G329Hr). Based in part on data collected at Subaru Telescope, which is operated by the National Astronomical Observatory of Japan. Based in part on observations made with the Nordic Optical Telescope, operated on the island of La Palma jointly by Denmark, Finland, Iceland, Norway, and Sweden, in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias.

RSRM top hat cover simulator lightning test, volume 1

NASA Technical Reports Server (NTRS)

1990-01-01

The test sequence was to measure electric and magnetic fields induced inside a redesigned solid rocket motor case when a simulated lightning discharge strikes an exposed top hat cover simulator. The test sequence was conducted between 21 June and 17 July 1990. Thirty-six high rate-of-rise Marx generator discharges and eight high current bank discharges were injected onto three different test article configurations. Attach points included three locations on the top hat cover simulator and two locations on the mounting bolts. Top hat cover simulator and mounting bolt damage and grain cover damage was observed. Overall electric field levels were well below 30 kilowatts/meter. Electric field levels ranged from 184.7 to 345.9 volts/meter and magnetic field levels were calculated from 6.921 to 39.73 amperes/meter. It is recommended that the redesigned solid rocket motor top hat cover be used in Configuration 1 or Configuration 2 as an interim lightning protection device until a lightweight cover can be designed.

Sufficient condition for a quantum state to be genuinely quantum non-Gaussian

NASA Astrophysics Data System (ADS)

Happ, L.; Efremov, M. A.; Nha, H.; Schleich, W. P.

2018-02-01

We show that the expectation value of the operator \\hat{{ \\mathcal O }}\\equiv \\exp (-c{\\hat{x}}2)+\\exp (-c{\\hat{p}}2) defined by the position and momentum operators \\hat{x} and \\hat{p} with a positive parameter c can serve as a tool to identify quantum non-Gaussian states, that is states that cannot be represented as a mixture of Gaussian states. Our condition can be readily tested employing a highly efficient homodyne detection which unlike quantum-state tomography requires the measurements of only two orthogonal quadratures. We demonstrate that our method is even able to detect quantum non-Gaussian states with positive–definite Wigner functions. This situation cannot be addressed in terms of the negativity of the phase-space distribution. Moreover, we demonstrate that our condition can characterize quantum non-Gaussianity for the class of superposition states consisting of a vacuum and integer multiples of four photons under more than 50 % signal attenuation.

Genetic variation in yield under hot ambient temperatures spotlights a role for cytokinin in protection of developing floral primordia.

PubMed

Sobol, Shiri; Chayut, Noam; Nave, Nahum; Kafle, Dinesh; Hegele, Martin; Kaminetsky, Rina; Wünsche, Jens N; Samach, Alon

2014-03-01

Unusually hot ambient temperatures (HAT) can cause pre-anthesis abortion of flowers in many diverse species, limiting crop production. This limitation is becoming more substantial with climate change. Flower primordia of passion fruit (Passiflora edulis Sims) vines exposed to HAT summers, normally abort. Flower abortion can also be triggered by gibberellin application. We screened for, and identified a genotype capable of reaching anthesis during summer as well as controlled HAT conditions, and also more resistant to gibberellin. Leaves of this genotype contained higher levels of endogenous cytokinin. We investigated a possible connection between higher cytokinin levels and response to gibberellin. Indeed, the effects of gibberellin application were partially suppressed in plants pretreated with cytokinin. Can higher cytokinin levels protect flowers from aborting under HAT conditions? In passion fruit, flowers at a specific stage showed more resistance in response to HAT after cytokinin application. We further tested this hypothesis in Arabidopsis. Transgenic lines with high or low cytokinin levels and cytokinin applications to wild-type plants supported a protective role for cytokinin on developing flowers exposed to HAT. Such findings may have important implications in future breeding programmes as well as field application of growth regulators. © 2013 John Wiley & Sons Ltd.

TNF-α-inducing protein of Helicobacter pylori induces epithelial-mesenchymal transition (EMT) in gastric cancer cells through activation of IL-6/STAT3 signaling pathway

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

Chen, Guodong; Tang, Na; Wang, Chao

Tumor necrosis factor (TNF)-α-inducing protein (Tipα) is a newly identified carcinogenic factor secreted by Helicobacter pylori (H. pylori). Although it has been proved that Tipα is a strong inducer of epithelial-mesenchymal transition (EMT), a crucial process of migration, the exact molecular mechanism is unknown. Current evidence indicates that the oncogenic transcription factor signal transducers and activators of transcription 3 (STAT3) is inappropriately activated in multiple malignancies, including gastric cancer. In this study, we showed that Tipα significantly down-regulated the expression of EMT-related markers E-cadherin as well as up-regulated N-cadherin and vimentin in SGC7901 cells, with typical morphological changes of EMT. Tipα alsomore » promoted proliferation and migration of SGC7901 cells. Furthermore, Tipα activated interleukin-6 (IL-6)/STAT3 signaling pathway in SGC7901 cells. The effects of Tipα treatment observed was abolished when we block IL-6/STAT3 signaling pathway. Altogether, our data demonstrated that Tipα may accelerate tumor aggressiveness in gastric cancer by promoting EMT through activation of IL-6/STAT3 pathway. - Highlights: • Tipα induces EMT and activates IL-6/STAT3 pathway in gastric cancer cells. • IL-6/STAT3 pathway inhibition reverses Tipα-induced proliferation and migration in gastric cancer cells. • Tipα induces EMT in gastric cancer cells via IL-6/STAT3 pathway activation.« less

Self-deflection of a bright soliton in a separate bright-dark spatial soliton pair based on a higher-order space charge field

NASA Astrophysics Data System (ADS)

Liu, Jin-Song; Hao, Zhong-Hua

2003-10-01

The self-deflection of a bright solitary beam can be controlled by a dark solitary beam via a parametric coupling effect between the bright and dark solitary beams in a separate bright-dark spatial soliton pair supported by an unbiased series photorefractive crystal circuit. The spatial shift of the bright solitary beam centre as a function of the input intensity of the dark solitary beam (hat rho) is investigated by taking into account the higher-order space charge field in the dynamics of the bright solitary beam via both numerical and perturbation methods under steady-state conditions. The deflection amount (Deltas0), defined as the value of the spatial shift at the output surface of the crystal, is a monotonic and nonlinear function of hat rho. When hat rho is weak or strong enough, Deltas0 is, in fact, unchanged with hat rho, whereas Deltas0 increases or decreases monotonically with hat rho in a middle range of hat rho. The corresponding variation range (deltas) depends strongly on the value of the input intensity of the bright solitary beam (r). There are some peak and valley values in the curve of deltas versus r under some conditions. When hat rho increases, the bright solitary beam can scan toward both the direction same as and opposite to the crystal's c-axis. Whether the direction is the same as or opposite to the c-axis depends on the parameter values and configuration of the crystal circuit, as well as the value of r. Some potential applications are discussed.

Reconciling large- and small-scale structure in Twin Higgs models

DOE PAGES

Prilepina, Valentina; Tsai, Yuhsin

2017-09-08

Here, we study possible extensions of the Twin Higgs model that solve the Hierarchy problem and simultaneously address problems of the large- and small-scale structures of the Universe. Besides naturally providing dark matter (DM) candidates as the lightest charged twin fermions, the twin sector contains a light photon and neutrinos, which can modify structure formation relative to the prediction from the ΛCDM paradigm. We focus on two viable scenarios. First, we study a Fraternal Twin Higgs model in which the spin-3/2 baryonmore » $$\\hat{Ω}$$~($$\\hat{b}$$$\\hat{b}$$$\\hat{b}$$) and the lepton twin tau $$\\hat{τ}$$ contribute to the dominant and subcomponent dark matter densities. A non-decoupled scattering between the twin tau and twin neutrino arising from a gauged twin lepton number symmetry provides a drag force that damps the density inhomogeneity of a dark matter subcomponent. Next, we consider the possibility of introducing a twin hydrogen atom $$\\hat{H}$$ as the dominant DM component. After recombination, a small fraction of the twin protons and leptons remains ionized during structure formation, and their scattering to twin neutrinos through a gauged U(1) B-L force provides the mechanism that damps the density inhomogeneity. Both scenarios realize the Partially Acoustic dark matter (PAcDM) scenario and explain the σ 8 discrepancy between the CMB and weak lensing results. Moreover, the self-scattering neutrino behaves as a dark fluid that enhances the size of the Hubble rate H 0 to accommodate the local measurement result while satisfying the CMB constraint. For the small-scale structure, the scattering of $$\\hat{Ω}$$ ’s and $$\\hat{H}$$’s through the twin photon exchange generates a self-interacting dark matter (SIDM) model that solves the mass deficit problem from dwarf galaxy to galaxy cluster scales. Furthermore, when varying general choices of the twin photon coupling, bounds from the dwarf galaxy and the cluster merger observations can set an upper limit on the twin electric coupling.« less

HATS-43b, HATS-44b, HATS-45b, and HATS-46b: Four Short-period Transiting Giant Planets in the Neptune–Jupiter Mass Range

NASA Astrophysics Data System (ADS)

Brahm, R.; Hartman, J. D.; Jordán, A.; Bakos, G. Á.; Espinoza, N.; Rabus, M.; Bhatti, W.; Penev, K.; Sarkis, P.; Suc, V.; Csubry, Z.; Bayliss, D.; Bento, J.; Zhou, G.; Mancini, L.; Henning, T.; Ciceri, S.; de Val-Borro, M.; Shectman, S.; Crane, J. D.; Arriagada, P.; Butler, P.; Teske, J.; Thompson, I.; Osip, D.; Díaz, M.; Schmidt, B.; Lázár, J.; Papp, I.; Sári, P.

2018-03-01

We report the discovery of four short-period extrasolar planets transiting moderately bright stars from photometric measurements of the HATSouth network coupled to additional spectroscopic and photometric follow-up observations. While the planet masses range from 0.26 to 0.90 {M}{{J}}, the radii are all approximately a Jupiter radii, resulting in a wide range of bulk densities. The orbital period of the planets ranges from 2.7 days to 4.7 days, with HATS-43b having an orbit that appears to be marginally non-circular (e = 0.173 ± 0.089). HATS-44 is notable for having a high metallicity ([{Fe}/{{H}}] = 0.320 ± 0.071). The host stars spectral types range from late F to early K, and all of them are moderately bright (13.3 < V < 14.4), allowing the execution of future detailed follow-up observations. HATS-43b and HATS-46b, with expected transmission signals of 2350 ppm and 1500 ppm, respectively, are particularly well suited targets for atmospheric characterization via transmission spectroscopy. The HATSouth network is operated by a collaboration consisting of Princeton University (PU), the Max Planck Institute für Astronomie (MPIA), the Australian National University (ANU), and the Pontificia Universidad Católica de Chile (PUC). The station at Las Campanas Observatory (LCO) of the Carnegie Institute is operated by PU in conjunction with PUC, the station at the High Energy Spectroscopic Survey (H.E.S.S.) site is operated in conjunction with MPIA, and the station at Siding Spring Observatory (SSO) is operated jointly with ANU. This paper includes data gathered with the MPG 2.2 m and ESO 3.6 m telescopes at the ESO Observatory in La Silla. This paper includes data gathered with the 6.5 meter Magellan Telescopes located at Las Campanas Observatory, Chile.

Socio-Economic and Cultural Determinants of Human African Trypanosomiasis at the Kenya – Uganda Transboundary

PubMed Central

Rutto, Jane Jemeli; Osano, Odipo; Thuranira, Elias Gitonga; Kurgat, Richard Kiptum; Odenyo, Victor Agab Omondi

2013-01-01

Background Kenya and Uganda have reported different Human African Trypanosomiasis incidences in the past more than three decades, with the latter recording more cases. This cross-sectional study assessed the demographic characteristics, tsetse and trypanosomiasis control practices, socio-economic and cultural risk factors influencing Trypanosoma brucei rhodesiense (T.b.r.) infection in Teso and Busia Districts, Western Kenya and Tororo and Busia Districts, Southeast Uganda. A conceptual framework was postulated to explain interactions of various socio-economic, cultural and tsetse control factors that predispose individuals and populations to HAT. Methods A cross-sectional household survey was conducted between April and October 2008. Four administrative districts reporting T.b.r and lying adjacent to each other at the international boundary of Kenya and Uganda were purposely selected. Household data collection was carried out in two villages that had experienced HAT and one other village that had no reported HAT case from 1977 to 2008 in each district. A structured questionnaire was administered to 384 randomly selected household heads or their representatives in each country. The percent of respondents giving a specific answer was reported. Secondary data was also obtained on socio-economic and political issues in both countries. Results Inadequate knowledge on the disease cycle and intervention measures contributed considerable barriers to HAT, and more so in Uganda than in Kenya. Gender-associated socio-cultural practices greatly predisposed individuals to HAT. Pesticides-based crop husbandry in the 1970's reportedly reduced vector population while vegetation of coffee and banana's and livestock husbandry directly increased occurrence of HAT. Livestock husbandry practices in the villages were strong predictors of HAT incidence. The residents in Kenya (6.7%) applied chemoprophylaxis and chemotherapeutic controls against trypanosomiasis to a larger extent than Uganda (2.1%). Conclusion Knowledge on tsetse and its control methods, culture, farming practice, demographic and socio-economic variables explained occurrence of HAT better than landscape features. PMID:23638206

Analysis of risk factors for T. brucei rhodesiense sleeping sickness within villages in south-east Uganda

PubMed Central

Zoller, Thomas; Fèvre, Eric M; Welburn, Susan C; Odiit, Martin; Coleman, Paul G

2008-01-01

Background Sleeping sickness (HAT) caused by T.b. rhodesiense is a major veterinary and human public health problem in Uganda. Previous studies have investigated spatial risk factors for T.b. rhodesiense at large geographic scales, but none have properly investigated such risk factors at small scales, i.e. within affected villages. In the present work, we use a case-control methodology to analyse both behavioural and spatial risk factors for HAT in an endemic area. Methods The present study investigates behavioural and occupational risk factors for infection with HAT within villages using a questionnaire-based case-control study conducted in 17 villages endemic for HAT in SE Uganda, and spatial risk factors in 4 high risk villages. For the spatial analysis, the location of homesteads with one or more cases of HAT up to three years prior to the beginning of the study was compared to all non-case homesteads. Analysing spatial associations with respect to irregularly shaped geographical objects required the development of a new approach to geographical analysis in combination with a logistic regression model. Results The study was able to identify, among other behavioural risk factors, having a family member with a history of HAT (p = 0.001) as well as proximity of a homestead to a nearby wetland area (p < 0.001) as strong risk factors for infection. The novel method of analysing complex spatial interactions used in the study can be applied to a range of other diseases. Conclusion Spatial risk factors for HAT are maintained across geographical scales; this consistency is useful in the design of decision support tools for intervention and prevention of the disease. Familial aggregation of cases was confirmed for T. b. rhodesiense HAT in the study and probably results from shared behavioural and spatial risk factors amongmembers of a household. PMID:18590541

A research on the postural stability of a person wearing the lower limb exoskeletal robot by the HAT model.

PubMed

Chang, Minsu; Kim, Yeongmin; Lee, Yoseph; Jeon, Doyoung

2017-07-01

This paper proposes a method of detecting the postural stability of a person wearing the lower limb exoskeletal robot with the HAT(Head-Arm-Trunk) model. Previous studies have shown that the human posture is stable when the CoM(Center of Mass) of the human body is placed on the BoS(Base of Support). In the case of the lower limb exoskeletal robot, the motion data, which are used for the CoM estimation, are acquired by sensors in the robot. The upper body, however, does not have sensors in each segment so that it may cause the error of the CoM estimation. In this paper, the HAT(Head-Arm-Trunk) model which combines head, arms, and torso into a single segment is considered because the motion of head and arms are unknown due to the lack of sensors. To verify the feasibility of HAT model, the reflecting markers are attached to each segment of the whole human body and the exact motion data are acquired by the VICON to compare the COM of the full body model and HAT model. The difference between the CoM with full body and that with HAT model is within 20mm for the various motions of head and arms. Based on the HAT model, the XCoM(Extrapolated Center of Mass) which includes the velocity of the CoM is used for prediction of the postural stability. The experiment of making unstable posture shows that the XCoM of the whole body based on the HAT model is feasible to detect the instance of postural instability earlier than the CoM by 20-250 msec. This result may be used for the lower limb exoskeletal robot to prepare for any action to prevent the falling down.

Smart helicopter rotor with active blade tips

NASA Astrophysics Data System (ADS)

Bernhard, Andreas Paul Friedrich

2000-10-01

The smart active blade tip (SABT) rotor is an on-blade rotor vibration reduction system, incorporating active blade tips that can be independently pitched with respect to the main blade. The active blade tip rotor development included an experimental test program culminating in a Mach scale hover test, and a parallel development of a coupled, elastic actuator and rotor blade analysis for preliminary design studies and hover performance prediction. The experimental testing focussed on a small scale rotor on a bearingless Bell-412 hub. The fabricated Mach-scale active-tip rotor has a diameter of 1.524 m, a blade chord of 76.2 mm and incorporated a 10% span active tip. The nominal operating speed is 2000 rpm, giving a tip Mach number of 0.47. The blade tips are driven by a novel piezo-induced bending-torsion coupled actuator beam, located spanwise in the hollow mid-cell of the main rotor blade. In hover at 2000 rpm, at 2 deg collective, and for an actuation of 125 Vrms, the measured blade tip deflection at the first four rotor harmonics is between +/-1.7 and +/-2.8 deg, increasing to +/-5.3 deg at 5/rev with resonant amplification. The corresponding oscillatory amplitude of the rotor thrust coefficient is between 0.7 · 10-3 and 1.3 · 10-1 at the first four rotor harmonics, increasing to 2.1 · 10-3 at 5/rev. In general, the experimental blade tip frequency response and corresponding rotor thrust response are well captured by the analysis. The flexbeam root flap bending moment is predicted in trend, but is significantly over-estimated. The blade tips did not deflect as expected at high collective settings, because of the blade tip shaft locking up in the bearing. This is caused by the high flap bending moment on the blade tip shaft. Redesign of the blade tip shaft assembly and bearing support is identified as the primary design improvement for future research. The active blade tip rotor was also used as a testbed for the evaluation of an adaptive neural-network based control algorithm. Effective background vibration reduction of an intentional 1/rev hover imbalance was demonstrated. The control algorithm also showed the capability to generate desired multi-frequency control loads on the hub, based on artificial signal injection into the vibration measurement. The research program demonstrates the technical feasibility of the active blade tip concept for vibration reduction and warrants further investigation in terms of closed loop forward flight tests in the windtunnel and full scale design studies.

Active Learning through Online Instruction

ERIC Educational Resources Information Center

Gulbahar, Yasemin; Kalelioglu, Filiz

2010-01-01

This article explores the use of proper instructional techniques in online discussions that lead to meaningful learning. The research study looks at the effective use of two instructional techniques within online environments, based on qualitative measures. "Brainstorming" and "Six Thinking Hats" were selected and implemented…

Adding tsetse control to medical activities contributes to decreasing transmission of sleeping sickness in the Mandoul focus (Chad).

PubMed

Mahamat, Mahamat Hissene; Peka, Mallaye; Rayaisse, Jean-Baptiste; Rock, Kat S; Toko, Mahamat Abdelrahim; Darnas, Justin; Brahim, Guihini Mollo; Alkatib, Ali Bachar; Yoni, Wilfrid; Tirados, Inaki; Courtin, Fabrice; Brand, Samuel P C; Nersy, Cyrus; Alfaroukh, Idriss Oumar; Torr, Steve J; Lehane, Mike J; Solano, Philippe

2017-07-01

Gambian sleeping sickness or HAT (human African trypanosomiasis) is a neglected tropical disease caused by Trypanosoma brucei gambiense transmitted by riverine species of tsetse. A global programme aims to eliminate the disease as a public health problem by 2020 and stop transmission by 2030. In the South of Chad, the Mandoul area is a persistent focus of Gambian sleeping sickness where around 100 HAT cases were still diagnosed and treated annually until 2013. Pre-2014, control of HAT relied solely on case detection and treatment, which lead to a gradual decrease in the number of cases of HAT due to annual screening of the population. Because of the persistence of transmission and detection of new cases, we assessed whether the addition of vector control to case detection and treatment could further reduce transmission and consequently, reduce annual incidence of HAT in Mandoul. In particular, we investigated the impact of deploying 'tiny targets' which attract and kill tsetse. Before tsetse control commenced, a census of the human population was conducted and their settlements mapped. A pre-intervention survey of tsetse distribution and abundance was implemented in November 2013 and 2600 targets were deployed in the riverine habitats of tsetse in early 2014, 2015 and 2016. Impact on tsetse and on the incidence of sleeping sickness was assessed through nine tsetse monitoring surveys and four medical surveys of the human population in 2014 and 2015. Mathematical modelling was used to assess the relative impact of tsetse control on incidence compared to active and passive screening. The census indicated that a population of 38674 inhabitants lived in the vicinity of the Mandoul focus. Within this focus in November 2013, the vector is Glossina fuscipes fuscipes and the mean catch of tsetse from traps was 0.7 flies/trap/day (range, 0-26). The catch of tsetse from 44 sentinel biconical traps declined after target deployment with only five tsetse being caught in nine surveys giving a mean catch of 0.005 tsetse/trap/day. Modelling indicates that 70.4% (95% CI: 51-95%) of the reduction in reported cases between 2013 and 2015 can be attributed to vector control with the rest due to medical intervention. Similarly tiny targets are estimated to have reduced new infections dramatically with 62.8% (95% CI: 59-66%) of the reduction due to tsetse control, and 8.5% (95% 8-9%) to enhanced passive detection. Model predictions anticipate that elimination as a public health problem could be achieved by 2018 in this focus if vector control and screening continue at the present level and, furthermore, there may have been virtually no transmission since 2015. This work shows that tiny targets reduced the numbers of tsetse in this focus in Chad, which may have interrupted transmission and the combination of tsetse control to medical detection and treatment has played a major role in reducing in HAT incidence in 2014 and 2015.

TAF10 and TAF10b partially redundant roles during Drosophila melanogaster morphogenesis.

PubMed

Pahi, Z; Borsos, B N; Vedelek, B; Shidlovskii, Y V; Georgieva, S G; Boros, I M; Pankotai, T

2017-01-01

Transcription of eukaryotic genes requires the cooperative action of the RNA polymerase complex, the general transcription factors (TFIIB, TFIID, TFIIE, TFIIF and TFIIH) and chromatin modifiers. The TFIID complex contributes to transcriptional activation by several mechanisms and has a subunit with associated histone acetyltransferase (HAT) activity. The histone modifier SAGA complex has both HAT and deubiquitylase (DUB) activities. TFIID and SAGA share several TBP-associated factors (TAFs), but not their HAT subunit. Recently, several duplicated TAF proteins have been identified in higher eukaryotes, but their functional diversity has been so far poorly characterized. Here, we report the functional similarities and differences of TAF10 and TAF10b, the two TAF10 orthologs of Drosophila melanogaster. Results from in silico modeling suggest that dTAF10 and dTAF10b have similar secondary structures characterized by the presence of a histone-fold domain. Additionally, dTAF10 and dTAF10b share interaction partners and show similar expression patterns in neuronal tissues. Nonetheless, dTAF10 and dTAF10b seem to have partly distinct functions. To investigate their roles, we generated dTaf10-dTaf10b double-mutants and rescued the mutant flies with transgenes, which allowed the translation of either dTAF10 or dTAF10b protein. We found that the loss of dTAF10b resulted in pupal lethality, while animals lacking dTAF10 were able to form puparium. dTaf10 mutant adults showed distorted eye morphology. During DNA repair, dTAF10 and dTAF10b act redundantly, suggesting that these proteins have distinct but partially overlapping functions.

Predictors of Shunt Dysfunction and Overall Survival in Patients with Variceal Bleeding Treated with Transjugular Portosystemic Shunt Creation Using the Fluency Stent Graft.

PubMed

Wan, Yue-Meng; Li, Yu-Hua; Xu, Ying; Wu, Hua-Mei; Li, Ying-Chun; Wu, Xi-Nan; Yang, Jin-Hui

2018-01-16

Transjugular intrahepatic portosystemic shunt (TIPS) is an established method for portal hypertension. This study was to investigate the long-term safety, technical success, and patency of TIPS, and to determine the risk factors and clinical impacts of shunt dysfunction. A total of 154 consecutive patients undergoing embolotherapy of gastric coronary vein and/or short gastric vein and TIPS creation were prospectively studied. Follow-up data included technical success, patency and revision of TIPS, and overall survival of patients. During the study, the primary and secondary technical success rates were 98.7% and 100%, respectively. Sixty-three patients developed shunt dysfunction, 30 with shunt stenosis and 33 with shunt occlusion. The cumulative 60-month primary, primary assisted, and secondary patency rates were 19.6%, 43.0%, and 93.4%, respectively. The cumulative 60-month overall survival rates were similar between the TIPS dysfunction group and the TIPS non-dysfunction group (68.6% vs. 58.6%, P = .096). Baseline portal vein thrombosis (P < .001), use of bare stents (P = .018), and portal pressure gradient (PPG) (P = .020) were independent predictors for shunt dysfunction, hepatocellular carcinoma (P < .001), and ascites (P = .003) for overall survival. The accuracy of PPG for shunt dysfunction was statistically significant (P < .001), and a cutoff value of 8.5 had 77.8% sensitivity and 64.8% specificity. The long-term safety, technical success, and patency of TIPS were good; baseline portal vein thrombosis, use of bare stents, and PPG were significantly associated with shunt dysfunction; shunt dysfunction has little impact on patients' long-term survival because of high secondary patency rates. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Demonstration of Human-Autonomy Teaming Principles

NASA Technical Reports Server (NTRS)

Shively, Robert Jay

2016-01-01

Known problems with automation include lack of mode awareness, automation brittleness, and risk of miscalibrated trust. Human-Autonomy Teaming (HAT) is essential for improving these problems. We have identified some critical components of HAT and ran a part-task study to introduce these components to a ground station that supports flight following of multiple aircraft. Our goal was to demonstrate, evaluate, and refine HAT principles. This presentation provides a brief summary of the study and initial findings.

A Common Proper Motion Stellar Companion to HAT-P-7

NASA Technical Reports Server (NTRS)

Grady, Carol A.; McElwain, Michael W.; Narita, Norio; Takahashi, Yasuhiro H.; Kuzuhara, Masayuki; Hirano, Teruyuki; Suenaga, Takuya

2012-01-01

We report that HAT-P-7 has a common proper motion stellar companion. The companion is located at approx. 3.9 arcsec to the east and estimated as an M5.5V dwarf based on its colors. We also confirm the presence of the third companion, which was first reported by Winn et al. (2009), based on long-term radial velocity measurements. We revisit the migration mechanism of HAT-P-7b given the presence of those companions, and propose sequential Kozai migration as a likely scenario in this system. This scenario may explain the reason for an outlier in the discussion of the spin-orbit alignment timescale for HAT-P-7b by Albrecht et al. (2012).

A Preliminary Study of a Propeller Powered by Gas Jets Issuing from the Blade Tips

DTIC Science & Technology

1946-11-01

ISSUING FROM THE BLADE TIPS By J. C. Sanders and N. D. Sanders Aircraft Engine Research Laboratory Cleveland, Ohio icaflit w<• w &£N •^5$" jm "^o*6w...propeller powered by Jets in the blade tips made by Roy in 1930 (reference 3) showed that this engine would be less efficient than;a reciprocating...development of the turbojet engine , which is .now of outstanding interest. The possibilities of the jet -operated propeller are re-exeroined and the

Disposition, Metabolism and Histone Deacetylase and Acetyltransferase Inhibition Activity of Tetrahydrocurcumin and Other Curcuminoids

PubMed Central

Novaes, Júlia T.; Sayre, Casey L.; Majeed, Muhammed; Ho, Emmanuel A.; Oliveira, Ana Luísa de P.; Martinez, Stephanie E.; Davies, Neal M.; Lakowski, Ted M.

2017-01-01

Tetrahydrocurcumin (THC), curcumin and calebin-A are curcuminoids found in turmeric (Curcuma longa). Curcuminoids have been established to have a variety of pharmacological activities and are used as natural health supplements. The purpose of this study was to identify the metabolism, excretion, antioxidant, anti-inflammatory and anticancer properties of these curcuminoids and to determine disposition of THC in rats after oral administration. We developed a UHPLC–MS/MS assay for THC in rat serum and urine. THC shows multiple redistribution phases with corresponding increases in urinary excretion rate. In-vitro antioxidant activity, histone deacetylase (HDAC) activity, histone acetyltransferase (HAT) activity and anti-inflammatory inhibitory activity were examined using commercial assay kits. Anticancer activity was determined in Sup-T1 lymphoma cells. Our results indicate THC was poorly absorbed after oral administration and primarily excreted via non-renal routes. All curcuminoids exhibited multiple pharmacological effects in vitro, including potent antioxidant activity as well as inhibition of CYP2C9, CYP3A4 and lipoxygenase activity without affecting the release of TNF-α. Unlike curcumin and calebin-A, THC did not inhibit HDAC1 and PCAF and displayed a weaker growth inhibition activity against Sup-T1 cells. We show evidence for the first time that curcumin and calebin-A inhibit HAT and PCAF, possibly through a Michael-addition mechanism. PMID:29023392

Diagnostic Accuracy and Feasibility of Serological Tests on Filter Paper Samples for Outbreak Detection of T.b. gambiense Human African Trypanosomiasis

PubMed Central

Hasker, Epco; Lutumba, Pascal; Mumba, Dieudonné; Lejon, Veerle; Büscher, Phillipe; Kande, Victor; Muyembe, Jean Jacques; Menten, Joris; Robays, Jo; Boelaert, Marleen

2010-01-01

Control of human African trypanosomiasis (HAT) in the Democratic Republic of Congo is based on mass population screening by mobile teams; a costly and labor-intensive approach. We hypothesized that blood samples collected on filter paper by village health workers and processed in a central laboratory might be a cost-effective alternative. We estimated sensitivity and specificity of micro-card agglutination test for trypanosomiasis (micro-CATT) and enzyme-linked immunosorbent assay (ELISA)/T.b. gambiense on filter paper samples compared with parasitology-based case classification and used the results in a Monte Carlo simulation of a lot quality assurance sampling (LQAS) approach. Micro-CATT and ELISA/T.b. gambiense showed acceptable sensitivity (92.7% [95% CI 87.4–98.0%] and 82.2% [95% CI 75.3–90.4%]) and very high specificity (99.4% [95% CI 99.0–99.9%] and 99.8% [95% CI 99.5–100%]), respectively. Conditional on high sample size per lot (≥ 60%), both tests could reliably distinguish a 2% from a zero prevalence at village level. Alternatively, these tests could be used to identify individual HAT suspects for subsequent confirmation. PMID:20682885

Various Regulatory Modes for Circadian Rhythmicity and Sexual Dimorphism in the Non-Neuronal Cardiac Cholinergic System.

PubMed

Oikawa, Shino; Kai, Yuko; Mano, Asuka; Ohata, Hisayuki; Nemoto, Takahiro; Kakinuma, Yoshihiko

2017-08-01

Cardiomyocytes possess a non-neuronal cardiac cholinergic system (NNCCS) regulated by a positive feedback system; however, its other regulatory mechanisms remain to be elucidated, which include the epigenetic control or regulation by the female sex steroid, estrogen. Here, the NNCCS was shown to possess a circadian rhythm; its activity was upregulated in the light-off phase via histone acetyltransferase (HAT) activity and downregulated in the light-on phase. Disrupting the circadian rhythm altered the physiological choline acetyltransferase (ChAT) expression pattern. The NNCCS circadian rhythm may be regulated by miR-345, independently of HAT, causing decreased cardiac ChAT expression. Murine cardiac ChAT expression and ACh contents were increased more in female hearts than in male hearts. This upregulation was downregulated by treatment with the estrogen receptor antagonist tamoxifen, and in contrast, estrogen reciprocally regulated cardiac miR-345 expression. These results suggest that the NNCCS is regulated by the circadian rhythm and is affected by sexual dimorphism.

Highly acidic C-terminal domain of pp32 is required for the interaction with histone chaperone, TAF-Ibeta.

PubMed

Lee, In-Seon; Oh, Sang-Min; Kim, Sung-Mi; Lee, Dong-Seok; Seo, Sang-Beom

2006-12-01

We have previously reported that INHAT (inhibitor of acetyltransferases) complex subunits, TAF (template activating factor)-Ialpha, TAF-Ibeta and pp32 can inhibit histone acetylation and HAT (histone acetyltransferase)-dependent transcription by binding to histones. Evidences are accumulating that INHAT complex subunits have important regulatory roles in various cellular activities such as replication, transcription, and apoptosis etc. However, how these subunits interact each other remains largely unknown. Using immunoprecipitation (IP) and protein-protein interaction assays with TAF-Ibeta and pp32 deletion mutant proteins, we identify INHAT complex subunits, TAF-Ibeta and pp32 interaction requires highly acidic C-terminal domain of pp32. We also show that the interaction between the INHAT complex subunits is stronger in the presence of histones. In this study, we report that the synergistic inhibition of HAT-mediated transcription by TAF-Ibeta and pp32 is dependent on the highly acidic C-terminal domain of pp32.

Virtual Screening of Phytochemicals to Novel Target (HAT) Rtt109 in Pneumocystis Jirovecii using Bioinformatics Tools.

PubMed

Sugumar, Ramya; Adithavarman, Abhinand Ponneri; Dakshinamoorthi, Anusha; David, Darling Chellathai; Ragunath, Padmavathi Kannan

2016-03-01

Pneumocystis jirovecii is a fungus that causes Pneumocystis pneumonia in HIV and other immunosuppressed patients. Treatment of Pneumocystis pneumonia with the currently available antifungals is challenging and associated with considerable adverse effects. There is a need to develop drugs against novel targets with minimal human toxicities. Histone Acetyl Transferase (HAT) Rtt109 is a potential therapeutic target in Pneumocystis jirovecii species. HAT is linked to transcription and is required to acetylate conserved lysine residues on histone proteins by transferring an acetyl group from acetyl CoA to form e-N-acetyl lysine. Therefore, inhibitors of HAT can be useful therapeutic options in Pneumocystis pneumonia. To screen phytochemicals against (HAT) Rtt109 using bioinformatics tool. The tertiary structure of Pneumocystis jirovecii (HAT) Rtt109 was modeled by Homology Modeling. The ideal template for modeling was obtained by performing Psi BLAST of the protein sequence. Rtt109-AcCoA/Vps75 protein from Saccharomyces cerevisiae (PDB structure 3Q35) was chosen as the template. The target protein was modeled using Swiss Modeler and validated using Ramachandran plot and Errat 2. Comprehensive text mining was performed to identify phytochemical compounds with antipneumonia and fungicidal properties and these compounds were filtered based on Lipinski's Rule of 5. The chosen compounds were subjected to virtual screening against the target protein (HAT) Rtt109 using Molegro Virtual Docker 4.5. Osiris Property Explorer and Open Tox Server were used to predict ADME-T properties of the chosen phytochemicals. Tertiary structure model of HAT Rtt 109 had a ProSA score of -6.57 and Errat 2 score of 87.34. Structure validation analysis by Ramachandran plot for the model revealed 97% of amino acids were in the favoured region. Of all the phytochemicals subjected to virtual screening against the target protein (HAT) Rtt109, baicalin exhibited highest binding affinity towards the target protein as indicated by the Molegro score of 130.68 and formed 16 H-bonds. The ADME-T property prediction revealed that baicalin was non-mutagenic, non-tumorigenic and had a drug likeness score of 0.87. Baicalin has good binding with Rtt 109 in Pneumocystis jirovecii and can be considered as a novel and valuable treatment option for Pneumocystis pneumonia patients after subjecting it to invivo and invitro studies.

Virtual Screening of Phytochemicals to Novel Target (HAT) Rtt109 in Pneumocystis Jirovecii using Bioinformatics Tools

PubMed Central

Adithavarman, Abhinand Ponneri; Dakshinamoorthi, Anusha; David, Darling Chellathai; Ragunath, Padmavathi Kannan

2016-01-01

Introduction Pneumocystis jirovecii is a fungus that causes Pneumocystis pneumonia in HIV and other immunosuppressed patients. Treatment of Pneumocystis pneumonia with the currently available antifungals is challenging and associated with considerable adverse effects. There is a need to develop drugs against novel targets with minimal human toxicities. Histone Acetyl Transferase (HAT) Rtt109 is a potential therapeutic target in Pneumocystis jirovecii species. HAT is linked to transcription and is required to acetylate conserved lysine residues on histone proteins by transferring an acetyl group from acetyl CoA to form e-N-acetyl lysine. Therefore, inhibitors of HAT can be useful therapeutic options in Pneumocystis pneumonia. Aim To screen phytochemicals against (HAT) Rtt109 using bioinformatics tool. Materials and Methods The tertiary structure of Pneumocystis jirovecii (HAT) Rtt109 was modeled by Homology Modeling. The ideal template for modeling was obtained by performing Psi BLAST of the protein sequence. Rtt109-AcCoA/Vps75 protein from Saccharomyces cerevisiae (PDB structure 3Q35) was chosen as the template. The target protein was modeled using Swiss Modeler and validated using Ramachandran plot and Errat 2. Comprehensive text mining was performed to identify phytochemical compounds with antipneumonia and fungicidal properties and these compounds were filtered based on Lipinski’s Rule of 5. The chosen compounds were subjected to virtual screening against the target protein (HAT) Rtt109 using Molegro Virtual Docker 4.5. Osiris Property Explorer and Open Tox Server were used to predict ADME-T properties of the chosen phytochemicals. Results Tertiary structure model of HAT Rtt 109 had a ProSA score of -6.57 and Errat 2 score of 87.34. Structure validation analysis by Ramachandran plot for the model revealed 97% of amino acids were in the favoured region. Of all the phytochemicals subjected to virtual screening against the target protein (HAT) Rtt109, baicalin exhibited highest binding affinity towards the target protein as indicated by the Molegro score of 130.68 and formed 16 H-bonds. The ADME-T property prediction revealed that baicalin was non-mutagenic, non-tumorigenic and had a drug likeness score of 0.87. Conclusion Baicalin has good binding with Rtt 109 in Pneumocystis jirovecii and can be considered as a novel and valuable treatment option for Pneumocystis pneumonia patients after subjecting it to invivo and invitro studies. PMID:27134887

HAT-P-17b,c: A TRANSITING, ECCENTRIC, HOT SATURN AND A LONG-PERIOD, COLD JUPITER

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

Howard, A. W.; Marcy, G. W.; Bakos, G. A.

2012-04-20

We report the discovery of HAT-P-17b,c, a multi-planet system with an inner transiting planet in a short-period, eccentric orbit and an outer planet in a 4.4 yr, nearly circular orbit. The inner planet, HAT-P-17b, transits the bright V = 10.54 early K dwarf star GSC 2717-00417, with an orbital period P = 10.338523 {+-} 0.000009 days, orbital eccentricity e = 0.342 {+-} 0.006, transit epoch T{sub c} = 2454801.16943 {+-} 0.00020 (BJD: barycentric Julian dates throughout the paper are calculated from Coordinated Universal Time (UTC)), and transit duration 0.1690 {+-} 0.0009 days. HAT-P-17b has a mass of 0.534 {+-} 0.018more » M{sub J} and radius of 1.010 {+-} 0.029 R{sub J} yielding a mean density of 0.64 {+-} 0.05 g cm{sup -3}. This planet has a relatively low equilibrium temperature in the range 780-927 K, making it an attractive target for follow-up spectroscopic studies. The outer planet, HAT-P-17c, has a significantly longer orbital period P{sub 2} = 1610 {+-} 20 days and a minimum mass m{sub 2}sin i{sub 2} = 1.31{sup +0.18}{sub -0.15} M{sub J}. The orbital inclination of HAT-P-17c is unknown as transits have not been observed and may not be present. The host star has a mass of 0.86 {+-} 0.04 M{sub Sun }, radius of 0.84 {+-} 0.02 R{sub Sun }, effective temperature 5246 {+-} 80 K, and metallicity [Fe/H] = 0.00 {+-} 0.08. HAT-P-17 is the second multi-planet system detected from ground-based transit surveys.« less

Gravitational collapse of conventional polytropic cylinder

NASA Astrophysics Data System (ADS)

Lou, Yu-Qing; Hu, Xu-Yao

2017-07-01

In reference to general polytropic and conventional polytropic hydrodynamic cylinders of infinite length with axial uniformity and axisymmetry under self-gravity, the dynamic evolution of central collapsing mass string in free-fall dynamic accretion phase is re-examined in details. We compare the central mass accretion rate and the envelope mass infall rate at small radii. Among others, we correct mistakes and typos of Kawachi & Hanawa (KH hereafter) and in particular prove that their key asymptotic free-fall solution involving polytropic index γ in the two power exponents is erroneous by analytical analyses and numerical tests. The correct free-fall asymptotic solutions at sufficiently small \\hat{r} (the dimensionless independent self-similar variable) scale as {˜ } -|ln \\hat{r}|^{1/2} in contrast to KH's ˜ -|ln \\hat{r}|^{(2-γ )/2} for the reduced bulk radial flow velocity and as {˜ } \\hat{r}^{-1}|ln \\hat{r}|^{-1/2} in contrast to KH's {˜ } \\hat{r}^{-1} |ln \\hat{r}|^{-(2-γ )/2} for the reduced mass density. We offer consistent scenarios for numerical simulation code testing and theoretical study on dynamic filamentary structure formation and evolution as well as pertinent stability properties. Due to unavoidable Jeans instabilities along the cylinder, such collapsing massive filaments or strings can further break up into clumps and segments of various lengths as well as clumps embedded within segments and evolve into chains of gravitationally collapsed objects (such as gaseous planets, brown dwarfs, protostars, white dwarfs, neutron stars, black holes in a wide mass range, globular clusters, dwarf spheroidals, galaxies, galaxy clusters and even larger mass reservoirs etc.) in various astrophysical and cosmological contexts as articulated by Lou & Hu recently. As an example, we present a model scheme for comparing with observations of molecular filaments for forming protostars, brown dwarfs and gaseous planets and so forth.

Energy output reduction and surface alteration of quartz and sapphire tips following Er:YAG laser contact irradiation for tooth enamel ablation.

PubMed

Eguro, Toru; Aoki, Akira; Maeda, Toru; Takasaki, Aristeo Atsushi; Hasegawa, Mitsuru; Ogawa, Masaaki; Suzuki, Takanori; Yonemoto, Kazuaki; Ishikawa, Isao; Izumi, Yuichi; Katsuumi, Ichiroh

2009-10-01

Despite the recent increase in application of Er:YAG laser for various dental treatments, limited information is available regarding the contact tips. This study examined the changes in energy output and surface condition of quartz and sapphire contact tips after Er:YAG laser contact irradiation for tooth enamel ablation. Ten sets of unused quartz or sapphire contact tips were employed for contact irradiation to sound enamel of extracted teeth. The teeth were irradiated with Er:YAG laser at approximately 75 J/cm(2)/pulse and 20 Hz under water spray for 60 minutes. The energy output was measured before and every 5 minutes after irradiation, and the changes in morphology and chemical composition of the contact surface were analyzed. The energy output significantly decreased with time in both tips. The energy output from the sapphire tips was generally higher on average than that of the quartz. The contact surfaces of all the used quartz tips were concave and irregular. Most of the sapphire tips also appeared rough with crater formation and fractures, except for a few tips in which a high energy output and the original smooth surface were maintained. Spots of melted tooth substances were seen attached to the surface of both tips. In contact enamel ablation, the sapphire tip appeared to be more resistant than the quartz tip. The quartz tips showed similar patterns of energy reduction and surface alteration, whereas the sapphire tips revealed a wider and more characteristic variation among tips. Lasers Surg. Med. 41:595-604, 2009. (c) 2009 Wiley-Liss, Inc.

Knock-Down of CsNRT2.1, a Cucumber Nitrate Transporter, Reduces Nitrate Uptake, Root length, and Lateral Root Number at Low External Nitrate Concentration

PubMed Central

Li, Yang; Li, Juanqi; Yan, Yan; Liu, Wenqian; Zhang, Wenna; Gao, Lihong; Tian, Yongqiang

2018-01-01

Nitrogen (N) is a macronutrient that plays a crucial role in plant growth and development. Nitrate (NO3-) is the most abundant N source in aerobic soils. Plants have evolved two adaptive mechanisms such as up-regulation of the high-affinity transport system (HATS) and alteration of the root system architecture (RSA), allowing them to cope with the temporal and spatial variation of NO3-. However, little information is available regarding the nitrate transporter in cucumber, one of the most important fruit vegetables in the world. In this study we isolated a nitrate transporter named CsNRT2.1 from cucumber. Analysis of the expression profile of the CsNRT2.1 showed that CsNRT2.1 is a high affinity nitrate transporter which mainly located in mature roots. Subcellular localization analysis revealed that CsNRT2.1 is a plasma membrane transporter. In N-starved CsNRT2.1 knock-down plants, both of the constitutive HATS (cHATS) and inducible HATS (iHATS) were impaired under low external NO3- concentration. Furthermore, the CsNRT2.1 knock-down plants showed reduced root length and lateral root numbers. Together, our results demonstrated that CsNRT2.1 played a dual role in regulating the HATS and RSA to acquire NO3- effectively under N limitation. PMID:29911677

Atmospheric Retrievals of HAT-P-16b and WASP-11b/HAT-P-10b

NASA Astrophysics Data System (ADS)

McIntyre, Kathleen; Harrington, Joseph; Challener, Ryan; Lenius, Maria; Hartman, Joel D.; Bakos, Gaspar A.; Blecic, Jasmina; Cubillos, Patricio E.; Cameron, Andrew

2018-01-01

We report Bayesian atmospheric retrievals performed on the exoplanets HAT-P-16b and WASP-11b/HAT-P-10b. HAT-P-16b is a hot (equilibrium temperature 1626 ± 40 K, assuming zero Bond albedo and efficient energy redistribution), 4.19 ± 0.09 Jupiter-mass exoplanet orbiting an F8 star every 2.775960 ± 0.000003 days (Buchhave et al 2010). WASP-11b/HAT-P-10b is a cooler (1020 ± 17 K), 0.487 ± 0.018 Jupiter-mass exoplanet orbiting a K3 star every 3.7224747 ± 0.0000065 days (Bakos et al. 2009, co-discovered by West et al. 2008). We observed secondary eclipses of both planets using the 3.6 μm and 4.5 μm channels of the Spitzer Space Telescope's Infrared Array Camera (program ID 60003). We applied our Photometry for Orbits, Eclipses, and Transits (POET) code to produce normalized eclipse light curves, and our Bayesian Atmospheric Radiative Transfer (BART) code to constrain the temperature-pressure profiles and atmospheric molecular abundances of the two planets. Spitzer is operated by the Jet Propulsion Laboratory, California Institute of Technology, under a contract with NASA. This work was supported by NASA Planetary Atmospheres grant NNX12AI69G and NASA Astrophysics Data Analysis Program grant NNX13AF38G.

Acute Increase in Hepatic Arterial Flow During TIPS Identified by Intravascular Flow Measurements

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

Radeleff, Boris, E-mail: Boris_Radeleff@med.uni-heidelberg.de; Sommer, Christof-Matthias; Heye, Tobias

2009-01-15

The purpose of this study was to investigate alterations of hepatic arterial flow during transjugular intrahepatic portosystemic stent shunt (TIPS) applying intravascular Doppler sonography. This prospective monocenter study included 25 patients with liver cirrhosis (alcohol induced [n = 19], chronic hepatitis associated [n = 3], primary biliary cirrhosis associated [n = 1], and cryptogenic [n = 2]) successfully treated with TIPS. All patients underwent intravascular hepatic arterial flow measurements during TIPS using an endoluminal flow sensor. The average arterial peak velocity (APV) and the maximum arterial peak velocity (MPV) were registered. Twenty-two patients (88%) showed increased APV, one patient (4%)more » showed unaffected APV, and two patients (8%) showed decreased APV after TIPS. The average portosystemic pressure gradient decreased significantly, from 22.0 {+-} 5.1 mmHg before TIPS to 11.0 {+-} 4.1 mmHg after TIPS (-50.0%; p < 0.0001). The average APV increased significantly, from 41.9 {+-} 17.8 cm/s before TIPS to 60.7 {+-} 19.0 cm/s after TIPS (+44.9%; p < 0.0001). The average MPV increased significantly, from 90.8 {+-} 31.7 cm/s before TIPS to 112.6 {+-} 34.9 cm/s after TIPS (+24.0%; p = 0.0002). These changes in perfusion set in within seconds after TIPS tract formation in all the patients with increased APV. We conclude that TIPS-induced portosystemic decompression leads to a significant increase in hepatic arterial flow. The changes occurred within seconds, suggesting a reflex-like mechanism.« less

Possible formation pathways for the low-density Neptune-mass planet HAT-P-26b

NASA Astrophysics Data System (ADS)

Ali-Dib, Mohamad; Lakhlani, Gunjan

2018-01-01

We investigate possible pathways for the formation of the low-density Neptune-mass planet HAT-P-26b. We use two different formation models based on pebble and planetesimal accretion, and includes gas accretion, disc migration and simple photoevaporation. The models track the atmospheric oxygen abundance, in addition to the orbital period, and mass of the forming planets, which we compare to HAT-P-26b. We find that pebble accretion can explain this planet more naturally than planetesimal accretion that fails completely unless we artificially enhance the disc metallicity significantly. Pebble accretion models can reproduce HAT-P-26b with either a high initial core mass and low amount of envelope enrichment through core erosion or pebbles dissolution, or the opposite, with both scenarios being possible. Assuming a low envelope enrichment factor as expected from convection theory and comparable to the values we can infer from the D/H measurements in Uranus and Neptune, our most probable formation pathway for HAT-P-26b is through pebble accretion starting around 10 au early in the disc's lifetime.

Relation of a†a terms to higher-order terms in the adiabatic expansion for large-amplitude collective motion

NASA Astrophysics Data System (ADS)

Sato, Koichi

2017-12-01

We investigate the relation of a^\\dagger a terms in the collective operator to the higher-order terms in the adiabatic self-consistent collective coordinate (ASCC) method. In the ASCC method, a state vector is written as e^{i\\hat G(q,p,n)}|φ(q)> with \\hat G(q,p,n), which is a function of the collective coordinate q, its conjugate momentum p, and the particle number n. According to the generalized Thouless theorem, \\hat G can be written as a linear combination of two-quasiparticle creation and annihilation operators a^\\dagger_μ a^\\dagger_ν and a_ν a_μ. We show that, if a^\\dagger a terms are included in \\hat G(q,p,n), it corresponds to the higher-order terms in the adiabatic expansion of \\hat G. This relation serves as a prescription to determine the higher-order collective operators from the a^\\dagger a part of the collective operator, once it is given, without solving the higher-order equations of motion.

Design and evaluation of a bolted joint for a discrete carbon-epoxy rod-reinforced hat section

NASA Technical Reports Server (NTRS)

Rousseau, Carl Q.; Baker, Donald J.

1996-01-01

The use of prefabricated pultruded carbon-epoxy rods has reduced the manufacturing complexity and costs of stiffened composite panels while increasing the damage tolerance of the panels. However, repairability of these highly efficient discrete stiffeners has been a concern. Design, analysis, and test results are presented in this paper for a bolted-joint repair for the pultruded rod concept that is capable of efficiently transferring axial loads in a hat-section stiffener on the upper skin segment of a heavily loaded aircraft wing component. A tension and a compression joint design were evaluated. The tension joint design achieved approximately 1.0% strain in the carbon-epoxy rod-reinforced hat-section and failed in a metal fitting at 166% of the design ultimate load. The compression joint design failed in the carbon-epoxy rod-reinforced hat-section test specimen area at approximately 0.7% strain and at 110% of the design ultimate load. This strain level of 0.7% in compression is similar to the failure strain observed in previously reported carbon-epoxy rod-reinforced hat-section column tests.

Test and Analysis of Composite Hat Stringer Pull-off Test Specimens

NASA Technical Reports Server (NTRS)

Li, Jian; OBrien, T. Kevin; Rousseau, Carl Q.

1996-01-01

Hat stringer pull-off tests were performed to evaluate the delamination failure mechanisms in the flange region for a rod-reinforced hat stringer section. A special test fixture was used to pull the hat off the stringer while reacting the pull-off load through roller supports at both stringer flanges. Microscopic examinations of the failed specimens revealed that failure occurred at the ply termination in the flange area where the flange of the stiffener is built up by adding 45/-45 tape plies on the top surface. Test results indicated that the as-manufactured microstructure in the flange region has a strong influence on the delamination initiation and the associated pull-off loads. Finite element models were created for each specimen with a detailed mesh based on micrographs of the critical location. A fracture mechanics approach and a mixed mode delamination criterion were used to predict the onset of delamination and the pull-off load. By modeling the critical local details of each specimen from micrographs, the model was able to accurately predict the hat stringer pull-off loads and replicate the variability in the test results.

Prevalence and Types of Coinfections in Sleeping Sickness Patients in Kenya (2000/2009)

PubMed Central

Kagira, J. M.; Maina, N.; Njenga, J.; Karanja, S. M.; Karori, S. M.; Ngotho, J. M.

2011-01-01

The occurrence of coinfections in human African trypanosomiasis (HAT) patients was investigated using a retrospective data of hospital records at the National Sleeping Sickness Referral Hospital in Alupe, Kenya. A total of 31 patients, 19 males and 12 females, were diagnosed with HAT between the years 2000 and 2009. The observed co-infections included malaria (100%), helminthosis (64.5%), typhoid (22.5%), urinary tract infections (16.1%), HIV (12.9%), and tuberculosis (3.2%). The species of helminthes observed included Ancylostoma duodenale (38.7%), Ascaris lumbricoides (45.7%), Strongyloides stercoralis (9.7%), and Taenia spp. (3.2%). The patients were also infected with Entamoeba spp. (32.3%) and Trichomonas hominis (22.6%) protozoan parasites. The main clinical signs observed at the point of admission included headache (74.2%), fever (48.4%), sleep disorders (45.2%), and general body pain (41.9%). The HAT patients were treated with suramin (early stage, 9/31) and melarsoprol (late stage, 22/31). In conclusion, the study has shown that HAT patients have multiple co-infections which may influence the disease pathogenesis and complicate management of HAT. PMID:21915184

Epidemiology of human African trypanosomiasis

PubMed Central

Franco, Jose R; Simarro, Pere P; Diarra, Abdoulaye; Jannin, Jean G

2014-01-01

Human African trypanosomiasis (HAT), or sleeping sickness, is caused by Trypanosoma brucei gambiense, which is a chronic form of the disease present in western and central Africa, and by Trypanosoma brucei rhodesiense, which is an acute disease located in eastern and southern Africa. The rhodesiense form is a zoonosis, with the occasional infection of humans, but in the gambiense form, the human being is regarded as the main reservoir that plays a key role in the transmission cycle of the disease. The gambiense form currently assumes that 98% of the cases are declared; the Democratic Republic of the Congo is the most affected country, with more than 75% of the gambiense cases declared. The epidemiology of the disease is mediated by the interaction of the parasite (trypanosome) with the vectors (tsetse flies), as well as with the human and animal hosts within a particular environment. Related to these interactions, the disease is confined in spatially limited areas called “foci”, which are located in Sub-Saharan Africa, mainly in remote rural areas. The risk of contracting HAT is, therefore, determined by the possibility of contact of a human being with an infected tsetse fly. Epidemics of HAT were described at the beginning of the 20th century; intensive activities have been set up to confront the disease, and it was under control in the 1960s, with fewer than 5,000 cases reported in the whole continent. The disease resurged at the end of the 1990s, but renewed efforts from endemic countries, cooperation agencies, and nongovernmental organizations led by the World Health Organization succeeded to raise awareness and resources, while reinforcing national programs, reversing the trend of the cases reported, and bringing the disease under control again. In this context, sustainable elimination of the gambiense HAT, defined as the interruption of the transmission of the disease, was considered as a feasible target for 2030. Since rhodesiense HAT is a zoonosis, where the animal reservoir plays a key role, the interruption of the disease’s transmission is not deemed feasible. PMID:25125985

Molecular insights into the recognition of N-terminal histone modifications by the BRPF1 bromodomain

PubMed Central

Poplawski, Amanda; Hu, Kaifeng; Lee, Woonghee; Natesan, Senthil; Peng, Danni; Carlson, Samuel; Shi, Xiaobing; Balaz, Stefan; Markley, John L.; Glass, Karen C.

2014-01-01

The monocytic leukemic zinc-finger (MOZ) histone acetyltransferase (HAT) acetylates free histones H3, H4, H2A, and H2B in vitro and is associated with up-regulation of gene transcription. The MOZ HAT functions as a quaternary complex with the bromodomain-PHD finger protein 1 (BRPF1), inhibitor of growth 5 (ING5), and hEaf6 subunits. BRPF1 links the MOZ catalytic subunit to the ING5 and hEaf6 subunits, thereby promoting MOZ HAT activity. Human BRPF1 contains multiple effector domains with known roles in gene transcription, and chromatin binding and remodeling. However, the biological function of the BRPF1 bromodomain remains unknown. Our findings reveal novel interactions of the BRPF1 bromodomain with multiple acetyllysine residues on the N-terminus of histones, and show it preferentially selects for H2AK5ac, H4K12ac and H3K14ac. We used chemical shift perturbation data from NMR titration experiments to map the BRPF1 bromodomain ligand binding pocket and identified key residues responsible for coordination of the post-translationally modified histones. Extensive molecular dynamics simulations were used to generate structural models of bromodomain-histone ligand complexes, to analyze H-bonding and other interactions, and to calculate the binding free energies. Our results outline the molecular mechanism driving binding specificity of the BRPF1 bromodomain for discrete acetyllysine residues on the N-terminal histone tails. Together these data provide insights on how histone recognition by the bromodomain directs the biological function of BRPF1, ultimately targeting the MOZ HAT complex to chromatin substrates. PMID:24333487

Head insulation and heat loss in the newborn.

PubMed Central

Stothers, J K

1981-01-01

The thermal balance of 13 term infants was measured in a closed-circuit metabolism chamber. Each was studied naked, then with a gamgee-lined hat, and finally with a 'cummerbund' made of a similar material and of similar dimensions. At 27 degrees C the oxygen consumption of the 'hatted' babies was only 85% and the total heat loss 75% of the values measured with the infants naked. The cummerbund offered no detectable benefit. An additional 10 infants were studied while wearing a tubegauze hat at environmental temperatures of 28.5 (+/- 0.5) degrees C. This type of hat gave no measurable thermal protection. It is concluded that a substantial reduction of thermal stress in adverse environments can be achieved simply and clearly by adequately covering the vault of the skull. PMID:7271287

Do Cryptic Reservoirs Threaten Gambiense-Sleeping Sickness Elimination?

PubMed

Büscher, Philippe; Bart, Jean-Mathieu; Boelaert, Marleen; Bucheton, Bruno; Cecchi, Giuliano; Chitnis, Nakul; Courtin, David; Figueiredo, Luisa M; Franco, José-Ramon; Grébaut, Pascal; Hasker, Epco; Ilboudo, Hamidou; Jamonneau, Vincent; Koffi, Mathurin; Lejon, Veerle; MacLeod, Annette; Masumu, Justin; Matovu, Enock; Mattioli, Raffaele; Noyes, Harry; Picado, Albert; Rock, Kat S; Rotureau, Brice; Simo, Gustave; Thévenon, Sophie; Trindade, Sandra; Truc, Philippe; Van Reet, Nick

2018-03-01

Trypanosoma brucei gambiense causes human African trypanosomiasis (HAT). Between 1990 and 2015, almost 440000 cases were reported. Large-scale screening of populations at risk, drug donations, and efforts by national and international stakeholders have brought the epidemic under control with <2200 cases in 2016. The World Health Organization (WHO) has set the goals of gambiense-HAT elimination as a public health problem for 2020, and of interruption of transmission to humans for 2030. Latent human infections and possible animal reservoirs may challenge these goals. It remains largely unknown whether, and to what extend, they have an impact on gambiense-HAT transmission. We argue that a better understanding of the contribution of human and putative animal reservoirs to gambiense-HAT epidemiology is mandatory to inform elimination strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Open Radio Communications Architecture Core Framework V1.1.0 Volume 1 Software Users Manual

DTIC Science & Technology

2005-02-01

on a PC utilizing the KDE desktop that comes with Red Hat Linux . The default desktop for most Red Hat Linux installations is the GNOME desktop. The...SCA) v2.2. The software was designed for a desktop computer running the Linux operating system (OS). It was developed in C++, uses ACE/TAO for CORBA...middleware, Xerces for the XML parser, and Red Hat Linux for the Operating System. The software is referred to as, Open Radio Communication

Shear buckling analysis of a hat-stiffened panel

NASA Technical Reports Server (NTRS)

Ko, William L.; Jackson, Raymond H.

1994-01-01

A buckling analysis was performed on a hat-stiffened panel subjected to shear loading. Both local buckling and global buckling were analyzed. The global shear buckling load was found to be several times higher than the local shear buckling load. The classical shear buckling theory for a flat plate was found to be useful in predicting the local shear buckling load of the hat-stiffened panel, and the predicted local shear buckling loads thus obtained compare favorably with the results of finite element analysis.

Experimental study of main rotor tip geometry and tail rotor interactions in hover. Volume 1. Text and figures

NASA Technical Reports Server (NTRS)

Balch, D. T.; Lombardi, J.

1985-01-01

A model scale hover test was conducted in the Sikorsky Aircraft Model rotor hover Facility to identify and quantify the impact of the tail rotor on the demonstrated advantages of advanced geometry tip configurations. The test was conducted using the Basic Model Test Rig and two scaled main rotor systems, one representing a 1/5.727 scale UH-60A BLACK HAWK and the others a 1/4.71 scale S-76. Eight alternate rotor tip configurations were tested, 3 on the BLACK HAWK rotor and 6 on the S-76 rotor. Four of these tips were then selected for testing in close proximity to an operating tail rotor (operating in both tractor and pusher modes) to determine if the performance advantages that could be obtained from the use of advanced geometry tips in a main rotor only environment would still exist in the more complex flow field involving a tail rotor. The test showed that overall the tail rotor effects on the advanced tip configurations tested are not substantially different from the effects on conventional tips.

Tip-Enhanced Raman Scattering Imaging of Two-Dimensional Tungsten Disulfide with Optimized Tip Fabrication Process.

PubMed

Lee, Chanwoo; Kim, Sung Tae; Jeong, Byeong Geun; Yun, Seok Joon; Song, Young Jae; Lee, Young Hee; Park, Doo Jae; Jeong, Mun Seok

2017-01-13

We successfully achieve the tip-enhanced nano Raman scattering images of a tungsten disulfide monolayer with optimizing a fabrication method of gold nanotip by controlling the concentration of etchant in an electrochemical etching process. By applying a square-wave voltage supplied from an arbitrary waveform generator to a gold wire, which is immersed in a hydrochloric acid solution diluted with ethanol at various ratios, we find that both the conical angle and radius of curvature of the tip apex can be varied by changing the ratio of hydrochloric acid and ethanol. We also suggest a model to explain the origin of these variations in the tip shape. From the systematic study, we find an optimal condition for achieving the yield of ~60% with the radius of ~34 nm and the cone angle of ~35°. Using representative tips fabricated under the optimal etching condition, we demonstrate the tip-enhanced Raman scattering experiment of tungsten disulfide monolayer grown by a chemical vapor deposition method with a spatial resolution of ~40 nm and a Raman enhancement factor of ~4,760.

Kepler and Ground-Based Transits of the exo-Neptune HAT-P-11b

NASA Technical Reports Server (NTRS)

Deming, Drake; Sada, Pedro V.; Jackson, Brian; Peterson, Steven W.; Agol, Eric; Knutson, Heather A.; Jennings, Donald E.; Haase, Plynn; Bays, Kevin

2011-01-01

We analyze 26 archival Kepler transits of the exo-Neptune HAT-P-11b, supplemented by ground-based transits observed in the blue (B band) and near-IR (J band). Both the planet and host star are smaller than previously believed; our analysis yields Rp = 4.31 R xor 0.06 R xor and Rs = 0.683 R solar mass 0.009 R solar mass, both about 3 sigma smaller than the discovery values. Our ground-based transit data at wavelengths bracketing the Kepler bandpass serve to check the wavelength dependence of stellar limb darkening, and the J-band transit provides a precise and independent constraint on the transit duration. Both the limb darkening and transit duration from our ground-based data are consistent with the new Kepler values for the system parameters. Our smaller radius for the planet implies that its gaseous envelope can be less extensive than previously believed, being very similar to the H-He envelope of GJ 436b and Kepler-4b. HAT-P-11 is an active star, and signatures of star spot crossings are ubiquitous in the Kepler transit data. We develop and apply a methodology to correct the planetary radius for the presence of both crossed and uncrossed star spots. Star spot crossings are concentrated at phases 0.002 and +0.006. This is consistent with inferences from Rossiter-McLaughlin measurements that the planet transits nearly perpendicular to the stellar equator. We identify the dominant phases of star spot crossings with active latitudes on the star, and infer that the stellar rotational pole is inclined at about 12 deg 5 deg to the plane of the sky. We point out that precise transit measurements over long durations could in principle allow us to construct a stellar Butterfly diagram to probe the cyclic evolution of magnetic activity on this active K-dwarf star.

PVT: an efficient computational procedure to speed up next-generation sequence analysis.

PubMed

Maji, Ranjan Kumar; Sarkar, Arijita; Khatua, Sunirmal; Dasgupta, Subhasis; Ghosh, Zhumur

2014-06-04

High-throughput Next-Generation Sequencing (NGS) techniques are advancing genomics and molecular biology research. This technology generates substantially large data which puts up a major challenge to the scientists for an efficient, cost and time effective solution to analyse such data. Further, for the different types of NGS data, there are certain common challenging steps involved in analysing those data. Spliced alignment is one such fundamental step in NGS data analysis which is extremely computational intensive as well as time consuming. There exists serious problem even with the most widely used spliced alignment tools. TopHat is one such widely used spliced alignment tools which although supports multithreading, does not efficiently utilize computational resources in terms of CPU utilization and memory. Here we have introduced PVT (Pipelined Version of TopHat) where we take up a modular approach by breaking TopHat's serial execution into a pipeline of multiple stages, thereby increasing the degree of parallelization and computational resource utilization. Thus we address the discrepancies in TopHat so as to analyze large NGS data efficiently. We analysed the SRA dataset (SRX026839 and SRX026838) consisting of single end reads and SRA data SRR1027730 consisting of paired-end reads. We used TopHat v2.0.8 to analyse these datasets and noted the CPU usage, memory footprint and execution time during spliced alignment. With this basic information, we designed PVT, a pipelined version of TopHat that removes the redundant computational steps during 'spliced alignment' and breaks the job into a pipeline of multiple stages (each comprising of different step(s)) to improve its resource utilization, thus reducing the execution time. PVT provides an improvement over TopHat for spliced alignment of NGS data analysis. PVT thus resulted in the reduction of the execution time to ~23% for the single end read dataset. Further, PVT designed for paired end reads showed an improved performance of ~41% over TopHat (for the chosen data) with respect to execution time. Moreover we propose PVT-Cloud which implements PVT pipeline in cloud computing system.

Sleeping Sickness in Travelers - Do They Really Sleep?

PubMed Central

Urech, Karin; Neumayr, Andreas; Blum, Johannes

2011-01-01

The number of imported Human African Trypanosomiasis (HAT) cases in non-endemic countries has increased over the last years. The objective of this analysis is to describe the clinical presentation of HAT in Caucasian travelers. Literature was screened (MEDLINE, Pubmed) using the terms “Human African Trypanosomiasis”, “travelers” and “expatriates”; all European languages except Slavic ones were included. Publications without clinical description of patients were only included in the epidemiological analysis. Forty-five reports on Caucasians with T.b. rhodesiense and 15 with T.b. gambiense infections were included in the analysis of the clinical parameters. Both species have presented with fever (T.b. rhodesiense 97.8% and T.b. gambiense 93.3%), headache (50% each) and a trypanosomal chancre (T.b. rhodesiense 84.4%, T.b. gambiense 46.7%). While sleeping disorders dominate the clinical presentation of HAT in endemic regions, there have been only rare reports in travelers: insomnia (T.b. rhodesiense 7.1%, T.b. gambiense 21.4%), diurnal somnolence (T.b. rhodesiense 4.8%, T.b. gambiense none). Surprisingly, jaundice has been seen in 24.2% of the Caucasian T.b. rhodesiense patients, but has never been described in HAT patients in endemic regions. These results contrast to the clinical presentation of T.b. gambiense and T.b. rhodesiense HAT in Africans in endemic regions, where the presentation of chronic T.b. gambiense and acute T.b. rhodesiense HAT is different. The analysis of 14 reports on T.b. gambiense HAT in Africans living in a non-endemic country shows that neurological symptoms such as somnolence (46.2%), motor deficit (64.3%) and reflex anomalies (14.3%) as well as psychiatric symptoms such as hallucinations (21.4%) or depression (21.4%) may dominate the clinical picture. Often, the diagnosis has been missed initially: some patients have even been hospitalized in psychiatric clinics. In travelers T.b. rhodesiense and gambiense present as acute illnesses and chancres are frequently seen. The diagnosis of HAT in Africans living outside the endemic region is often missed or delayed, leading to presentation with advanced stages of the disease. PMID:22069503

Sleeping sickness in travelers - do they really sleep?

PubMed

Urech, Karin; Neumayr, Andreas; Blum, Johannes

2011-11-01

The number of imported Human African Trypanosomiasis (HAT) cases in non-endemic countries has increased over the last years. The objective of this analysis is to describe the clinical presentation of HAT in Caucasian travelers. Literature was screened (MEDLINE, Pubmed) using the terms "Human African Trypanosomiasis", "travelers" and "expatriates"; all European languages except Slavic ones were included. Publications without clinical description of patients were only included in the epidemiological analysis. Forty-five reports on Caucasians with T.b. rhodesiense and 15 with T.b. gambiense infections were included in the analysis of the clinical parameters. Both species have presented with fever (T.b. rhodesiense 97.8% and T.b. gambiense 93.3%), headache (50% each) and a trypanosomal chancre (T.b. rhodesiense 84.4%, T.b. gambiense 46.7%). While sleeping disorders dominate the clinical presentation of HAT in endemic regions, there have been only rare reports in travelers: insomnia (T.b. rhodesiense 7.1%, T.b. gambiense 21.4%), diurnal somnolence (T.b. rhodesiense 4.8%, T.b. gambiense none). Surprisingly, jaundice has been seen in 24.2% of the Caucasian T.b. rhodesiense patients, but has never been described in HAT patients in endemic regions. These results contrast to the clinical presentation of T.b. gambiense and T.b. rhodesiense HAT in Africans in endemic regions, where the presentation of chronic T.b. gambiense and acute T.b. rhodesiense HAT is different. The analysis of 14 reports on T.b. gambiense HAT in Africans living in a non-endemic country shows that neurological symptoms such as somnolence (46.2%), motor deficit (64.3%) and reflex anomalies (14.3%) as well as psychiatric symptoms such as hallucinations (21.4%) or depression (21.4%) may dominate the clinical picture. Often, the diagnosis has been missed initially: some patients have even been hospitalized in psychiatric clinics. In travelers T.b. rhodesiense and gambiense present as acute illnesses and chancres are frequently seen. The diagnosis of HAT in Africans living outside the endemic region is often missed or delayed, leading to presentation with advanced stages of the disease.

Intracellular Ca(2+) and K(+) concentration in Brassica oleracea leaf induces differential expression of transporter and stress-related genes.

PubMed

Lee, Jeongyeo; Kim, Jungeun; Choi, Jae-Pil; Lee, MiYe; Kim, Min Keun; Lee, Young Han; Hur, Yoonkang; Nou, Ill-Sup; Park, Sang Un; Min, Sung Ran; Kim, HyeRan

2016-03-09

One of the most important members of the genus Brassica, cabbage, requires a relatively high level of calcium for normal growth (Plant Cell Environ 7: 397-405, 1984; Plant Physiol 60: 854-856, 1977). Localized Ca(2+) deficiency in cabbage leaves causes tip-burn, bringing about serious economic losses (Euphytica 9:203-208, 1960; Ann Bot 43:363-372, 1979; Sci Hortic 14:131-138, 1981). Although it has been known that the occurrence of tip-burn is related to Ca(2+) deficiency, there is limited information on the underlying mechanisms of tip-burn or the relationship between Ca(2+) and tip-burn incidence. To obtain more information on the genetic control of tip-burn symptoms, we focused on the identification of genes differentially expressed in response to increasing intracellular Ca(2+) and K(+) concentrations in B. oleracea lines derived from tip-burn susceptible, tip-burn resistant cabbages (B. oleracea var. capitata), and kale (B. oleracea var. acephala). We compared the levels of major macronutrient cations, including Ca(2+) and K(+), in three leaf segments, the leaf apex (LA), middle of leaf (LM), and leaf base (LB), of tip-burn susceptible, tip-burn resistant cabbages, and kale. Ca(2+) and K(+) concentrations were highest in kale, followed by tip-burn resistant and then tip-burn susceptible cabbages. These cations generally accumulated to a greater extent in the LB than in the LA. Transcriptome analysis identified 58,096 loci as putative non-redundant genes in the three leaf segments of the three B. oleracea lines and showed significant changes in expression of 27,876 loci based on Ca(2+) and K(+) levels. Among these, 1844 loci were identified as tip-burn related phenotype-specific genes. Tip-burn resistant cabbage and kale-specific genes were largely related to stress and transport activity based on GO annotation. Tip-burn resistant cabbage and kale plants showed phenotypes clearly indicative of heat-shock, freezing, and drought stress tolerance compared to tip-burn susceptible cabbages, demonstrating a correlation between intracellular Ca(2+) and K(+) concentrations and tolerance of abiotic stress with differential gene expression. We selected 165 genes that were up- or down-regulated in response to increasing Ca(2+) and K(+) concentrations in the three leaf segments of the three plant lines. Gene ontology enrichment analysis indicated that these genes participated in regulatory metabolic processes or stress responses. Our results indicate that the genes involved in regulatory metabolic processes or stress responses were differentially expressed in response to increasing Ca(2+) and K(+) concentrations in the B. oleracea leaf. Our transcriptome data and the genes identified may serve as a starting point for understanding the mechanisms underlying essential macronutrient deficiencies in plants, as well as the features of tip-burn in cabbage and other Brassica species.

Species-Specific Inactivation of Triosephosphate Isomerase from Trypanosoma brucei: Kinetic and Molecular Dynamics Studies.

PubMed

Vázquez-Raygoza, Alejandra; Cano-González, Lucia; Velázquez-Martínez, Israel; Trejo-Soto, Pedro Josué; Castillo, Rafael; Hernández-Campos, Alicia; Hernández-Luis, Francisco; Oria-Hernández, Jesús; Castillo-Villanueva, Adriana; Avitia-Domínguez, Claudia; Sierra-Campos, Erick; Valdez-Solana, Mónica; Téllez-Valencia, Alfredo

2017-11-24

Human African Trypanosomiasis (HAT), a disease that provokes 2184 new cases a year in Sub-Saharan Africa, is caused by Trypanosoma brucei . Current treatments are limited, highly toxic, and parasite strains resistant to them are emerging. Therefore, there is an urgency to find new drugs against HAT. In this context, T. brucei depends on glycolysis as the unique source for ATP supply; therefore, the enzyme triosephosphate isomerase (TIM) is an attractive target for drug design. In the present work, three new benzimidazole derivatives were found as TbTIM inactivators (compounds 1 , 2 and 3 ) with an I 50 value of 84, 82 and 73 µM, respectively. Kinetic analyses indicated that the three molecules were selective when tested against human TIM (HsTIM) activity. Additionally, to study their binding mode in TbTIM, we performed a 100 ns molecular dynamics simulation of TbTIM-inactivator complexes. Simulations showed that the binding of compounds disturbs the structure of the protein, affecting the conformations of important domains such as loop 6 and loop 8. In addition, the physicochemical and drug-like parameters showed by the three compounds suggest a good oral absorption. In conclusion, these molecules will serve as a guide to design more potent inactivators that could be used to obtain new drugs against HAT.

Molecular identification of T. brucei s.l. in tsetse flies after long-term permanence in field traps.

PubMed

Gomes, Joana; Leão, Celia; Ferreira, Filipa; Afonso, Maria Odete; Santos, Catarina; Josenando, Theophile; Seixas, Jorge; Atouguia, Jorge; Centeno-Lima, Sonia

2009-10-24

Tsetse flies (Glossina spp.) are responsible for the transmission of trypanosomes, agents of animal and Human African Trypanosomiasis (HAT). These diseases are associated with considerable animal and human economical loss, morbidity and mortality. The correct identification of trypanosomes species infecting tsetse flies is crucial for adequate control measures. Identification presently requires technically difficult, cumbersome and expensive on-site fly dissection. To obviate this difficulty we explored the possibility of correctly identifying trypanosomes in tsetse collected, under field conditions, only for number determination. Tsetse flies, that remained exposed for weeks in field traps in the Vista Alegre HAT focus in Angola, were obtained. The flies were not dissected on site and were stored at room temperature for months. DNA extraction using the whole tsetse bodies and PCR analysis were performed in 73 randomly chosen flies. Despite the extensive degradation of the tsetse, DNA extraction was conducted successfully in 62 out of the 73 flies. PCR analysis detected the presence of T. brucei s.l DNA in 3.2 % of the tsetse. This approach could be cost-effective and suitable for vector related HAT control activities in the context of countries where entomological trained personnel is missing and financial resources are limited.

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.

Numerical simulations of heat transfer distribution of a two-pass square channel with V-rib turbulator and bleed holes

NASA Astrophysics Data System (ADS)

Kumar, Sourabh; Amano, R. S.; Lucci, Jose Martinez

2013-08-01

The blade tip region in gas turbine encounters high thermal loads due to temperature difference and hence efforts for high durability and safe operations are essential. Improved and robust methods of cooling are required to downgrade heat transfer rate to turbine blades. The blade tip regions, which are exposed to high gas flow, suffers high local thermal load which are due to external tip leakage. Jet impingement, pin cooling etc. are techniques used for cooling blades. A more usual way is to use serpentine passage with 180-degree turn. In this study, numerical simulation of heat transfer distribution of a two-pass square channel with rib turbulators and bleed holes were done. Periodical rib turbulators and bleed holes were used in the channel. The ribs arrangement were 60 degree V rib, 60 degree inverted V ribs, combination of 60 degree V rib at inlet and 60 inverted V rib at outlet section and combination of Inverted V at inlet and V rib at the outlet. The results were numerically computed using Fluent with Reynolds number of 12,500 and 28,500. Turbulence models used for computations were k-ω-SST and RSM. Temperature based and shear stress based techniques were used for heat transfer distribution prediction. The results for 60 degree V rib, 60 degree inverted V ribs were compared with the experimental results for validation of the results obtained. Detailed distribution shows distinctive peaks in heat transfer around bleed holes and rib turbulator. Comparisons of the overall performance of the models with different orientation of rib turbulator are presented. It is found that due to the combination of 60 degree inverted V rib in inlet and 60 V rib in outlet with bleed holes provides better heat treatment. It is suggested that the use of rib turbulator with bleed holes provides suitable for augmenting blade cooling to achieve an optimal balance between thermal and mechanical design requirements.

Application of winglets and/or wing tip extensions with active load control on the Boeing 747

NASA Technical Reports Server (NTRS)

Allison, R. L.; Perkin, B. R.; Schoenman, R. L.

1978-01-01

The application of wing tip modifications and active control technology to the Boeing 747 airplane for the purpose of improving fuel efficiency is considered. Wing tip extensions, wing tip winglets, and the use of the outboard ailerons for active wing load alleviation are described. Modest performance improvements are indicated. A costs versus benefits approach is taken to decide which, if any, of the concepts warrant further development and flight test leading to possible incorporation into production airplanes.

Tips on Mainstreaming: Do's and Don'ts in Activity Programs.

ERIC Educational Resources Information Center

Practical Pointers, 1978

1978-01-01

The document provides 10 brief articles on activities for mainstreamed handicapped students. Included are the following titles: "Tips on Mainstreaminq--Do's and Don'ts for Activity Programs;""Mainstreaming--A Goal and A Process;""What To Do When You Meet a Handicapped Person;""Tips for Dealing with Handicapped Persons;""Relatinq to Orthopedically…

Structure-Thermodynamics-Antioxidant Activity Relationships of Selected Natural Phenolic Acids and Derivatives: An Experimental and Theoretical Evaluation

PubMed Central

Zheng, Jie; Liang, Guizhao

2015-01-01

Phenolic acids and derivatives have potential biological functions, however, little is known about the structure-activity relationships and the underlying action mechanisms of these phenolic acids to date. Herein we investigate the structure-thermodynamics-antioxidant relationships of 20 natural phenolic acids and derivatives using DPPH• scavenging assay, density functional theory calculations at the B3LYP/6-311++G(d,p) levels of theory, and quantitative structure-activity relationship (QSAR) modeling. Three main working mechanisms (HAT, SETPT and SPLET) are explored in four micro-environments (gas-phase, benzene, water and ethanol). Computed thermodynamics parameters (BDE, IP, PDE, PA and ETE) are compared with the experimental radical scavenging activities against DPPH•. Available theoretical and experimental investigations have demonstrated that the extended delocalization and intra-molecular hydrogen bonds are the two main contributions to the stability of the radicals. The C = O or C = C in COOH, COOR, C = CCOOH and C = CCOOR groups, and orthodiphenolic functionalities are shown to favorably stabilize the specific radical species to enhance the radical scavenging activities, while the presence of the single OH in the ortho position of the COOH group disfavors the activities. HAT is the thermodynamically preferred mechanism in the gas phase and benzene, whereas SPLET in water and ethanol. Furthermore, our QSAR models robustly represent the structure-activity relationships of these explored compounds in polar media. PMID:25803685

Structure-thermodynamics-antioxidant activity relationships of selected natural phenolic acids and derivatives: an experimental and theoretical evaluation.

PubMed

Chen, Yuzhen; Xiao, Huizhi; Zheng, Jie; Liang, Guizhao

2015-01-01

Phenolic acids and derivatives have potential biological functions, however, little is known about the structure-activity relationships and the underlying action mechanisms of these phenolic acids to date. Herein we investigate the structure-thermodynamics-antioxidant relationships of 20 natural phenolic acids and derivatives using DPPH• scavenging assay, density functional theory calculations at the B3LYP/6-311++G(d,p) levels of theory, and quantitative structure-activity relationship (QSAR) modeling. Three main working mechanisms (HAT, SETPT and SPLET) are explored in four micro-environments (gas-phase, benzene, water and ethanol). Computed thermodynamics parameters (BDE, IP, PDE, PA and ETE) are compared with the experimental radical scavenging activities against DPPH•. Available theoretical and experimental investigations have demonstrated that the extended delocalization and intra-molecular hydrogen bonds are the two main contributions to the stability of the radicals. The C = O or C = C in COOH, COOR, C = CCOOH and C = CCOOR groups, and orthodiphenolic functionalities are shown to favorably stabilize the specific radical species to enhance the radical scavenging activities, while the presence of the single OH in the ortho position of the COOH group disfavors the activities. HAT is the thermodynamically preferred mechanism in the gas phase and benzene, whereas SPLET in water and ethanol. Furthermore, our QSAR models robustly represent the structure-activity relationships of these explored compounds in polar media.

BRD4 Regulates Transcription via Intrinsic HAT Activity | Center for Cancer Research

Cancer.gov

In order to express a gene, its DNA must be accessible to the transcription machinery. This requires chromatin de-compaction, which depends on the addition of acetyl groups to lysine residues on histones, thereby weakening interactions between histones and DNA and between adjacent nucleosomes.

Probing the parameters of the HAT-P-2 system

NASA Astrophysics Data System (ADS)

Bailey, Elizabeth; Naoz, Smadar; Batygin, Konstantin

2018-04-01

The HAT-P-2 system contributes an exceptional set of parameters to the exoplanetary inventory. HAT-P-2b weighs in at approximately 9 Jupiter masses, residing on one of the most eccentric, close-in orbits of any hot Jupiter (e~0.5, a~0.07). The identification of an RV trend points to the existence of an additional, long-period companion, which may have facilitated Kozai-Lidov cycles in the system over its multi-Gyr history. The well-constrained parameters of HAT-P-2b present an opportunity to predict the parameters of the perturber, and furthermore, to assess the tidal dissipation involved in the system's evolution. In this work, we employ an octupole-level secular model to account for the interaction of the two massive planets, thus classifying the system's deviations away from purely quadrupolar dynamics.

Immunoexpression of HDAC1, HDAC2, and HAT1 in actinic cheilitis and lip squamous cell carcinoma.

PubMed

Chrun, E S; Modolo, F; Vieira, Dsc; Borges-Júnior, Áls; Castro, R G; Daniel, F I

2017-05-01

Acetylation and deacetylation are the most studied covalent histone modifications resulting in transcriptional regulation with histone deacetylases (HDAC) and histone acetyltransferases (HAT) as the main associated enzymes. These enzymes overexpression induces abnormal transcription of key genes that regulate important cellular functions, such as proliferation, cell cycle regulation, and apoptosis. Thus, the expression of different HATs and HDACs has been evaluated in various cancers. To investigate HDAC1, HDAC2 and HAT1 expression in lip squamous cell carcinoma (LSCC) and actinic cheilitis (AC) and to demonstrate their correlation with DNA metyltransferases (DNMTs). Thirty cases of lip squamous cell carcinoma (LSCC), thirty cases of actinic cheilitis (AC), and 28 cases of non-neoplastic epithelium as control were selected for immunohistochemical investigation. Nuclear HDAC2 immunopositivity was significantly higher in AC (75.07% ± 29.70) when compared with LSCC (51.06% ± 39.02). HDAC1 and HAT1 nuclear immunostaining were higher in AC, with no statistical significance. When comparing data with our previous study, we found a positive correlation between HDAC1 X DNMT1/DNMT3b, HDAC2 X DNMT3b, and HAT1 X DNMT1/DNMT3b for certain studied groups. This study showed higher levels of nuclear HDAC2 immunopositivity in AC, possibly indicating that this enzyme plays a key role in lip photocarcinogenesis early stages. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A novel hAT element in Bombyx mori and Rhodnius prolixus: its relationship with miniature inverted repeat transposable elements (MITEs) and horizontal transfer.

PubMed

Zhang, H-H; Shen, Y-H; Xu, H-E; Liang, H-Y; Han, M-J; Zhang, Z

2013-10-01

Comparative analysis of transposable elements (TEs) from different species can make it possible to reconstruct their history over evolutionary time. In this study, we identified a novel hAT element in Bombyx mori and Rhodnius prolixus with characteristic GGGCGGCA repeats in its subterminal region. Meanwhile, phylogenetic analysis demonstrated that the elements in these two species might represent a separate cluster of the hAT superfamily. Strikingly, a previously identified miniature inverted repeat transposable element (MITE) shared high identity with this autonomous element across the entire length, supporting the hypothesis that MITEs are derived from the internal deletion of DNA transposons. Interestingly, identity of the consensus sequences of this novel hAT element between B. mori and R. prolixus, which diverged about 370 million years ago, was as high as 96.5% over their full length (about 3.6 kb) at the nucleotide level. The patchy distribution amongst species, coupled with overall lack of intense purifying selection acting on this element, suggest that this novel hAT element might have experienced horizontal transfer between the ancestors of B. mori and R. prolixus. Our results highlight that this novel hAT element could be used as a potential tool for germline transformation of R. prolixus to control the transmission of Trypanosoma cruzi, which causes Chagas disease. © 2013 Royal Entomological Society.

Speech Recognition of Bimodal Cochlear Implant Recipients Using a Wireless Audio Streaming Accessory for the Telephone.

PubMed

Wolfe, Jace; Morais, Mila; Schafer, Erin

2016-02-01

The goals of the present investigation were (1) to evaluate recognition of recorded speech presented over a mobile telephone for a group of adult bimodal cochlear implant users, and (2) to measure the potential benefits of wireless hearing assistance technology (HAT) for mobile telephone speech recognition using bimodal stimulation (i.e., a cochlear implant in one ear and a hearing aid on the other ear). A three-by-two-way repeated measures design was used to evaluate mobile telephone sentence-recognition performance differences obtained in quiet and in noise with and without the wireless HAT accessory coupled to the hearing aid alone, CI sound processor alone, and in the bimodal condition. Outpatient cochlear implant clinic. Sixteen bimodal users with Nucleus 24, Freedom, CI512, or CI422 cochlear implants participated in this study. Performance was measured with and without the use of a wireless HAT for the telephone used with the hearing aid alone, CI alone, and bimodal condition. CNC word recognition in quiet and in noise with and without the use of a wireless HAT telephone accessory in the hearing aid alone, CI alone, and bimodal conditions. Results suggested that the bimodal condition gave significantly better speech recognition on the mobile telephone with the wireless HAT. A wireless HAT for the mobile telephone provides bimodal users with significant improvement in word recognition in quiet and in noise over the mobile telephone.

Spatially resolved thermal desorption/ionization coupled with mass spectrometry

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

Jesse, Stephen; Van Berkel, Gary J; Ovchinnikova, Olga S

2013-02-26

A system and method for sub-micron analysis of a chemical composition of a specimen are described. The method includes providing a specimen for evaluation and a thermal desorption probe, thermally desorbing an analyte from a target site of said specimen using the thermally active tip to form a gaseous analyte, ionizing the gaseous analyte to form an ionized analyte, and analyzing a chemical composition of the ionized analyte. The thermally desorbing step can include heating said thermally active tip to above 200.degree. C., and positioning the target site and the thermally active tip such that the heating step forms themore » gaseous analyte. The thermal desorption probe can include a thermally active tip extending from a cantilever body and an apex of the thermally active tip can have a radius of 250 nm or less.« less

Electron-bombarded 〈110〉-oriented tungsten tips for stable tunneling electron emission

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

Yamada, T. K.; Abe, T.; Nazriq, N. M. K.

A clean tungsten (W) tip apex with a robust atomic plane is required for producing a stable tunneling electron emission under strong electric fields. Because a tip apex fabricated from a wire by aqueous chemical etching is covered by impurity layers, heating treatment in ultra-high vacuum is experimentally known to be necessary. However, strong heating frequently melts the tip apex and causes unstable electron emissions. We investigated quantitatively the tip apex and found a useful method to prepare a tip with stable tunneling electron emissions by controlling electron-bombardment heating power. Careful characterizations of the tip structures were performed with combinationsmore » of using field emission I–V curves, scanning electron microscopy, X-ray diffraction (transmitted Debye-Scherrer and Laue) with micro-parabola capillary, field ion microscopy, and field emission microscopy. Tips were chemically etched from (1) polycrystalline W wires (grain size ∼1000 nm) and (2) long-time heated W wires (grain size larger than 1 mm). Heating by 10-40 W (10 s) was found to be good enough to remove oxide layers and produced stable electron emission; however, around 60 W (10 s) heating was threshold power to increase the tip radius, typically +10 ± 5 nm (onset of melting). Further, the grain size of ∼1000 nm was necessary to obtain a conical shape tip apex.« less

Curcumin Attenuation of Lipopolysaccharide Induced Cardiac Hypertrophy in Rodents

PubMed Central

Graham, Thomas; Reddy, Gopal

2013-01-01

To study the ameliorating effects of curcumin in lipopolysaccharide (LPS) induced cardiac hypertrophy, mice were assigned to 4 groups (3 males and 3 females in each group): (A) control, (B) curcumin: 100 μg/kg of body weight by intraperitoneal route (IP), (C) LPS: 60 mg/kg (IP), and (D) LPS + curcumin: both at previously stated concentrations by IP route. All mice were sacrificed as 12 hr and 24 hrs groups accordingly after LPS injection. The hearts were collected, photographed for cardiomegaly, and weighed to compare heart weight/brain weight (HW/BW) in mg/mg. For immunohistochemistry, the tissue sections were exposed to histone H3, H4 and acetylated histone H3, H4 antibody. LPS induced a significant increase in histone acetylation as shown by intense staining. In curcumin + LPS treated mice nuclear staining was similar to the control group indicating that curcumin traversed the histone acetylation activity of the LPS. To further check the mechanism of action of curcumin, p300 protein acetylation levels were analyzed. This study suggests that the probable mechanism of action of curcumin is via the reduction of p300 HAT activity. PMID:24236240

Impaired TIP60-mediated H4K16 acetylation accounts for the aberrant chromatin accumulation of 53BP1 and RAP80 in Fanconi anemia pathway-deficient cells.

PubMed

Renaud, Emilie; Barascu, Aurelia; Rosselli, Filippo

2016-01-29

To rescue collapsed replication forks cells utilize homologous recombination (HR)-mediated mechanisms to avoid the induction of gross chromosomal abnormalities that would be generated by non-homologous end joining (NHEJ). Using DNA interstrand crosslinks as a replication barrier, we investigated how the Fanconi anemia (FA) pathway promotes HR at stalled replication forks. FA pathway inactivation results in Fanconi anemia, which is associated with a predisposition to cancer. FANCD2 monoubiquitination and assembly in subnuclear foci appear to be involved in TIP60 relocalization to the chromatin to acetylates histone H4K16 and prevents the binding of 53BP1 to its docking site, H4K20Me2. Thus, FA pathway loss-of-function results in accumulation of 53BP1, RIF1 and RAP80 at damaged chromatin, which impair DNA resection at stalled replication fork-associated DNA breaks and impede HR. Consequently, DNA repair in FA cells proceeds through the NHEJ pathway, which is likely responsible for the accumulation of chromosome abnormalities. We demonstrate that the inhibition of NHEJ or deacetylase activity rescue HR in FA cells. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Adding tsetse control to medical activities contributes to decreasing transmission of sleeping sickness in the Mandoul focus (Chad)

PubMed Central

Mahamat, Mahamat Hissene; Peka, Mallaye; Rayaisse, Jean-Baptiste; Rock, Kat S.; Toko, Mahamat Abdelrahim; Darnas, Justin; Brahim, Guihini Mollo; Yoni, Wilfrid; Tirados, Inaki; Courtin, Fabrice; Brand, Samuel P. C.; Nersy, Cyrus; Alfaroukh, Idriss Oumar; Torr, Steve J.; Lehane, Mike J.; Solano, Philippe

2017-01-01

Background Gambian sleeping sickness or HAT (human African trypanosomiasis) is a neglected tropical disease caused by Trypanosoma brucei gambiense transmitted by riverine species of tsetse. A global programme aims to eliminate the disease as a public health problem by 2020 and stop transmission by 2030. In the South of Chad, the Mandoul area is a persistent focus of Gambian sleeping sickness where around 100 HAT cases were still diagnosed and treated annually until 2013. Pre-2014, control of HAT relied solely on case detection and treatment, which lead to a gradual decrease in the number of cases of HAT due to annual screening of the population. Methods Because of the persistence of transmission and detection of new cases, we assessed whether the addition of vector control to case detection and treatment could further reduce transmission and consequently, reduce annual incidence of HAT in Mandoul. In particular, we investigated the impact of deploying ‘tiny targets’ which attract and kill tsetse. Before tsetse control commenced, a census of the human population was conducted and their settlements mapped. A pre-intervention survey of tsetse distribution and abundance was implemented in November 2013 and 2600 targets were deployed in the riverine habitats of tsetse in early 2014, 2015 and 2016. Impact on tsetse and on the incidence of sleeping sickness was assessed through nine tsetse monitoring surveys and four medical surveys of the human population in 2014 and 2015. Mathematical modelling was used to assess the relative impact of tsetse control on incidence compared to active and passive screening. Findings The census indicated that a population of 38674 inhabitants lived in the vicinity of the Mandoul focus. Within this focus in November 2013, the vector is Glossina fuscipes fuscipes and the mean catch of tsetse from traps was 0.7 flies/trap/day (range, 0–26). The catch of tsetse from 44 sentinel biconical traps declined after target deployment with only five tsetse being caught in nine surveys giving a mean catch of 0.005 tsetse/trap/day. Modelling indicates that 70.4% (95% CI: 51–95%) of the reduction in reported cases between 2013 and 2015 can be attributed to vector control with the rest due to medical intervention. Similarly tiny targets are estimated to have reduced new infections dramatically with 62.8% (95% CI: 59–66%) of the reduction due to tsetse control, and 8.5% (95% 8–9%) to enhanced passive detection. Model predictions anticipate that elimination as a public health problem could be achieved by 2018 in this focus if vector control and screening continue at the present level and, furthermore, there may have been virtually no transmission since 2015. Conclusion This work shows that tiny targets reduced the numbers of tsetse in this focus in Chad, which may have interrupted transmission and the combination of tsetse control to medical detection and treatment has played a major role in reducing in HAT incidence in 2014 and 2015. PMID:28750007

Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for {beta}-lactam acetylation.

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

He, H.; Ding, Y.; Bartlam, M.

2003-01-31

Tabtoxin resistance protein (TTR) is an enzyme that renders tabtoxin-producing pathogens, such as Pseudomonas syringae, tolerant to their own phytotoxins. Here, we report the crystal structure of TTR complexed with its natural cofactor, acetyl coenzyme A (AcCoA), to 1.55 {angstrom} resolution. The binary complex forms a characteristic 'V' shape for substrate binding and contains the four motifs conserved in the GCN5-related N-acetyltransferase (GNAT) superfamily, which also includes the histone acetyltransferases (HATs). A single-step mechanism is proposed to explain the function of three conserved residues, Glu92, Asp130 and Tyr141, in catalyzing the acetyl group transfer to its substrate. We also reportmore » that TTR possesses HAT activity and suggest an evolutionary relationship between TTR and other GNAT members.« less

Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for beta-lactam acetylation.

PubMed

He, Hongzhen; Ding, Yi; Bartlam, Mark; Sun, Fei; Le, Yi; Qin, Xincheng; Tang, Hong; Zhang, Rongguang; Joachimiak, Andrzej; Liu, Jinyuan; Zhao, Nanming; Rao, Zihe

2003-01-31

Tabtoxin resistance protein (TTR) is an enzyme that renders tabtoxin-producing pathogens, such as Pseudomonas syringae, tolerant to their own phytotoxins. Here, we report the crystal structure of TTR complexed with its natural cofactor, acetyl coenzyme A (AcCoA), to 1.55A resolution. The binary complex forms a characteristic "V" shape for substrate binding and contains the four motifs conserved in the GCN5-related N-acetyltransferase (GNAT) superfamily, which also includes the histone acetyltransferases (HATs). A single-step mechanism is proposed to explain the function of three conserved residues, Glu92, Asp130 and Tyr141, in catalyzing the acetyl group transfer to its substrate. We also report that TTR possesses HAT activity and suggest an evolutionary relationship between TTR and other GNAT members.

Design and Evaluation of a Bolted Joint for a Discrete Carbon-Epoxy Rod-Reinforced Hat Section

NASA Technical Reports Server (NTRS)

Baker, Donald J.; Rousseau, Carl Q.

1996-01-01

The use of pre-fabricated pultruded carbon-epoxy rods has reduced the manufacturing complexity and costs of stiffened composite panels while increasing the damage tolerance of the panels. However, repairability of these highly efficient discrete stiffeners has been a concern. Design, analysis, and test results are presented in this paper for a bolted-joint repair for the pultruded rod concept that is capable of efficiently transferring axial loads in a hat-section stiffener on the upper skin segment of a heavily loaded aircraft wing component. A tension and a compression joint design were evaluated. The tension joint design achieved approximately 1.0 percent strain in the carbon-epoxy rod-reinforced hat-section and failed in a metal fitting at 166 percent of the design ultimate load. The compression joint design failed in the carbon-epoxy rod-reinforced hat-section test specimen area at approximately 0.7 percent strain and at 110 percent of the design ultimate load. This strain level of 0.7 percent in compression is similar to the failure strain observed in previously reported carbon-epoxy rod-reinforced hat-section column tests.

Transmission Spectrum of HAT-P-11b

NASA Image and Video Library

2014-09-24

A plot of the transmission spectrum for exoplanet HAT-P-11b, with data from NASA Kepler, Hubble and Spitzer observatories combined. The results show a robust detection of water absorption in the Hubble data.

Bi-Directional Communication: A Critical Component of HAT

NASA Technical Reports Server (NTRS)

Shively, Robert J.

2016-01-01

Known problems with automation include lack of mode awareness, automation brittleness, and risk of miscalibrated trust. Human-Autonomy Teaming (HAT) is essential for improving these problems. This presentation outlines critical components for Human-Autonomy Teaming.

Pollen-tube tip growth requires a balance of lateral propagation and global inhibition of Rho-family GTPase activity

PubMed Central

Hwang, Jae-Ung; Wu, Guang; Yan, An; Lee, Yong-Jik; Grierson, Claire S.; Yang, Zhenbiao

2010-01-01

Rapid tip growth allows for efficient development of highly elongated cells (e.g. neuronal axons, fungal hyphae and pollen tubes) and requires an elaborate spatiotemporal regulation of the growing region. Here, we use the pollen tube as a model to investigate the mechanism regulating the growing region. ROPs (Rho-related GTPases from plants) are essential for pollen tip growth and display oscillatory activity changes in the apical plasma membrane (PM). By manipulating the ROP activity level, we showed that the PM distribution of ROP activity as an apical cap determines the tip growth region and that efficient tip growth requires an optimum level of the apical ROP1 activity. Excessive ROP activation induced the enlargement of the tip growth region, causing growth depolarization and reduced tube elongation. Time-lapse analysis suggests that the apical ROP1 cap is generated by lateral propagation of a localized ROP activity. Subcellular localization and gain- and loss-of-function analyses suggest that RhoGDI- and RhoGAP-mediated global inhibition limits the lateral propagation of apical ROP1 activity. We propose that the balance between the lateral propagation and the global inhibition maintains an optimal apical ROP1 cap and generates the apical ROP1 activity oscillation required for efficient pollen-tube elongation. PMID:20053639

Investigation of tip sonication effects on structural quality of graphene nanoplatelets (GNPs) for superior solvent dispersion.

PubMed

Baig, Zeeshan; Mamat, Othman; Mustapha, Mazli; Mumtaz, Asad; Munir, Khurram S; Sarfraz, Mansoor

2018-07-01

The exceptional properties of graphene and its structural uniqueness can improve the performance of nanocomposites if it can attain the uniform dispersion. Tip sonication assisted graphene solvent dispersion has been emerged as an efficient approach but it can cause significant degradation of graphene structure. This study aimed to evaluate the parametric influence of tip sonication on the characteristics of sp 2 carbon structure in graphene nanoplatelets by varying the sonication time and respective energy at three different amplitudes (60%, 80% and 100%). The study is essential to identify appropriate parameters so as to achieve high-quality and defect-free graphene with a highly desirable aspect ratio after solvent dispersion for composite reinforcement. Quantitative approach via Raman spectroscopy is used to find the defect ratio and lateral size of graphene evolved under the effect of tip sonication parameters. Results imply that the defect ratio is steady and increases continually with GNPs, along with the transformation to the nano-crystalline stage I up to 60 min sonication at all amplitudes. Exfoliation was clearly observed at all amplitudes together with sheet re-stacking due to considerable size reduction of sheets with large quantity. Finally, considerable GNPs fragmentation occurred during sonication with increased amplitude and time as confirmed by the reduction of sp 2 domain (La) and flake size. This also validates the formation of edge-type defect in graphene. Convincingly, lower amplitude and time (up to 60 min) produce better results for a low defect content and larger particle size as quantified by Raman analysis. Copyright © 2018 Elsevier B.V. All rights reserved.

Analyses of some exoplanets' transits and transit timing variations

NASA Astrophysics Data System (ADS)

Püsküllü, ćaǧlar; Soydugan, Faruk

2017-02-01

We present solutions of the transit light curves and transit timing variations (TTVs) analyses of the exoplanets HAT-P-5b, HAT-P-9b and HAT-P-25b. Transit light curves were collected at Çanakkale Onsekiz Mart University Observatory and TUBITAK National Observatory. The models were produced by WINFITTER program and stellar, planetary and orbital properties were obtained and discussed. We gave new transit times and generated TTVs with them by appending additional data based on Exoplanet Transit Database (ETD). Significant signals at the TTVs were also investigated.

The 3DBiopsy Prostate Biopsy System: Preclinical Investigation of a Needle, Actuator, and Specimen Collection Device Allowing Sampling of Individualized Prostate Lengths Between 20 and 60 mm.

PubMed

Stone, Nelson N; Mouraviev, Vladimir; Schechter, David; Lucia, M Scott; Smith, Elizabeth E; Arangua, Paul; Hoenemeyer, John; Rosa, Jim; Bawa, Rajan; Crawford, E David

2017-09-01

To increase the likelihood of detecting anterior cancers within the prostate and provide a specimen that spans the length of the gland. Newly designed 17- and 15-gauge (G) biopsy needles, a variable actuator, and an integrated pathology system intended for the longer cores were developed and tested for this purpose. Testing was performed comparing 2 common cannula tip grinds, a Vet-point (sharp tip) and a Menghini-point (atraumatic tip), and were tested against 18-G Bard Monopty in porcine kidney. A variable actuator was developed to fire the needle 20-60 mm and tested in cadaver prostates. The aggregate firings for 3 different shot lengths comparing the Vet- with the Menghini-tip cannulas demonstrated 91% vs 85.2% fill (length of specimen/length of core bed, P = .007). A 15-G trocar needle with the Vet-tip cannula also had the best performance, with an aggregate standard deviation of 6.4% across 3 firing ranges and a minimum to maximum specimen length of 81%-105% of potential fill. Cadaver testing with the Vet-tip needles in the actuator for the transrectal (17-G) and transperineal (15-G) biopsies demonstrated mean fills of 93.3% and 76.5%, respectively. The new transrectal ultrasound needle obtained a 2-fold increase in specimen length over the standard Bard device (P <.001). Longer and consistent cores were obtained using the new biopsy needles. Combined with an adjustable actuator, the physician can obtain specimens that include peripheral and anterior zone tissue in 1 core. Determination of cancer location on the longer specimens could enhance focal therapy planning. Copyright © 2017 Elsevier Inc. All rights reserved.

Reactions of the phthalimide N-oxyl radical (PINO) with activated phenols: the contribution of π-stacking interactions to hydrogen atom transfer rates.

PubMed

D'Alfonso, Claudio; Bietti, Massimo; DiLabio, Gino A; Lanzalunga, Osvaldo; Salamone, Michela

2013-02-01

The kinetics of reactions of the phthalimide N-oxyl radical (PINO) with a series of activated phenols (2,2,5,7,8-pentamethylchroman-6-ol (PMC), 2,6-dimethyl- and 2,6-di-tert-butyl-4-substituted phenols) were investigated by laser flash photolysis in CH(3)CN and PhCl in order to establish if the reactions with PINO can provide a useful tool for evaluating the radical scavenging ability of phenolic antioxidants. On the basis of the small values of deuterium kinetic isotope effects, the relatively high and negative ρ values in the Hammett correlations and the results of theoretical calculations, we suggest that these reactions proceed by a hydrogen atom transfer (HAT) mechanism having a significant degree of charge transfer resulting from a π-stacked conformation between PINO and the aromatic ring of the phenols. Kinetic solvent effects were analyzed in detail for the hydrogen transfer from 2,4,6-trimethylphenol to PINO and the data obtained are in accordance with the Snelgrove-Ingold equation for HAT. Experimental rate constants for the reactions of PINO with activated phenols are in accordance with those predicted by applying the Marcus cross relation.

Novel Insect Leaf-Mining after the End-Cretaceous Extinction and the Demise of Cretaceous Leaf Miners, Great Plains, USA

PubMed Central

Donovan, Michael P.; Wilf, Peter; Labandeira, Conrad C.; Johnson, Kirk R.; Peppe, Daniel J.

2014-01-01

Plant and associated insect-damage diversity in the western U.S.A. decreased significantly at the Cretaceous-Paleogene (K-Pg) boundary and remained low until the late Paleocene. However, the Mexican Hat locality (ca. 65 Ma) in southeastern Montana, with a typical, low-diversity flora, uniquely exhibits high damage diversity on nearly all its host plants, when compared to all known local and regional early Paleocene sites. The same plant species show minimal damage elsewhere during the early Paleocene. We asked whether the high insect damage diversity at Mexican Hat was more likely related to the survival of Cretaceous insects from refugia or to an influx of novel Paleocene taxa. We compared damage on 1073 leaf fossils from Mexican Hat to over 9000 terminal Cretaceous leaf fossils from the Hell Creek Formation of nearby southwestern North Dakota and to over 9000 Paleocene leaf fossils from the Fort Union Formation in North Dakota, Montana, and Wyoming. We described the entire insect-feeding ichnofauna at Mexican Hat and focused our analysis on leaf mines because they are typically host-specialized and preserve a number of diagnostic morphological characters. Nine mine damage types attributable to three of the four orders of leaf-mining insects are found at Mexican Hat, six of them so far unique to the site. We found no evidence linking any of the diverse Hell Creek mines with those found at Mexican Hat, nor for the survival of any Cretaceous leaf miners over the K-Pg boundary regionally, even on well-sampled, surviving plant families. Overall, our results strongly relate the high damage diversity on the depauperate Mexican Hat flora to an influx of novel insect herbivores during the early Paleocene, possibly caused by a transient warming event and range expansion, and indicate drastic extinction rather than survivorship of Cretaceous insect taxa from refugia. PMID:25058404

Flexural fatigue life prediction of closed hat-section using materially nonlinear axial fatigue characteristics

NASA Technical Reports Server (NTRS)

Razzaq, Zia

1989-01-01

Straight or curved hat-section members are often used as structural stiffeners in aircraft. For instance, they are employed as stiffeners for the dorsal skin as well as in the aerial refueling adjacent area structure in F-106 aircraft. The flanges of the hat-section are connected to the aircraft skin. Thus, the portion of the skin closing the hat-section interacts with the section itself when resisting the stresses due to service loads. The flexural fatigue life of such a closed section is estimated using materially nonlinear axial fatigue characteristics. It should be recognized that when a structural shape is subjected to bending, the fatigue life at the neutral axis is infinity since the normal stresses are zero at that location. Conversely, the fatigue life at the extreme fibers where the normal bending stresses are maximum can be expected to be finite. Thus, different fatigue life estimates can be visualized at various distances from the neural axis. The problem becomes compounded further when significant portions away from the neutral axis are stressed into plastic range. A theoretical analysis of the closed hat-section subjected to flexural cyclic loading is first conducted. The axial fatigue characteristics together with the related axial fatigue life formula and its inverted form given by Manson and Muralidharan are adopted for an aluminum alloy used in aircraft construction. A closed-form expression for predicting the flexural fatigue life is then derived for the closed hat-section including materially nonlinear action. A computer program is written to conduct a study of the variables such as the thicknesses of the hat-section and the skin, and the type of alloy used. The study has provided a fundamental understanding of the flexural fatigue life characteristics of a practical structural component used in aircraft when materially nonlinear action is present.

Radiofrequency energy antenna coupling to common laparoscopic instruments: practical implications.

PubMed

Jones, Edward L; Robinson, Thomas N; McHenry, Jennifer R; Dunn, Christina L; Montero, Paul N; Govekar, Henry R; Stiegmann, Greg V

2012-11-01

Electromagnetic coupling can occur between the monopolar "Bovie" instrument and other laparoscopic instruments without direct contact by a phenomenon termed antenna coupling. The purpose of this study was to determine if, and to what extent, radiofrequency energy couples to other common laparoscopic instruments and to describe practical steps that can minimize the magnitude of antenna coupling. In a laparoscopic simulator, monopolar radiofrequency energy was delivered to an L-hook. The tips of standard, nonelectrical laparoscopic instruments (either an unlit 10 mm telescope or a 5 mm grasper) were placed adjacent to bovine liver tissue and were never in contact with the active electrode. Thermal imaging quantified the change in tissue temperature nearest the tip of the telescope or grasper at the end of a 5 s activation of the active electrode. A 5 s activation (30 watts, coagulation mode, 4 cm separation between instruments) increased tissue temperature compared with baseline adjacent to the grasper tip (2.2 ± 2.2 °C; p = 0.013) and telescope tip (38.2 ± 8.0 °C; p < 0.001). The laparoscopic telescope tip increased tissue temperature more than the laparoscopic grasper tip (p < 0.001). Lowering the generator power from 30 to 15 Watts decreased the heat generated at the telescope tip (38.2 ± 8.0 vs. 13.5 ± 7.5 °C; p < 0.001). Complete separation of the camera/light cords and the active electrode cord decreased the heat generated near the telescope tip compared with parallel bundling of the cords (38.2 ± 8.0 vs. 15.7 ± 11.6 °C; p < 0.001). Commonly used laparoscopic instruments couple monopolar radiofrequency energy without direct contact with the active electrode, a phenomenon that results in heat transfer from a nonelectrically active instrument tip to adjacent tissue. Practical steps to minimize heat transfer resulting from antenna coupling include reducing the monopolar generator power setting and avoiding of parallel bundling of the telescope and active electrode cords.

Survival Bayesian Estimation of Exponential-Gamma Under Linex Loss Function

NASA Astrophysics Data System (ADS)

Rizki, S. W.; Mara, M. N.; Sulistianingsih, E.

2017-06-01

This paper elaborates a research of the cancer patients after receiving a treatment in cencored data using Bayesian estimation under Linex Loss function for Survival Model which is assumed as an exponential distribution. By giving Gamma distribution as prior and likelihood function produces a gamma distribution as posterior distribution. The posterior distribution is used to find estimatior {\\hat{λ }}BL by using Linex approximation. After getting {\\hat{λ }}BL, the estimators of hazard function {\\hat{h}}BL and survival function {\\hat{S}}BL can be found. Finally, we compare the result of Maximum Likelihood Estimation (MLE) and Linex approximation to find the best method for this observation by finding smaller MSE. The result shows that MSE of hazard and survival under MLE are 2.91728E-07 and 0.000309004 and by using Bayesian Linex worths 2.8727E-07 and 0.000304131, respectively. It concludes that the Bayesian Linex is better than MLE.

Trypanosomiasis Control, Democratic Republic of Congo, 1993–2003

PubMed Central

Lutumba, Pascal; Robays, Jo; Bilenge, Constantin Miaka mia; Mesu, Victor Kande Betu Ku; Molisho, Didier; Declercq, Johan; Van der Veken, Wim; Meheus, Filip; Jannin, Jean

2005-01-01

In the Democratic Republic of Congo (DRC), human African trypanosomiasis (HAT) reached unprecedented levels in the 1990s. To assess recent trends and evaluate control efforts, we analyzed epidemiologic and financial data collected by all agencies involved in HAT control in DRC from 1993 to 2003. Funds allocated to control populations, as well as to the population screened, doubled from 1993 to 1997 and from 1998 to 2003. The number of cases detected decreased from 26,000 new cases per year in 1998 to 11,000 in 2003. Our analysis shows that HAT control in DRC is almost completely dependent on international aid and that sudden withdrawal of such aid in 1990 had a long-lasting effect. Since 1998, control efforts intensified because of renewed donor interest, including a public-private partnership, and this effort led to a major reduction in HAT incidence. To avoid reemergence of this disease, such efforts should be sustained. PMID:16229766

HAT-P-26b: A Neptune-mass exoplanet with a well-constrained heavy element abundance

NASA Astrophysics Data System (ADS)

Wakeford, Hannah R.; Sing, David K.; Kataria, Tiffany; Deming, Drake; Nikolov, Nikolay; Lopez, Eric D.; Tremblin, Pascal; Amundsen, David S.; Lewis, Nikole K.; Mandell, Avi M.; Fortney, Jonathan J.; Knutson, Heather; Benneke, Björn; Evans, Thomas M.

2017-05-01

A correlation between giant-planet mass and atmospheric heavy elemental abundance was first noted in the past century from observations of planets in our own Solar System and has served as a cornerstone of planet-formation theory. Using data from the Hubble and Spitzer Space Telescopes from 0.5 to 5 micrometers, we conducted a detailed atmospheric study of the transiting Neptune-mass exoplanet HAT-P-26b. We detected prominent H2O absorption bands with a maximum base-to-peak amplitude of 525 parts per million in the transmission spectrum. Using the water abundance as a proxy for metallicity, we measured HAT-P-26b’s atmospheric heavy element content (4.8-4.0+21.5 times solar). This likely indicates that HAT-P-26b’s atmosphere is primordial and obtained its gaseous envelope late in its disk lifetime, with little contamination from metal-rich planetesimals.

Human-Autonomy Teaming: Supporting Dynamically Adjustable Collaboration

NASA Technical Reports Server (NTRS)

Shively, Jay

2017-01-01

This presentation is a technical update for the NATO-STO HFM-247 working group. Our progress on four goals will be discussed. For Goal 1, a conceptual model of HAT is presented. HAT looks to make automation act as more of a teammate, by having it communicate with human operators in a more human, goal-directed, manner which provides transparency into the reasoning behind automated recommendations and actions. This, in turn, permits more trust in the automation when it is appropriate, and less when it is not, allowing a more targeted supervision of automated functions. For Goal 2, we wanted to test these concepts and principles. We present findings from a recent simulation and describe two in progress. Goal 3 was to develop pattern(s) of HAT solution(s). These were originally presented at HCII 2016 and are reviewed. Goal 4 is to develop a re-usable HAT software agent. This is an ongoing effort to be delivered October 2017.

Novel synthetic lethality screening method identifies TIP60-dependent radiation sensitivity in the absence of BAF180.

PubMed

Hopkins, Suzanna R; McGregor, Grant A; Murray, Johanne M; Downs, Jessica A; Savic, Velibor

2016-10-01

In recent years, research into synthetic lethality and how it can be exploited in cancer treatments has emerged as major focus in cancer research. However, the lack of a simple to use, sensitive and standardised assay to test for synthetic interactions has been slowing the efforts. Here we present a novel approach to synthetic lethality screening based on co-culturing two syngeneic cell lines containing individual fluorescent tags. By associating shRNAs for a target gene or control to individual fluorescence labels, we can easily follow individual cell fates upon siRNA treatment and high content imaging. We have demonstrated that the system can recapitulate the functional defects of the target gene depletion and is capable of discovering novel synthetic interactors and phenotypes. In a trial screen, we show that TIP60 exhibits synthetic lethality interaction with BAF180, and that in the absence of TIP60, there is an increase micronuclei dependent on the level of BAF180 loss, significantly above levels seen with BAF180 present. Moreover, the severity of the interactions correlates with proxy measurements of BAF180 knockdown efficacy, which may expand its usefulness to addressing synthetic interactions through titratable hypomorphic gene expression. Copyright © 2016. Published by Elsevier B.V.

Ovarian steroid hormones modulate the expression of progesterone receptors and histone acetylation patterns in uterine leiomyoma cells.

PubMed

Sant'Anna, Gabriela Dos Santos; Brum, Ilma Simoni; Branchini, Gisele; Pizzolato, Lolita Schneider; Capp, Edison; Corleta, Helena von Eye

2017-08-01

Uterine leiomyomas are the most common benign smooth muscle cell tumors in women. Estrogen (E2), progesterone (P4) and environmental factors play important roles in the development of these tumors. New treatments, such as mifepristone, have been proposed. We evaluated the gene expression of total (PRT) and B (PRB) progesterone receptors, and the histone acetyltransferase (HAT) and deacetylase (HDAC) activity after treatment with E2, P4 and mifepristone (RU486) in primary cell cultures from uterine leiomyoma and normal myometrium. Compared to myometrium, uterine leiomyoma cells showed an increase in PRT mRNA expression when treated with E2, and increase in PRB mRNA expression when treated with E2 and P4. Treatment with mifepristone had no significant impact on mRNA expression in these cells. The HDAC activity was higher in uterine leiomyoma compared to myometrial cells after treatment with E2 and E2 + P4 + mifepristone. HAT activity was barely detectable. Our results suggest that ovarian steroid hormones modulate PR, and mifepristone was unable to decrease PRT and PRB mRNA. The higher activity of HDAC leiomyoma cells could be involved in transcriptional repression of genes implicated in normal myometrium cell function, contributing to the maintenance and growth of uterine leiomyoma.

Validation of Splicing Events in Transcriptome Sequencing Data

PubMed Central

Kaisers, Wolfgang; Ptok, Johannes; Schwender, Holger; Schaal, Heiner

2017-01-01

Genomic alignments of sequenced cellular messenger RNA contain gapped alignments which are interpreted as consequence of intron removal. The resulting gap-sites, genomic locations of alignment gaps, are landmarks representing potential splice-sites. As alignment algorithms report gap-sites with a considerable false discovery rate, validations are required. We describe two quality scores, gap quality score (gqs) and weighted gap information score (wgis), developed for validation of putative splicing events: While gqs solely relies on alignment data wgis additionally considers information from the genomic sequence. FASTQ files obtained from 54 human dermal fibroblast samples were aligned against the human genome (GRCh38) using TopHat and STAR aligner. Statistical properties of gap-sites validated by gqs and wgis were evaluated by their sequence similarity to known exon-intron borders. Within the 54 samples, TopHat identifies 1,000,380 and STAR reports 6,487,577 gap-sites. Due to the lack of strand information, however, the percentage of identified GT-AG gap-sites is rather low. While gap-sites from TopHat contain ≈89% GT-AG, gap-sites from STAR only contain ≈42% GT-AG dinucleotide pairs in merged data from 54 fibroblast samples. Validation with gqs yields 156,251 gap-sites from TopHat alignments and 166,294 from STAR alignments. Validation with wgis yields 770,327 gap-sites from TopHat alignments and 1,065,596 from STAR alignments. Both alignment algorithms, TopHat and STAR, report gap-sites with considerable false discovery rate, which can drastically be reduced by validation with gqs and wgis. PMID:28545234

The Scientific Method, Diagnostic Bayes, and How to Detect Epistemic Errors

NASA Astrophysics Data System (ADS)

Vrugt, J. A.

2015-12-01

In the past decades, Bayesian methods have found widespread application and use in environmental systems modeling. Bayes theorem states that the posterior probability, P(H|D) of a hypothesis, H is proportional to the product of the prior probability, P(H) of this hypothesis and the likelihood, L(H|hat{D}) of the same hypothesis given the new/incoming observations, \\hat {D}. In science and engineering, H often constitutes some numerical simulation model, D = F(x,.) which summarizes using algebraic, empirical, and differential equations, state variables and fluxes, all our theoretical and/or practical knowledge of the system of interest, and x are the d unknown parameters which are subject to inference using some data, \\hat {D} of the observed system response. The Bayesian approach is intimately related to the scientific method and uses an iterative cycle of hypothesis formulation (model), experimentation and data collection, and theory/hypothesis refinement to elucidate the rules that govern the natural world. Unfortunately, model refinement has proven to be very difficult in large part because of the poor diagnostic power of residual based likelihood functions tep{gupta2008}. This has inspired te{vrugt2013} to advocate the use of 'likelihood-free' inference using approximate Bayesian computation (ABC). This approach uses one or more summary statistics, S(\\hat {D}) of the original data, \\hat {D} designed ideally to be sensitive only to one particular process in the model. Any mismatch between the observed and simulated summary metrics is then easily linked to a specific model component. A recurrent issue with the application of ABC is self-sufficiency of the summary statistics. In theory, S(.) should contain as much information as the original data itself, yet complex systems rarely admit sufficient statistics. In this article, we propose to combine the ideas of ABC and regular Bayesian inference to guarantee that no information is lost in diagnostic model evaluation. This hybrid approach, coined diagnostic Bayes, uses the summary metrics as prior distribution and original data in the likelihood function, or P(x|\\hat {D}) ∝ P(x|S(\\hat {D})) L(x|\\hat {D}). A case study illustrates the ability of the proposed methodology to diagnose epistemic errors and provide guidance on model refinement.

Fractional Yields Inferred from Halo and Thick Disk Stars

NASA Astrophysics Data System (ADS)

Caimmi, R.

2013-12-01

Linear [Q/H]-[O/H] relations, Q = Na, Mg, Si, Ca, Ti, Cr, Fe, Ni, are inferred from a sample (N=67) of recently studied FGK-type dwarf stars in the solar neighbourhood including different populations (Nissen and Schuster 2010, Ramirez et al. 2012), namely LH (N=24, low-α halo), HH (N=25, high-α halo), KD (N=16, thick disk), and OL (N=2, globular cluster outliers). Regression line slope and intercept estimators and related variance estimators are determined. With regard to the straight line, [Q/H]=a_{Q}[O/H]+b_{Q}, sample stars are displayed along a "main sequence", [Q,O] = [a_{Q},b_{Q},Δ b_{Q}], leaving aside the two OL stars, which, in most cases (e.g. Na), lie outside. The unit slope, a_{Q}=1, implies Q is a primary element synthesised via SNII progenitors in the presence of a universal stellar initial mass function (defined as simple primary element). In this respect, Mg, Si, Ti, show hat a_{Q}=1 within ∓2hatσ_ {hat a_{Q}}; Cr, Fe, Ni, within ∓3hatσ_{hat a_{Q}}; Na, Ca, within ∓ rhatσ_{hat a_{Q}}, r>3. The empirical, differential element abundance distributions are inferred from LH, HH, KD, HA = HH + KD subsamples, where related regression lines represent their theoretical counterparts within the framework of simple MCBR (multistage closed box + reservoir) chemical evolution models. Hence, the fractional yields, hat{p}_{Q}/hat{p}_{O}, are determined and (as an example) a comparison is shown with their theoretical counterparts inferred from SNII progenitor nucleosynthesis under the assumption of a power-law stellar initial mass function. The generalized fractional yields, C_{Q}=Z_{Q}/Z_{O}^{a_{Q}}, are determined regardless of the chemical evolution model. The ratio of outflow to star formation rate is compared for different populations in the framework of simple MCBR models. The opposite situation of element abundance variation entirely due to cosmic scatter is also considered under reasonable assumptions. The related differential element abundance distribution fits to the data, as well as its counterpart inferred in the opposite limit of instantaneous mixing in the presence of chemical evolution, while the latter is preferred for HA subsample.

A Role for Histone Deacetylases in the Cellular and Behavioral Mechanisms Underlying Learning and Memory

ERIC Educational Resources Information Center

Mahgoub, Melissa; Monteggia, Lisa M.

2014-01-01

Histone deacetylases (HDACs) are a family of chromatin remodeling enzymes that restrict access of transcription factors to the DNA, thereby repressing gene expression. In contrast, histone acetyltransferases (HATs) relax the chromatin structure allowing for an active chromatin state and promoting gene transcription. Accumulating data have…

Structure-Based Virtual Screening and Biochemical Evaluation for the Identification of Novel Trypanosoma Brucei Aldolase Inhibitors.

PubMed

Ferreira, Leonardo L G; Ferreira, Rafaela S; Palomino, David L; Andricopulo, Adriano D

2018-04-27

The glycolytic enzyme fructose-1,6-bisphosphate aldolase is a validated molecular target in human African trypanosomiasis (HAT) drug discovery, a neglected tropical disease (NTD) caused by the protozoan Trypanosoma brucei. Herein, a structure-based virtual screening (SBVS) approach to the identification of novel T. brucei aldolase inhibitors is described. Distinct molecular docking algorithms were used to screen more than 500,000 compounds against the X-ray structure of the enzyme. This SBVS strategy led to the selection of a series of molecules which were evaluated for their activity on recombinant T. brucei aldolase. The effort led to the discovery of structurally new ligands able to inhibit the catalytic activity the enzyme. The predicted binding conformations were additionally investigated in molecular dynamics simulations, which provided useful insights into the enzyme-inhibitor intermolecular interactions. The molecular modeling results along with the enzyme inhibition data generated practical knowledge to be explored in further structure-based drug design efforts in HAT drug discovery. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Experimental and computational investigation of the tip clearance flow in a transonic axial compressor rotor

NASA Astrophysics Data System (ADS)

Suder, Kenneth L.; Celestina, Mark L.

1995-06-01

Experimental and computational techniques are used to investigate tip clearance flows in a transonic axial compressor rotor at design and part speed conditions. Laser anemometer data acquired in the endwall region are presented for operating conditions near peak efficiency and near stall at 100% design speed and at near peak efficiency at 60% design speed. The role of the passage shock/leakage vortex interaction in generating endwall blockage is discussed. As a result of the shock/vortex interaction at design speed, the radial influence of the tip clearance flow extends to 20 times the physical tip clearance height. At part speed, in the absence of the shock, the radial extent is only 5 times the tip clearance height. Both measurements and analysis indicate that under part-speed operating conditions a second vortex, which does not originate from the tip leakage flow, forms in the endwall region within the blade passage and exits the passage near midpitch. Mixing of the leakage vortex with primary flow downstream of the rotor at both design and part speed conditions is also discussed.

Experimental and Computational Investigation of the Tip Clearance Flow in a Transonic Axial Compressor Rotor

NASA Technical Reports Server (NTRS)

Suder, Kenneth L.; Celestina, Mark L.

1995-01-01

Experimental and computational techniques are used to investigate tip clearance flows in a transonic axial compressor rotor at design and part speed conditions. Laser anemometer data acquired in the endwall region are presented for operating conditions near peak efficiency and near stall at 100% design speed and at near peak efficiency at 60% design speed. The role of the passage shock/leakage vortex interaction in generating endwall blockage is discussed. As a result of the shock/vortex interaction at design speed, the radial influence of the tip clearance flow extends to 20 times the physical tip clearance height. At part speed, in the absence of the shock, the radial extent is only 5 times the tip clearance height. Both measurements and analysis indicate that under part-speed operating conditions a second vortex, which does not originate from the tip leakage flow, forms in the endwall region within the blade passage and exits the passage near midpitch. Mixing of the leakage vortex with primary flow downstream of the rotor at both design and part speed conditions is also discussed.

[Hemodynamic changes in portal system after transjugular intrahepatic portosystemic shunts (TIPS)].

PubMed

Li, W; Xiao, Y; Xu, H

1995-08-01

In this study portal venous flow (PVF), splenic venous flow (SPVF), hepatic artery volume (HAV), and portal pressure were measured before and after TIPS in 11 patients with portal hypertension. The results were compared with those of normal controls. In the normal controls PVF averaged 947.2 +/- 133.4ml/min, SPVF 239.6 +/- 116.3ml/min, and HAV 241.6 +/- 78.8ml/min. In the TIPS group before and after TIPS, PVF was 883.2 +/- 233.4ml/min vs. 958.7 +/- 185.2ml/min; SPVF was 448.9 +/- 111.6ml/min vs. 333.1 +/- 101.5ml/min; HVP was 225.3 +/- 122.7ml/min vs. 249.3 +/- 103.8ml/min. Portal pressure dropped from 3.94kPa +/- 0.46 to 2.52 +/- 0.60kPa after TIPS. We conclude that in patients after TIPS portal pressure drops blood flow in the truck of the portal vein increases, flow of hepatic tissue decreases, and blood flow in splenic vein decreases. Blood flow in hepatic aftery was not significantly changed.

Shear Wave Elastography of the Spleen for Monitoring Transjugular Intrahepatic Portosystemic Shunt Function: A Pilot Study.

PubMed

Gao, Jing; Zheng, Xiao; Zheng, Yuan-Yi; Zuo, Guo-Qing; Ran, Hai-Tao; Auh, Yong Ho; Waldron, Levi; Chan, Tiffany; Wang, Zhi-Gang

2016-05-01

To assess the feasibility of splenic shear wave elastography in monitoring transjugular intrahepatic portosystemic shunt (TIPS) function. We measured splenic shear wave velocity (SWV), main portal vein velocity (PVV), and splenic vein velocity (SVV) in 33 patients 1 day before and 3 days to 12 months after TIPS placement. We also measured PVV, SVV, and SWV in 10 of 33 patients with TIPS dysfunction 1 day before and 3 to 6 days after TIPS revision. Analyses included differences in portosystemic pressure gradient (PPG), PVV, SVV, and mean SWV before and after TIPS procedures; comparison of median SWV before and after TIPS procedures; differences in PVV, SVV, and SWV before and at different times up to 12 months after TIPS placement; accuracy of PVV, SVV, and SWV in determining TIPS dysfunction; and correlation between PPG and SWV. During 12 months of follow-up, 23 of 33 patients had functioning TIPS, and 10 had TIPS dysfunction. The median SWV was significantly different before and after primary TIPS placement (3.60 versus 3.05 m/s; P = .005), as well as before and after revision (3.73 versus 3.06 m/s; P = .003). The PPG, PVV, and SVV were also significantly different before and after TIPS placement and revision (P < .001). The PPG and SWV decreased, whereas PVV and SVV increased, after successful TIPS procedures. A positive correlation was observed between PPG and SWV (r = 0.70; P < .001), and a negative correlation was observed between PPG and PVV and SVV (r = -0.65; P < .001). The areas under the receiver operating characteristic curve for PVV, SVV, and SWV in determining TIPS dysfunction were 0.82, 0.84, and 0.81, respectively. Splenic SWV is compatible with splenoportal venous velocity in quantitatively monitoring TIPS function and determining TIPS dysfunction. © 2016 by the American Institute of Ultrasound in Medicine.

Rotorcraft In-Plane Noise Reduction Using Active/Passive Approaches with Induced Vibration Tracking

NASA Astrophysics Data System (ADS)

Chia, Miang Hwee

A comprehensive study of the use of active and passive approaches for in-plane noise reduction, including the vibrations induced during noise reduction, was conducted on a hingeless rotor configuration resembling the MBB BO-105 rotor. First, a parametric study was performed to examine the effects of rotor blade stiffness on the vibration and noise reduction performance of a 20%c plain trailing edge flap and a 1.5%c sliding microflap. This was accomplished using a comprehensive code AVINOR (for Active VIbration and NOise Reduction). A two-dimensional unsteady reduced order aerodynamic model (ROM), using the Rational Function Approximation approach and CFD-based oscillatory aerodynamic load data, was used in the comprehensive code. The study identified a hingeless blade configuration with torsional frequency of 3.17/rev as an optimum configuration for studying vibration and noise reduction using on-blade control devices such as flaps or microflaps. Subsequently, a new suite of computational tools capable of predicting in-plane low frequency sound pressure level (LFSPL) rotorcraft noise and its control was developed, replacing the acoustic module WOPWOP in AVINOR with a new acoustic module HELINOIR (for HELIcopter NOIse Reduction), which overcomes certain limitations associated with WOPWOP. The new suite, consisting of the AVINOR/HELINOIR combination, was used to study active flaps, as well as microflaps operating in closed-loop mode for in-plane noise reduction. An alternative passive in-plane noise reduction approach using modification to the blade tip in the 10%R outboard region was also studied. The new suite consisting of the AVINOR/HELINOIR combination based on a compact aeroacoustic model was validated by comparing with wind tunnel test results, and subsequently verified by comparing with computational results. For active control, the in-plane noise reduction obtained with a single 20%c plain trailing edge flap during level flight at a moderate advance ratio was examined. Different configurations of far-field and near-field feedback microphone locations were examined to develop a fundamental understanding of the feedback microphone locations on the noise reduction process A near-field microphone located on the tip of a nose boom was found to produce a LFSPL reduction of up to 6dB. However, this noise reduction was accompanied by an out-of-plane noise increase of 18dB and 60% increase in vertical hub shear. For passive control, three tip geometries having sweep, dihedral, and anhedral, were considered. The tip dihedral reduced LFSPL by up to 2dB without a vibratory load penalty. However, this was accompanied by an increase in the mid frequency sound pressure levels (MFSPL). The tip sweep and tip anhedral produced an increase in in-plane LFSPL below the horizon. A comparison of the active and passive approaches indicated that active approaches implemented by a plain flap with a feedback microphone located on the nose boom is superior to the passive control approaches. However, there is a general trade-off between LFSPL reduction, MFSPL generation and vibratory hub loads induced by noise control.

`Up-regulation of histone acetylation induced by social defeat mediates the conditioned rewarding effects of cocaine.

PubMed

Montagud-Romero, S; Montesinos, J; Pascual, M; Aguilar, M A; Roger-Sanchez, C; Guerri, C; Miñarro, J; Rodríguez-Arias, M

2016-10-03

Social defeat (SD) induces a long-lasting increase in the rewarding effects of psychostimulants measured using the self-administration and conditioned place procedures (CPP). However, little is known about the epigenetic changes induced by social stress and about their role in the increased response to the rewarding effects of psychostimulants. Considering that histone acetylation regulates transcriptional activity and contributes to drug-induced behavioral changes, we addressed the hypothesis that SD induces transcriptional changes by histone modifications associated with the acquisition of place conditioning. After a fourth defeat, H3(K9) acetylation was decreased in the hippocampus, while there was an increase of HAT and a decrease of HDAC levels in the cortex. Three weeks after the last defeat, mice displayed an increase in histone H4(K12) acetylation and an upregulation of histone acetyl transferase (HAT) activity in the hippocampus. In addition, H3(K4)me3, which is closely associated with transcriptional initiation, was also augmented in the hippocampus three weeks after the last defeat. Inhibition of HAT by curcumin (100mg/kg) before each SD blocked the increase in the conditioned reinforcing effects of 1mg/kg of cocaine, while inhibition of HDAC by valproic acid (500mg/kg) before social stress potentiated cocaine-induced CPP. Preference was reinstated when animals received a priming dose of 0.5mg/kg of cocaine, an effect that was absent in untreated defeated mice. These results suggest that the experience of SD induces chromatin remodeling, alters histone acetylation and methylation, and modifies the effects of cocaine on place conditioning. They also point to epigenetic mechanisms as potential avenues leading to new treatments for the long-term effects of social stress on drug addiction. Copyright © 2016 Elsevier Inc. All rights reserved.

Interplay between chromatin modulators and histone acetylation regulates the formation of accessible chromatin in the upstream regulatory region of fission yeast fbp1.

PubMed

Adachi, Akira; Senmatsu, Satoshi; Asada, Ryuta; Abe, Takuya; Hoffman, Charles S; Ohta, Kunihiro; Hirota, Kouji

2018-05-03

Numerous noncoding RNA transcripts are detected in eukaryotic cells. Noncoding RNAs transcribed across gene promoters are involved in the regulation of mRNA transcription via chromatin modulation. This function of noncoding RNA transcription was first demonstrated for the fission yeast fbp1 gene, where a cascade of noncoding RNA transcription events induces chromatin remodeling to facilitate transcription factor binding. We recently demonstrated that the noncoding RNAs from the fbp1 upstream region facilitate binding of the transcription activator Atf1 and thereby promote histone acetylation. Histone acetylation by histone acetyl transferases (HATs) and ATP-dependent chromatin remodelers (ADCRs) are implicated in chromatin remodeling, but the interplay between HATs and ADCRs in this process has not been fully elucidated. Here, we examine the roles played by two distinct ADCRs, Snf22 and Hrp3, and by the HAT Gcn5 in the transcriptional activation of fbp1. Snf22 and Hrp3 redundantly promote disassembly of chromatin in the fbp1 upstream region. Gcn5 critically contributes to nucleosome eviction in the absence of either Snf22 or Hrp3, presumably by recruiting Hrp3 in snf22∆ cells and Snf22 in hrp3∆ cells. Conversely, Gcn5-dependent histone H3 acetylation is impaired in snf22∆/hrp3∆ cells, suggesting that both redundant ADCRs induce recruitment of Gcn5 to the chromatin array in the fbp1 upstream region. These results reveal a previously unappreciated interplay between ADCRs and histone acetylation in which histone acetylation facilitates recruitment of ADCRs, while ADCRs are required for histone acetylation.

Catalytic alkylation of remote C-H bonds enabled by proton-coupled electron transfer

NASA Astrophysics Data System (ADS)

Choi, Gilbert J.; Zhu, Qilei; Miller, David C.; Gu, Carol J.; Knowles, Robert R.

2016-11-01

Despite advances in hydrogen atom transfer (HAT) catalysis, there are currently no molecular HAT catalysts that are capable of homolysing the strong nitrogen-hydrogen (N-H) bonds of N-alkyl amides. The motivation to develop amide homolysis protocols stems from the utility of the resultant amidyl radicals, which are involved in various synthetically useful transformations, including olefin amination and directed carbon-hydrogen (C-H) bond functionalization. In the latter process—a subset of the classical Hofmann-Löffler-Freytag reaction—amidyl radicals remove hydrogen atoms from unactivated aliphatic C-H bonds. Although powerful, these transformations typically require oxidative N-prefunctionalization of the amide starting materials to achieve efficient amidyl generation. Moreover, because these N-activating groups are often incorporated into the final products, these methods are generally not amenable to the direct construction of carbon-carbon (C-C) bonds. Here we report an approach that overcomes these limitations by homolysing the N-H bonds of N-alkyl amides via proton-coupled electron transfer. In this protocol, an excited-state iridium photocatalyst and a weak phosphate base cooperatively serve to remove both a proton and an electron from an amide substrate in a concerted elementary step. The resultant amidyl radical intermediates are shown to promote subsequent C-H abstraction and radical alkylation steps. This C-H alkylation represents a catalytic variant of the Hofmann-Löffler-Freytag reaction, using simple, unfunctionalized amides to direct the formation of new C-C bonds. Given the prevalence of amides in pharmaceuticals and natural products, we anticipate that this method will simplify the synthesis and structural elaboration of amine-containing targets. Moreover, this study demonstrates that concerted proton-coupled electron transfer can enable homolytic activation of common organic functional groups that are energetically inaccessible using traditional HAT-based approaches.

Catalytic alkylation of remote C-H bonds enabled by proton-coupled electron transfer.

PubMed

Choi, Gilbert J; Zhu, Qilei; Miller, David C; Gu, Carol J; Knowles, Robert R

2016-11-10

Despite advances in hydrogen atom transfer (HAT) catalysis, there are currently no molecular HAT catalysts that are capable of homolysing the strong nitrogen-hydrogen (N-H) bonds of N-alkyl amides. The motivation to develop amide homolysis protocols stems from the utility of the resultant amidyl radicals, which are involved in various synthetically useful transformations, including olefin amination and directed carbon-hydrogen (C-H) bond functionalization. In the latter process-a subset of the classical Hofmann-Löffler-Freytag reaction-amidyl radicals remove hydrogen atoms from unactivated aliphatic C-H bonds. Although powerful, these transformations typically require oxidative N-prefunctionalization of the amide starting materials to achieve efficient amidyl generation. Moreover, because these N-activating groups are often incorporated into the final products, these methods are generally not amenable to the direct construction of carbon-carbon (C-C) bonds. Here we report an approach that overcomes these limitations by homolysing the N-H bonds of N-alkyl amides via proton-coupled electron transfer. In this protocol, an excited-state iridium photocatalyst and a weak phosphate base cooperatively serve to remove both a proton and an electron from an amide substrate in a concerted elementary step. The resultant amidyl radical intermediates are shown to promote subsequent C-H abstraction and radical alkylation steps. This C-H alkylation represents a catalytic variant of the Hofmann-Löffler-Freytag reaction, using simple, unfunctionalized amides to direct the formation of new C-C bonds. Given the prevalence of amides in pharmaceuticals and natural products, we anticipate that this method will simplify the synthesis and structural elaboration of amine-containing targets. Moreover, this study demonstrates that concerted proton-coupled electron transfer can enable homolytic activation of common organic functional groups that are energetically inaccessible using traditional HAT-based approaches.

Genotoxicity profile of fexinidazole--a drug candidate in clinical development for human African trypanomiasis (sleeping sickness).

PubMed

Tweats, David; Bourdin Trunz, Bernadette; Torreele, Els

2012-09-01

The parasitic disease human African trypanomiasis (HAT), also known as sleeping sickness, is a highly neglected fatal condition endemic in sub-Saharan Africa, which is poorly treated with medicines that are toxic, no longer effective or very difficult to administer. New, safe, effective and easy-to-use treatments are urgently needed. Many nitroimidazoles possess antibacterial and antiprotozoal activity and examples such as tinidazole are used to treat trichomoniasis and guardiasis, but concerns about toxicity including genotoxicity limit their usefulness. Fexinidazole, a 2-substituted 5-nitroimidazole rediscovered by the Drugs for Neglected Diseases initiative (DNDi) after extensive compound mining of public and pharmaceutical company databases, has the potential to become a short-course, safe and effective oral treatment, curing both acute and chronic HAT. This paper describes the genotoxicity profile of fexinidazole and its two active metabolites, the sulfoxide and sulfone derivatives. All the three compounds are mutagenic in the Salmonella/Ames test; however, mutagenicity is either attenuated or lost in Ames Salmonella strains that lack one or more nitroreductase(s). It is known that these enzymes can nitroreduce compounds with low redox potentials, whereas their mammalian cell counterparts cannot, under normal conditions. Fexinidazole and its metabolites have low redox potentials and all mammalian cell assays to detect genetic toxicity, conducted for this study either in vitro (micronucleus test in human lymphocytes) or in vivo (ex vivo unscheduled DNA synthesis in rats; bone marrow micronucleus test in mice), were negative. Thus, fexinidazole does not pose a genotoxic hazard to patients and represents a promising drug candidate for HAT. Fexinidazole is expected to enter Phase II clinical trials in 2012.

Wacław Szybalski's contribution to immunotherapy: HGPRT mutation & HAT selection as first steps to gene therapy and hybrid techniques in mammalian cells.

PubMed

Bigda, Jacek J; Koszałka, Patrycja

2013-08-10

In this report we describe Wacław Szybalski's fundamental contribution to gene therapy and immunotherapy. His 1962 PNAS paper (Szybalska and Szybalski, 1962) documented the first successful gene repair in mammalian cells. Furthermore, this was also the first report on the HAT selection method used later in many applications. Most importantly, somatic cell fusion and HAT selection were subsequently used to develop monoclonal antibody technology, which contributed significantly to the progress of today's medicine. Copyright © 2013 Elsevier B.V. All rights reserved.

Virtual sorting hat™ technology for the matching of candidates to residency training programs.

PubMed

Gouda, Pishoy; Cormican, Martin

2016-12-01

The matching of medical students and trainees to appropriate training programmes poses many challenges, including financial cost and applicant stress. There are few studies that have examined alternatives to the current process of matching candidates to specialist training. Case reports from Hogwarts School of Witchcraft and Wizardry ™ have suggested that wearable technology may be used to assign individuals with particular sets of skills and virtues to an appropriate house. Investigators developed a modified sorting hat in the form of an online, cross-sectional survey. The virtual sorting hat was delivered to medical students at the National University of Ireland, Galway, and medical practitioners practising in the associated hospitals and communities. Pearson's chi-square was used to demonstrate correlations between the allocation of participants to Hogwarts' houses by virtual sorting hat technology and expressed higher specialist training preference. Virtual sorting hat technology, applied to medical undergraduates and postgraduates, allocated most participants to Hufflepuff ™ (44%) and Ravenclaw ™ (32%). Allocation to Gryffindor was associated with preference for surgery and allocation to Slytherin ™ with preference for psychiatry. Virtual sorting hat technology requires significant refinement before application to medical muggles ™ . © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

HAT-P-50b, HAT-P-51b, HAT-P-52b, and HAT-P-53b: Three Transiting Hot Jupiters and a Transiting Hot Saturn From the HATNet Survey

NASA Astrophysics Data System (ADS)

Hartman, J. D.; Bhatti, W.; Bakos, G. Á.; Bieryla, A.; Kovács, G.; Latham, D. W.; Csubry, Z.; de Val-Borro, M.; Penev, K.; Buchhave, L. A.; Torres, G.; Howard, A. W.; Marcy, G. W.; Johnson, J. A.; Isaacson, H.; Sato, B.; Boisse, I.; Falco, E.; Everett, M. E.; Szklenar, T.; Fulton, B. J.; Shporer, A.; Kovács, T.; Hansen, T.; Béky, B.; Noyes, R. W.; Lázár, J.; Papp, I.; Sári, P.

2015-12-01

We report the discovery and characterization of four transiting exoplanets by the HATNet survey. The planet HAT-P-50b has a mass of 1.35 {M}{{J}} and radius of 1.29 {R}{{J}}, and orbits a bright (V=11.8 mag) M=1.27 {M}⊙ , R=1.70 {R}⊙ star every P=3.1220 days. The planet HAT-P-51b has a mass of 0.31 {M}{{J}} and radius of 1.29 {R}{{J}}, and orbits a V=13.4 mag, M=0.98 {M}⊙ , R=1.04 {R}⊙ star with a period of P=4.2180 days. The planet HAT-P-52b has a mass of 0.82 {M}{{J}} and radius of 1.01 {R}{{J}}, and orbits a V=14.1 mag, M=0.89 {M}⊙ , R=0.89 {R}⊙ star with a period of P=2.7536 days. The planet HAT-P-53b has a mass of 1.48 {M}{{J}} and radius of 1.32 {R}{{J}}, and orbits a V=13.7 mag, M=1.09 {M}⊙ , R=1.21 {R}⊙ star with a period of P=1.9616 days. All four planets are consistent with having circular orbits and have masses and radii measured to better than 10% precision. The low stellar jitter and favorable {R}p/{R}\\star ratio for HAT-P-51 make it a promising target for measuring the Rossiter-McLaughlin effect for a Saturn-mass planet. Based on observations obtained with the Hungarian-made Automated Telescope Network. Based on observations obtained at the W. M. Keck Observatory, which is operated by the University of California and the California Institute of Technology. Keck time has been granted by NOAO (A245Hr) and NASA (N154Hr, N130Hr). Based on data collected at Subaru Telescope, which is operated by the National Astronomical Observatory of Japan. Based on observations made with the Nordic Optical Telescope, operated on the island of La Palma jointly by Denmark, Finland, Iceland, Norway, Sweden, in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias. Based on observations obtained with the Tillinghast Reflector 1.5 m telescope and the 1.2 m telescope, both operated by the Smithsonian Astrophysical Observatory at the Fred Lawrence Whipple Observatory in AZ. Based on radial velocities obtained with the Sophie spectrograph mounted on the 1.93 m telescope at Observatoire de Haute-Provence. Based on observations obtained with facilities of the Las Cumbres Observatory Global Telescope.

Overview of a Preliminary Destination Mission Concept for a Human Orbital Mission to the Martial Moons

NASA Technical Reports Server (NTRS)

Mazanek, D. D.; Abell, P. A.; Antol, J.; Barbee, B. W.; Beaty, D. W.; Bass, D. S.; Castillo-Rogez, J. C.; Coan, D. A.; Colaprete, A.; Daugherty, K. J.;

Sleeping Sickness in the 'Omics Era.

PubMed

Tiberti, Natalia; Sanchez, Jean-Charles

2018-03-08

Sleeping sickness is a neglected tropical disease caused by Trypanosoma brucei parasites, affecting the poorest communities in sub-Saharan Africa. The great efforts done by the scientific community, local governments, and non-governmental organizations (NGOs) via active patients' screening, vector control, and introduction of improved treatment regimens have significantly contributed to the reduction of human African trypanosomiasis (HAT) incidence during the last 15 years. Consequently, the WHO has announced the objective of HAT elimination as a public health problem by 2020. Studies at both parasite and host levels have improved our understanding of the parasite biology and the mechanisms of parasite interaction with its mammalian host. In this review, the impact that 'omics studies have had on sleeping sickness by revealing novel properties of parasite's subcellular organelles are summarized, by highlighting changes induced in the host during the infection and by proposing potential disease markers and therapeutic targets. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analysis of Geophysical Data Bases and Models for Spacecraft Interactions.

DTIC Science & Technology

1986-10-31

Comp. Phys., 12, 124 (1973). 4. A. B. Langdon and B. F. Lasinski, in "Methods in Computational Physics", Volume 9, B. Alder et al, eds., Academic Press...ADA174441. 7. Chen, F.F., Electric Probes, in "Plasma Diagnostic Techniques", ed. by R.H. Huddlestone and L.L. Lennard, Academic Press, N.Y. 1965. 8...q~. i-o raf t p4)51 t i i n , the -"fj’P I f o,A it** t hat p< in1 the spa-Puraft ’- Attitude anid sp, p A~ta t tie I’ ielt iti1,ai .,f IheP maqn e

A Scalable Heuristic for Viral Marketing Under the Tipping Model

DTIC Science & Technology

2013-09-01

removal of high-degree nodes. The rest of the paper is organized as follows. In Section 2, we provide formal definitions of the tipping model. This is...that must be activated for it to become activate as well. A Scalable Heuristic for Viral Marketing Under the Tipping Model 3 Definition 1 (Threshold...returns a set of active nodes after one time step. Definition 2 (Activation Function) Given a threshold function, θ, an ac- tivation function Aθ maps

An Interprofessional Web-Based Resource for Health Professions Preceptors

PubMed Central

McLeod, Elizabeth; Kwong, Mona; Tidball, Glynnis; Collins, John; Neufeld, Lois; Drynan, Donna

2012-01-01

Objective. To develop a Web-based preceptor education resource for healthcare professionals and evaluate its usefulness. Methods. Using an open source platform, 8 online modules called “E-tips for Practice Education” (E-tips) were developed that focused on topics identified relevant across healthcare disciplines. A cross-sectional survey design was used to evaluate the online resource. Ninety preceptors from 10 health disciplines affiliated with the University of British Columbia evaluated the E-tips. Results. The modules were well received by preceptors, with all participants indicating that they would recommend these modules to their colleagues, over 80% indicating the modules were very to extremely applicable, and over 60% indicating that E-tips had increased their confidence in their ability to teach. Conclusion. Participants reported E-tips to be highly applicable to their teaching role as preceptors. Given their multidisciplinary focus, these modules address a shared language and ideas about clinical teaching among those working in multi-disciplinary settings. PMID:23193332

Turbine blade tip flow discouragers

DOEpatents

Bunker, Ronald Scott

2000-01-01

A turbine assembly comprises a plurality of rotating blade portions in a spaced relation with a stationery shroud. The rotating blade portions comprise a root section, a tip portion and an airfoil. The tip portion has a pressure side wall and a suction side wall. A number of flow discouragers are disposed on the blade tip portion. In one embodiment, the flow discouragers extend circumferentially from the pressure side wall to the suction side wall so as to be aligned generally parallel to the direction of rotation. In an alternative embodiment, the flow discouragers extend circumferentially from the pressure side wall to the suction side wall so as to be aligned at an angle in the range between about 0.degree. to about 60.degree. with respect to a reference axis aligned generally parallel to the direction of rotation. The flow discouragers increase the flow resistance and thus reduce the flow of hot gas flow leakage for a given pressure differential across the blade tip portion so as to improve overall turbine efficiency.

Clinical profiles, disease outcome and co-morbidities among T. b. rhodesiense sleeping sickness patients in Uganda.

PubMed

Kato, Charles D; Nanteza, Ann; Mugasa, Claire; Edyelu, Andrew; Matovu, Enock; Alibu, Vincent P

2015-01-01

The acute form of Human African Trypanosomiasis (HAT, also known as Sleeping sickness) caused by Trypanosoma brucei rhodesiense has been shown to have a wide spectrum of focus specific clinical presentation and severity in East and Southern Africa. Indeed HAT occurs in regions endemic for other tropical diseases, however data on how these co-morbidities might complicate the clinical picture and affect disease outcome remains largely scanty. We here describe the clinical presentation, presence of co-infections, and how the latter impact on HAT prognosis. We carried out a retrospective analysis of clinical data from 258 sleeping sickness patients reporting to Lwala hospital between 2005 and 2012. The mean patient age was 28.6 years with a significant number of cases below 18 years (p< 0.0001). About 93.4% of the cases were diagnosed as late stage (p< 0.0001). The case fatality rate was 10.5% with post treatment reactive encephalopathys reported in 7.9% of the cases, of whom 36.8% eventually died. Fever was significantly (p = 0.045) higher in patients under 18 years. Of the early stage patients, 26.7% and 6.7% presented with late stage signs of sleep disorder and mental confusion respectively. Among the co-infections, malaria was significantly more prevalent (28.9%; p< 0.0001) followed by urinary tract infections (4.2%). Co-infections were present in 14.3% of in-hospital deaths, 38.5% of which were recorded as Malaria. Malaria was significantly more common in patients under 18 years (45.5%; p< 0.02), and was reported in 60% of the fatal cases in this age group. We show a wide spectrum of sleeping sickness clinical presentation and disease outcome that was apparently not significantly influenced by concurrent infections. It would thus be interesting to determine the host and/or parasite factors that might be responsible for the observed diverse clinical presentation.

Rural Health Care Workers and Local Residents Health Status in Yulong County of Yunnan Province China and Hat Yai City of Songkhla Mansion Thailand.

PubMed

Fanwei, Q U; Yanling, J; Chongsuvivatwong, V; Liabsuetrakul, T; Yan, L; Le, C; Runsheng, J

2017-01-01

To compare health status between Hat Yai city of Songkhla Province in Thailand and Yulong county of Yunnan province in China about rural health care workers and local residents, analyzing of both differences, learning from the advanced experience and practice of Thailand, adjusting policy, especially for the implementation of measures to improve the lack of human resources construction of Yulong County rural health, promote the level of rural health service of Lijiang. A qualitative study consisting of focus group discussions and individual in-depth interviews were conducted in Rural Health Care Workers and Local Residents Health Status in Yulong County of Yunnan Province China and Hat Yai City of Songkhla Mansion Thailand from. Compared to 41(100%) bachelor's degree of medical staffs in Hat Yai, this accounted only 94 (42%) bachelor's degree of medical staffs in Yulong county hospital, and 31 (12%)in townships hospitals. For medical workers in Hat Yai, they have at least one time on-job training per year, but for Yulong county, only 144 (29%)of the medical personnel participated in the training per year. Health expenditures of Yulong county was mainly borne by the local government, and medical insurance coverage rate is 217,107 (99%). Insurance average awareness of Hat Yai is 4449 (66.4%), Yulong County is 62,501 (28.5%), P<0.001, there are statistically significant differences between two cities. Thailand has good experience in training, well-paid, motivating and retaining talent for rural health human resources; multi-pronged, mechanism innovation, establish and perfect the system of human resources for health, is the essential way to solve the problem.

Contribution of the patient–horse relationship to substance use disorder treatment: Patients’ experiences

PubMed Central

Brenna, Ida H.; Kogstad, Norunn; Arnevik, Espen A.; Ravndal, Edle

2016-01-01

Background A good therapeutic relationship is a strong predictor of successful treatment in addiction and other psychological illness. Recent studies of horse-assisted therapy (HAT) have drawn attention to the importance of the client's relationship to the horse in psychotherapy. Few have reported on the patient's own perspective and none have reported specifically on the human–horse relationship in substance use disorder (SUD) treatment and its implications for health and well-being. Aim This article explores SUD patients’ own experience of their relationship with the horse and their perceptions of its contribution to their therapy. Methods As part of a large mixed-method study of HAT in SUD treatment, we used semi-structured interviews of eight patients to gather information about their experiences of HAT. From the data obtained, the relationship with the horse was found to be a significant part of participants’ HAT experience. It is therefore the subject of the current phenomenological study, in which thematic analysis was used to investigate how the participants constructed the reality of their relationship with the horse(s) and their perceptions of the consequences of that reality in SUD treatment. Results Participants’ own descriptions suggest that the horses were facilitators of a positive self-construct and provided important emotional support during treatment. Analysis found relationship with the horse, emotional effect, and mastery to be important and interrelated themes. The findings were interpreted within an attachment theory context. Conclusion The results appear to be consistent with key addiction treatment theories and with findings in HAT theoretical and empirical studies. They add to our understanding of the impact of HAT on SUD treatment. However, further research is needed into both the construct validity of the patient–horse therapeutic relationship and the possible variance within and between different populations. PMID:27291162

Detergent-Induced Stabilization and Improved 3D Map of the Human Heteromeric Amino Acid Transporter 4F2hc-LAT2

PubMed Central

Harder, Daniel; Stauffer, Mirko; Jeckelmann, Jean-Marc; Brühlmann, Béla; Rosell, Albert; Ilgü, Hüseyin; Kovar, Karin; Palacín, Manuel; Fotiadis, Dimitrios

2014-01-01

Human heteromeric amino acid transporters (HATs) are membrane protein complexes that facilitate the transport of specific amino acids across cell membranes. Loss of function or overexpression of these transporters is implicated in several human diseases such as renal aminoacidurias and cancer. HATs are composed of two subunits, a heavy and a light subunit, that are covalently connected by a disulphide bridge. Light subunits catalyse amino acid transport and consist of twelve transmembrane α-helix domains. Heavy subunits are type II membrane N-glycoproteins with a large extracellular domain and are involved in the trafficking of the complex to the plasma membrane. Structural information on HATs is scarce because of the difficulty in heterologous overexpression. Recently, we had a major breakthrough with the overexpression of a recombinant HAT, 4F2hc-LAT2, in the methylotrophic yeast Pichia pastoris. Microgram amounts of purified protein made possible the reconstruction of the first 3D map of a human HAT by negative-stain transmission electron microscopy. Here we report the important stabilization of purified human 4F2hc-LAT2 using a combination of two detergents, i.e., n-dodecyl-β-D-maltopyranoside and lauryl maltose neopentyl glycol, and cholesteryl hemisuccinate. The superior quality and stability of purified 4F2hc-LAT2 allowed the measurement of substrate binding by scintillation proximity assay. In addition, an improved 3D map of this HAT could be obtained. The detergent-induced stabilization of the purified human 4F2hc-LAT2 complex presented here paves the way towards its crystallization and structure determination at high-resolution, and thus the elucidation of the working mechanism of this important protein complex at the molecular level. PMID:25299125

Detergent-induced stabilization and improved 3D map of the human heteromeric amino acid transporter 4F2hc-LAT2.

PubMed

Meury, Marcel; Costa, Meritxell; Harder, Daniel; Stauffer, Mirko; Jeckelmann, Jean-Marc; Brühlmann, Béla; Rosell, Albert; Ilgü, Hüseyin; Kovar, Karin; Palacín, Manuel; Fotiadis, Dimitrios

2014-01-01

Human heteromeric amino acid transporters (HATs) are membrane protein complexes that facilitate the transport of specific amino acids across cell membranes. Loss of function or overexpression of these transporters is implicated in several human diseases such as renal aminoacidurias and cancer. HATs are composed of two subunits, a heavy and a light subunit, that are covalently connected by a disulphide bridge. Light subunits catalyse amino acid transport and consist of twelve transmembrane α-helix domains. Heavy subunits are type II membrane N-glycoproteins with a large extracellular domain and are involved in the trafficking of the complex to the plasma membrane. Structural information on HATs is scarce because of the difficulty in heterologous overexpression. Recently, we had a major breakthrough with the overexpression of a recombinant HAT, 4F2hc-LAT2, in the methylotrophic yeast Pichia pastoris. Microgram amounts of purified protein made possible the reconstruction of the first 3D map of a human HAT by negative-stain transmission electron microscopy. Here we report the important stabilization of purified human 4F2hc-LAT2 using a combination of two detergents, i.e., n-dodecyl-β-D-maltopyranoside and lauryl maltose neopentyl glycol, and cholesteryl hemisuccinate. The superior quality and stability of purified 4F2hc-LAT2 allowed the measurement of substrate binding by scintillation proximity assay. In addition, an improved 3D map of this HAT could be obtained. The detergent-induced stabilization of the purified human 4F2hc-LAT2 complex presented here paves the way towards its crystallization and structure determination at high-resolution, and thus the elucidation of the working mechanism of this important protein complex at the molecular level.

Atmospheric circulation of eccentric hot Jupiter HAT-P-2B

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

Lewis, Nikole K.; Showman, Adam P.; Fortney, Jonathan J.

The hot Jupiter HAT-P-2b has become a prime target for Spitzer Space Telescope observations aimed at understanding the atmospheric response of exoplanets on highly eccentric orbits. Here we present a suite of three-dimensional atmospheric circulation models for HAT-P-2b that investigate the effects of assumed atmospheric composition and rotation rate on global scale winds and thermal patterns. We compare and contrast atmospheric models for HAT-P-2b, which assume one and five times solar metallicity, both with and without TiO/VO as atmospheric constituents. Additionally we compare models that assume a rotation period of half, one, and two times the nominal pseudo-synchronous rotation period.more » We find that changes in assumed atmospheric metallicity and rotation rate do not significantly affect model predictions of the planetary flux as a function of orbital phase. However, models in which TiO/VO are present in the atmosphere develop a transient temperature inversion between the transit and secondary eclipse events that results in significant variations in the timing and magnitude of the peak of the planetary flux compared with models in which TiO/VO are omitted from the opacity tables. We find that no one single atmospheric model can reproduce the recently observed full orbit phase curves at 3.6, 4.5 and 8.0 μm, which is likely due to a chemical process not captured by our current atmospheric models for HAT-P-2b. Further modeling and observational efforts focused on understanding the chemistry of HAT-P-2b's atmosphere are needed and could provide key insights into the interplay between radiative, dynamical, and chemical processes in a wide range of exoplanet atmospheres.« less

Contribution of the patient-horse relationship to substance use disorder treatment: Patients' experiences.

PubMed

Kern-Godal, Ann; Brenna, Ida H; Kogstad, Norunn; Arnevik, Espen A; Ravndal, Edle

2016-01-01

A good therapeutic relationship is a strong predictor of successful treatment in addiction and other psychological illness. Recent studies of horse-assisted therapy (HAT) have drawn attention to the importance of the client's relationship to the horse in psychotherapy. Few have reported on the patient's own perspective and none have reported specifically on the human-horse relationship in substance use disorder (SUD) treatment and its implications for health and well-being. This article explores SUD patients' own experience of their relationship with the horse and their perceptions of its contribution to their therapy. As part of a large mixed-method study of HAT in SUD treatment, we used semi-structured interviews of eight patients to gather information about their experiences of HAT. From the data obtained, the relationship with the horse was found to be a significant part of participants' HAT experience. It is therefore the subject of the current phenomenological study, in which thematic analysis was used to investigate how the participants constructed the reality of their relationship with the horse(s) and their perceptions of the consequences of that reality in SUD treatment. Participants' own descriptions suggest that the horses were facilitators of a positive self-construct and provided important emotional support during treatment. Analysis found relationship with the horse, emotional effect, and mastery to be important and interrelated themes. The findings were interpreted within an attachment theory context. The results appear to be consistent with key addiction treatment theories and with findings in HAT theoretical and empirical studies. They add to our understanding of the impact of HAT on SUD treatment. However, further research is needed into both the construct validity of the patient-horse therapeutic relationship and the possible variance within and between different populations.

A SEARCH FOR ADDITIONAL PLANETS IN FIVE OF THE EXOPLANETARY SYSTEMS STUDIED BY THE NASA EPOXI MISSION

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

Ballard, Sarah; Charbonneau, David; Holman, Matthew J.

We present time series photometry and constraints on additional planets in five of the exoplanetary systems studied by the EPOCh (Extrasolar Planet Observation and Characterization) component of the NASA EPOXI mission: HAT-P-4, TrES-3, TrES-2, WASP-3, and HAT-P-7. We conduct a search of the high-precision time series for photometric transits of additional planets. We find no candidate transits with significance higher than our detection limit. From Monte Carlo tests of the time series using putative periods from 0.5 days to 7 days, we demonstrate the sensitivity to detect Neptune-sized companions around TrES-2, sub-Saturn-sized companions in the HAT-P-4, TrES-3, and WASP-3 systems,more » and Saturn-sized companions around HAT-P-7. We investigate in particular our sensitivity to additional transits in the dynamically favorable 3:2 and 2:1 exterior resonances with the known exoplanets: if we assume coplanar orbits with the known planets, then companions in these resonances with HAT-P-4b, WASP-3b, and HAT-P-7b would be expected to transit, and we can set lower limits on the radii of companions in these systems. In the nearly grazing exoplanetary systems TrES-3 and TrES-2, additional coplanar planets in these resonances are not expected to transit. However, we place lower limits on the radii of companions that would transit if the orbits were misaligned by 2.{sup 0}0 and 1.{sup 0}4 for TrES-3 and TrES-2, respectively.« less

Phosphorus and nitrate nitrogen in runoff following fertilizer application to turfgrass.

PubMed

Shuman, L M

2002-01-01

Intensively managed golf courses are perceived by the public as possibly adding nutrients to surface waters via surface transport. An experiment was designed to determine the transport of nitrate N and phosphate P from simulated golf course fairways of 'Tifway' bermudagrass [Cynodon dactylon (L.) Pers.]. Fertilizer treatments were 10-10-10 granular at three rates and rainfall events were simulated at four intervals after treatment (hours after treatment, HAT). Runoff volume was directly related to simulated rainfall amounts and soil moisture at the time of the event and varied from 24.3 to 43.5% of that added for the 50-mm events and 3.1 to 27.4% for the 25-mm events. The highest concentration and mass of phosphorus in runoff was during the first simulated rainfall event at 4 HAT with a dramatic decrease at 24 HAT and subsequent events. Nitrate N concentrations were low in the runoff water (approximately 0.5 mg L-1) for the first three runoff events and highest (approximately 1-1.5 mg L-1) at 168 HAT due to the time elapsed for conversion of ammonia to nitrate. Nitrate N mass was highest at the 4 and 24 HAT events and stepwise increases with rate were evident at 24 HAT. Total P transported for all events was 15.6 and 13.8% of that added for the two non-zero rates, respectively. Total nitrate N transported was 1.5 and 0.9% of that added for the two rates, respectively. Results indicate that turfgrass management should include applying minimum amounts of irrigation after fertilizer application and avoiding application before intense rain or when soil is very moist.

Measurements of Tip Vortices from a Full-Scale UH-60A Rotor by Retro- Reflective Background Oriented Schlieren and Stereo Photogrammetry

NASA Technical Reports Server (NTRS)

Schairer, Edward; Kushner, Laura K.; Heineck, James T.

2013-01-01

Positions of vortices shed by a full-scale UH-60A rotor in forward flight were measured during a test in the National Full- Scale Aerodynamics Complex at NASA Ames Research Center. Vortices in a region near the tip of the advancing blade were visualized from two directions by Retro-Reflective Background-Oriented Schlieren (RBOS). Correspondence of points on the vortex in the RBOS images from both cameras was established using epipolar geometry. The object-space coordinates of the vortices were then calculated from the image-plane coordinates using stereo photogrammetry. One vortex from the tip of the blade that had most recently passed was visible in most of the data. The visibility of the vortices was greatest at high thrust and low advance ratios. At these favorable conditions, vortices from the most recent passages of all four blades were detected. The vortex positions were in good agreement with PIV data for a case where PIV measurements were also made. RBOS and photogrammetry provided measurements of the angle at which each vortex passed through the PIV plane.

Epidemiology of Sleeping Sickness in Boffa (Guinea): Where Are the Trypanosomes?

PubMed Central

Kagbadouno, Moise Saa; Camara, Mamadou; Rouamba, Jeremi; Rayaisse, Jean-Baptiste; Traoré, Ibrahima Sory; Camara, Oumou; Onikoyamou, Mory Fassou; Courtin, Fabrice; Ravel, Sophie; de Meeûs, Thierry; Bucheton, Bruno; Jamonneau, Vincent; Solano, Philippe

2012-01-01

Human African Trypanosomiasis (HAT) in West Africa is a lethal, neglected disease caused by Trypanosoma brucei gambiense transmitted by the tsetse Glossina palpalis gambiensis. Although the littoral part of Guinea with its typical mangrove habitat is the most prevalent area in West Africa, very few data are available on the epidemiology of the disease in such biotopes. As part of a HAT elimination project in Guinea, we carried a cross-sectional study of the distribution and abundance of people, livestock, tsetse and trypanosomes in the focus of Boffa. An exhaustive census of the human population was done, together with spatial mapping of the area. Entomological data were collected, a human medical survey was organized together with a survey in domestic animals. In total, 45 HAT cases were detected out of 14445 people who attended the survey, these latter representing 50.9% of the total population. Potential additional carriers of T. b. gambiense were also identified by the trypanolysis test (14 human subjects and two domestic animals). No trypanosome pathogenic to animals were found, neither in the 874 tsetse dissected nor in the 300 domestic animals sampled. High densities of tsetse were found in places frequented by humans, such as pirogue jetties, narrow mangrove channels and watering points. The prevalence of T. b. gambiense in humans, combined to low attendance of the population at risk to medical surveys, and to an additional proportion of human and animal carriers of T. b. gambiense who are not treated, highlights the limits of strategies targeting HAT patients only. In order to stop T. b. gambiense transmission, vector control should be added to the current strategy of case detection and treatment. Such an integrated strategy will combine medical surveillance to find and treat cases, and vector control activities to protect people from the infective bites of tsetse. PMID:23272259

Governing for Enterprise Security

DTIC Science & Technology

2005-06-01

1 2 W hat Is Governing for Enterprise Security? ................................................ 5 3 W hat Are the Risks ...oversight and coordination 2. Areas of responsibility 3. Risk measurement 4. Monitoring and testing 5 . Reporting 6. Acceptable residual risk These...and O pportunities? ............................................... 10 3.1 Enterprise Risk and Enterprise Security Risk

A ginseng PgTIP1 gene whose protein biological activity related to Ser(128) residue confers faster growth and enhanced salt stress tolerance in Arabidopsis.

PubMed

Li, Jia; Cai, Weiming

2015-05-01

Water movement across cellular membranes is mostly regulated by aquaporins. A tonoplast intrinsic protein PgTIP1 from Panax ginseng has been found to play an important role in plant growth and development, and also in the response of plants to abiotic stress. However, the regulation of its function and activity remains unknown. To answer this question, mutated forms of PgTIP1 were made by replacing Ser(128) with Ala (named S128A) or Asp (named S128D), and also by replacing Thr(54) with Ala (named T54A) or Asp (named T54D). Then, wild type or mutated PgTIP1 was expressed in yeast and water transport was monitored in protoplasts. The substitution of Ser(128) abolished the water channel activity of PgTIP1, while the substitution of Thr(54) did not inhibit its activity. Moreover, the overexpression of PgTIP1 but not S128A or S128D in Arabidopsis significantly increased plant growth as determined by biomass production, it also had a beneficial effect on salt stress tolerance. Importantly, the overexpression of PgTIP1 led to the altered expression of stress-related genes, which made the plants more tolerant to salt stress. Our results demonstrated that PgTIP1 conferred faster growth and enhanced tolerance to salt in Arabidopsis, and that its biological activity related to Ser(128) residue. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

A spin-orbit alignment for the hot Jupiter HATS-3b

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

Addison, B. C.; Tinney, C. G.; Wright, D. J.

We have measured the alignment between the orbit of HATS-3b (a recently discovered, slightly inflated Hot Jupiter) and the spin axis of its host star. Data were obtained using the CYCLOPS2 optical-fiber bundle and its simultaneous calibration system feeding the UCLES spectrograph on the Anglo-Australian Telescope. The sky-projected spin-orbit angle of λ = 3° ± 25° was determined from spectroscopic measurements of the Rossiter-McLaughlin effect. This is the first exoplanet discovered through the HATSouth transit survey to have its spin-orbit angle measured. Our results indicate that the orbital plane of HATS-3b is consistent with being aligned to the spin axismore » of its host star. The low obliquity of the HATS-3 system, which has a relatively hot mid F-type host star, agrees with the general trend observed for Hot Jupiter host stars with effective temperatures >6250 K to have randomly distributed spin-orbit angles.« less

HAT-P-26b: A Neptune-mass exoplanet with a well-constrained heavy element abundance.

PubMed

Wakeford, Hannah R; Sing, David K; Kataria, Tiffany; Deming, Drake; Nikolov, Nikolay; Lopez, Eric D; Tremblin, Pascal; Amundsen, David S; Lewis, Nikole K; Mandell, Avi M; Fortney, Jonathan J; Knutson, Heather; Benneke, Björn; Evans, Thomas M

2017-05-12

A correlation between giant-planet mass and atmospheric heavy elemental abundance was first noted in the past century from observations of planets in our own Solar System and has served as a cornerstone of planet-formation theory. Using data from the Hubble and Spitzer Space Telescopes from 0.5 to 5 micrometers, we conducted a detailed atmospheric study of the transiting Neptune-mass exoplanet HAT-P-26b. We detected prominent H 2 O absorption bands with a maximum base-to-peak amplitude of 525 parts per million in the transmission spectrum. Using the water abundance as a proxy for metallicity, we measured HAT-P-26b's atmospheric heavy element content ([Formula: see text] times solar). This likely indicates that HAT-P-26b's atmosphere is primordial and obtained its gaseous envelope late in its disk lifetime, with little contamination from metal-rich planetesimals. Copyright © 2017, American Association for the Advancement of Science.

Neuromuscular Fatigue During a Modified Biering-Sørensen Test in Subjects with and Without Low Back Pain

PubMed Central

Pitcher, Mark J.; Behm, David G.; MacKinnon, Scott N.

2007-01-01

Studies employing modified Biering-Sørenson tests have reported that low back endurance is related to the potential for developing low back pain. Understanding the manner in which spinal musculature fatigues in people with and without LBP is necessary to gain insight into the sensitivity of the modified Biering-Sørenson test to differentiate back health. Twenty male volunteers were divided into a LBP group of subjects with current subacute or a history of LBP that limited their activity (n = 10) and a control group (n = 10). The median frequency of the fast Fourier transform was calculated from bilateral surface electromyography (EMG) of the upper lumbar erector spinae (ULES), lower lumbar erector spinae (LLES) and biceps femoris while maintaining a prescribed modified Biering-Sørensen test position and exerting isometric forces equivalent to 100, 120, 140 and 160% of the estimated mass of the head-arms-trunk (HAT) segment. Time to failure was also investigated across the percentages of HAT. Fatigue time decreased with increasing load and differences between groups increased as load increased, however these differences were not significant. Significant differences in the EMG median frequency between groups occurred in the right biceps femoris (p ≤ 0.05) with significant pairwise differences occurring at 140% for the left biceps femoris and at 160% for the right biceps femoris. There were significant pairwise differences at 120% for average EMG of the right biceps femoris and at 140% for the right ULES, and right and left biceps femoris (p ≤ 0.05). The modified Biering-Sørensen test as usually performed at 100% HAT is not sufficient to demonstrate significant differences between controls and subjects with varying degrees of mild back disability based on the Oswestry classification. Key pointsThe results do not wholly support the modified Biering-Sørensen test utilizing resistance of 100% HAT to discern differences in fatigue in subjects with mild low back pain.A greater activation of the biceps femoris by low back pain individuals probably contributed to the lack of significant differences in back fatigue times.The possibility exists that subjects with more sophisticated strategies could yield higher fatigue times despite inferior neuromuscular fatigue and the existence of low back pain. PMID:24149491

HATS-17b: A Transiting Compact Warm Jupiter in a 16.3 Day Circular Orbit

NASA Astrophysics Data System (ADS)

Brahm, R.; Jordán, A.; Bakos, G. Á.; Penev, K.; Espinoza, N.; Rabus, M.; Hartman, J. D.; Bayliss, D.; Ciceri, S.; Zhou, G.; Mancini, L.; Tan, T. G.; de Val-Borro, M.; Bhatti, W.; Csubry, Z.; Bento, J.; Henning, T.; Schmidt, B.; Rojas, F.; Suc, V.; Lázár, J.; Papp, I.; Sári, P.

2016-04-01

We report the discovery of HATS-17b, the first transiting warm Jupiter of the HATSouth network. HATS-17b transits its bright (V = 12.4) G-type ({M}\\star = 1.131+/- 0.030 {M}⊙ , {R}\\star = {1.091}-0.046+0.070 {R}⊙ ) metal-rich ([Fe/H] = +0.3 dex) host star in a circular orbit with a period of P = 16.2546 days. HATS-17b has a very compact radius of 0.777+/- 0.056 {R}{{J}} given its Jupiter-like mass of 1.338+/- 0.065 {M}{{J}}. Up to 50% of the mass of HATS-17b may be composed of heavy elements in order to explain its high density with current models of planetary structure. HATS-17b is the longest period transiting planet discovered to date by a ground-based photometric survey, and is one of the brightest transiting warm Jupiter systems known. The brightness of HATS-17 will allow detailed follow-up observations to characterize the orbital geometry of the system and the atmosphere of the planet. The HATSouth network is operated by a collaboration consisting of Princeton University (PU), the Max Planck Institute für Astronomie (MPIA), the Australian National University (ANU), and the Pontificia Universidad Católica de Chile (PUC). The station at Las Campanas Observatory (LCO) of the Carnegie Institute is operated by PU in conjunction with PUC, the station at the High Energy Spectroscopic Survey (H.E.S.S.) site is operated in conjunction with MPIA, and the station at Siding Spring Observatory (SSO) is operated jointly with ANU. This paper includes data gathered with the MPG 2.2 m telescope at the ESO Observatory in La Silla and with the 3.9 m AAT in Siding Spring Observatory. This paper uses observations obtained with facilities of the Las Cumbres Observatory Global Telescope. Based on observations taken with the HARPS spectrograph (ESO 3.6 m telescope at La Silla) under programme 097.C-0571.

PVT: An Efficient Computational Procedure to Speed up Next-generation Sequence Analysis

PubMed Central

2014-01-01

Background High-throughput Next-Generation Sequencing (NGS) techniques are advancing genomics and molecular biology research. This technology generates substantially large data which puts up a major challenge to the scientists for an efficient, cost and time effective solution to analyse such data. Further, for the different types of NGS data, there are certain common challenging steps involved in analysing those data. Spliced alignment is one such fundamental step in NGS data analysis which is extremely computational intensive as well as time consuming. There exists serious problem even with the most widely used spliced alignment tools. TopHat is one such widely used spliced alignment tools which although supports multithreading, does not efficiently utilize computational resources in terms of CPU utilization and memory. Here we have introduced PVT (Pipelined Version of TopHat) where we take up a modular approach by breaking TopHat’s serial execution into a pipeline of multiple stages, thereby increasing the degree of parallelization and computational resource utilization. Thus we address the discrepancies in TopHat so as to analyze large NGS data efficiently. Results We analysed the SRA dataset (SRX026839 and SRX026838) consisting of single end reads and SRA data SRR1027730 consisting of paired-end reads. We used TopHat v2.0.8 to analyse these datasets and noted the CPU usage, memory footprint and execution time during spliced alignment. With this basic information, we designed PVT, a pipelined version of TopHat that removes the redundant computational steps during ‘spliced alignment’ and breaks the job into a pipeline of multiple stages (each comprising of different step(s)) to improve its resource utilization, thus reducing the execution time. Conclusions PVT provides an improvement over TopHat for spliced alignment of NGS data analysis. PVT thus resulted in the reduction of the execution time to ~23% for the single end read dataset. Further, PVT designed for paired end reads showed an improved performance of ~41% over TopHat (for the chosen data) with respect to execution time. Moreover we propose PVT-Cloud which implements PVT pipeline in cloud computing system. PMID:24894600

Targeting Dysregulated Epigenetic Enzymes for Prostate Cancer Treatment

DTIC Science & Technology

2016-10-01

decreased protein levels of SIRT2 leads to the inability to down-regulate the hyper -acetylated form of p300. SIRT2-dependent deacetylation of p300...nature06546. 32. Thompson PR, Wang D, Wang L, Fulco M, Pediconi N, Zhang D, et al. Regulation of the p300 HAT domain via a novel activation loop . Nat Struct

Clare Soper's Hat: New Education Fellowship Correspondence between Bloomsbury and New Zealand, 1938-1946

ERIC Educational Resources Information Center

Middleton, Sue

2013-01-01

Broadening horizons beyond nations, transnational histories trace global flows connecting people and places. Historians have studied the New Education Fellowship (NEF) as a global network. Focused within the nation, research on New Zealand's involvement with NEF has emphasised how its activities before the Second World War impacted on the Labour…

CERT: Center of Excellence in Rotorcraft Technology

NASA Technical Reports Server (NTRS)

2002-01-01

The research objectives of this effort are to understand the physical processes that influence the formation of the tip vortex of a rotor in advancing flight, and to develop active and passive means of weakening the tip vortex during conditions when strong blade-vortex-interaction effects are expected. A combined experimental, analytical, and computational effort is being employed. Specifically, the following efforts are being pursued: 1. Analytical evaluation and design of combined elastic tailoring and active material actuators applicable to rotor blade tips. 2. Numerical simulations of active and passive tip devices. 3. LDV Measurement of the near and far wake behind rotors in forward flight.

The weakly coupled fractional one-dimensional Schrödinger operator with index 1 < α <= 2

NASA Astrophysics Data System (ADS)

Hatzinikitas, Agapitos N.

2010-12-01

Considering the space fractional Weyl operator hat{P}^{α } on the separable Hilbert space H=L^2({R},dx) we determine the asymptotic behavior of both the free Green's function and its variation with respect to energy in one dimension for bound states. Later, we specify the Birman-Schwinger representation for the Schrödinger operator hat{H}_g=K_{α }hat{P}^{α }+ghat{V} and extract the finite-rank portion which is essential for the asymptotic expansion of the ground state. Finally, we determine necessary and sufficient conditions for there to be a bound state for small coupling constant g.

Costs Of Using “Tiny Targets” to Control Glossina fuscipes fuscipes, a Vector of Gambiense Sleeping Sickness in Arua District of Uganda

PubMed Central

Shaw, Alexandra P. M.; Tirados, Inaki; Mangwiro, Clement T. N.; Esterhuizen, Johan; Lehane, Michael J.; Torr, Stephen J.; Kovacic, Vanja

2015-01-01

Introduction To evaluate the relative effectiveness of tsetse control methods, their costs need to be analysed alongside their impact on tsetse populations. Very little has been published on the costs of methods specifically targeting human African trypanosomiasis Methodology/Principal Findings In northern Uganda, a 250 km2 field trial was undertaken using small (0.5 X 0.25 m) insecticide-treated targets (“tiny targets”). Detailed cost recording accompanied every phase of the work. Costs were calculated for this operation as if managed by the Ugandan vector control services: removing purely research components of the work and applying local salaries. This calculation assumed that all resources are fully used, with no spare capacity. The full cost of the operation was assessed at USD 85.4 per km2, of which USD 55.7 or 65.2% were field costs, made up of three component activities (target deployment: 34.5%, trap monitoring: 10.6% and target maintenance: 20.1%). The remaining USD 29.7 or 34.8% of the costs were for preliminary studies and administration (tsetse surveys: 6.0%, sensitisation of local populations: 18.6% and office support: 10.2%). Targets accounted for only 12.9% of the total cost, other important cost components were labour (24.1%) and transport (34.6%). Discussion Comparison with the updated cost of historical HAT vector control projects and recent estimates indicates that this work represents a major reduction in cost levels. This is attributed not just to the low unit cost of tiny targets but also to the organisation of delivery, using local labour with bicycles or motorcycles. Sensitivity analyses were undertaken, investigating key prices and assumptions. It is believed that these costs are generalizable to other HAT foci, although in more remote areas, with denser vegetation and fewer people, costs would increase, as would be the case for other tsetse control techniques. PMID:25811956

Contact Whiskers for Millimeter Wave Diodes

NASA Technical Reports Server (NTRS)

Kerr, A. R.; Grange, J. A.; Lichtenberger, J. A.

1978-01-01

Several techniques are investigated for making short conical tips on wires (whiskers) used for contacting millimeter-wave Schottky diodes. One procedure, using a phosphoric and chromic acid etching solution (PCE), is found to give good results on 12 microns phosphor-bronze wires. Full cone angles of 60 degrees-80 degrees are consistently obtained, compared with the 15 degrees-20 degrees angles obtained with the widely used sodium hydroxide etch. Methods are also described for cleaning, increasing the tip diameter (i.e. blunting), gold plating, and testing the contact resistance of the whiskers. The effects of the whisker tip shape on the electrical resistance, inductance, and capacitance of the whiskers are studied, and examples given for typical sets of parameters.

The AICD interacting protein DAB1 is up-regulated in Alzheimer frontal cortex brain samples and causes deregulation of proteins involved in gene expression changes.

PubMed

Müller, T; Loosse, C; Schrötter, A; Schnabel, A; Helling, S; Egensperger, R; Marcus, K

2011-08-01

AICD is the intracellular subdomain of the amyloid precursor protein thought to play a pivotal role as a potential transcription factor that might be of relevance for the pathophysiology of Alzheimer's disease. For its signal transduction potential AICD requires interacting proteins like FE65 and TIP60. However, many other proteins were described being able to bind to AICD. Here, we studied mRNA levels of AICD interacting proteins and found one of them (DAB1) strongly up-regulated in human post-mortem frontal cortex brain samples of AD patients. Subsequent cell culture experiments revealed that elevated DAB1 level results in the deregulation of the cellular proteome. We found the proliferation associated protein 2G4 as well as the guanine monophosphate synthetase (GMPS) significantly up-regulated in DAB1 over-expressing cells. Both proteins can be involved in cellular transcription processes supporting the hypothesis that DAB1 acts via modification of the AICD-dependent transcriptionally active complex. Of note, expression of the three components of the putative transcription complex (AICD, FE65, and TIP60 (AFT)) also revealed deregulation of the GMPS protein in an opposite fashion. Our results point to a putative relevance of AICD-dependent mechanisms in AD, caused by protein abundance changes of AICD interacting proteins, as shown for DAB1 in this work.

Sleep and rhythm changes at the time of Trypanosoma brucei invasion of the brain parenchyma in the rat.

PubMed

Seke Etet, Paul F; Palomba, Maria; Colavito, Valeria; Grassi-Zucconi, Gigliola; Bentivoglio, Marina; Bertini, Giuseppe

2012-05-01

Human African trypanosomiasis (HAT), or sleeping sickness, is a severe disease caused by Trypanosoma brucei (T.b.). The disease hallmark is sleep alterations. Brain involvement in HAT is a crucial pathogenetic step for disease diagnosis and therapy. In this study, a rat model of African trypanosomiasis was used to assess changes of sleep-wake, rest-activity, and body temperature rhythms in the time window previously shown as crucial for brain parenchyma invasion by T.b. to determine potential biomarkers of this event. Chronic radiotelemetric monitoring in Sprague-Dawley rats was used to continuously record electroencephalogram, electromyogram, rest-activity, and body temperature in the same animals before (baseline recording) and after infection. Rats were infected with T.b. brucei. Data were acquired from 1 to 20 d after infection (parasite neuroinvasion initiates at 11-13 d post-infection in this model), and were compared to baseline values. Sleep parameters were manually scored from electroencephalographic-electromyographic tracings. Circadian rhythms of sleep time, slow-wave activity, rest-activity, and body temperature were studied using cosinor rhythmometry. Results revealed alterations of most of the analyzed parameters. In particular, sleep pattern and sleep-wake organization plus rest-activity and body temperature rhythms exhibited early quantitative and qualitative alterations, which became marked around the time interval crucial for parasite neuroinvasion or shortly after. Data derived from actigrams showed close correspondence with those from hypnograms, suggesting that rest-activity could be useful to monitor sleep-wake alterations in African trypanosomiasis.

78 FR 52870 - Airworthiness Directives; Beechcraft Corporation Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-27

... the front spar cap angles and hat section structure of the vertical stabilizer. This proposed AD would require inspections of the vertical stabilizer spar angles and hat section for cracks with corrective... information identified in this proposed AD, contact Beechcraft Corporation at address: 10511 E. Central...

WASP-12b and HAT-P-8b are Members of Triple Star Systems

NASA Astrophysics Data System (ADS)

Bechter, Eric B.; Crepp, Justin R.; Ngo, Henry; Knutson, Heather A.; Batygin, Konstantin; Hinkley, Sasha; Muirhead, Philip S.; Johnson, John Asher; Howard, Andrew W.; Montet, Benjamin T.; Matthews, Christopher T.; Morton, Timothy D.

2014-06-01

We present high spatial resolution images that demonstrate that WASP-12b and HAT-P-8b orbit the primary stars of hierarchical triple star systems. In each case, two distant companions with colors and brightnesses consistent with M dwarfs co-orbit the hot Jupiter planet host as well as one another. Our adaptive optics images spatially resolve the secondary around WASP-12, previously identified by Bergfors et al. and Crossfield et al. into two distinct sources separated by 84.3 ± 0.6 mas (21 ± 3 AU). We find that the secondary to HAT-P-8, also identified by Bergfors et al., is in fact composed of two stars separated by 65.3 ± 0.5 mas (15 ± 1 AU). Our follow-up observations demonstrate physical association through common proper motion. HAT-P-8 C has a particularly low mass, which we estimate to be 0.18 ± 0.02 M ⊙ using photometry. Due to their hierarchy, WASP-12 BC and HAT-P-8 BC will enable the first dynamical mass determination for hot Jupiter stellar companions. These previously well studied planet hosts now represent higher-order multi-star systems with potentially complex dynamics, underscoring the importance of diffraction-limited imaging and providing additional context for understanding the migrant population of transiting hot Jupiters.

Planet-induced Stellar Pulsations in HAT-P-2's Eccentric System

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

Wit, Julien de; Lewis, Nikole K.; Knutson, Heather A.

2017-02-20

Extrasolar planets on eccentric short-period orbits provide a laboratory in which to study radiative and tidal interactions between a planet and its host star under extreme forcing conditions. Studying such systems probes how the planet’s atmosphere redistributes the time-varying heat flux from its host and how the host star responds to transient tidal distortion. Here, we report the insights into the planet–star interactions in HAT-P-2's eccentric planetary system gained from the analysis of ∼350 hr of 4.5 μ m observations with the Spitzer Space Telescope . The observations show no sign of orbit-to-orbit variability nor of orbital evolution of themore » eccentric planetary companion, HAT-P-2 b. The extensive coverage allows us to better differentiate instrumental systematics from the transient heating of HAT-P-2 b’s 4.5 μ m photosphere and yields the detection of stellar pulsations with an amplitude of approximately 40 ppm. These pulsation modes correspond to exact harmonics of the planet’s orbital frequency, indicative of a tidal origin. Transient tidal effects can excite pulsation modes in the envelope of a star, but, to date, such pulsations had only been detected in highly eccentric stellar binaries. Current stellar models are unable to reproduce HAT-P-2's pulsations, suggesting that our understanding of the interactions at play in this system is incomplete.« less

WASP-35b, WASP-48b, AND HAT-P-30b/WASP-51b: TWO NEW PLANETS AND AN INDEPENDENT DISCOVERY OF A HAT PLANET

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

Enoch, B.; Brown, D. J. A.; Cameron, A. Collier

2011-09-15

We report the detection of WASP-35b, a planet transiting a metal-poor ([Fe/H] = -0.15) star in the Southern hemisphere, WASP-48b, an inflated planet which may have spun-up its slightly evolved host star of 1.75 R{sub sun} in the Northern hemisphere, and the independent discovery of HAT-P-30b/WASP-51b, a new planet in the Northern hemisphere. Using WASP, RISE, Faulkes Telescope South, and TRAPPIST photometry, with CORALIE, SOPHIE, and NOT spectroscopy, we determine that WASP-35b has a mass of 0.72 {+-} 0.06 M{sub J} and radius of 1.32 {+-} 0.05R{sub J} , and orbits with a period of 3.16 days, WASP-48b has amore » mass of 0.98 {+-} 0.09 M{sub J} , radius of 1.67 {+-} 0.10 R{sub J} , and orbits in 2.14 days, while HAT-P-30b/WASP-51b, with an orbital period of 2.81 days, is found to have a mass of 0.76 {+-} 0.05 M{sub J} and radius of 1.42 {+-} 0.03 R{sub J} , agreeing with values of 0.71 {+-} 0.03 M{sub J} and 1.34 {+-} 0.07 R{sub J} reported for HAT-P-30b.« less

WASP-12b AND HAT-P-8b are members of triple star systems

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

Bechter, Eric B.; Crepp, Justin R.; Matthews, Christopher T.

2014-06-10

We present high spatial resolution images that demonstrate that WASP-12b and HAT-P-8b orbit the primary stars of hierarchical triple star systems. In each case, two distant companions with colors and brightnesses consistent with M dwarfs co-orbit the hot Jupiter planet host as well as one another. Our adaptive optics images spatially resolve the secondary around WASP-12, previously identified by Bergfors et al. and Crossfield et al. into two distinct sources separated by 84.3 ± 0.6 mas (21 ± 3 AU). We find that the secondary to HAT-P-8, also identified by Bergfors et al., is in fact composed of two starsmore » separated by 65.3 ± 0.5 mas (15 ± 1 AU). Our follow-up observations demonstrate physical association through common proper motion. HAT-P-8 C has a particularly low mass, which we estimate to be 0.18 ± 0.02 M {sub ☉} using photometry. Due to their hierarchy, WASP-12 BC and HAT-P-8 BC will enable the first dynamical mass determination for hot Jupiter stellar companions. These previously well studied planet hosts now represent higher-order multi-star systems with potentially complex dynamics, underscoring the importance of diffraction-limited imaging and providing additional context for understanding the migrant population of transiting hot Jupiters.« less

Planet-induced Stellar Pulsations in HAT-P-2's Eccentric System

NASA Astrophysics Data System (ADS)

de Wit, Julien; Lewis, Nikole K.; Knutson, Heather A.; Fuller, Jim; Antoci, Victoria; Fulton, Benjamin J.; Laughlin, Gregory; Deming, Drake; Shporer, Avi; Batygin, Konstantin; Cowan, Nicolas B.; Agol, Eric; Burrows, Adam S.; Fortney, Jonathan J.; Langton, Jonathan; Showman, Adam P.

2017-02-01

Extrasolar planets on eccentric short-period orbits provide a laboratory in which to study radiative and tidal interactions between a planet and its host star under extreme forcing conditions. Studying such systems probes how the planet’s atmosphere redistributes the time-varying heat flux from its host and how the host star responds to transient tidal distortion. Here, we report the insights into the planet-star interactions in HAT-P-2's eccentric planetary system gained from the analysis of ˜350 hr of 4.5 μm observations with the Spitzer Space Telescope. The observations show no sign of orbit-to-orbit variability nor of orbital evolution of the eccentric planetary companion, HAT-P-2 b. The extensive coverage allows us to better differentiate instrumental systematics from the transient heating of HAT-P-2 b’s 4.5 μm photosphere and yields the detection of stellar pulsations with an amplitude of approximately 40 ppm. These pulsation modes correspond to exact harmonics of the planet’s orbital frequency, indicative of a tidal origin. Transient tidal effects can excite pulsation modes in the envelope of a star, but, to date, such pulsations had only been detected in highly eccentric stellar binaries. Current stellar models are unable to reproduce HAT-P-2's pulsations, suggesting that our understanding of the interactions at play in this system is incomplete.

Fuel injection assembly for gas turbine engine combustor

NASA Technical Reports Server (NTRS)

Candy, Anthony J. (Inventor); Glynn, Christopher C. (Inventor); Barrett, John E. (Inventor)

2002-01-01

A fuel injection assembly for a gas turbine engine combustor, including at least one fuel stem, a plurality of concentrically disposed tubes positioned within each fuel stem, wherein a cooling supply flow passage, a cooling return flow passage, and a tip fuel flow passage are defined thereby, and at least one fuel tip assembly connected to each fuel stem so as to be in flow communication with the flow passages, wherein an active cooling circuit for each fuel stem and fuel tip assembly is maintained by providing all active fuel through the cooling supply flow passage and the cooling return flow passage during each stage of combustor operation. The fuel flowing through the active cooling circuit is then collected so that a predetermined portion thereof is provided to the tip fuel flow passage for injection by the fuel tip assembly.

The effect of leverage and/or influential on structure-activity relationships.

PubMed

Bolboacă, Sorana D; Jäntschi, Lorentz

2013-05-01

In the spirit of reporting valid and reliable Quantitative Structure-Activity Relationship (QSAR) models, the aim of our research was to assess how the leverage (analysis with Hat matrix, h(i)) and the influential (analysis with Cook's distance, D(i)) of QSAR models may reflect the models reliability and their characteristics. The datasets included in this research were collected from previously published papers. Seven datasets which accomplished the imposed inclusion criteria were analyzed. Three models were obtained for each dataset (full-model, h(i)-model and D(i)-model) and several statistical validation criteria were applied to the models. In 5 out of 7 sets the correlation coefficient increased when compounds with either h(i) or D(i) higher than the threshold were removed. Withdrawn compounds varied from 2 to 4 for h(i)-models and from 1 to 13 for D(i)-models. Validation statistics showed that D(i)-models possess systematically better agreement than both full-models and h(i)-models. Removal of influential compounds from training set significantly improves the model and is recommended to be conducted in the process of quantitative structure-activity relationships developing. Cook's distance approach should be combined with hat matrix analysis in order to identify the compounds candidates for removal.

Ligand-accelerated activation of strong C-H bonds of alkanes by a (salen)ruthenium(VI)-nitrido complex.

PubMed

Man, Wai-Lun; Lam, William W Y; Kwong, Hoi-Ki; Yiu, Shek-Man; Lau, Tai-Chu

2012-09-03

Kinetic and mechanistic studies on the intermolecular activation of strong C-H bonds of alkanes by a (salen)ruthenium(VI) nitride were performed. The initial, rate-limiting step, the hydrogen atom transfer (HAT) from the alkane to Ru(VI)≡N, generates Ru(V)=NH and RC·HCH(2)R. The following steps involve N-rebound and desaturation. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cold Weather and Cardiovascular Disease

MedlinePlus

... This traps air between layers, forming a protective insulation. Also, wear a hat or head scarf. Heat can be lost through your head. And ears ... which traps air between layers forming a protective insulation. Wear a hat because much of your body’s heat can be lost through your head. Learn CPR. ...

RSRM top hat cover simulator lightning test, volume 2. Appendix A: Resistance measurements. Appendix B: Lightning test data plots

NASA Technical Reports Server (NTRS)

1990-01-01

Resistance measurements are given in graphical for when a simulated lightning discharge strikes on an exposed top hat cover simulator. The test sequence was to measure the electric and magnetic fields induced inside a redesigned solid rocket motor case.

HATS: A Design Procedure for Routine Business Documents.

ERIC Educational Resources Information Center

Baker, William H.

2001-01-01

Describes an approach to teaching students a basic design process for routine business documents like memos, letters, and reports. Outlines the design principles of HATS (Headings, Access, Typography, and Spacing), how they apply in before-and-after fashion to various documents, and discusses an assignment in which students redesign an existing…

Compressive buckling analysis of hat-stiffened panel

NASA Technical Reports Server (NTRS)

Ko, William L.; Jackson, Raymond H.

1991-01-01

Buckling analysis was performed on a hat-stiffened panel subjected to uniaxial compression. Both local buckling and global buckling were analyzed. It was found that the global buckling load was several times higher than the buckling load. The predicted local buckling loads compared favorably with both experimental data and finite-element analysis.

Helper Hats

ERIC Educational Resources Information Center

Ashbrook, Peggy

2010-01-01

Special clothing is worn by "community helpers" such as police officers, nurses, firefighters, cafeteria workers, dentists, and waste management workers as they do their jobs. The special clothing allows workers to be safe. Therefore, exploring how hats help community workers do their jobs can be a way to introduce the idea of how the shape or…

An Exoplanet Spinning Up Its Star

NASA Astrophysics Data System (ADS)

Kohler, Susanna

2016-11-01

We know that the large masses of stars govern the orbits of the planets that circle them but a large, close-in planet can also influence the rotation of its host star. A recently discovered, unusual hot Jupiter may be causing its star to spin faster than it should.Exotic PlanetsHot Jupiters are gas giants of roughly Jupiters size that orbit close in to their host stars. Though these planets are easy to detect their large sizes and frequent transits mean surveys have a good chance of catching them we havent found many of them, suggesting that planetary systems containing hot Jupiters are fairly unusual.The period-folded light curve of HATS-18, revealing the transit of the hot Jupiter HATS-18b. The period is P=0.8378 days. [Penev et al. 2016]Studying this exotic population of planets, however, can help us to better understand how gas giants form and evolve in planetary systems. New observations of hot Jupiters may also reveal how stars and close-in planets interact through radiation, gravity, and magnetic fields.The recent discovery of a transiting hot Jupiter a little over 2000 light-years away therefore presents an exciting opportunity!A Speeding GiantThe discovery of HATS-18b, a planet of roughly 2 times Jupiters mass and 1.3 times its radius, was announced in a study led by Kaloyan Penev (Princeton University). The planet was discovered using the HATSouth transit survey network, which includes instruments in Chile, Namibia, and Australia, and follow-up photometry and spectroscopy was conducted at a variety of ground-based observatories.HATS-18bs properties are particularly unusual: this hot Jupiter is zipping around its host star which is very similar to the Sun at the incredible pace of one orbit every 0.84 days. HATS-18bs orbit is more than 20 times closer to its host star than Mercurys is to the Sun, bringing it so close it nearly grazes the stars surface!Size of the planetary orbit relative to the stellar radius as a function of the stellar rotation period, for transiting planets with orbital periods shorter than 2 days and masses greater than 0.1 Jupiter masses. HATS-18b is denoted by the red star. [Penev et al. 2016]Tidal InteractionsWhat happens when a massive planet orbits this close to its star? Tidal interactions between the star and the planet cause tidal dissipation in the star, resulting in decay of the planets orbit. But there may be an additional effect of this interaction in the case of HATS-18b, the authors claim: the planet may be transferring some of its angular momentum to the star.As stars age, they should gradually spin slower as they lose angular momentum viastellar winds. But Penev and collaborators note that this exoplanets host star, HATS-18, spins roughly three times as fast asits inferred age suggests it should. The authors conclude that the angular momentum lost by the planet as its orbit shrinks is deposited in the star, causing the star to spin up.HATS-18 is an excellent laboratory for studying how very short-period planets interact with their stars in fact, Penev and collaborators have already used their observations of the system to constrain models of tidal dissipation from Sun-like stars. Additional observations of HATS-18 and other short-period systems should allow us to further test models of how planetary systems form and evolve.CitationK. Penev et al 2016 AJ 152 127. doi:10.3847/0004-6256/152/5/127

Effect of ultrasonic tip designs on intraradicular post removal.

PubMed

Aguiar, Anny Carine Barros; de Meireles, Daniely Amorim; Marques, André Augusto Franco; Sponchiado Júnior, Emílio Carlos; Garrido, Angela Delfina Bitencourt; Garcia, Lucas da Fonseca Roberti

2014-11-01

To evaluate the effect of different ultrasonic tip designs on intraradicular post removal. The crowns of forty human canine teeth were removed, and after biomechanical preparation and filling, the roots were embedded in acrylic resin blocks. The post spaces were made, and root canal molding was performed with self-cured acrylic resin. After casting (Cu-Al), the posts were cemented with zinc phosphate cement. The specimens were randomly separated into 4 groups (n = 10), as follows: G1 - no ultrasonic vibration (control); G2 - ultrasonic vibration using an elongated cylindrical-shaped and active rounded tip; G3 - ultrasonic vibration with a flattened convex and linear active tip; G4 - ultrasonic vibration with active semicircular tapered tip. Ultrasonic vibration was applied for 15 seconds on each post surface and tensile test was performed in a Universal Testing Machine (Instron 4444 - 1 mm/min). G4 presented the highest mean values, however, with no statistically significant difference in comparison to G3 (P > 0.05). G2 presented the lowest mean values with statistically significant difference to G3 and G4 (P < 0.05). Ultrasonic vibration with elongated cylindrical-shaped and active rounded tip was most effective in reducing force required for intraradicular post removal.

Investigation of plant hormone level changes in shoot tips of longan (Dimocarpus longan Lour.) treated with potassium chlorate by liquid chromatography-electrospray ionization mass spectrometry.

PubMed

Susawaengsup, Chanthana; Rayanakorn, Mongkon; Wongpornchai, Sugunya; Wangkarn, Sunanta

2011-08-15

The endogenous levels of indole-3-acetic acid (IAA), gibberellins (GAs), abscisic acid (ABA) and cytokinins (CKs) and their changes were investigated in shoot tips of ten longan (Dimocarpus longan Lour.) trees for off-season flowering until 60 days after potassium chlorate treatment in comparison with those of ten control (untreated) longan trees. These analytes were extracted and interfering matrices removed with a single mixed-mode solid phase extraction under optimum conditions. The recoveries at three levels of concentration were in the range of 72-112%. The endogenous plant hormones were separated and quantified by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). Detection limits based on the signal-to-noise ratio ranged from 10 ng mL(-1) for gibberellin A4 (GA4) to 200 ng mL(-1) for IAA. Within the first week after potassium chlorate treatment, dry weight (DW) amounts in the treated longan shoot tips of four gibberellins, namely: gibberellin A1(GA1), gibberellic acid (GA3), gibberellin A19 (GA19) and gibberellin A20 (GA20), were found to increase to approximately 25, 50, 20 and 60 ng g(-1) respectively, all of which were significantly higher than those of the controls. In contrast, gibberellin A8 (GA8) obtained from the treated longan was found to decrease to approximately 20 ng g(-1)DW while that of the control increased to around 80 ng g(-1)DW. Certain CKs which play a role in leaf bud induction, particularly isopentenyl adenine (iP), isopentenyl adenosine (iPR) and dihydrozeatin riboside (DHZR), were found to be present in amounts of approximately 20, 50 and 60 ng g(-1)DW in the shoot tips of the control longan. The analytical results obtained from the two-month off-season longan flowering period indicate that high GA1, GA3, GA19 and GA20 levels in the longan shoot tips contribute to flower bud induction while high levels of CKs, IAA and ABA in the control longan contribute more to the vegetative development. Copyright © 2011 Elsevier B.V. All rights reserved.

Visualization and Quantification of Rotor Tip Vortices in Helicopter Flows

NASA Technical Reports Server (NTRS)

Kao, David L.; Ahmad, Jasim U.; Holst, Terry L.

2015-01-01

This paper presents an automated approach for effective extraction, visualization, and quantification of vortex core radii from the Navier-Stokes simulations of a UH-60A rotor in forward flight. We adopt a scaled Q-criterion to determine vortex regions and then perform vortex core profiling in these regions to calculate vortex core radii. This method provides an efficient way of visualizing and quantifying the blade tip vortices. Moreover, the vortices radii are displayed graphically in a plane.

Hydrogen test of a small, low specific speed centrifugal pump stage

NASA Technical Reports Server (NTRS)

1991-01-01

A small, low specific speed centrifugal pump stage with a 2 inch tip diameter, .030 inch tip width shrouded impeller and volute collector was tested with liquid hydrogen as the pumped fluid. The hydrodynamic design of the pump stage is summarized and the noncavitating and cavitating performance results are presented. Test speeds were 60 and 80 percent of the 77,000 rpm design speed. Liquid hydrogen test results are compared with data from previous tests of the stage in water.

Direct cooling of the catheter tip increases safety for CMR-guided electrophysiological procedures

PubMed Central

2012-01-01

Background One of the safety concerns when performing electrophysiological (EP) procedures under magnetic resonance (MR) guidance is the risk of passive tissue heating due to the EP catheter being exposed to the radiofrequency (RF) field of the RF transmitting body coil. Ablation procedures that use catheters with irrigated tips are well established therapeutic options for the treatment of cardiac arrhythmias and when used in a modified mode might offer an additional system for suppressing passive catheter heating. Methods A two-step approach was chosen. Firstly, tests on passive catheter heating were performed in a 1.5 T Avanto system (Siemens Healthcare Sector, Erlangen, Germany) using a ASTM Phantom in order to determine a possible maximum temperature rise. Secondly, a phantom was designed for simulation of the interface between blood and the vascular wall. The MR-RF induced temperature rise was simulated by catheter tip heating via a standard ablation generator. Power levels from 1 to 6 W were selected. Ablation duration was 120 s with no tip irrigation during the first 60 s and irrigation at rates from 2 ml/min to 35 ml/min for the remaining 60 s (Biotronik Qiona Pump, Berlin, Germany). The temperature was measured with fluoroscopic sensors (Luxtron, Santa Barbara, CA, USA) at a distance of 0 mm, 2 mm, 4 mm, and 6 mm from the catheter tip. Results A maximum temperature rise of 22.4°C at the catheter tip was documented in the MR scanner. This temperature rise is equivalent to the heating effect of an ablator's power output of 6 W at a contact force of the weight of 90 g (0.883 N). The catheter tip irrigation was able to limit the temperature rise to less than 2°C for the majority of examined power levels, and for all examined power levels the residual temperature rise was less than 8°C. Conclusion Up to a maximum of 22.4°C, the temperature rise at the tissue surface can be entirely suppressed by using the catheter's own irrigation system. The irrigated tip system can be used to increase MR safety of EP catheters by suppressing the effects of unwanted passive catheter heating due to RF exposure from the MR scanner. PMID:22296883

A comparison of two intraosseous anesthetic techniques in mandibular posterior teeth.

PubMed

Gallatin, Juliane; Reader, Al; Nusstein, John; Beck, Mike; Weaver, Joel

2003-11-01

A number of studies have evaluated the Stabident (Fairfax Dental, Miami) intraosseous anesthesia technique. A second intraosseous technique--the X-tip system (X-tip Technologies, Lakewood, N.J.)--has been introduced, but no scientific studies have yet compared its effectiveness to that of the Stabident system. The authors undertook a study to compare the two systems' anesthetic outcomes in primary intraosseous injections in mandibular posterior teeth. The authors, using a crossover design, randomly administered a primary Stabident intraosseous injection and a primary X-tip intraosseous injection, at two separate appointments, to 41 subjects. Subjects were asked if they perceived an increase in heart rate with the intraosseous injections. The research team blind-tested each subject's first molar, second molar and second premolar with a pulp tester at two-minute cycles for 60 minutes after the injection. Anesthesia was considered successful when two consecutive pulp tester readings of 80 were obtained. Anesthetic success rates for the Stabident technique and the X-tip technique, respectively, were 93 percent and 93 percent for the first molar; 95 percent and 95 percent for the second molar; and 81 percent and 83 percent for the second premolar, with no significant differences (P > .05) between the two techniques. For both intraosseous techniques, onset of pulpal anesthesia occurred within the first two minutes, but the duration of anesthesia declined steadily over the 60 minutes. Eighty-five percent of the subjects had a perceived increase in heart rate with the Stabident injection and 93 percent with the X-tip injection, with no significant differences (P > .05) between the techniques. The two primary intraosseous injection techniques were similar regarding anesthetic success, onset, duration and perceived heart rate increases.

Red Hat Enterprise Virtualization - KVM-based infrastructure services at BNL

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

Cortijo, D.

2011-06-14

Over the past 18 months, BNL has moved a large percentage of its Linux-based servers and services into a Red Hat Enterprise Virtualization (RHEV) environment. This presentation will address our approach to virtualization, critical decision points, and a discussion of our implementation. Specific topics will include an overview of hardware and software requirements, networking, and storage; discussion of the decision of Red Hat solution over competing products (VMWare, Xen, etc); details on some of the features of RHEV - both current and on their roadmap; Review of performance and reliability gains since deployment completion; path forward for RHEV at BNLmore » and caveats and potential problems.« less

Evaporative Cooling in a Holographic Atom Trap

NASA Technical Reports Server (NTRS)

Newell, Raymond

2003-01-01

We present progress on evaporative cooling of Rb-87 atoms in our Holographic Atom Trap (HAT). The HAT is formed by the interference of five intersecting YAG laser beams: atoms are loaded from a vapor-cell MOT into the bright fringes of the interference pattern through the dipole force. The interference pattern is composed of Talbot fringes along the direction of propagation of the YAG beams, prior to evaporative cooling each Talbot fringe contains 300,000 atoms at 50 micro-K and peak densities of 2 x 10(exp 14)/cu cm. Evaporative cooling is achieved through adiabatically decreasing the intensity of the YAG laser. We present data and calculations covering a range of HAT geometries and cooling procedures.

Trends in tans and skin protection in Australian fashion magazines, 1982 through 1991.

PubMed Central

Chapman, S; Marks, R; King, M

1992-01-01

We rated 3971 photographs of models from midsummer editions of six Australian fashion magazines from 1982-1983 to 1990-1991 for tan on a 9-point scale, for the presence of hats, for sun-protective clothing, and for shade setting. With the exception of the 1990-1991 sample, there was an increasing proportion of light tans over the years. Men were more likely to be deeply tanned than were women. The proportion of models wearing hats followed an increasing linear trend across the five periods. Three quarters of the outdoor photographs were taken in unshaded settings. In unshaded settings, 17% of the women and 5% of the men wore hats. PMID:1456348

Modulating p56Lck in T-Cells by a Chimeric Peptide Comprising Two Functionally Different Motifs of Tip from Herpesvirus saimiri

PubMed Central

Vernot, Jean-Paul; Perdomo-Arciniegas, Ana María; Pérez-Quintero, Luis Alberto; Martínez, Diego Fernando

2015-01-01

The Lck interacting protein Tip of Herpesvirus saimiri is responsible for T-cell transformation both in vitro and in vivo. Here we designed the chimeric peptide hTip-CSKH, comprising the Lck specific interacting motif CSKH of Tip and its hydrophobic transmembrane sequence (hTip), the latter as a vector targeting lipid rafts. We found that hTip-CSKH can induce a fivefold increase in proliferation of human and Aotus sp. T-cells. Costimulation with PMA did not enhance this proliferation rate, suggesting that hTip-CSKH is sufficient and independent of further PKC stimulation. We also found that human Lck phosphorylation was increased earlier after stimulation when T-cells were incubated previously with hTip-CSKH, supporting a strong signalling and proliferative effect of the chimeric peptide. Additionally, Lck downstream signalling was evident with hTip-CSKH but not with control peptides. Importantly, hTip-CSKH could be identified in heavy lipid rafts membrane fractions, a compartment where important T-cell signalling molecules (LAT, Ras, and Lck) are present during T-cell activation. Interestingly, hTip-CSKH was inhibitory to Jurkat cells, in total agreement with the different signalling pathways and activation requirements of this leukemic cell line. These results provide the basis for the development of new compounds capable of modulating therapeutic targets present in lipid rafts. PMID:26539553

Modulating p56Lck in T-Cells by a Chimeric Peptide Comprising Two Functionally Different Motifs of Tip from Herpesvirus saimiri.

PubMed

Vernot, Jean-Paul; Perdomo-Arciniegas, Ana María; Pérez-Quintero, Luis Alberto; Martínez, Diego Fernando

2015-01-01

The Lck interacting protein Tip of Herpesvirus saimiri is responsible for T-cell transformation both in vitro and in vivo. Here we designed the chimeric peptide hTip-CSKH, comprising the Lck specific interacting motif CSKH of Tip and its hydrophobic transmembrane sequence (hTip), the latter as a vector targeting lipid rafts. We found that hTip-CSKH can induce a fivefold increase in proliferation of human and Aotus sp. T-cells. Costimulation with PMA did not enhance this proliferation rate, suggesting that hTip-CSKH is sufficient and independent of further PKC stimulation. We also found that human Lck phosphorylation was increased earlier after stimulation when T-cells were incubated previously with hTip-CSKH, supporting a strong signalling and proliferative effect of the chimeric peptide. Additionally, Lck downstream signalling was evident with hTip-CSKH but not with control peptides. Importantly, hTip-CSKH could be identified in heavy lipid rafts membrane fractions, a compartment where important T-cell signalling molecules (LAT, Ras, and Lck) are present during T-cell activation. Interestingly, hTip-CSKH was inhibitory to Jurkat cells, in total agreement with the different signalling pathways and activation requirements of this leukemic cell line. These results provide the basis for the development of new compounds capable of modulating therapeutic targets present in lipid rafts.

Activating Learning in Engineering Education Using ICT and the Concept of "Flipping the Classroom"

ERIC Educational Resources Information Center

Lucke, Terry; Dunn, Peter K.; Christie, Michael

2017-01-01

This case study trialled the introduction of a student-response system (Top Hat) in a third-year engineering Fluid Mechanics course (n = 44) to improve student engagement, motivation and cognition. It was recognised that for the potential benefits of student-response systems (SRSs) to be fully realised, more time must be allocated for student…

Mechanistic insight into the photoredox catalysis of anti-Markovnikov alkene hydrofunctionalization reactions

DOE PAGES

Romero, Nathan A.; Nicewicz, David A.

2014-11-12

Here, we describe our efforts to understand the key mechanistic aspects of the previously reported alkene hydrofunctionalization reactions using 9-mesityl-10-methylacridinium (Mes-Acr +) as a photoredox catalyst. Importantly, we are able to detect alkene cation radical intermediates, and confirm that phenylthiyl radical is capable of oxidizing the persistent acridinyl radical in a fast process that unites the catalytic activity of the photoredox and hydrogen atom transfer (HAT) manifolds. Additionally, we present evidence that diphenyl disulfide ((PhS) 2) operates on a common catalytic cycle with thiophenol (PhSH) by way of photolytic cleaveage of the disulfide bond. Transition structure analysis of the HATmore » step using DFT reveals that the activation barrier for H atom donation from PhSH is significantly lower than 2-phenylmalononitrile (PMN) due to structural reorganization. In the early stages of the reaction, Mes-Acr + is observed to engage in off-cycle adduct formation, presumably as buildup of PhS – becomes significant. The kinetic differences between PhSH and (PhS) 2 as HAT catalysts indicate that the proton transfer step may have significant rate limiting influence.« less

Fisetin Protects DNA Against Oxidative Damage and Its Possible Mechanism.

PubMed

Wang, Tingting; Lin, Huajuan; Tu, Qian; Liu, Jingjing; Li, Xican

2016-06-01

The paper tries to assess the protective effect of fisetin against •OH-induced DNA damage, then to investigate the possible mechanism. The protective effect was evaluated based on the content of malondialdehyde (MDA). The possible mechanism was analyzed using various antioxidant methods in vitro, including •OH scavenging (deoxyribose degradation), •O2 (-) scavenging (pyrogallol autoxidation), DPPH• scavenging, ABTS•(+) scavenging, and Cu(2+)-reducing power assays. Fisetin increased dose-dependently its protective percentages against •OH-induced DNA damage (IC50 value =1535.00±29.60 µM). It also increased its radical-scavenging percentages in a dose-dependent manner in various antioxidants assays. Its IC50 values in •OH scavenging, •O2(-) scavenging, DPPH• scavenging, ABTS•(+) scavenging, and Cu(2+)-reducing power assays, were 47.41±4.50 µM, 34.05±0.87 µM, 9.69±0.53 µM, 2.43±0.14 µM, and 1.49±0.16 µM, respectively. Fisetin can effectively protect DNA against •OH-induced oxidative damage possibly via reactive oxygen species (ROS) scavenging approach, which is assumed to be hydrogen atom (H•) and/or single electron (e) donation (HAT/SET) pathways. In the HAT pathway, the 3',4'-dihydroxyl moiety in B ring of fisetin is thought to play an important role, because it can be ultimately oxidized to a stable ortho-benzoquinone form.

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

Brown, D. J. A.; Collier Cameron, A.; Enoch, B.

We present measurements of the spin-orbit alignment angle, {lambda}, for the hot Jupiter systems WASP-32, WASP-38, and HAT-P-27/WASP-40, based on data obtained using the HARPS spectrograph. We analyze the Rossiter-McLaughlin effect for all three systems and also carry out Doppler tomography for WASP-32 and WASP-38. We find that WASP-32 (T {sub eff} = 6140{sup +90} {sub -100} K) is aligned, with an alignment angle of {lambda} = 10.{sup 0}5{sup +6.4} {sub -6.5} obtained through tomography, and that WASP-38 (T {sub eff} = 6180{sup +40} {sub -60} K) is also aligned, with tomographic analysis yielding {lambda} = 7.{sup 0}5{sup +4.7} {submore » -6.1}. The latter result provides an order-of-magnitude improvement in the uncertainty in {lambda} compared to the previous analysis of Simpson et al. We are only able to loosely constrain the angle for HAT-P-27/WASP-40 (T{sub eff} = 5190{sup +160} {sub -170} K) to {lambda} = 24.{sup 0}2{sup +76.0}{sub -44.5}, owing to the poor signal-to-noise ratio of our data. We consider this result a non-detection under a slightly updated version of the alignment test of Brown et al. We place our results in the context of the full sample of spin-orbit alignment measurements, finding that they provide further support for previously established trends.« less

Uncertainty of tipping elements on risk analysis in hydrology under climate change

NASA Astrophysics Data System (ADS)

Kiguchi, M.; Iseri, Y.; Tawatari, R.; Kanae, S.; Oki, T.

2015-12-01

Risk analysis in this study characterizes the events that could be caused by climate change and estimates their effects on society. In order to characterize climate change risks, events that might be caused by climate change will be investigated focusing on critical geophysical phenomena such as changes in thermohaline circulation (THC) in oceans and the large-scale melting of the Greenland and other ice sheets. The results of numerical experiments with climate models and paleoclimate studies will be referenced in listing up these phenomena. The trigger mechanisms, tendency to occur and relationship of these phenomena to global climate will be clarified. To clarify that relationship between the RCP scenarios and tipping elements, we identified which year tipping elements in case of "Arctic summer sea ice" and "Greenland ice sheet" are appeared using the increase of global average temperature in 5 GCMs under RCP (2.6, 4.5, 6.0, and 8.5) from Zickfeld et al. (2013) and IPCC (2013), and tipping point of each tipping elements from IPCC (2013). In case of "Greenland ice sheet" (Tipping point takes a value within the range of 1.0oC and 4.0oC), we found that "Greenland ice sheet" may melt down when the tipping point is 1.0oC as lowest value. On the other hand, when tipping point sets as 4.0oC, it may not melt down except for RCP 8.5. As above, we show the uncertainty of tipping point itself. In future, it is necessary how to reflect such uncertainty in risk analysis in hydrology.

Parallel transjugular intrahepatic portosystemic shunt for controlling portal hypertension complications in cirrhotic patients.

PubMed

He, Fu-Liang; Wang, Lei; Yue, Zhen-Dong; Zhao, Hong-Wei; Liu, Fu-Quan

2014-09-07

To evaluate the feasibility of a second parallel transjugular intrahepatic portosystemic shunt (TIPS) to reduce portal venous pressure and control complications of portal hypertension. From January 2011 to December 2012, 10 cirrhotic patients were treated for complications of portal hypertension. The demographic data, operative data, postoperative recovery data, hemodynamic data, and complications were analyzed. Ten patients underwent a primary and parallel TIPS. Technical success rate was 100% with no technical complications. The mean duration of the first operation was 89.20 ± 29.46 min and the second operation was 57.0 ± 12.99 min. The mean portal system pressure decreased from 54.80 ± 4.16 mmHg to 39.0 ± 3.20 mmHg after the primary TIPS and from 44.40 ± 3.95 mmHg to 26.10 ± 4.07 mmHg after the parallel TIPS creation. The mean portosystemic pressure gradient decreased from 43.80 ± 6.18 mmHg to 31.90 ± 2.85 mmHg after the primary TIPS and from 35.60 ± 2.72 mmHg to 15.30 ± 3.27 mmHg after the parallel TIPS creation. Clinical improvement was seen in all patients after the parallel TIPS creation. One patient suffered from transient grade I hepatic encephalopathy (HE) after the primary TIPS and four patients experienced transient grade I-II after the parallel TIPS procedure. Mean hospital stay after the first and second operations were 15.0 ± 3.71 d and 16.90 ± 5.11 d (P = 0.014), respectively. After a mean 14.0 ± 3.13 mo follow-up, ascites and bleeding were well controlled and no stenosis of the stents was found. Parallel TIPS is an effective approach for controlling portal hypertension complications.

Six Thinking Hats and Social Workers' Innovative Competence: An Experimental Study

ERIC Educational Resources Information Center

Azeez, Razaq Olugbenga

2016-01-01

Employees, no doubt, are the main force in organizations, and their innovative behaviours are vital for outcome efficacy. Innovative organisations, therefore, need creative employees who generate new ideas for product or process of innovation. This study investigated the effect of six thinking hats creativity technique on innovative competence of…

Heteromeric amino acid transporters. In search of the molecular bases of transport cycle mechanisms.

PubMed

Palacín, Manuel; Errasti-Murugarren, Ekaitz; Rosell, Albert

2016-06-15

Heteromeric amino acid transporters (HATs) are relevant targets for structural studies. On the one hand, HATs are involved in inherited and acquired human pathologies. On the other hand, these molecules are the only known examples of solute transporters composed of two subunits (heavy and light) linked by a disulfide bridge. Unfortunately, structural knowledge of HATs is scarce and limited to the atomic structure of the ectodomain of a heavy subunit (human 4F2hc-ED) and distant prokaryotic homologues of the light subunits that share a LeuT-fold. Recent data on human 4F2hc/LAT2 at nanometer resolution revealed 4F2hc-ED positioned on top of the external loops of the light subunit LAT2. Improved resolution of the structure of HATs, combined with conformational studies, is essential to establish the structural bases for light subunit recognition and to evaluate the functional relevance of heavy and light subunit interactions for the amino acid transport cycle. © 2016 Authors; published by Portland Press Limited.

[Research advance on mechanism and application of HATs and HDACs in epithelial-mesenchymal transition of lung cancer].

PubMed

Chang, Rui; You, Jiacong; Zhou, Qinghua

2013-04-01

Lung cancer is one of the most common diseases that endanger health and life of people domestically. A number of recurrence and death of lung cancer originated from metastasis. As a key step in metastasis of lung cancer, epithelial to mesenchymal transition involved down-regulation of E-cadherin, as well as regulated by EMT transcription factors. HATs and HDACs is a protein family that catalyzes acetylation and deacetylation of histones. Not only they have vital functions in tumor pathogenesis, but also participate in the EMT of lung cancer. HATs and HDACs interact with certain EMT transcription factors. Moreover, the function of these EMT transcription factors may be regulated by acetylation, which has influence on EMT program in lung cancer. Therefore, this review introduces the event of HATs and HDACs function in EMT of lung cancer, and investigate the molecular mechanism of their interaction. Then, the potential of HDAC inhibitor utilization in the inhibition of EMT and lung cancer therapy were discussed, as to pave the way for the related basic research and clinical practice.

Mof-associated complexes have overlapping and unique roles in regulating pluripotency in embryonic stem cells and during differentiation

PubMed Central

Ravens, Sarina; Fournier, Marjorie; Ye, Tao; Stierle, Matthieu; Dembele, Doulaye; Chavant, Virginie; Tora, Làszlò

2014-01-01

The histone acetyltransferase (HAT) Mof is essential for mouse embryonic stem cell (mESC) pluripotency and early development. Mof is the enzymatic subunit of two different HAT complexes, MSL and NSL. The individual contribution of MSL and NSL to transcription regulation in mESCs is not well understood. Our genome-wide analysis show that i) MSL and NSL bind to specific and common sets of expressed genes, ii) NSL binds exclusively at promoters, iii) while MSL binds in gene bodies. Nsl1 regulates proliferation and cellular homeostasis of mESCs. MSL is the main HAT acetylating H4K16 in mESCs, is enriched at many mESC-specific and bivalent genes. MSL is important to keep a subset of bivalent genes silent in mESCs, while developmental genes require MSL for expression during differentiation. Thus, NSL and MSL HAT complexes differentially regulate specific sets of expressed genes in mESCs and during differentiation. DOI: http://dx.doi.org/10.7554/eLife.02104.001 PMID:24898753

Relative Photometry of HAT-P-1b Occultations

NASA Astrophysics Data System (ADS)

Béky, Bence; Holman, Matthew J.; Gilliland, Ronald L.; Bakos, Gáspár Á.; Winn, Joshua N.; Noyes, Robert W.; Sasselov, Dimitar D.

2013-06-01

We present Hubble Space Telescope (HST) Space Telescope Imaging Spectrograph observations of two occultations of the transiting exoplanet HAT-P-1b. By measuring the planet to star flux ratio near opposition, we constrain the geometric albedo of the planet, which is strongly linked to its atmospheric temperature gradient. An advantage of HAT-P-1 as a target is its binary companion ADS 16402 A, which provides an excellent photometric reference, simplifying the usual steps in removing instrumental artifacts from HST time-series photometry. We find that without this reference star, we would need to detrend the lightcurve with the time of the exposures as well as the first three powers of HST orbital phase, and this would introduce a strong bias in the results for the albedo. However, with this reference star, we only need to detrend the data with the time of the exposures to achieve the same per-point scatter, therefore we can avoid most of the bias associated with detrending. Our final result is a 2σ upper limit of 0.64 for the geometric albedo of HAT-P-1b between 577 and 947 nm.

Coating of tips for electrochemical scanning tunneling microscopy by means of silicon, magnesium, and tungsten oxides

NASA Astrophysics Data System (ADS)

Salerno, Marco

2010-09-01

Different combinations of metal tips and oxide coatings have been tested for possible operation in electrochemical scanning tunneling microscopy. Silicon and magnesium oxides have been thermally evaporated onto gold and platinum-iridium tips, respectively. Two different thickness values have been explored for both materials, namely, 40 and 120 nm for silicon oxide and 20 and 60 nm for magnesium oxide. Alternatively, tungsten oxide has been grown on tungsten tips via electrochemical anodization. In the latter case, to seek optimal results we have varied the pH of the anodizing electrolyte between one and four. The oxide coated tips have been first inspected by means of scanning electron microscopy equipped with microanalysis to determine the morphological results of the coating. Second, the coated tips have been electrically characterized ex situ for stability in time by means of cyclic voltammetry in 1 M aqueous KCl supporting electrolyte, both bare and supplemented with K3[Fe(CN)6] complex at 10 mM concentration in milliQ water as an analyte. Only the tungsten oxide coated tungsten tips have shown stable electrical behavior in the electrolyte. For these tips, the uncoated metal area has been estimated from the electrical current levels, and they have been successfully tested by imaging a gold grating in situ, which provided stable results for several hours. The successful tungsten oxide coating obtained at pH=4 has been assigned to the WO3 form.

Coating of tips for electrochemical scanning tunneling microscopy by means of silicon, magnesium, and tungsten oxides.

PubMed

Salerno, Marco

2010-09-01

Different combinations of metal tips and oxide coatings have been tested for possible operation in electrochemical scanning tunneling microscopy. Silicon and magnesium oxides have been thermally evaporated onto gold and platinum-iridium tips, respectively. Two different thickness values have been explored for both materials, namely, 40 and 120 nm for silicon oxide and 20 and 60 nm for magnesium oxide. Alternatively, tungsten oxide has been grown on tungsten tips via electrochemical anodization. In the latter case, to seek optimal results we have varied the pH of the anodizing electrolyte between one and four. The oxide coated tips have been first inspected by means of scanning electron microscopy equipped with microanalysis to determine the morphological results of the coating. Second, the coated tips have been electrically characterized ex situ for stability in time by means of cyclic voltammetry in 1 M aqueous KCl supporting electrolyte, both bare and supplemented with K(3)[Fe(CN)(6)] complex at 10 mM concentration in milliQ water as an analyte. Only the tungsten oxide coated tungsten tips have shown stable electrical behavior in the electrolyte. For these tips, the uncoated metal area has been estimated from the electrical current levels, and they have been successfully tested by imaging a gold grating in situ, which provided stable results for several hours. The successful tungsten oxide coating obtained at pH=4 has been assigned to the WO(3) form.

Effect of In Situ Annealing Treatment on the Mobility and Morphology of TIPS-Pentacene-Based Organic Field-Effect Transistors.

PubMed

Yang, Fuqiang; Wang, Xiaolin; Fan, Huidong; Tang, Ying; Yang, Jianjun; Yu, Junsheng

2017-08-23

In this work, organic field-effect transistors (OFETs) with a bottom gate top contact structure were fabricated by using a spray-coating method, and the influence of in situ annealing treatment on the OFET performance was investigated. Compared to the conventional post-annealing method, the field-effect mobility of OFET with 60 °C in situ annealing treatment was enhanced nearly four times from 0.056 to 0.191 cm 2 /Vs. The surface morphologies and the crystallization of TIPS-pentacene films were characterized by optical microscope, atomic force microscope, and X-ray diffraction. We found that the increased mobility was mainly attributed to the improved crystallization and highly ordered TIPS-pentacene molecules.

Effect of In Situ Annealing Treatment on the Mobility and Morphology of TIPS-Pentacene-Based Organic Field-Effect Transistors

NASA Astrophysics Data System (ADS)

Yang, Fuqiang; Wang, Xiaolin; Fan, Huidong; Tang, Ying; Yang, Jianjun; Yu, Junsheng

2017-08-01

In this work, organic field-effect transistors (OFETs) with a bottom gate top contact structure were fabricated by using a spray-coating method, and the influence of in situ annealing treatment on the OFET performance was investigated. Compared to the conventional post-annealing method, the field-effect mobility of OFET with 60 °C in situ annealing treatment was enhanced nearly four times from 0.056 to 0.191 cm2/Vs. The surface morphologies and the crystallization of TIPS-pentacene films were characterized by optical microscope, atomic force microscope, and X-ray diffraction. We found that the increased mobility was mainly attributed to the improved crystallization and highly ordered TIPS-pentacene molecules.

Influence of different seasons during late gestation on Holstein cows' colostrum and postnatal adaptive capability of their calves

NASA Astrophysics Data System (ADS)

Trifković, Julijana; Jovanović, Ljubomir; Đurić, Miloje; Stevanović-Đorđević, Snežana; Milanović, Svetlana; Lazarević, Miodrag; Sladojević, Željko; Kirovski, Danijela

2018-06-01

Season may affect calves' thermal comfort and behavior, but the data related to the overall influence of seasonal variations on dams' colostrum and postnatal adaptive capability of calves are limited. The aim of this study was to measure the effects of a 49-day-long low air temperature (LAT) season (5.20 ± 0.46 °C mean air temperature) and a 53-day-long high air temperature (HAT) season (27.40 ± 0.39 °C mean air temperature) on dams' colostrum quality and physiological, biochemical, hormonal, and oxidative stress parameters of their calves during the first 7 days of life. The dams' colostrum was sampled at 2, 14, and 26 h after calving, before feeding of their calves. Calves' blood samples were taken before the first colostrum intake and on days 1, 2, 3, and 7 of life. Calves' physiological parameters were measured on days 0 and 7. HAT season significantly reduced the quality of dams' colostrum. The ingestion of the low-quality colostrum, combined with the thermal discomfort during HAT season, probably provoked impaired physiological, biochemical, hormonal, and oxidative stress parameters in samples taken from the post-colostral calves. Additionally, intravenous glucose tolerance test was performed on day 7, which suggested an enhanced insulin response in HAT season calves. This study highlights the importance of adequate supporting strategies for the care of the late gestation cows and postnatal calves during the HAT season.

pureS2HAT: S 2HAT-based Pure E/B Harmonic Transforms

NASA Astrophysics Data System (ADS)

Grain, J.; Stompor, R.; Tristram, M.

2011-10-01

The pS2HAT routines allow efficient, parallel calculation of the so-called 'pure' polarized multipoles. The computed multipole coefficients are equal to the standard pseudo-multipoles calculated for the apodized sky maps of the Stokes parameters Q and U subsequently corrected by so-called counterterms. If the applied apodizations fullfill certain boundary conditions, these multipoles correspond to the pure multipoles. Pure multipoles of one type, i.e., either E or B, are ensured not to contain contributions from the other one, at least to within numerical artifacts. They can be therefore further used in the estimation of the sky power spectra via the pseudo power spectrum technique, which has to however correctly account for the applied apodization on the one hand, and the presence of the counterterms, on the other. In addition, the package contains the routines permitting calculation of the spin-weighted apodizations, given an input scalar, i.e., spin-0 window. The former are needed to compute the counterterms. It also provides routines for maps and window manipulations. The routines are written in C and based on the S2HAT library, which is used to perform all required spherical harmonic transforms as well as all inter-processor communication. They are therefore parallelized using MPI and follow the distributed-memory computational model. The data distribution patterns, pixelization choices, conventions etc are all as those assumed/allowed by the S2HAT library.

Design and Parametric Sizing of Deep Space Habitats Supporting NASA'S Human Space Flight Architecture Team

NASA Technical Reports Server (NTRS)

Toups, Larry; Simon, Matthew; Smitherman, David; Spexarth, Gary

2012-01-01

NASA's Human Space Flight Architecture Team (HAT) is a multi-disciplinary, cross-agency study team that conducts strategic analysis of integrated development approaches for human and robotic space exploration architectures. During each analysis cycle, HAT iterates and refines the definition of design reference missions (DRMs), which inform the definition of a set of integrated capabilities required to explore multiple destinations. An important capability identified in this capability-driven approach is habitation, which is necessary for crewmembers to live and work effectively during long duration transits to and operations at exploration destinations beyond Low Earth Orbit (LEO). This capability is captured by an element referred to as the Deep Space Habitat (DSH), which provides all equipment and resources for the functions required to support crew safety, health, and work including: life support, food preparation, waste management, sleep quarters, and housekeeping.The purpose of this paper is to describe the design of the DSH capable of supporting crew during exploration missions. First, the paper describes the functionality required in a DSH to support the HAT defined exploration missions, the parameters affecting its design, and the assumptions used in the sizing of the habitat. Then, the process used for arriving at parametric sizing estimates to support additional HAT analyses is detailed. Finally, results from the HAT Cycle C DSH sizing are presented followed by a brief description of the remaining design trades and technological advancements necessary to enable the exploration habitation capability.

Emotion recognition through static faces and moving bodies: a comparison between typically developed adults and individuals with high level of autistic traits

PubMed Central

Actis-Grosso, Rossana; Bossi, Francesco; Ricciardelli, Paola

2015-01-01

We investigated whether the type of stimulus (pictures of static faces vs. body motion) contributes differently to the recognition of emotions. The performance (accuracy and response times) of 25 Low Autistic Traits (LAT group) young adults (21 males) and 20 young adults (16 males) with either High Autistic Traits or with High Functioning Autism Spectrum Disorder (HAT group) was compared in the recognition of four emotions (Happiness, Anger, Fear, and Sadness) either shown in static faces or conveyed by moving body patch-light displays (PLDs). Overall, HAT individuals were as accurate as LAT ones in perceiving emotions both with faces and with PLDs. Moreover, they correctly described non-emotional actions depicted by PLDs, indicating that they perceived the motion conveyed by the PLDs per se. For LAT participants, happiness proved to be the easiest emotion to be recognized: in line with previous studies we found a happy face advantage for faces, which for the first time was also found for bodies (happy body advantage). Furthermore, LAT participants recognized sadness better by static faces and fear by PLDs. This advantage for motion kinematics in the recognition of fear was not present in HAT participants, suggesting that (i) emotion recognition is not generally impaired in HAT individuals, (ii) the cues exploited for emotion recognition by LAT and HAT groups are not always the same. These findings are discussed against the background of emotional processing in typically and atypically developed individuals. PMID:26557101

Emotion recognition through static faces and moving bodies: a comparison between typically developed adults and individuals with high level of autistic traits.

PubMed

Actis-Grosso, Rossana; Bossi, Francesco; Ricciardelli, Paola

2015-01-01

We investigated whether the type of stimulus (pictures of static faces vs. body motion) contributes differently to the recognition of emotions. The performance (accuracy and response times) of 25 Low Autistic Traits (LAT group) young adults (21 males) and 20 young adults (16 males) with either High Autistic Traits or with High Functioning Autism Spectrum Disorder (HAT group) was compared in the recognition of four emotions (Happiness, Anger, Fear, and Sadness) either shown in static faces or conveyed by moving body patch-light displays (PLDs). Overall, HAT individuals were as accurate as LAT ones in perceiving emotions both with faces and with PLDs. Moreover, they correctly described non-emotional actions depicted by PLDs, indicating that they perceived the motion conveyed by the PLDs per se. For LAT participants, happiness proved to be the easiest emotion to be recognized: in line with previous studies we found a happy face advantage for faces, which for the first time was also found for bodies (happy body advantage). Furthermore, LAT participants recognized sadness better by static faces and fear by PLDs. This advantage for motion kinematics in the recognition of fear was not present in HAT participants, suggesting that (i) emotion recognition is not generally impaired in HAT individuals, (ii) the cues exploited for emotion recognition by LAT and HAT groups are not always the same. These findings are discussed against the background of emotional processing in typically and atypically developed individuals.

The challenging problem of disease staging in human African trypanosomiasis (sleeping sickness): a new approach to a circular question.

PubMed

Njamnshi, Alfred K; Gettinby, George; Kennedy, Peter G E

2017-05-01

Human African trypanosomiasis (HAT), also known as sleeping sickness, puts millions of people at risk in sub-Saharan Africa and is a neglected parasitic disease that is almost always fatal if untreated or inadequately treated. HAT manifests itself in two stages that are difficult to distinguish clinically. The problem of staging in HAT is extremely important since treatment options, some of which are highly toxic, are directly linked to the disease stage. Several suggested investigations for disease staging have been problematic because of the lack of an existing gold standard with which to compare new clinical staging markers. The somewhat arbitrary current criteria based on the cerebrospinal fluid (CSF) white blood cell (WBC) count have been widely used, but the new potential biomarkers are generally compared with these, thereby making the problem somewhat circular in nature. We propose an alternative 'reverse' approach to address this problem, conceptualised as using appropriate statistical methods to test the performance of combinations of established laboratory variables as staging biomarkers to correlate with the CSF WBC/trypanosomes and clinical features of HAT. This approach could lead to the use of established laboratory staging markers, potentially leading to a gold standard for staging and clinical follow-up of HAT. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Influence of different seasons during late gestation on Holstein cows' colostrum and postnatal adaptive capability of their calves.

PubMed

Trifković, Julijana; Jovanović, Ljubomir; Đurić, Miloje; Stevanović-Đorđević, Snežana; Milanović, Svetlana; Lazarević, Miodrag; Sladojević, Željko; Kirovski, Danijela

2018-06-01

Season may affect calves' thermal comfort and behavior, but the data related to the overall influence of seasonal variations on dams' colostrum and postnatal adaptive capability of calves are limited. The aim of this study was to measure the effects of a 49-day-long low air temperature (LAT) season (5.20 ± 0.46 °C mean air temperature) and a 53-day-long high air temperature (HAT) season (27.40 ± 0.39 °C mean air temperature) on dams' colostrum quality and physiological, biochemical, hormonal, and oxidative stress parameters of their calves during the first 7 days of life. The dams' colostrum was sampled at 2, 14, and 26 h after calving, before feeding of their calves. Calves' blood samples were taken before the first colostrum intake and on days 1, 2, 3, and 7 of life. Calves' physiological parameters were measured on days 0 and 7. HAT season significantly reduced the quality of dams' colostrum. The ingestion of the low-quality colostrum, combined with the thermal discomfort during HAT season, probably provoked impaired physiological, biochemical, hormonal, and oxidative stress parameters in samples taken from the post-colostral calves. Additionally, intravenous glucose tolerance test was performed on day 7, which suggested an enhanced insulin response in HAT season calves. This study highlights the importance of adequate supporting strategies for the care of the late gestation cows and postnatal calves during the HAT season.

Influence of different seasons during late gestation on Holstein cows' colostrum and postnatal adaptive capability of their calves

NASA Astrophysics Data System (ADS)

Trifković, Julijana; Jovanović, Ljubomir; Đurić, Miloje; Stevanović-Đorđević, Snežana; Milanović, Svetlana; Lazarević, Miodrag; Sladojević, Željko; Kirovski, Danijela

2018-02-01

Season may affect calves' thermal comfort and behavior, but the data related to the overall influence of seasonal variations on dams' colostrum and postnatal adaptive capability of calves are limited. The aim of this study was to measure the effects of a 49-day-long low air temperature (LAT) season (5.20 ± 0.46 °C mean air temperature) and a 53-day-long high air temperature (HAT) season (27.40 ± 0.39 °C mean air temperature) on dams' colostrum quality and physiological, biochemical, hormonal, and oxidative stress parameters of their calves during the first 7 days of life. The dams' colostrum was sampled at 2, 14, and 26 h after calving, before feeding of their calves. Calves' blood samples were taken before the first colostrum intake and on days 1, 2, 3, and 7 of life. Calves' physiological parameters were measured on days 0 and 7. HAT season significantly reduced the quality of dams' colostrum. The ingestion of the low-quality colostrum, combined with the thermal discomfort during HAT season, probably provoked impaired physiological, biochemical, hormonal, and oxidative stress parameters in samples taken from the post-colostral calves. Additionally, intravenous glucose tolerance test was performed on day 7, which suggested an enhanced insulin response in HAT season calves. This study highlights the importance of adequate supporting strategies for the care of the late gestation cows and postnatal calves during the HAT season.

HAT-P-26b: A Neptune-mass Exoplanet with Primordial Solar Heavy Element Abundance

NASA Astrophysics Data System (ADS)

Wakeford, Hannah R.; Sing, David K.; Kataria, Tiffany; Deming, Drake; Nikolov, Nikolay; Lopez, Eric; Tremblin, Pascal; Skalid Amundsen, David; Lewis, Nikole K.; Mandell, Avi; Fortney, Jonathan J.; Knutson, Heather; Benneke, Björn; Evans, Tom M.

2017-01-01

A trend in giant planet mass and atmospheric heavy elemental abundance was first noted last century from observations of planets in our own solar system. These four data points from Jupiter, Saturn, Uranus, and Neptune have served as a corner stone of planet formation theory. Here we add another point in the mass-metallicity trend from a detailed observational study of the extrasolar planet HAT-P-26b, which inhabits the critical mass regime near Neptune and Uranus. Neptune-sized worlds are among the most common planets in our galaxy and frequently exist in orbital periods very different from that of our own solar system ice giants. Atmospheric studies are the principal window into these worlds, and thereby into their formation and evolution, beyond those of our own solar system. Using the Hubble Space Telescope and Spitzer, from the optical to the infrared, we conducted a detailed atmospheric study of the Neptune-mass exoplanet HAT-P-26b over 0.5 to 4.5 μm. We detect prominent H2O absorption at 1.4 μm to 525 ppm in the atmospheric transmission spectrum. We determine that HAT-P-26b’s atmosphere is not rich in heavy elements (≈1.8×solar), which goes distinctly against the solar system mass-metallicity trend. This likely indicates that HAT-P-26b’s atmosphere is primordial and obtained its gaseous envelope late in its disk lifetime with little contamination from metal-rich planetesimals.

HAT-P-26b: A Neptune-mass Exoplanet with Primordial Solar Heavy Element Abundance

NASA Astrophysics Data System (ADS)

Wakeford, Hannah; Sing, David; Deming, Drake; Kataria, Tiffany; Lopez, Eric

2016-10-01

A trend in giant planet mass and atmospheric heavy elemental abundance was first noted last century from observations of planets in our own solar system. These four data points from Jupiter, Saturn, Uranus, and Neptune have served as a corner stone of planet formation theory. Here we add another point in the mass-metallicity trend from a detailed observational study of the extrasolar planet HAT-P-26b, which inhabits the critical mass regime near Neptune and Uranus. Neptune-sized worlds are among the most common planets in our galaxy and frequently exist in orbital periods very different from that of our own solar system ice giants. Atmospheric studies are the principal window into these worlds, and thereby into their formation and evolution, beyond those of our own solar system. Using the Hubble Space Telescope and Spitzer, from the optical to the infrared, we conducted a detailed atmospheric study of the Neptune-mass exoplanet HAT-P-26b over 0.5 to 4.5 μm. We detect prominent H2O absorption at 1.4 μm to 525 ppm in the atmospheric transmission spectrum. We determine that HAT-P-26b's atmosphere is not rich in heavy elements (≈1.8×solar), which goes distinctly against the solar system mass-metallicity trend. This likely indicates that HAT-P-26b's atmosphere is primordial and obtained its gaseous envelope late in its disk lifetime with little contamination from metal-rich planetesimals.

Structure of the Hat Creek graben region: Implications for the structure of the Hat Creek graben and transfer of right-lateral shear from the Walker Lane north of Lassen Peak, northern California, from gravity and magnetic anomalies

USGS Publications Warehouse

Langenheim, Victoria; Jachens, Robert C.; Clynne, Michael A.; Muffler, L. J. Patrick

2016-01-01

Interpretation of magnetic and new gravity data provides constraints on the geometry of the Hat Creek Fault, the amount of right-lateral offset in the area between Mt. Shasta and Lassen Peak, and confirmation of the influence of pre-existing structure on Quaternary faulting. Neogene volcanic rocks coincide with short-wavelength magnetic anomalies of both normal and reversed polarity, whereas a markedly smoother magnetic field occurs over the Klamath Mountains and its Paleogene cover. Although the magnetic field over the Neogene volcanic rocks is complex, the Hat Creek Fault, which is one of the most prominent normal faults in the region and forms the eastern margin of the Hat Creek Valley, is marked by the eastern edge of a north-trending magnetic and gravity high 20-30 km long. Modeling of these anomalies indicates that the fault is a steeply dipping (~75-85°) structure. The spatial relationship of the fault as modeled by the potential-field data, the youngest strand of the fault, and relocated seismicity suggests that deformation continues to step westward across the valley, consistent with a component of right-lateral slip in an extensional environment. Filtered aeromagnetic data highlight a concealed magnetic body of Mesozoic or older age north of Hat Creek Valley. The body’s northwest margin strikes northeast and is linear over a distance of ~40 km. Within the resolution of the aeromagnetic data (1-2 km), we discern no right-lateral offset of this body. Furthermore, Quaternary faults change strike or appear to end, as if to avoid this concealed magnetic body and to pass along its southeast edge, suggesting that pre-existing crustal structure influenced younger faulting, as previously proposed based on gravity data.

HAT-P-32b AND HAT-P-33b: TWO HIGHLY INFLATED HOT JUPITERS TRANSITING HIGH-JITTER STARS

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

Hartman, J. D.; Bakos, G. A.; Torres, G.

2011-11-20

We report the discovery of two exoplanets transiting high-jitter stars. HAT-P-32b orbits the bright V = 11.289 late-F-early-G dwarf star GSC 3281-00800, with a period P = 2.150008 {+-} 0.000001 d. The stellar and planetary masses and radii depend on the eccentricity of the system, which is poorly constrained due to the high-velocity jitter ({approx}80 m s{sup -1}). Assuming a circular orbit, the star has a mass of 1.16 {+-} 0.04 M{sub Sun} and radius of 1.22 {+-} 0.02 R{sub Sun }, while the planet has a mass of 0.860 {+-} 0.164 M{sub J} and a radius of 1.789 {+-}more » 0.025 R{sub J}. The second planet, HAT-P-33b, orbits the bright V = 11.188 late-F dwarf star GSC 2461-00988, with a period P = 3.474474 {+-} 0.000001 d. As for HAT-P-32, the stellar and planetary masses and radii of HAT-P-33 depend on the eccentricity, which is poorly constrained due to the high jitter ({approx}50 m s{sup -1}). In this case, spectral line bisector spans (BSs) are significantly anti-correlated with the radial velocity residuals, and we are able to use this correlation to reduce the residual rms to {approx}35 m s{sup -1}. We find that the star has a mass of 1.38 {+-} 0.04 M{sub Sun} and a radius of 1.64 {+-} 0.03 R{sub Sun} while the planet has a mass of 0.762 {+-} 0.101 M{sub J} and a radius of 1.686 {+-} 0.045 R{sub J} for an assumed circular orbit. Due to the large BS variations exhibited by both stars we rely on detailed modeling of the photometric light curves to rule out blend scenarios. Both planets are among the largest radii transiting planets discovered to date.« less

A literature review of economic evaluations for a neglected tropical disease: human African trypanosomiasis ("sleeping sickness").

PubMed

Sutherland, C Simone; Yukich, Joshua; Goeree, Ron; Tediosi, Fabrizio

2015-02-01

Human African trypanosomiasis (HAT) is a disease caused by infection with the parasite Trypanosoma brucei gambiense or T. b. rhodesiense. It is transmitted to humans via the tsetse fly. Approximately 70 million people worldwide were at risk of infection in 1995, and approximately 20,000 people across Africa are infected with HAT. The objective of this review was to identify existing economic evaluations in order to summarise cost-effective interventions to reduce, control, or eliminate the burden of HAT. The studies included in the review were compared and critically appraised in order to determine if there were existing standardised methods that could be used for economic evaluation of HAT interventions or if innovative methodological approaches are warranted. A search strategy was developed using keywords and was implemented in January 2014 in several databases. The search returned a total of 2,283 articles. After two levels of screening, a total of seven economic evaluations were included and underwent critical appraisal using the Scottish Intercollegiate Guidelines Network (SIGN) Methodology Checklist 6: Economic Evaluations. Results from the existing studies focused on the cost-effectiveness of interventions for the control and reduction of disease transmission. Modelling was a common method to forecast long-term results, and publications focused on interventions by category, such as case detection, diagnostics, drug treatments, and vector control. Most interventions were considered cost-effective based on the thresholds described; however, the current treatment, nifurtomix-eflornithine combination therapy (NECT), has not been evaluated for cost-effectiveness, and considerations for cost-effective strategies for elimination have yet to be completed. Overall, the current evidence highlights the main components that play a role in control; however, economic evaluations of HAT elimination strategies are needed to assist national decision makers, stakeholders, and key funders. These analyses would be of use, as HAT is currently being prioritized as a neglected tropical disease (NTD) to reach elimination by 2020.

Aerodynamic tailoring of the Learjet Model 60 wing

NASA Technical Reports Server (NTRS)

Chandrasekharan, Reuben M.; Hawke, Veronica M.; Hinson, Michael L.; Kennelly, Robert A., Jr.; Madson, Michael D.

1993-01-01

The wing of the Learjet Model 60 was tailored for improved aerodynamic characteristics using the TRANAIR transonic full-potential computational fluid dynamics (CFD) code. A root leading edge glove and wing tip fairing were shaped to reduce shock strength, improve cruise drag and extend the buffet limit. The aerodynamic design was validated by wind tunnel test and flight test data.

Aerodynamic Characteristics of a Revised Target Drone Vehicle at Mach Numbers from 1.60 to 2.86

NASA Technical Reports Server (NTRS)

Blair, A. B., Jr.; Babb, C. Donald

1968-01-01

An investigation has been conducted in the Langley Unitary Plan wind tunnel to determine the aerodynamic characteristics of a revised target drone vehicle through a Mach number range from 1.60 to 2.86. The vehicle had canard surfaces and a swept clipped-delta wing with twin tip-mounted vertical tails.

Health-related quality of life in HIV/AIDS patients on antiretroviral therapy at a tertiary care facility in Zimbabwe.

PubMed

Mafirakureva, N; Dzingirai, B; Postma, M J; van Hulst, M; Khoza, S

2016-07-01

Health-related quality of life (HRQoL) is a broad concept reflecting a patient's general subjective perception of the effect of an illness or intervention on physical, psychological and social aspects of their daily life. HRQoL among patients infected with HIV has become an important indicator of impact of disease and treatment outcomes. A cross-sectional survey was carried out at Chitungwiza Central Hospital, Zimbabwe, to assess HRQoL in patients with HIV/AIDS receiving antiretroviral therapy (ART), using two validated instruments. The HIV/AIDS-targeted quality of life (HAT-QoL) and EuroQoL Five-dimensions-Three-level (EQ-5D-3L) instruments were used to assess HRQoL. Internal consistency reliability and convergent validity of the two instruments were also evaluated. For construct validity, the relationships between HRQoL scores and socio-economic and HIV/AIDS-related characteristics were explored. The median scores for the HAT-QoL dimensions ranged from 33.3 (financial worries) to 100 (HIV mastery). A considerably low HAT-QoL dimension score of 50.0 was observed for sexual function. There were ceiling effects for all HAT-QoL dimension scores except for financial worries and disclosure worries. Floor effects were observed for financial worries and sexual function. The median of the EQ-5D-3L index and visual analogue scale (VAS) was 0.81 and 79.0, respectively. There were no floor or ceiling effects for both the EQ-5D-3L index and VAS. The overall scale Cronbach's alpha was 0.83 for HAT-Qol and 0.67 for EQ-5D-3L. HAT-QoL demonstrated good convergent validity with EQ-5D index (0.58) and VAS (0.40). A higher level of HRQoL was positively and significantly related to income, education and employment. The patients' self-reported HRQoL was generally satisfactory in all the HAT-QoL dimensions as well as the two components on the EQ-5D-3L instrument. The two instruments demonstrated good measurement properties in HIV/AIDS patients receiving ART and have potential for use, alongside biomarkers, in monitoring outcomes of interventions.

Fexinidazole--a new oral nitroimidazole drug candidate entering clinical development for the treatment of sleeping sickness.

PubMed

Torreele, Els; Bourdin Trunz, Bernadette; Tweats, David; Kaiser, Marcel; Brun, Reto; Mazué, Guy; Bray, Michael A; Pécoul, Bernard

2010-12-21

Human African trypanosomiasis (HAT), also known as sleeping sickness, is a fatal parasitic disease caused by trypanosomes. Current treatment options for HAT are scarce, toxic, no longer effective, or very difficult to administer, in particular for the advanced, fatal stage of the disease (stage 2, chronic HAT). New safe, effective and easy-to-use treatments are urgently needed. Here it is shown that fexinidazole, a 2-substituted 5-nitroimidazole rediscovered by the Drugs for Neglected Diseases initiative (DNDi) after extensive compound mining efforts of more than 700 new and existing nitroheterocycles, could be a short-course, safe and effective oral treatment curing both acute and chronic HAT and that could be implemented at the primary health care level. To complete the preclinical development and meet the regulatory requirements before initiating human trials, the anti-parasitic properties and the pharmacokinetic, metabolic and toxicological profile of fexinidazole have been assessed. Standard in vitro and in vivo anti-parasitic activity assays were conducted to assess drug efficacy in experimental models for HAT. In parallel, a full range of preclinical pharmacology and safety studies, as required by international regulatory guidelines before initiating human studies, have been conducted. Fexinidazole is moderately active in vitro against African trypanosomes (IC₅₀ against laboratory strains and recent clinical isolates ranged between 0.16 and 0.93 µg/mL) and oral administration of fexinidazole at doses of 100 mg/kg/day for 4 days or 200 mg/kg/day for 5 days cured mice with acute and chronic infection respectively, the latter being a model for the advanced and fatal stage of the disease when parasites have disseminated into the brain. In laboratory animals, fexinidazole is well absorbed after oral administration and readily distributes throughout the body, including the brain. The absolute bioavailability of oral fexinidazole was 41% in mice, 30% in rats, and 10% in dogs. Furthermore, fexinidazole is rapidly metabolised in vivo to at least two biologically active metabolites (a sulfoxide and a sulfone derivative) that likely account for a significant portion of the therapeutic effect. Key pharmacokinetic parameter after oral absorption in mice for fexinidazole and its sulfoxide and sulfone metabolites are a C(max) of 500, 14171 and 13651 ng/mL respectively, and an AUC₀₋₂₄ of 424, 45031 and 96286 h.ng/mL respectively. Essentially similar PK profiles were observed in rats and dogs. Toxicology studies (including safety pharmacology and 4-weeks repeated-dose toxicokinetics in rat and dog) have shown that fexinidazole is well tolerated. The No Observed Adverse Event Levels in the 4-weeks repeated dose toxicity studies in rats and dogs was 200 mg/kg/day in both species, with no issues of concern identified for doses up to 800 mg/kg/day. While fexinidazole, like many nitroheterocycles, is mutagenic in the Ames test due to bacterial specific metabolism, it is not genotoxic to mammalian cells in vitro or in vivo as assessed in an in vitro micronucleus test on human lymphocytes, an in vivo mouse bone marrow micronucleus test, and an ex vivo unscheduled DNA synthesis test in rats. The results of the preclinical pharmacological and safety studies indicate that fexinidazole is a safe and effective oral drug candidate with no untoward effects that would preclude evaluation in man. The drug has entered first-in-human phase I studies in September 2009. Fexinidazole is the first new clinical drug candidate with the potential for treating advanced-stage sleeping sickness in thirty years.

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