Innovative T Cell-Targeted Therapy for Ovarian Cancer

DTIC Science & Technology

2014-10-01

cell effector functions: a blend of innate programming and acquired plasticity. Nat Rev Immunol 2010; 10(7): 467-78. 22. Gomes AQ, Martins DS...costimulator (ICOS) is critical for the development of human T(H)17 cells . Sci Transl Med 2010; 2(55): 55ra78. 36. Cua DJ, Tato CM. Innate IL-17...intestinal epithelial lympho- cytes (17, 18). In contrast, circulating γδ T cells can be found in the blood and lymphoid organs, and are dominated by γδ

Molecular Profiles for Lung Cancer Pathogenesis and Detection in US Veterans

DTIC Science & Technology

2011-10-01

data was analyzed using the BRB-ArrayTools v .4.1.0 developed by Dr. Richard Simon and the BRB-ArrayTools Development Team and then normalized and log...Spira A, Beane J, Shah V , et al. Effects of cigarette smoke on the human airway epithelial cell transcriptome. Proc Natl Acad Sci U S A 2004;101:10143...10148 15. Spira A, Beane JE, Shah V , et al. Airway epithelial gene expression in the diagnostic evaluation of smokers with suspect lung cancer. Nat

Learning Complex Cell Invariance from Natural Videos: A Plausibility Proof

DTIC Science & Technology

2007-12-26

is in the McGovern Institute for Brain Research at MIT, as well as in the Dept. of Brain & Cognitive Sciences, and which is affiliated with the...stimulation induce plasticity? Proc. Nat. Acad. Sci. USA, 92:9682–9686. Deco, G. and Rolls, E. T. (2004). A neurodynamical cor- tical model of visual attention...and invariant object recognition. Vision Res, 44(6):621–42. Deco, G. and Rolls, E. T. (2005). Neurodynamics of biased competition and cooperation for

Advancing Individualized Medicine by Understanding Phenotypic Integration Using the Human Skeleton as a Model System

DTIC Science & Technology

2011-09-01

Angle ( NSA ) was measured as the angle formed between the neck axis and the shaft axis. The trochanter-to-trochanter distance was measured as the...Rev Neurosci 7(7):563-74. 4. Hopkins SR, Harms CA 2004 Gender and pulmonary gas exchange during exercise. Exerc Sport Sci Rev 32(2):50-6. 5...Marder E 2009 Functional consequences of animal- to-animal variation in circuit parameters. Nat Neurosci 12(11):1424-30. 7. Ruff C 2005 Growth tracking of

Atlas/State Data Abstract for the United States, Fiscal Year 1982

DTIC Science & Technology

1982-01-01

Fiorida (FL) 12 28 Georgia (GA) 13 30 Hawaii (HI) 14 32 Idaho 0Ui)) 15 34 Illinois (IL) 16 36 Indiana (IN) 17 38 Iowa (IA) 18 40 Kansas (KS) 19 42... IDAHO 0 25 50 75 100 I I I I’ Sc.I. in Mies ®BOISE * IDAHO FALLS NAVAL NUCLEAR POWER r TRAINING UNIT MOUNTAIN HOME AFB 48 • NAT. GUARD LINCOLN...INDUSTRIAL OTHER (NHO. @ 9 < TRAINING; ETC.) DEPOT&SUPPLY D ɠ> 34 IDAHO FISCAL YEAR 1982 (DOLLARS IN THOUSANDS) I N avy. I Other Personnel/Expenditures

The Role of Amplified Wild-Type Neu in the Etiology of Breast Cancer

DTIC Science & Technology

2004-07-01

mutations that were found, only one (a C - T change of chromosome 5 (data not shown). DAPI banding patterns of nucleotide 2137) was present in clones...activation. Proc. NatI. Acad. Sci. USA 93, 8878-8883. Koelsch, B.U. (1998). Assignment of erbB2 to rat chromosome band 1Oq32.1 by in situ...was used to map the integration site of the neu transgene in lines 6500 and 2477. Line 6500 contained -3-6 copies of the transgene in chromosome 10

AltitudeOmics: The Basic Biology of Human Acclimatization to High Altitude

DTIC Science & Technology

2013-09-01

News Physiol Sci 17: 17–21, 2002. 62. Willie CK, Macleod DB, Shaw AD, Smith KJ, Tzeng YC, Eves ND, Ikeda K, Graham J, Lewis NC, Day TA, Ainslie PN...transcranial magnetic stimulation. J Physiol 551, 661-671. Willie, C. K., Macleod, D. B., Shaw , A. D., Smith, K. J., Tzeng, Y. C., Eves, N. D., Ikeda...blood flow. Davis, Philadelphia. Willie CK, Macleod DB, Shaw AD, Smith KJ, Tzeng YC, Eves ND, Ikeda K, Graham J, Lewis NC, Day TA & Ainslie PN

Cross-cultural differences in preference for recovery of mobility among spinal cord injury rehabilitation professionals.

PubMed

Ditunno, P L; Patrick, M; Stineman, M; Morganti, B; Townson, A F; Ditunno, J F

2006-09-01

Direct observation of a constrained consensus-building process in three culturally independent five-person panels of rehabilitation professionals from the US, Italy and Canada. To illustrate cultural differences in belief among rehabilitation professionals about the relative importance of alternative functional goals during spinal cord injury (SCI) rehabilitation. Spinal Cord Injury Units in Philadelphia-USA, Rome-Italy and Vancouver-Canada. Each of the three panels came to independent consensus about recovery priorities in SCI utilizing the features resource trade-off game. The procedure involves trading imagined levels of independence (resources) across different functional items (features) assuming different stages of recovery. Sphincter management was of primary importance to all three groups. The Italian and Canadian rehabilitation professionals, however, showed preference for walking over wheelchair mobility at lower stages of assumed recovery, whereas the US professionals set wheelchair independence at a higher priority than walking. These preliminary results suggest cross-cultural recovery priority differences among SCI rehabilitation professionals. These dissimilarities in preference may reflect disparities in values, cultural expectations and health care policies.

Pressure Effect on Hydrogen Tunneling and Vibrational Spectrum in α-Mn

NASA Astrophysics Data System (ADS)

Kolesnikov, Alexander; Podlesnyak, Andrey; Sadykov, Ravil; Antonov, Vladimir; Kuzovnikov, Michail; Ehlers, Georg; Granroth, Garrett

The pressure effect on the tunneling mode and vibrational spectra of hydrogen in α-MnH0.07 has been studied by inelastic neutron scattering. Applying hydrostatic pressure of up to 30 kbar is shown to shift both the hydrogen optical modes and the tunneling peak to higher energies. First-principles calculations show that the potential for hydrogen in α-Mn becomes overall steeper with increasing pressure. At the same time, the barrier height and its extent in the direction of tunneling decrease and the calculations predict significant changes of the dynamics of hydrogen in α-Mn at 100 kbar, when the estimated tunneling splitting of the hydrogen ground state exceeds the barrier height. Acknowledgments: Research at ORNL SNS was supported by the Sci. User Facilities Division, Office BES, US DOE, and was sponsored by the LDRD Program of ORNL, managed by UT-Battelle, LLC, for the US DOE. It used resources of the Nat. Energy Res. Sci. Comp. Center, which is supported by the Office of Sci. US DOE under Contract No. DE-AC02-05CH11231. A support by a Grant of the Program on Elementary Particle Physics, Fundamental Nuclear Physics and Nuclear Techn. RAS is also acknowledged.

Selected Electrical and Thermal Properties of Undoped Nickel Oxide

DTIC Science & Technology

1978-08-01

ooooa aata, t at a, aWa Wo aOa) + + .......+ ..+ ......+ +...+.+.+4+.+4 4+4 ... 4 ..... o T, n.-A r~~.rato COw cC%(0 I~a n oenmfLr. NatO WN. 0nr 00 f. n C...Band Phenomena," Parks, R. D., ed. (Plenum, New York, 1977), p. 551-554. 23. Emin, D. and Holstein , T., Ann. Phys. (NY) 53, 439-520 (1969). Friedman,i...L. and Holstein , T., Ann. Phys. (NY) 21, 494-549 (1963). Emin, D., Ann. Phys. (NY) 64, 336-395 (1971). , 24. Kim, K. S. and Winograd, N., Surf. Sci

A simplified method for extracting androgens from avian egg yolks

USGS Publications Warehouse

Kozlowski, C.P.; Bauman, J.E.; Hahn, D.C.

2009-01-01

Female birds deposit significant amounts of steroid hormones into the yolks of their eggs. Studies have demonstrated that these hormones, particularly androgens, affect nestling growth and development. In order to measure androgen concentrations in avian egg yolks, most authors follow the extraction methods outlined by Schwabl (1993. Proc. Nat. Acad. Sci. USA 90:11446-11450). We describe a simplified method for extracting androgens from avian egg yolks. Our method, which has been validated through recovery and linearity experiments, consists of a single ethanol precipitation that produces substantially higher recoveries than those reported by Schwabl.

Rehabilitation and future participation of youth following spinal cord injury: caregiver perspectives.

PubMed

House, L A; Russell, H F; Kelly, E H; Gerson, A; Vogel, L C

2009-12-01

Cross-sectional survey. To examine caregivers' perspectives on the effectiveness of rehabilitative support experienced by youth with spinal cord injury (SCI) during acute rehabilitation and after community reintegration in terms of their community participation. Data collection took place at the three Shriners SCI hospitals: Chicago, Philadelphia, and Northern California. A total of 132 primary caregivers of youth with SCI completed a survey on what their child had experienced during and after rehabilitation to enhance their community participation. Caregivers found technical support from staff (41%), motivation and encouragement from staff (25%), and education (17%) to be the most important factors during rehabilitation for encouraging their child's future participation in school or community activities. Caregivers found involvement in activities (30%), personal resilience (22%) and interactions with others with disabilities (13%) to be important experiences since rehabilitation in terms of their child's participation in school and community activities. Caregivers who responded that something they experienced during rehabilitation was helpful to participation had children who had been injured longer and who were older at time of injury. In addition, caregivers who reported that something they have experienced since their child's rehabilitation has been helpful in terms of participation also had children who were older at time of injury. Findings from this study can be used to help professionals tailor rehabilitation programs to better meet the needs of youth with SCI and their families, thereby increasing chances of successful reintegration back into their communities.

31Cl beta decay and the 30P31S reaction rate in nova nucleosynthesis

NASA Astrophysics Data System (ADS)

Bennett, Michael; Wrede, C.; Brown, B. A.; Liddick, S. N.; Pérez-Loureiro, D.; NSCL e12028 Collaboration

2016-03-01

The 30P31S reaction rate is critical for modeling the final isotopic abundances of ONe nova nucleosynthesis, identifying the origin of presolar nova grains, and calibrating proposed nova thermometers. Unfortunately, this rate is essentially experimentally unconstrained because the strengths of key 31S proton capture resonances are not known, due to uncertainties in their spins and parities. Using a 31Cl beam produced at the National Superconducting Cyclotron Laboratory, we have populated several 31S states for study via beta decay and devised a new decay scheme which includes updated beta feedings and gamma branchings as well as multiple states previously unobserved in 31Cl beta decay. Results of this study, including the unambiguous identification due to isospin mixing of a new l = 0 , Jπ = 3 /2+ 31S resonance directly in the middle of the Gamow Window, will be presented, and significance to the evaluation of the 30P31S reaction rate will be discussed. Work supported by U.S. Natl. Sci. Foundation (Grants No. PHY-1102511, PHY-1404442, PHY-1419765, and PHY-1431052); U.S. Dept. of Energy, Natl. Nucl. Security Administration (Award No. DE-NA0000979); Nat. Sci. and Eng. Research Council of Canada.

Changes in consensus arylamine N-acetyltransferase (NAT) gene nomenclature

PubMed Central

Hein, David W.; Boukouvala, Sotiria; Grant, Denis M.; Minchin, Rodney F.; Sim, Edith

2008-01-01

Changes in consensus arylamine N-acetyltransferase (NAT) gene nomenclature determined at the 2007 international NAT workshop include: 1) Alleles in all species except mouse and rat are all uppercase. For mouse and rat, the first letter is upper case followed by lower case. 2) The nomenclature system is now species-specific. Thus, NAT2*1 (chicken), NAT2*2 & NAT2*3 (rabbit), Nat2*8 Nat2*9, Nat2*22 & Nat2*23 (mouse), NAT2*15, NAT2*16A & NAT2*16B (Syrian hamster), and NAT2*20, NAT2*21A & NAT2*21B (rat) are retired and renumbered within a species. A species modifier incorporated into the allele designation is written in upper case Roman font, e.g., (MOUSE)Nat1*1 is now the reference Nat1 allele in mouse; and 3) The NAT website also can now be accessed at a webbalias address: http://N-acetyltransferasenomenclature.louisville.edu. New NAT alleles should continue to be submitted to the NAT nomenclature committee for inclusion on the website to ensure proper categorization and to continue consistency in nomenclature. PMID:18334921

Evolution of insect arylalkylamine N-acetyltransferases: Structural evidence from the yellow fever mosquito, Aedes aegypti

PubMed Central

Han, Qian; Robinson, Howard; Ding, Haizhen; Christensen, Bruce M.; Li, Jianyong

2012-01-01

Arylalkylamine N-acetyltransferase (aaNAT) catalyzes the transacetylation from acetyl-CoA to arylalkylamines. aaNATs are involved in sclerotization and neurotransmitter inactivation in insects. Phyletic distribution analysis confirms three clusters of aaNAT-like sequences in insects: typical insect aaNAT, polyamine NAT-like aaNAT, and mosquito unique putative aaNAT (paaNAT). Here we studied three proteins: aaNAT2, aaNAT5b, and paaNAT7, each from a different cluster. aaNAT2, a protein from the typical insect aaNAT cluster, uses histamine as a substrate as well as the previously identified arylalkylamines. aaNAT5b, a protein from polyamine NAT -like aaNAT cluster, uses hydrazine and histamine as substrates. The crystal structure of aaNAT2 was determined using single-wavelength anomalous dispersion methods, and that of native aaNAT2, aaNAT5b and paaNAT7 was detected using molecular replacement techniques. All three aaNAT structures have a common fold core of GCN5-related N-acetyltransferase superfamily proteins, along with a unique structural feature: helix/helices between β3 and β4 strands. Our data provide a start toward a more comprehensive understanding of the structure–function relationship and physiology of aaNATs from the mosquito Aedes aegypti and serve as a reference for studying the aaNAT family of proteins from other insect species. The structures of three different types of aaNATs may provide targets for designing insecticides for use in mosquito control. PMID:22753468

Fluorescent labeling of SNAP-tagged proteins in cells.

PubMed

Lukinavičius, Gražvydas; Reymond, Luc; Johnsson, Kai

2015-01-01

One of the most prominent self-labeling tags is SNAP-tag. It is an in vitro evolution product of the human DNA repair protein O (6)-alkylguanine-DNA alkyltransferase (hAGT) that reacts specifically with benzylguanine (BG) and benzylchloropyrimidine (CP) derivatives, leading to covalent labeling of SNAP-tag with a synthetic probe (Gronemeyer et al., Protein Eng Des Sel 19:309-316, 2006; Curr Opin Biotechnol 16:453-458, 2005; Keppler et al., Nat Biotechnol 21:86-89, 2003; Proc Natl Acad Sci U S A 101:9955-9959, 2004). SNAP-tag is well suited for the analysis and quantification of fused target protein using fluorescence microscopy techniques. It provides a simple, robust, and versatile approach to the imaging of fusion proteins under a wide range of experimental conditions.

Catalytic properties and heat stabilities of novel recombinant human N-acetyltransferase 2 allozymes support existence of genetic heterogeneity within the slow acetylator phenotype.

PubMed

Hein, David W; Doll, Mark A

2017-08-01

Human N-acetyltransferase 2 (NAT2) catalyzes the N-acetylation of numerous aromatic amine drugs such as sulfamethazine (SMZ) and hydrazine drugs such as isoniazid (INH). NAT2 also catalyzes the N-acetylation of aromatic amine carcinogens such as 2-aminofluorene and the O- and N,O-acetylation of aromatic amine and heterocyclic amine metabolites. Genetic polymorphism in NAT2 modifies drug efficacy and toxicity as well as cancer risk. Acetyltransferase catalytic activities and heat stability associated with six novel NAT2 haplotypes (NAT2*6C, NAT2*14C, NAT2*14D, NAT2*14E, NAT2*17, and NAT2*18) were compared with that of the reference NAT2*4 haplotype following recombinant expression in Escherichia coli. N-acetyltransferase activities towards SMZ and INH were significantly (p < 0.0001) lower when catalyzed by the novel recombinant human NAT2 allozymes compared to NAT2 4. SMZ and INH N-acetyltransferase activities catalyzed by NAT2 14C and NAT2 14D were significantly lower (p < 0.001) than catalyzed by NAT2 6C and NAT2 14E. N-Acetylation catalyzed by recombinant human NAT2 17 was over several hundred-fold lower than by recombinant NAT2 4 precluding measurement of its kinetic or heat inactivation constants. Similar results were observed for the O-acetylation of N-hydroxy-2-aminofluorene and N-hydroxy-2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine and the intramolecular N,O-acetylation of N-hydroxy-N-acetyl-2-aminofluorene. The apparent V max of the novel recombinant NAT2 allozymes NAT2 6C, NAT2 14C, NAT2 14D, and NAT2 14E towards AF, 4-aminobiphenyl (ABP), and 3,2'-dimethyl-4-aminobiphenyl (DMABP) were each significantly (p < 0.001) lower while their apparent K m values did not differ significantly (p > 0.05) from recombinant NAT2 4. The apparent V max catalyzed by NAT2 14C and NAT2 14D were significantly lower (p < 0.05) than the apparent V max catalyzed by NAT2 6C and NAT2 14E towards AF, ABP, and DMABP. Heat inactivation rate constants for recombinant human NAT2 14C, 14D, 14E, and 18 were significantly (p < 0.05) higher than NAT2 4. These results provide further evidence of genetic heterogeneity within the NAT2 slow acetylator phenotype.

Cuticular Biominerals of the Terrestrial Crustacean Oniscus asellus (Isopoda, Linnaeus 1758)

NASA Astrophysics Data System (ADS)

Mergelsberg, S. T.; Mukhopadhyay, B.; Dove, P. M.

2013-12-01

Biomineralization is a phenomenon observed in many eukaryotic organisms and evidence suggests this process began relatively early in the evolution of multicellular life (Marin F et al. 1996). Crustaceans form a large fraction of all eukaryotic biomineralizers by incorporating calcium carbonate (CaCO3) into their cuticle. Terrestrial species are challenged in their production of CaCO3 by the absence of calcium-rich waters. To cope with this limitation, the terrestrial crustacean Oniscus asellus recycles up to 80% (Auzou G 1953) of its total calcium during the molting process. This feat is accomplished by separate molting of the front and back cuticle, with temporary storage of the calcium carbonate as amorphous calcium carbonate (ACC) in the front half (Ziegler A 1997). These processes infer a highly efficient and regulated mechanism for biomineralization that is most likely orchestrated by a myriad of proteins (Ziegler A et al. 2012). Until recently, investigations of biomineralization were largely directed toward understanding morphology and large-scale chemistry of the minerals, ignoring the mechanistic roles of biomacromolecules in mineralization processes. More recent work suggests a high involvement of these compounds on the formation of biominerals and, in some cases, the specific polymorphs thereof (Keene EC et al. 2010). This study focuses on identifying the components of the biological mineralization matrix at each stage of the process. Using chemical demineralization of the stored ACC, all biomacromolecules can be separated and purified for subsequent analysis by MALDI-TOF mass spectrometry. To link the localized biochemistry more intimately to the polymorph of calcium carbonate that forms in the animal, the inorganic phase (';the mineral') will be monitored at each life stage using XRD and TEM. This analysis will reveal the organic components of a very precise biomineralization mechanism and may shed insight on its evolutionary origin. References: Marin F, Westbroek P et al., 1996, Proc Nat Acad Sci 93:1554-1559 Auzou G, 1953, L Ann Sci Nat 15:71-98 Ziegler A, 1997, Zoomorphology 117:181-187 Ziegler A et al., 2012, Cryst Growth Des 12:646-655 Keene EC et al., 2010, Cryst Growth Des 10:1383-1389

Fundamental period of Italian reinforced concrete buildings: comparison between numerical, experimental and Italian code simplified values

NASA Astrophysics Data System (ADS)

Ditommaso, Rocco; Carlo Ponzo, Felice; Auletta, Gianluca; Iacovino, Chiara; Nigro, Antonella

2015-04-01

Aim of this study is a comparison among the fundamental period of reinforced concrete buildings evaluated using the simplified approach proposed by the Italian Seismic code (NTC 2008), numerical models and real values retrieved from an experimental campaign performed on several buildings located in Basilicata region (Italy). With the intention of proposing simplified relationships to evaluate the fundamental period of reinforced concrete buildings, scientists and engineers performed several numerical and experimental campaigns, on different structures all around the world, to calibrate different kind of formulas. Most of formulas retrieved from both numerical and experimental analyses provides vibration periods smaller than those suggested by the Italian seismic code. However, it is well known that the fundamental period of a structure play a key role in the correct evaluation of the spectral acceleration for seismic static analyses. Generally, simplified approaches impose the use of safety factors greater than those related to in depth nonlinear analyses with the aim to cover possible unexpected uncertainties. Using the simplified formula proposed by the Italian seismic code the fundamental period is quite higher than fundamental periods experimentally evaluated on real structures, with the consequence that the spectral acceleration adopted in the seismic static analysis may be significantly different than real spectral acceleration. This approach could produces a decreasing in safety factors obtained using linear and nonlinear seismic static analyses. Finally, the authors suggest a possible update of the Italian seismic code formula for the simplified estimation of the fundamental period of vibration of existing RC buildings, taking into account both elastic and inelastic structural behaviour and the interaction between structural and non-structural elements. Acknowledgements This study was partially funded by the Italian Civil Protection Department within the project DPC-RELUIS 2014 - RS4 ''Seismic observatory of structures and health monitoring''. References R. Ditommaso, M. Vona, M. R. Gallipoli and M. Mucciarelli (2013). Evaluation and considerations about fundamental periods of damaged reinforced concrete buildings. Nat. Hazards Earth Syst. Sci., 13, 1903-1912, 2013. www.nat-hazards-earth-syst-sci.net/13/1903/2013. doi:10.5194/nhess-13-1903-2013

PlantNATsDB: a comprehensive database of plant natural antisense transcripts.

PubMed

Chen, Dijun; Yuan, Chunhui; Zhang, Jian; Zhang, Zhao; Bai, Lin; Meng, Yijun; Chen, Ling-Ling; Chen, Ming

2012-01-01

Natural antisense transcripts (NATs), as one type of regulatory RNAs, occur prevalently in plant genomes and play significant roles in physiological and pathological processes. Although their important biological functions have been reported widely, a comprehensive database is lacking up to now. Consequently, we constructed a plant NAT database (PlantNATsDB) involving approximately 2 million NAT pairs in 69 plant species. GO annotation and high-throughput small RNA sequencing data currently available were integrated to investigate the biological function of NATs. PlantNATsDB provides various user-friendly web interfaces to facilitate the presentation of NATs and an integrated, graphical network browser to display the complex networks formed by different NATs. Moreover, a 'Gene Set Analysis' module based on GO annotation was designed to dig out the statistical significantly overrepresented GO categories from the specific NAT network. PlantNATsDB is currently the most comprehensive resource of NATs in the plant kingdom, which can serve as a reference database to investigate the regulatory function of NATs. The PlantNATsDB is freely available at http://bis.zju.edu.cn/pnatdb/.

Arylamine N-acetyltransferases: from drug metabolism and pharmacogenetics to drug discovery

PubMed Central

Sim, E; Abuhammad, A; Ryan, A

2014-01-01

Arylamine N-acetyltransferases (NATs) are polymorphic drug-metabolizing enzymes, acetylating arylamine carcinogens and drugs including hydralazine and sulphonamides. The slow NAT phenotype increases susceptibility to hydralazine and isoniazid toxicity and to occupational bladder cancer. The two polymorphic human NAT loci show linkage disequilibrium. All mammalian Nat genes have an intronless open reading frame and non-coding exons. The human gene products NAT1 and NAT2 have distinct substrate specificities: NAT2 acetylates hydralazine and human NAT1 acetylates p-aminosalicylate (p-AS) and the folate catabolite para-aminobenzoylglutamate (p-abaglu). Human NAT2 is mainly in liver and gut. Human NAT1 and its murine homologue are in many adult tissues and in early embryos. Human NAT1 is strongly expressed in oestrogen receptor-positive breast cancer and may contribute to folate and acetyl CoA homeostasis. NAT enzymes act through a catalytic triad of Cys, His and Asp with the architecture of the active site-modulating specificity. Polymorphisms may cause unfolded protein. The C-terminus helps bind acetyl CoA and differs among NATs including prokaryotic homologues. NAT in Salmonella typhimurium supports carcinogen activation and NAT in mycobacteria metabolizes isoniazid with polymorphism a minor factor in isoniazid resistance. Importantly, nat is in a gene cluster essential for Mycobacterium tuberculosis survival inside macrophages. NAT inhibitors are a starting point for novel anti-tuberculosis drugs. Human NAT1-specific inhibitors may act in biomarker detection in breast cancer and in cancer therapy. NAT inhibitors for co-administration with 5-aminosalicylate (5-AS) in inflammatory bowel disease has prompted ongoing investigations of azoreductases in gut bacteria which release 5-AS from prodrugs including balsalazide. PMID:24467436

Role of N-acetyltransferase 2 acetylation polymorphism in 4, 4'-methylene bis (2-chloroaniline) biotransformation.

PubMed

Hein, David W; Zhang, Xiaoyan; Doll, Mark A

2018-02-01

Arylamine N-acetyltransferase 1 (NAT1) and 2 (NAT2) catalyze the acetylation of arylamine carcinogens. Single nucleotide polymorphisms in the NAT2 coding exon present in NAT2 haplotypes encode allozymes with reduced N-acetyltransferase activity towards the N-acetylation of arylamine carcinogens and the O-acetylation of their N-hydroxylated metabolites. NAT2 acetylator phenotype modifies urinary bladder cancer risk following exposures to arylamine carcinogens such as 4-aminobiphenyl. 4, 4'-methylene bis (2-chloroaniline) (MOCA) is a Group 1 carcinogen for which a role of the NAT2 acetylation polymorphism on cancer risk is unknown. We investigated the role of NAT2 and the genetic acetylation polymorphism on both MOCA N-acetylation and N-hydroxy-MOCA O-acetylation. MOCA N-acetylation exhibited a robust gene dose response in rabbit liver cytosol and in cryopreserved human hepatocytes derived from individuals of rapid, intermediate and slow acetylator NAT2 genotype. MOCA exhibited about 4-fold higher affinity for recombinant human NAT2 than NAT1. Recombinant human NAT2*4 (reference) and 15 variant recombinant human NAT2 allozymes catalyzed both the N-acetylation of MOCA and the O-acetylation of N-hydroxy-MOCA. Human NAT2 5, NAT2 6, NAT2 7 and NAT2 14 allozymes catalyzed MOCA N-acetylation and N-hydroxy-O-acetylation at rates much lower than the reference NAT2 4 allozyme. In conclusion, our results show that NAT2 acetylator genotype has an important role in MOCA metabolism and suggest that risk assessments related to MOCA exposures consider accounting for NAT2 acetylator phenotype in the analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

Infusing Authentic Inquiry into Biotechnology

NASA Astrophysics Data System (ADS)

Hanegan, Nikki L.; Bigler, Amber

2009-10-01

Societal benefit depends on the general public's understandings of biotechnology (Betsch in World J Microbiol Biotechnol 12:439-443, 1996; Dawson and Cowan in Int J Sci Educ 25(1):57-69, 2003; Schiller in Business Review: Federal Reserve Bank of Philadelphia (Fourth Quarter), 2002; Smith and Emmeluth in Am Biol Teach 64(2):93-99, 2002). A National Science Foundation funded survey of high school biology teachers reported that hands-on biotechnology education exists in advanced high school biology in the United States, but is non-existent in mainstream biology coursework (Micklos et al. in Biotechnology labs in American high schools, 1998). The majority of pre-service teacher content preparation courses do not teach students appropriate content knowledge through the process of inquiry. A broad continuum exists when discussing inquiry-oriented student investigations (Hanegan et al. in School Sci Math J 109(2):110-134, 2009). Depending on the amount of structure in teacher lessons, inquiries can often be categorized as guided or open. The lesson can be further categorized as simple or authentic (Chinn and Malhotra in Sci Educ 86(2):175-218, 2002). Although authentic inquiries provide the best opportunities for cognitive development and scientific reasoning, guided and simple inquiries are more often employed in the classroom (Crawford in J Res Sci Teach 37(9):916-937, 2000; NRC in Inquiry and the national science education standards: a guide for teaching and learning, 2000). For the purposes of this study we defined inquiry as "authentic" if original research problems were resolved (Hanegan et al. in School Sci Math J 109(2):110-134, 2009; Chinn and Malhotra in Sci Educ 86(2):175-218, 2002; Roth in Authentic school science: knowing and learning in open-inquiry science laboratories, 1995). The research question to guide this study through naturalistic inquiry research methods was: How will participants express whether or not an authentic inquiry experience enhanced their understanding of biotechnology? As respondents explored numerous ideas in order to develop a workable research question, struggled to create a viable protocol, executed their experiment, and then evaluated their results, they commented on unexpected topics regarding the nature of science as well as specific content knowledge relating to their experiments. Four out of five participants reported they learned the most during authentic inquiry laboratory experience.

Effect of common NAT2 variant alleles in the acetylation of the major clonazepam metabolite, 7-aminoclonazepam.

PubMed

Olivera, M; Martínez, C; Gervasini, G; Carrillo, J A; Ramos, S; Benítez, J; García-Martin, E; Agúndez, J A G

2007-01-01

We investigated the role of NAT2 on clonazepam acetylation, using transiently expressed human NAT2 alleles. The NAT25*B and the NAT2*6A variant alleles cause a 20 and 22-fold reduction in the Vmax, respectively. We conclude that NAT2 is responsible for 7-aminoclonazepam acetylation and that NAT2 gene polymorphisms impair such metabolic pathway.

Genetic heterogeneity among slow acetylator N-acetyltransferase 2 phenotypes in cryopreserved human hepatocytes.

PubMed

Doll, Mark A; Hein, David W

2017-07-01

Genetic polymorphisms in human N-acetyltransferase 2 (NAT2) modify the metabolism of numerous drugs and carcinogens. These genetic polymorphisms modify both drug efficacy and toxicity and cancer risk associated with carcinogen exposure. Previous studies have suggested phenotypic heterogeneity among different NAT2 slow acetylator genotypes. NAT2 phenotype was investigated in vitro and in situ in samples of human hepatocytes obtained from various NAT2 slow and intermediate NAT2 acetylator genotypes. NAT2 gene dose response (NAT2*5B/*5B > NAT2*5B/*6A > NAT2*6A/*6A) was observed towards the N-acetylation of the NAT2-specific drug sulfamethazine by human hepatocytes both in vitro and in situ. N-acetylation of 4-aminobiphenyl, an arylamine carcinogen substrate for both N-acetyltransferase 1 and NAT2, showed the same trend both in vitro and in situ although the differences were not significant (p > 0.05). The N-acetylation of the N-acetyltransferase 1-specific substrate p-aminobenzoic acid did not follow this trend. In comparisons of NAT2 intermediate acetylator genotypes, differences in N-acetylation between NAT2*4/*5B and NAT2*4/*6B hepatocytes were not observed in vitro or in situ towards any of these substrates. These results further support phenotypic heterogeneity among NAT2 slow acetylator genotypes, consistent with differential risks of drug failure or toxicity and cancer associated with carcinogen exposure.

Arylamine N-acetyltransferase 1 in situ N-acetylation on CD3+ peripheral blood mononuclear cells correlate with NATb mRNA and NAT1 haplotype.

PubMed

Salazar-González, Raúl A; Turiján-Espinoza, Eneida; Hein, David W; Niño-Moreno, Perla C; Romano-Moreno, Silvia; Milán-Segovia, Rosa C; Portales-Pérez, Diana P

2018-02-01

Human arylamine N-acetyltransferase 1 (NAT1) is responsible for the activation and elimination of xenobiotic compounds and carcinogens. Genetic polymorphisms in NAT1 modify both drug efficacy and toxicity. Previous studies have suggested a role for NAT1 in the development of several diseases. The aim of the present study was to evaluate NAT1 protein expression and in situ N-acetylation capacity in peripheral blood mononuclear cells (PBMC), as well as their possible associations with the expression of NAT1 transcript and NAT1 genotype. We report NAT1 protein, mRNA levels, and N-acetylation in situ activity for PBMC obtained from healthy donors. NAT1-specific protein expression was higher in CD3+ cells than other major immune cell subtypes (CD19 or CD56 cells). N-acetylation of pABA varied markedly among the PBMC of participants, but correlated very significantly with levels of NAT1 transcripts. NAT1*4 subjects showed significantly (p = 0.017) higher apparent pABA V max of 71.3 ± 3.7 versus the NAT1*14B subjects apparent V max of 58.5 ± 2.5 nmoles Ac-pABA/24 h/million cells. Levels of pABA N-acetylation activity at each concentration of substrate evaluated also significantly correlated with NAT1 mRNA levels for all samples (p < 0.0001). This highly significant correlation was maintained for samples with the NAT1*4 (p = 0.002) and NAT1*14B haplotypes (p = 0.0106). These results provide the first documentation that NAT1-catalyzed N-acetylation in PBMC is higher in T cell than in other immune cell subtypes and that individual variation in N-acetylation capacity is dependent upon NAT1 mRNA and NAT1 haplotype.

Functional Effects of Genetic Polymorphisms in the N-acetyltransferase 1 Coding and 3′ Untranslated Regions

PubMed Central

Zhu, Yuanqi; States, J. Christopher; Wang, Yang; Hein, David W.

2011-01-01

BACKGROUND The functional effects of N-acetyltransferase 1 (NAT1) polymorphisms and haplotypes are poorly understood, compromising the validity of associations reported with diseases including birth defects and numerous cancers. METHODS We investigated the effects of genetic polymorphisms within the NAT1 coding region and the 3′-untranslated region (3′-UTR) and their associated haplotypes on N- and O-acetyltransferase catalytic activities, and NAT1 mRNA and protein levels following recombinant expression in COS-1 cells. RESULTS 1088T>A (rs1057126; 3′-UTR) and 1095C>A (rs15561; 3′-UTR) each slightly reduced NAT1 catalytic activity and NAT1 mRNA and protein levels. A 9-base pair (TAATAATAA) deletion between nucleotides 1065-1090 (3′-UTR) reduced NAT1 catalytic activity and NAT1 mRNA and protein levels. In contrast, a 445G>A (rs4987076; V149I), 459G>A (rs4986990; T153T), 640T>G (rs4986783; S214A) coding region haplotype present in NAT1*11 increased NAT1 catalytic activity and NAT1 protein, but not NAT1 mRNA levels. A combination of the 9-base pair (TAATAATAA) deletion and the 445G>A, 459G>A, 640T>G coding region haplotypes, both present in NAT1*11, appeared to neutralize the opposing effects on NAT1 protein and catalytic activity, resulting in levels of NAT1 protein and catalytic activity that did not differ significantly from the NAT1*4 reference. CONCLUSIONS Since 1095C>A (3′-UTR) is the sole polymorphism present in NAT1*3, our data suggests that NAT1*3 is not functionally equivalent to the NAT1*4 reference. Furthermore, our findings provide biological support for reported associations of 1088T>A and 1095C>A polymorphisms with birth defects. PMID:21290563

NATpipe: an integrative pipeline for systematical discovery of natural antisense transcripts (NATs) and phase-distributed nat-siRNAs from de novo assembled transcriptomes

PubMed Central

Yu, Dongliang; Meng, Yijun; Zuo, Ziwei; Xue, Jie; Wang, Huizhong

2016-01-01

Nat-siRNAs (small interfering RNAs originated from natural antisense transcripts) are a class of functional small RNA (sRNA) species discovered in both plants and animals. These siRNAs are highly enriched within the annealed regions of the NAT (natural antisense transcript) pairs. To date, great research efforts have been taken for systematical identification of the NATs in various organisms. However, developing a freely available and easy-to-use program for NAT prediction is strongly demanded by researchers. Here, we proposed an integrative pipeline named NATpipe for systematical discovery of NATs from de novo assembled transcriptomes. By utilizing sRNA sequencing data, the pipeline also allowed users to search for phase-distributed nat-siRNAs within the perfectly annealed regions of the NAT pairs. Additionally, more reliable nat-siRNA loci could be identified based on degradome sequencing data. A case study on the non-model plant Dendrobium officinale was performed to illustrate the utility of NATpipe. Finally, we hope that NATpipe would be a useful tool for NAT prediction, nat-siRNA discovery, and related functional studies. NATpipe is available at www.bioinfolab.cn/NATpipe/NATpipe.zip. PMID:26858106

N-Acetyltransferase 2 (NAT2) polymorphism as a risk modifier of susceptibility to pediatric acute lymphoblastic leukemia.

PubMed

Kamel, Azza M; Ebid, Gamal T A; Moussa, Heba S

2015-08-01

N-Acetyltransferases (NAT) have been known to modify the risk to a variety of solid tumors. However, the role of NAT2 polymorphism in risk susceptibility to childhood acute lymphoblastic leukemia (ALL) is still not well known. We performed a case-control study to determine if the common NAT2 polymorphisms play a role in altering susceptibility to pediatric ALL. DNA of 92 pediatric ALL patients and 312 healthy controls was analyzed for the NAT2 polymorphisms using the PCR-RFLP method. The wild-type NAT2*4 was encountered in 8.6 % of patients versus 11.8 % of controls (P = 0.23). The rapid acetylators NAT2*12 803A>G, AG, GG, and AG/GG were overrepresented in controls (P = 0.0001; odds ratio (OR) 0.22, 0.19, and 0.21 respectively). NAT2*5D 341T>C and NAT2*11A 481C>T were of comparable frequencies. For their combination, NAT2*5A, a slow acetylator, both TCTT and CCCT were overrepresented in patients (P < 0.001; OR 15.8 and 17.9 respectively). NAT2*5B (803A>G, 341T>C, 481C>T) was overrepresented in controls (P < 0.001; OR 0.12). Apparently, 803A>G ameliorated the combined effect of 341T>C and 481C>T. A similar effect was obtained with NAT2*5C (341T>A, 803A>G) (P < 0.0001; OR 0.11). For slow acetylator NAT2*7A 857G>A, GA and GA/AA were overrepresented in patients (P = 0.009 and 0.01; OR 2.74 and 2.72 respectively). NAT2*13 282C>T, NAT2*6B 590G>A, and NAT2*14A 191G>A were of comparable frequencies. NAT2 282C>A in combination with NAT2 857G>A (NAT2*7B) showed a synergistic effect in patients versus controls (P < 0.0001; OR 3.51). In conclusion, NAT2 gene polymorphism(s) with slow acetylator phenotype is generally associated with the risk of development of ALL in children.

NAT2 gene diversity and its evolutionary trajectory in the Americas.

PubMed

Bisso-Machado, R; Ramallo, V; Paixão-Côrtes, V R; Acuña-Alonzo, V; Demarchi, D A; Sandoval, J R S; Granara, A A S; Salzano, F M; Hünemeier, T; Bortolini, M C

2016-11-01

N-acetyltransferase 2 (NAT2) is responsible for metabolizing xenobiotics; NAT2 polymorphisms lead to three phenotypes: rapid, intermediate and slow acetylators. We aimed to investigate NAT2 diversity in Native Americans. NAT2 exon 2 was sequenced for 286 individuals from 21 populations (Native American and American Mestizos). Excluding the basal/rapid haplotype NAT2*4, the most frequent haplotypes are NAT2*5B (35.95%) in hunter-gatherers and NAT2*7B (20.61%) and NAT2*5B (19.08%) in agriculturalists that were related to the slow phenotype. A new haplotype was identified in two Amerindians. Data from the ~44 kb region surrounding NAT2 in 819 individuals from Africa, East-Asia, Europe and America were used in additional analyses. No significant differences in the acetylator NAT2 haplotype and phenotype distributions were found between Native American populations practicing farming and/or herding and those practicing hunting and gathering, probably because of the absence or weakness of selection pressures and presence of demographic and random processes preventing detection of any selection signal.

Congenic rats with higher arylamine N-acetyltransferase 2 activity exhibit greater carcinogen-induced mammary tumor susceptibility independent of carcinogen metabolism.

PubMed

Stepp, Marcus W; Doll, Mark A; Samuelson, David J; Sanders, Mary Ann G; States, J Christopher; Hein, David W

2017-03-31

Recent investigations suggest role(s) of human arylamine N-acetyltransferase 1 (NAT1) in breast cancer. Rat NAT2 is orthologous to human NAT1 and the gene products are functional homologs. We conducted in vivo studies using F344.WKY-Nat2 rapid/slow rats, congenic at rat Nat2 for high (rapid) and low (slow) arylamine N-acetyltransferase activity, to assess a possible role for rat NAT2 in mammary tumor susceptibility. Mammary carcinogens, methylnitrosourea (MNU) and 7,12-dimethylbenzanthracene (DMBA) neither of which is metabolized by N-acetyltransferase, were administered to assess mammary tumors. MNU was administered at 3 or 8 weeks of age. DMBA was administered at 8 weeks of age. NAT2 enzymatic activity and endogenous acetyl-coenzyme A (AcCoA) levels were measured in tissue samples and embryonic fibroblasts isolated from the congenic rats. Tumor latency was shorter in rapid NAT2 rats compared to slow NAT2 rats, with statistical significance for MNU administered at 3 and 8 weeks of age (p = 0.009 and 0.050, respectively). Tumor multiplicity and incidence were higher in rapid NAT2 rats compared to slow NAT2 rats administered MNU or DMBA at 8 weeks of age (MNU, p = 0.050 and 0.035; DMBA, p = 0.004 and 0.027, respectively). Recombinant rat rapid-NAT2, as well as tissue samples and embryonic fibroblasts derived from rapid NAT2 rats, catalyzed p-aminobenzoic acid N-acetyl transfer and folate-dependent acetyl-coenzyme A (AcCoA) hydrolysis at higher rates than those derived from rat slow-NAT2. Embryonic fibroblasts isolated from rapid NAT2 rats displayed lower levels of cellular AcCoA than slow NAT2 rats (p < 0.01). A novel role for rat NAT2 in mammary cancer was discovered unrelated to carcinogen metabolism, suggesting a role for human NAT1 in breast cancer.

Arylamine N-acetyltransferase 2 gene polymorphism in an Algerian population.

PubMed

Chelouti, Hiba; Khelil, Malika

2017-09-01

The arylamine N-acetyltransferase 2 (NAT2) is a key enzyme in the biotransformation of xenobiotics. NAT2 gene polymorphisms have been associated with the risk of isoniazid hepatotoxicity and these polymorphisms change among different populations. The objective of this study is to investigate NAT2 polymorphisms in order to predict the prevalence of NAT2 phenotype in an Algerian population. Genotyping of NAT2 was done using a PCR-RFLP method. Haplotype was analysed using the software package PHASE, version 2.0. The major haplotypes were NAT2*5B (23.72%), NAT2*6 A (18.61%), NAT2*4 (14.60%) and NAT2*5 F (10%). The average of the expected slow acetylator phenotype was 53%. Our results suggest that the high frequency of slow acetylator phenotype requires investigation into its possible association with ATDH.

Twenty-first century vaccines

PubMed Central

Rappuoli, Rino

2011-01-01

In the twentieth century, vaccination has been possibly the greatest revolution in health. Together with hygiene and antibiotics, vaccination led to the elimination of many childhood infectious diseases and contributed to the increase in disability-free life expectancy that in Western societies rose from 50 to 78–85 years (Crimmins, E. M. & Finch, C. E. 2006 Proc. Natl Acad. Sci. USA 103, 498–503; Kirkwood, T. B. 2008 Nat. Med 10, 1177–1185). In the twenty-first century, vaccination will be expected to eliminate the remaining childhood infectious diseases, such as meningococcal meningitis, respiratory syncytial virus, group A streptococcus, and will address the health challenges of this century such as those associated with ageing, antibiotic resistance, emerging infectious diseases and poverty. However, for this to happen, we need to increase the public trust in vaccination so that vaccines can be perceived as the best insurance against most diseases across all ages. PMID:21893537

Fabrication of micron scale metallic structures on photo paper substrates by low temperature photolithography for device applications

NASA Astrophysics Data System (ADS)

Cooke, M. D.; Wood, D.

2015-11-01

Using commercial standard paper as a substrate has a significant cost reduction implication over other more expensive substrate materials by approximately a factor of 100 (Shenton et al 2015 EMRS Spring Meeting; Zheng et al 2013 Nat. Sci. Rep. 3 1786). Discussed here is a novel process which allows photolithography and etching of simple metal films deposited on paper substrates, but requires no additional facilities to achieve it. This allows a significant reduction in feature size down to the micron scale over devices made using more conventional printing solutions which are of the order of tens of microns. The technique has great potential for making cheap disposable devices with additional functionality, which could include flexibility and foldability, simple disposability, porosity and low weight requirements. The potential for commercial applications and scale up is also discussed.

The existence results and Tikhonov regularization method for generalized mixed variational inequalities in Banach spaces

NASA Astrophysics Data System (ADS)

Wang, Min

2017-06-01

This paper aims to establish the Tikhonov regularization method for generalized mixed variational inequalities in Banach spaces. For this purpose, we firstly prove a very general existence result for generalized mixed variational inequalities, provided that the mapping involved has the so-called mixed variational inequality property and satisfies a rather weak coercivity condition. Finally, we establish the Tikhonov regularization method for generalized mixed variational inequalities. Our findings extended the results for the generalized variational inequality problem (for short, GVIP( F, K)) in R^n spaces (He in Abstr Appl Anal, 2012) to the generalized mixed variational inequality problem (for short, GMVIP(F,φ , K)) in reflexive Banach spaces. On the other hand, we generalized the corresponding results for the generalized mixed variational inequality problem (for short, GMVIP(F,φ ,K)) in R^n spaces (Fu and He in J Sichuan Norm Univ (Nat Sci) 37:12-17, 2014) to reflexive Banach spaces.

Induction of neuronal axon outgrowth by Shati/Nat8l by energy metabolism in mice cultured neurons.

PubMed

Sumi, Kazuyuki; Uno, Kyosuke; Matsumura, Shohei; Miyamoto, Yoshiaki; Furukawa-Hibi, Yoko; Muramatsu, Shin-Ichi; Nabeshima, Toshitaka; Nitta, Atsumi

2015-09-09

A novel N-acetyltransferase, Shati/Nat8l, was identified in the nucleus accumbens of mice repeatedly treated with methamphetamine (METH). Shati/Nat8l has been reported to inhibit the pharmacological action induced by METH. Shati/Nat8l produces N-acetylaspartate from aspartate and acetyl-CoA. Previously, we reported that overexpression of Shati/Nat8l in nucleus accumbens attenuates the response to METH by N-acetylaspartylglutamate (which is derived from N-acetylaspartate)-mGluR3 signaling in the mice brain. In the present study, to clarify the type of cells that produce Shati/Nat8l, we carried out in-situ hybridization for the detection of Shati/Nat8l mRNA along with immunohistochemical studies using serial sections of mice brain. Shati/Nat8l mRNA was detected in neuronal cells, but not in astrocytes or microglia cells. Next, we investigated the function of Shati/Nat8l in the neuronal cells in mice brain; then, we used an adeno-associated virus vector containing Shati/Nat8l for transfection and overexpression of Shati/Nat8l protein into the primary cultured neurons to investigate the contribution toward the neuronal activity of Shati/Nat8l. Overexpression of Shati/Nat8l in the mice primary cultured neurons induced axonal growth, but not dendrite elongation at day 1.5 (DIV). This finding indicated that Shati/Nat8l contributes toward neuronal development. LY341495, a selective group II mGluRs antagonist, did not abolish this axonal growth, and N-acetylaspartylglutamate itself did not abolish axon outgrowth in the same cultured system. The cultured neurons overexpressing Shati/Nat8l contained high ATP, suggesting that axon outgrowth is dependent on energy metabolism. This study shows that Shati/Nat8l in the neuron may induce axon outgrowth by ATP synthesis and not through mGluR3 signaling.

Wet-Bulb-Globe Temperature Data Report

DTIC Science & Technology

2015-03-01

Hour Min Pressure Dry Nat Wet Globe Dry Nat Wet Globe Dry Nat Wet Globe Wind Cld amt Cld type Obscuration Quest RH Kestrel RH VPSc RH S1 WBGT Q WBGT...Wet Globe Dry Nat Wet Globe Dry Nat Wet Globe Wind Cld amt Cld type Obscuration Quest RH Kestrel RH VPSc RH S1 WBGT Q WBGT K2 WBGT GMT millibars deg F...Dry Nat Wet Globe Dry Nat Wet Globe Wind Cld amt Cld type Obscuration Quest RH Kestrel RH VPSc RH S1 WBGT Q WBGT K2 WBGT GMT millibars deg F deg F deg

Rapid birth-and-death evolution of the xenobiotic metabolizing NAT gene family in vertebrates with evidence of adaptive selection

PubMed Central

2013-01-01

Background The arylamine N-acetyltransferases (NATs) are a unique family of enzymes widely distributed in nature that play a crucial role in the detoxification of aromatic amine xenobiotics. Considering the temporal changes in the levels and toxicity of environmentally available chemicals, the metabolic function of NATs is likely to be under adaptive evolution to broaden or change substrate specificity over time, making NATs a promising subject for evolutionary analyses. In this study, we trace the molecular evolutionary history of the NAT gene family during the last ~450 million years of vertebrate evolution and define the likely role of gene duplication, gene conversion and positive selection in the evolutionary dynamics of this family. Results A phylogenetic analysis of 77 NAT sequences from 38 vertebrate species retrieved from public genomic databases shows that NATs are phylogenetically unstable genes, characterized by frequent gene duplications and losses even among closely related species, and that concerted evolution only played a minor role in the patterns of sequence divergence. Local signals of positive selection are detected in several lineages, probably reflecting response to changes in xenobiotic exposure. We then put a special emphasis on the study of the last ~85 million years of primate NAT evolution by determining the NAT homologous sequences in 13 additional primate species. Our phylogenetic analysis supports the view that the three human NAT genes emerged from a first duplication event in the common ancestor of Simiiformes, yielding NAT1 and an ancestral NAT gene which in turn, duplicated in the common ancestor of Catarrhini, giving rise to NAT2 and the NATP pseudogene. Our analysis suggests a main role of purifying selection in NAT1 protein evolution, whereas NAT2 was predicted to mostly evolve under positive selection to change its amino acid sequence over time. These findings are consistent with a differential role of the two human isoenzymes and support the involvement of NAT1 in endogenous metabolic pathways. Conclusions This study provides unequivocal evidence that the NAT gene family has evolved under a dynamic process of birth-and-death evolution in vertebrates, consistent with previous observations made in fungi. PMID:23497148

Structures and functions of insect arylalkylamine N-acetyltransferase (iaaNAT); a key enzyme for physiological and behavioral switch in arthropods

PubMed Central

Hiragaki, Susumu; Suzuki, Takeshi; Mohamed, Ahmed A. M.; Takeda, Makio

2015-01-01

The evolution of N-acetyltransfeases (NATs) seems complex. Vertebrate arylalkylamine N-acetyltransferase (aaNAT) has been extensively studied since it leads to the synthesis of melatonin, a multifunctional neurohormone prevalent in photoreceptor cells, and is known as a chemical token of the night. Melatonin also serves as a scavenger for reactive oxygen species. This is also true with invertebrates. NAT therefore has distinct functional implications in circadian function, as timezymes (aaNAT), and also xenobiotic reactions (arylamine NAT or simply NAT). NATs belong to a broader enzyme group, the GCN5-related N-acetyltransferase superfamily. Due to low sequence homology and a seemingly fast rate of structural differentiation, the nomenclature for NATs can be confusing. The advent of bioinformatics, however, has helped to classify this group of enzymes; vertebrates have two distinct subgroups, the timezyme type and the xenobiotic type, which has a wider substrate range including imidazolamine, pharmacological drugs, environmental toxicants and even histone. Insect aaNAT (iaaNAT) form their own clade in the phylogeny, distinct from vertebrate aaNATs. Arthropods are unique, since the phylum has exoskeleton in which quinones derived from N-acetylated monoamines function in coupling chitin and arthropodins. Monoamine oxidase (MAO) activity is limited in insects, but NAT-mediated degradation prevails. However, unexpectedly iaaNAT occurs not only among arthropods but also among basal deuterostomia, and is therefore more apomorphic. Our analyses illustrate that iaaNATs has unique physiological roles but at the same time it plays a role in a timezyme function, at least in photoperiodism. Photoperiodism has been considered as a function of circadian system but the detailed molecular mechanism is not well understood. We propose a molecular hypothesis for photoperiodism in Antheraea pernyi based on the transcription regulation of NAT interlocked by the circadian system. Therefore, the enzyme plays both unique and universal roles in insects. The unique role of iaaNATs in physiological regulation urges the targeting of this system for integrated pest management (IPM). We indeed showed a successful example of chemical compound screening with reconstituted enzyme and further attempts seem promising. PMID:25918505

Structures and functions of insect arylalkylamine N-acetyltransferase (iaaNAT); a key enzyme for physiological and behavioral switch in arthropods.

PubMed

Hiragaki, Susumu; Suzuki, Takeshi; Mohamed, Ahmed A M; Takeda, Makio

2015-01-01

The evolution of N-acetyltransfeases (NATs) seems complex. Vertebrate arylalkylamine N-acetyltransferase (aaNAT) has been extensively studied since it leads to the synthesis of melatonin, a multifunctional neurohormone prevalent in photoreceptor cells, and is known as a chemical token of the night. Melatonin also serves as a scavenger for reactive oxygen species. This is also true with invertebrates. NAT therefore has distinct functional implications in circadian function, as timezymes (aaNAT), and also xenobiotic reactions (arylamine NAT or simply NAT). NATs belong to a broader enzyme group, the GCN5-related N-acetyltransferase superfamily. Due to low sequence homology and a seemingly fast rate of structural differentiation, the nomenclature for NATs can be confusing. The advent of bioinformatics, however, has helped to classify this group of enzymes; vertebrates have two distinct subgroups, the timezyme type and the xenobiotic type, which has a wider substrate range including imidazolamine, pharmacological drugs, environmental toxicants and even histone. Insect aaNAT (iaaNAT) form their own clade in the phylogeny, distinct from vertebrate aaNATs. Arthropods are unique, since the phylum has exoskeleton in which quinones derived from N-acetylated monoamines function in coupling chitin and arthropodins. Monoamine oxidase (MAO) activity is limited in insects, but NAT-mediated degradation prevails. However, unexpectedly iaaNAT occurs not only among arthropods but also among basal deuterostomia, and is therefore more apomorphic. Our analyses illustrate that iaaNATs has unique physiological roles but at the same time it plays a role in a timezyme function, at least in photoperiodism. Photoperiodism has been considered as a function of circadian system but the detailed molecular mechanism is not well understood. We propose a molecular hypothesis for photoperiodism in Antheraea pernyi based on the transcription regulation of NAT interlocked by the circadian system. Therefore, the enzyme plays both unique and universal roles in insects. The unique role of iaaNATs in physiological regulation urges the targeting of this system for integrated pest management (IPM). We indeed showed a successful example of chemical compound screening with reconstituted enzyme and further attempts seem promising.

Structure of carbonate melts at high pressure

NASA Astrophysics Data System (ADS)

Hudspeth, J.; Sanloup, C.; Cochain, B.; Konopkova, Z.; Afonina, V.; Morgenroth, W.

2015-12-01

Carbonate melts are rare magmas with only a single active volcano (Oldoinyo Lengai,Tanzania [1]). They are of fundamental interest for their role in the Earth's deep carbon cycle and are of immense economic importance due to their affinity for REE strategic metals (niobium, uranium, tantalum, etc). They have remarkable physical properties such as very low viscosity [2] and magmatic temperatures for alkaline carbonate lavas [3] and it has been predicted that their compressibility could be significantly higher than that of silicate melts [4,5]. Despite the atomic structure of carbonate melts being fundamental for controlling their physical and chemical behavior in natural systems, very few structural studies have been reported and these have been largely computational. Here we present initial structural investigations of carbonate melts at mantle pressures using in situ x-ray diffraction in diamond anvil cells. The structure factor S(Q) is transformed to obtain the real space pair distribution function G(R) which describes the local and intermediate range atomic ordering allowing bond length and coordination number changes with pressure to be determined. [1] Krafft and Keller, Science 245:168-170, 1989 [2] Yono et al., Nat. Commun. 5:5091, 2014 [3] Dobson et al., Earth Planet. Sci. Lett. 143:207-215, 1996 [4] Genge et al., Earth Planet. Sci. Lett. 131:225-238, 1995 [5] Jones et al., Rev. Mineral. Geochem. 75:289-322, 2013

N-acetyltransferase polymorphisms are associated with risk of lymphoma subtypes.

PubMed

Cocco, Pierluigi; Zucca, Mariagrazia; Sanna, Sonia; Satta, Giannina; Nonne, Tinucia; Angelucci, Emanuele; Gabbas, Attilio; Rais, Marco; Malpeli, Giorgio; Campagna, Marcello; Scarpa, Aldo; G Ennas, Maria

2016-06-01

Genes encoding for arylamine N-acetyltransferase 1 and 2 (NAT1 and NAT2) have been investigated with alternate findings in relation to risk of non-Hodgkin lymphoma (NHL). We tested functional haplotype-based NAT1 and NAT2 gene polymorphisms in relation to risk of lymphoma overall and its major B cell subtypes, diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL) and chronic lymphocytic leukaemia (CLL). We used allele specific primers and multiplex PCR to detect NAT1 and NAT2 haplotypes in 248 patients with incident lymphoma and 208 population controls. We inferred the NAT1 rapid and slow acetylator and the NAT2 rapid, intermediate or slow acetylator phenotype, based on published functional data on the respective genotypes. Odds ratios and 95% confidence intervals (95% CIs) for lymphoma, B-NHL, DLBCL, FL, CLL, and other B-NHL combined associated with the inferred rapid NAT1 acetylator and with the intermediate and slow NAT2 acetylator phenotypes were estimated with unconditional and polytomous logistic regression analysis, adjusting for age, gender and education. NAT1 rapid acetylators showed a 2.8-fold excess risk (95% CI 1.5-5.2) for lymphoma (all subtypes combined). Risk was highest for CLL and FL, with significant heterogeneity detected across subtypes. Risk also increased with decreasing NAT2 acetylating capacity with no heterogeneity detected across B cell lymphoma subtypes. Risks did not vary by gender. Although poor statistical power was a major limitation in our study, larger studies and pooled analyses are warranted to test whether NAT1 and NAT2 gene polymorphisms might modulate risk of specific lymphoma subtypes through the varying metabolic activity of their products. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Importance of the Evaluation of N-Acetyltransferase Enzyme Activity Prior to 5-Aminosalicylic Acid Medication for Ulcerative Colitis.

PubMed

Matthis, Andrea L; Zhang, Bin; Denson, Lee A; Yacyshyn, Bruce R; Aihara, Eitaro; Montrose, Marshall H

2016-08-01

5-aminosalicylic acid (5-ASA) is a classic anti-inflammatory drug for the treatment of ulcerative colitis. N-acetyltransferase (NAT) enzymes convert 5-ASA to its metabolite N-acetyl-5-ASA, and it is unresolved whether 5-ASA or N-acetyl-5-ASA is the effective therapeutic molecule. We previously demonstrated that colonic production of N-acetyl-5-ASA (NAT activity) is decreased in dextran sulfate sodium-induced colitis. Our hypothesis is that 5-ASA is the therapeutic molecule to improve colitis, with the corollary that altered NAT activity affects drug efficacy. Since varying clinical effectiveness of 5-ASA has been reported, we also ask if NAT activity varies with inflammation in pediatric or adult patients. Acute colonic inflammation was induced in C57BL/6 NAT wild-type (WT) or knockout mice, using 3.5% dextran sulfate sodium (w/v) concurrent with 5-ASA treatment. Adult and pediatric rectosigmoid biopsies were collected from control or patients with ulcerative colitis. Tissue was analyzed for NAT and myeloperoxidase activity. Dextran sulfate sodium-induced colitis was of similar severity in both NAT WT and knockout mice, and NAT activity was significantly decreased in NAT WT mice. In the setting of colitis, 5-ASA significantly restored colon length and decreased myeloperoxidase activity in NAT knockout but not in WT mice. Myeloperoxidase activity negatively correlated with NAT activity in pediatric patients, but correlation was not observed in adult patients. Inflammation decreases NAT activity in the colon of mice and human pediatric patients. Decreased NAT activity enhances the therapeutic effect of 5-ASA in mice. A NAT activity assay could be useful to help predict the efficacy of 5-ASA therapy.

Natural antisense transcripts are significantly involved in regulation of drought stress in maize.

PubMed

Xu, Jie; Wang, Qi; Freeling, Micheal; Zhang, Xuecai; Xu, Yunbi; Mao, Yan; Tang, Xin; Wu, Fengkai; Lan, Hai; Cao, Moju; Rong, Tingzhao; Lisch, Damon; Lu, Yanli

2017-05-19

Natural antisense transcripts (NATs) are a prominent and complex class of regulatory RNAs. Using strand-specific RNA sequencing, we identified 1769 sense and antisense transcript pairs (NAT pairs) in two maize inbreds with different sensitivity to drought, as well as in two derivative recombination inbred lines (RILs). A significantly higher proportion of NATs relative to non-NATs are specifically expressed under water stress (WS). Surprisingly, expression of sense and antisense transcripts produced by NAT pairs is significantly correlated, particularly under WS. We found an unexpected large proportion of NATs with protein coding potential, as estimated by ribosome release scores. Small RNAs significantly accumulate within NAT pairs, with 21 nt smRNA particularly enriched in overlapping regions of these pairs of genes. The abundance of these smRNAs is significantly altered in the leafbladeless1 mutant, suggesting that these genes may be regulated by the tasiRNA pathway. Further, NATs are significantly hypomethylated and include fewer transposable element sequences relative to non-NAT genes. NAT gene regions also exhibit higher levels of H3K36me3, H3K9ac, and H3K4me3, but lower levels of H3K27me3, indicating that NAT gene pairs generally exhibit an open chromatin configuration. Finally, NAT pairs in 368 diverse maize inbreds and 19 segregating populations were specifically enriched for polymorphisms associated with drought tolerance. Taken together, the data highlight the potential impact of that small RNAs and histone modifications have in regulation of NAT expression, and the significance of NATs in response to WS. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

23. North Philadelphia Station. Philadelphia, Philadelphia Co., PA. Sec. 1101, ...

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

23. North Philadelphia Station. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 84.55. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

Half a decade of mini-pool nucleic acid testing: Cost-effective way for improving blood safety in India

PubMed Central

Chandrashekar, Shivaram

2014-01-01

Background and Objectives: It is well established that Nucleic acid testing (NAT) reduces window phase of transfusion transmissible infections (TTI) and helps improve blood safety. NAT testing can be done individually or in pools. The objectives of this study were to determine the utility, feasibility and cost effectiveness of an in-house minipool-NAT(MP-NAT). Materials and Methods: Blood donors were screened by history, tested by ELISA and sero-negative samples were subjected to an in-house NAT by using reverse transcriptase-polymerase chain reaction (RT-PCR). Testing was done in mini-pools of size eight (8). Positive pools were repeated with individual samples. Results: During the study period of Oct 2005-Sept 2010 (5 years) all blood donors (n=53729) were screened by ELISA. Of which 469 (0.87%) were positive for HIV-1, HBV or HCV. Sero-negative samples (n=53260) were screened by in-house MP-NAT. HIV-NAT yield was 1/53260 (n=1) and HBV NAT yield (n=2) was 1/26630. Conclusion: NAT yield was lower than other India studies possibly due to the lower sero-reactivity amongst our donors. Nevertheless it intercepted 9 lives including the components prepared. The in-house assay met our objective of improving blood safety at nominal cost and showed that it is feasible to set up small molecular biology units in medium-large sized blood banks and deliver blood within 24-48 hours. The utility of NAT (NAT yield) will vary based on the donor population, the type of serological test used, the nature of kit employed and the sensitivity of NAT test used. The limitations of our in-house MP-NAT consisted of stringent sample preparation requirements, with labor and time involved. The benefits of our MP-NAT were that it acted as a second level of check for ELISA tests, was relatively inexpensive compared to ID-NAT and did not need sophisticated equipment. PMID:24678172

A pilot study of the modulation of sirtuins on arylamine N-acetyltransferase 1 and 2 enzymatic activity.

PubMed

Turiján-Espinoza, Eneida; Salazar-González, Rául Alejandro; Uresti-Rivera, Edith Elena; Hernández-Hernández, Gloria Estela; Ortega-Juárez, Montserrat; Milán, Rosa; Portales-Pérez, Diana

2018-03-01

Arylamine N -acetyltransferase (NAT; E.C. 2.3.1.5) enzymes are responsible for the biotransformation of several arylamine and hydrazine drugs by acetylation. In this process, the acetyl group transferred to the acceptor substrate produces NAT deacetylation and, in consequence, it is susceptible of degradation. Sirtuins are protein deacetylases, dependent on nicotine adenine dinucleotide, which perform post-translational modifications on cytosolic proteins. To explore possible sirtuin participation in the enzymatic activity of arylamine NATs, the expression levels of NAT1, NAT2, SIRT1 and SIRT6 in peripheral blood mononuclear cells (PBMC) from healthy subjects were examined by flow cytometry and Western blot. The in situ activity of the sirtuins on NAT enzymatic activity was analyzed by HPLC, in the presence or absence of an agonist (resveratrol) and inhibitor (nicotinamide) of sirtuins. We detected a higher percentage of positive cells for NAT2 in comparison with NAT1, and higher numbers of SIRT1+ cells compared to SIRT6 in lymphocytes. In situ NAT2 activity in the presence of NAM inhibitors was higher than in the presence of its substrate, but not in the presence of resveratrol. In contrast, the activity of NAT1 was not affected by sirtuins. These results showed that NAT2 activity might be modified by sirtuins.

N-Acetyltransferase 2 Genotypes Are Associated With Diisocyanate-Induced Asthma.

PubMed

Yucesoy, Berran; Kissling, Grace E; Johnson, Victor J; Lummus, Zana L; Gautrin, Denyse; Cartier, André; Boulet, Louis-Philippe; Sastre, Joaquin; Quirce, Santiago; Tarlo, Susan M; Cruz, Maria-Jesus; Munoz, Xavier; Luster, Michael I; Bernstein, David I

2015-12-01

To investigate whether genetic variants of N-acetyltransferase (NAT) genes are associated with diisocyanate asthma (DA). The study population consisted of 354 diisocyanate-exposed workers. Genotyping was performed using a 5'-nuclease polymerase chain reaction assay. The NAT2 rs2410556 and NAT2 rs4271002 variants were significantly associated with DA in the univariate analysis. In the first logistic regression model comparing DA+ and asymptomatic worker groups, the rs2410556 (P = 0.004) and rs4271002 (P < 0.001) single nucleotide polymorphisms and the genotype combination, NAT2 rs4271002*NAT1 rs11777998, showed associations with DA risk (P = 0.014). In the second model comparing DA+ and DA- groups, NAT2 rs4271002 variant and the combined genotype, NAT1 rs8190845*NAT2 rs13277605, were significantly associated with DA risk (P = 0.022, P = 0.036, respectively). These findings suggest that variations in the NAT2 gene and their interactions contribute to DA susceptibility.

Rapid high-silica magma generation in basalt-dominated rift settings

NASA Astrophysics Data System (ADS)

Berg, Sylvia E.; Troll, Valentin R.; Burchardt, Steffi; Deegan, Frances M.; Riishuus, Morten S.; Whitehouse, Martin J.; Harris, Chris; Freda, Carmela; Ellis, Ben S.; Krumbholz, Michael; Gústafsson, Ludvik E.

2015-04-01

The processes that drive large-scale silicic magmatism in basalt-dominated provinces have been widely debated for decades, with Iceland being at the centre of this discussion [1-5]. Iceland hosts large accumulations of silicic rocks in a largely basaltic oceanic setting that is considered by some workers to resemble the situation documented for the Hadean [6-7]. We have investigated the time scales and processes of silicic volcanism in the largest complete pulse of Neogene rift-related silicic magmatism preserved in Iceland (>450 km3), which is a potential analogue of initial continent nucleation in early Earth. Borgarfjörður Eystri in NE-Iceland hosts silicic rocks in excess of 20 vol.%, which exceeds the ≤12 vol% usual for Iceland [3,8]. New SIMS zircon ages document that the dominantly explosive silicic pulse was generated within a ≤2 Myr window (13.5 ± 0.2 to 12.2 ± 03 Ma), and sub-mantle zircon δ18O values (1.2 to 4.5 ± 0.2‰, n=337) indicate ≤33% assimilation of low-δ18O hydrothermally-altered crust (δ18O=0‰), with intense crustal melting at 12.5 Ma, followed by rapid termination of silicic magma production once crustal fertility declined [9]. This silicic outburst was likely caused by extensive rift flank volcanism due to a rift relocation and a flare of the Iceland plume [4,10] that triggered large-scale crustal melting and generated mixed-origin silicic melts. High-silica melt production from a basaltic parent was replicated in a set of new partial melting experiments of regional hydrated basalts, conducted at 800-900°C and 150 MPa, that produced silicic melt pockets up to 77 wt.% SiO2. Moreover, Ti-in-zircon thermometry from Borgarfjörður Eystri give a zircon crystallisation temperature ~713°C (Ti range from 2.4 to 22.1 ppm, average=7.7 ppm, n=142), which is lower than recorded elsewhere in Iceland [11], but closely overlaps with the zircon crystallisation temperatures documented for Hadean zircon populations [11-13], hinting at crustal recycling as a key process. Our results therefore provide a mechanism and a time-scale for rapid, voluminous silicic magma generation in modern and ancient basalt-dominated rift setting, such as Afar, Taupo, and potentially early Earth. The Neogene plume-related rift flank setting of NE-Iceland may thus constitute a plausible geodynamic and compositional analogue for generating silicic (continental) crust in the subduction-free setting of a young Earth (e.g. ≥3 Ga [14]). [1] Bunsen, R. 1851. Ann. Phys. Chem. 159, 197-272. [2] MacDonald R., et al., 1987. Mineral. Mag. 51, 183-202. [3] Jonasson, K., 2007. J. Geodyn. 43, 101-117. [4] Martin, E., et al., 2011. Earth Planet. Sci. Lett. 311, 28-38. [5] Charreteur, G., et al., 2013.Contrib. Mineral. Petr. 166, 471- 490. [6] Willbold, E., et al., 2009. Earth Planet. Sci. Lett. 279, 44-52. [7] Reimink, J.R., et al., 2014. Nat. Geosci. 7, 529-533. [8] Gústafsson, L.E., et al., 1989. Jökull 39, 75-89. [9] Meade, F.C., et al., 2014. Nat. comm. 5. [10] Óskarsson, B.V., Riishuus, M.S., 2013. J. Volcanol. Geoth. Res. 267, 92-118. [11] Carley, T.L., et al., 2014. Earth Planet. Sci. Lett. 405, 85-97. [12] Trail, D., et al., 2007. Geochem. Geophys. Geosyst.8, Q06014. [13] Harrison, T.M. et al., 2008. Earth Planet. Sci. Lett.268, 476-486. [14] Kamber, B. S., et al., 2005. Earth Planet. Sci. Lett. 240, 276-290.

Deficiency of N-acetyltransferase increases the interactions of isoniazid with endobiotics in mouse liver.

PubMed

Wang, Pengcheng; Shehu, Amina I; Lu, Jie; Joshi, Rujuta H; Venkataramanan, Raman; Sugamori, Kim S; Grant, Denis M; Zhong, Xiao-Bo; Ma, Xiaochao

2017-12-01

Acetylation is the major metabolic pathway of isoniazid (INH) mediated by N-acetyltransferases (NATs). Previous reports suggest that slow acetylators have higher risks of INH hepatotoxicity than rapid acetylators, but the detailed mechanisms remain elusive. The current study used Nat1/2(-/-) mice to mimic NAT slow metabolizers and to investigate INH metabolism in the liver. We found that INH acetylation is abolished in the liver of Nat1/2(-/-) mice, suggesting that INH acetylation is fully dependent on NAT1/2. In addition to the acetylation pathway, INH can be hydrolyzed to form hydrazine (Hz) and isonicotinic acid (INA). We found that INA level was not altered in the liver of Nat1/2(-/-) mice, indicating that deficiency of NAT1/2 has no effect on INH hydrolysis. Because INH acetylation was abolished and INH hydrolysis was not altered in Nat1/2(-/-) mice, we expected an extremely high level of INH in the liver. However, we only observed a modest accumulation of INH in the liver of Nat1/2(-/-) mice, suggesting that there are alternative pathways in INH metabolism in NAT1/2 deficient condition. Our further studies revealed that the conjugated metabolites of INH with endobiotics, including fatty acids and vitamin B6, were significantly increased in the liver of Nat1/2(-/-) mice. In summary, this study illustrated that deficiency of NAT1/2 decreases INH acetylation, but increases the interactions of INH with endobiotics in the liver. These findings can be used to guide future studies on the mechanisms of INH hepatotoxicity in NAT slow metabolizers. Copyright © 2017 Elsevier Inc. All rights reserved.

NATb/NAT1*4 promotes greater arylamine N-acetyltransferase 1 mediated DNA adducts and mutations than NATa/NAT1*4 following exposure to 4-aminobiphenyl

PubMed Central

Millner, Lori M.; Doll, Mark A.; Cai, Jian; States, J. Christopher; Hein, David W.

2011-01-01

N -acetyltransferase 1 (NAT1) is a phase II metabolic enzyme responsible for the biotransformation of aromatic and heterocyclic amine carcinogens such as 4-aminobiphenyl (ABP). NAT1 catalyzes N-acetylation of arylamines as well as the O-acetylation of N-hydroxylated arylamines. O-acetylation leads to the formation of electrophilic intermediates that result in DNA adducts and mutations. NAT1 is transcribed from a major promoter, NATb, and an alternative promoter, NATa, resulting in mRNAs with distinct 5′-untranslated regions (UTR). NATa mRNA is expressed primarily in the kidney, liver, trachea and lung while NATb mRNA has been detected in all tissues studied. To determine if differences in 5′-UTR have functional effect upon NAT1 activity and DNA adducts or mutations following exposure to ABP, pcDNA5/FRT plasmid constructs were prepared for transfection of full length human mRNAs including the 5′-UTR derived from NATa or NATb, the open reading frame, and 888 nucleotides of the 3′-UTR. Following stable transfection of NATb/NAT1*4 or NATa/NAT1*4 into nucleotide excision repair (NER) deficient Chinese hamster ovary cells, N-acetyltransferase activity (in vitro and in situ), mRNA, and protein expression were higher in NATb/NAT1*4 than NATa/NAT1*4 transfected cells (p<0.05). Consistent with NAT1 expression and activity, ABP-induced DNA adducts and hypoxanthine phosphoribosyl transferase mutants were significantly higher (p<0.05) in NATb/NAT1*4 than in NATa/NAT1*4 transfected cells following exposure to ABP. These differences observed between NATa and NATb suggest that the 5′-UTRs are differentially regulated. PMID:21837760

N-acetyltransferase 1*10 genotype in bladder cancer patients.

PubMed

Höhne, Svetlana; Gerullis, Holger; Blaszkewicz, Meinolf; Selinski, Silvia; Hengstler, Jan G; Otto, Thomas; Golka, Klaus

2017-01-01

In a large bladder cancer study in the greater Berlin area with 425 cases and 343 controls, the haplotype N-acetyltransferase 1*10 (NAT1*10) was associated with a decreased bladder cancer risk. In a recently published meta-analysis, results of the studies were found to be inconclusive. Therefore, the aim of this study was to investigate the frequency of NAT1*10 in bladder cancer patients and controls recruited in an area without industries reported to be associated with increased bladder cancer risk. Rs1057126 (1088 T > A) and rs15561 (1095 C > A) were determined in 412 bladder cancer patients and 415 controls without a known history of malignancies. With these two single-nucleotide polymorphisms (SNP), it was possible to distinguish between NAT1*4 (wild type), NAT1*3 (1095 C > A), and NAT1*10 (1088 T > A, 1095C > A). The frequencies of the determined NAT1 haplotypes did not differ markedly between cases and controls: NAT1*4: 74%, NAT1*3: 6%, NAT1*10: 20%. Bladder cancer risk was not significantly modulated by NAT1*10/*10 (OR 1.03, 95% CI 0.71-1.48) but was higher for NAT1*3/*3 genotypes (OR 2.05, 95% CI 1.32-3.21). In contrast to the Berlin study from 2001, data in present study demonstrated that NAT1*10 haplotype was not associated with a significantly decreased bladder cancer risk. This may be due to local effects in the greater Berlin area, particularly at the time of investigation. The findings of the present study are in agreement with observations of a recently published meta-analysis which also showed no relevant impact of NAT1*10 haplotype on bladder cancer risk. The impact of the rare NAT1*3/*3 genotype was significant but this may be attributed to rarity without major practical relevance.

Systemic functional expression of N-acetyltransferase polymorphism in the F344 Nat2 congenic rat

PubMed Central

Hein, David W.; Bendaly, Jean; Neale, Jason R.; Doll, Mark A.

2008-01-01

Rat lines congenic for the rat N-acetyltransferase 2 [(RAT)Nat2] gene were constructed and characterized. F344 (homozygous Nat2 rapid) males were mated to WKY (homozygous Nat2 slow) females to produce heterozygous F1. F1 females were then backcrossed to F344 males. Heterozygous acetylator female progeny from this and each successive backcross were identified by rat Nat2 genotyping and mated with F344 rapid acetylator males. Following ten generations of backcross mating, heterozygous acetylator brother/sister progeny were mated to produce the homozgygous rapid and slow acetylator Nat2 congenic rat lines. p-Aminobenzoic acid (selective for rat NAT2) and 4-aminobiphenyl N-acetyltransferase activities were expressed in all tissues examined (liver, lung, esophagus, stomach, small intestine, colon, pancreas, kidney, skin, leukocytes, and urinary bladder in male and female rats and in breast of female and prostate of male rats). NAT2 expression in rat extrahepatic tissues was much higher than in liver. In each tissue, activities were Nat2-genotype dependent, with highest levels in homozygous rapid acetylators, intermediate levels in heterozygous acetylators, and lowest in homozygous slow acetylators. Sulfamethazine (selective for rat NAT1) N-acetyltransferase activities were observed in all tissues examined in both male and female rats except for breast (females), bladder and leukocytes. In each tissue, the activity was Nat2-genotype independent, with similar levels in homozygous rapid, heterozygous, and homozygous slow acetylators. These congenic rat lines are useful to investigate the role of NAT2 genetic polymorphism in susceptibility to cancers related to arylamine carcinogen exposures. PMID:18799801

Insight into cofactor recognition in arylamine N-acetyltransferase enzymes: structure of Mesorhizobium loti arylamine N-acetyltransferase in complex with coenzyme A.

PubMed

Xu, Ximing; Li de la Sierra-Gallay, Inés; Kubiak, Xavier; Duval, Romain; Chaffotte, Alain F; Dupret, Jean Marie; Haouz, Ahmed; Rodrigues-Lima, Fernando

2015-02-01

Arylamine N-acetyltransferases (NATs) are xenobiotic metabolizing enzymes that catalyze the acetyl-CoA-dependent acetylation of arylamines. To better understand the mode of binding of the cofactor by this family of enzymes, the structure of Mesorhizobium loti NAT1 [(RHILO)NAT1] was determined in complex with CoA. The F42W mutant of (RHILO)NAT1 was used as it is well expressed in Escherichia coli and displays enzymatic properties similar to those of the wild type. The apo and holo structures of (RHILO)NAT1 F42W were solved at 1.8 and 2 Å resolution, respectively. As observed in the Mycobacterium marinum NAT1-CoA complex, in (RHILO)NAT1 CoA binding induces slight structural rearrangements that are mostly confined to certain residues of its `P-loop'. Importantly, it was found that the mode of binding of CoA is highly similar to that of M. marinum NAT1 but different from the modes reported for Bacillus anthracis NAT1 and Homo sapiens NAT2. Therefore, in contrast to previous data, this study shows that different orthologous NATs can bind their cofactors in a similar way, suggesting that the mode of binding CoA in this family of enzymes is less diverse than previously thought. Moreover, it supports the notion that the presence of the `mammalian/eukaryotic insertion loop' in certain NAT enzymes impacts the mode of binding CoA by imposing structural constraints.

Arylamine n-acetyltransferases in eukaryotic microorganisms

USDA-ARS?s Scientific Manuscript database

Microorganisms can survive highly toxic environments through numerous xenobiotic metabolizing enzymes, including arylamine N-acetyltransferases (NATs). NAT genes are present in bacteria, archaea, protists and fungi. In lower taxa of fungi, NAT genes are found in chytridiomycetes. In Dikarya, NAT gen...

Suitability of the HAM-Nat test and TMS module "basic medical-scientific understanding" for medical school selection

PubMed Central

Hissbach, Johanna; Feddersen, Lena; Sehner, Susanne; Hampe, Wolfgang

2012-01-01

Aims: Tests with natural-scientific content are predictive of the success in the first semesters of medical studies. Some universities in the German speaking countries use the ‘Test for medical studies’ (TMS) for student selection. One of its test modules, namely “medical and scientific comprehension”, measures the ability for deductive reasoning. In contrast, the Hamburg Assessment Test for Medicine, Natural Sciences (HAM-Nat) evaluates knowledge in natural sciences. In this study the predictive power of the HAM-Nat test will be compared to that of the NatDenk test, which is similar to the TMS module “medical and scientific comprehension” in content and structure. Methods: 162 medical school beginners volunteered to complete either the HAM-Nat (N=77) or the NatDenk test (N=85) in 2007. Until spring 2011, 84.2% of these successfully completed the first part of the medical state examination in Hamburg. Via different logistic regression models we tested the predictive power of high school grade point average (GPA or “Abiturnote”) and the test results (HAM-Nat and NatDenk) with regard to the study success criterion “first part of the medical state examination passed successfully up to the end of the 7th semester” (Success7Sem). The Odds Ratios (OR) for study success are reported. Results: For both test groups a significant correlation existed between test results and study success (HAM-Nat: OR=2.07; NatDenk: OR=2.58). If both admission criteria are estimated in one model, the main effects (GPA: OR=2.45; test: OR=2.32) and their interaction effect (OR=1.80) are significant in the HAM-Nat test group, whereas in the NatDenk test group only the test result (OR=2.21) significantly contributes to the variance explained. Conclusions: On their own both HAM-Nat and NatDenk have predictive power for study success, but only the HAM-Nat explains additional variance if combined with GPA. The selection according to HAM-Nat and GPA has under the current circumstances of medical school selection (many good applicants and only a limited number of available spaces) the highest predictive power of all models. PMID:23255967

Imaging quantum transport using scanning gate microscopy

NASA Astrophysics Data System (ADS)

Hackens, Benoit

2014-03-01

Quantum transport in nanodevices is usually probed thanks to measurements of the electrical resistance or conductance, which lack the spatial resolution necessary to probe electron behaviour inside the devices. In this talk, we will show that scanning gate microscopy (SGM) yields real-space images of quantum transport phenomena inside archetypal mesoscopic devices such as quantum point contacts and quantum rings. We will first discuss the SGM technique, which is based on mapping the electrical conductance of a device as an electrically-biased sharp metallic tip scans in its vicinity. With SGM, we demonstrated low temperature imaging of the electron probability density and interferences in embedded mesoscopic quantum rings [B. Hackens et al., Nat. Phys. 2, 826 (2006)]. At high magnetic field, thanks to the SGM conductance maps, one can decrypt complex transport phenomena such as tunneling between quantum Hall edge state, either direct or through localized states [B. Hackens et al., Nat. Comm. 1, 39 (2010)]. Moreover, the technique also allows to perform local spectroscopy of electron transport through selected localized states [F. Martins et al., New J. of Phys. 15, 013049 (2013); F. Martins et al., Sci. Rep. 3, 1416 (2013)]. Overall, these examples show that scanning gate microscopy is a powerful tool for imaging charge carrier behavior inside devices fabricated from a variety of materials, and opens the way towards a more intimate manipulation of charge and quasiparticle transport. This work was performed in collaboration with F. Martins, S. Faniel, B. Brun, M. Pala, X. Wallart, L. Desplanque, B. Rosenow, T. Ouisse, H. Sellier, S. Huant and V. Bayot.

The background is remapped across saccades.

PubMed

Cha, Oakyoon; Chong, Sang Chul

2014-02-01

Physiological studies have found that neurons prepare for impending eye movements, showing anticipatory responses to stimuli presented at the location of the post-saccadic receptive fields (RFs) (Wurtz in Vis Res 48:2070-2089, 2008). These studies proposed that visual neurons with shifting RFs prepared for the stimuli they would process after an impending saccade. Additionally, psychophysical studies have shown behavioral consequences of those anticipatory responses, including the transfer of aftereffects (Melcher in Nat Neurosci 10:903-907, 2007) and the remapping of attention (Rolfs et al. in Nat Neurosci 14:252-258, 2011). As the physiological studies proposed, the shifting RF mechanism explains the transfer of aftereffects. Recently, a new mechanism based on activation transfer via a saliency map was proposed, which accounted for the remapping of attention (Cavanagh et al. in Trends Cogn Sci 14:147-153, 2010). We hypothesized that there would be different aspects of the remapping corresponding to these different neural mechanisms. This study found that the information in the background was remapped to a similar extent as the figure, provided that the visual context remained stable. We manipulated the status of the figure and the ground in the saliency map and showed that the manipulation modulated the remapping of the figure and the ground in different ways. These results suggest that the visual system has an ability to remap the background as well as the figure, but lacks the ability to modulate the remapping of the background based on the visual context, and that different neural mechanisms might work together to maintain visual stability across saccades.

Critical de Broglie wavelength in superconductors

NASA Astrophysics Data System (ADS)

Talantsev, E. F.

2018-03-01

There are growing numbers of experimental evidences that the self-field critical currents, Jc(sf,T), are a new instructive tool to investigate fundamental properties of superconductors ranging from atomically thin films [M. Liao et al., Nat. Phys. 6 (2018), https://doi.org/10.1038/s41567-017-0031-6; E. F. Talantsev et al., 2D Mater. 4 (2017) 025072; A. Fete et al., Appl. Phys. Lett. 109 (2016) 192601] to millimeter-scale samples [E. F. Talantsev et al., Sci. Rep. 7 (2017) 10010]. The basic empirical equation which quantitatively accurately described experimental Jc(sf,T) was proposed by Talantsev and Tallon [Nat. Commun. 6 (2015) 7820] and it was the relevant critical field (i.e. thermodynamic field, Bc, for type-I and lower critical field, Bc1, for type-II superconductors) divided by the London penetration depth, λL. In this paper, we report new findings relating to this empirical equation. It is that the critical wavelength of the de Broglie wave, λdB,c, of the superconducting charge carrier which within a numerical pre-factor is equal to the largest of two characteristic lengths of Ginzburg-Landau theory, i.e. the coherence length, ξ, for type-I superconductors or the London penetration depth, λL, for type-II superconductors. We also formulate a microscopic criterion for the onset of dissipative transport current flow: ps ṡ 2ṡλL ln(1+2ṡ(λL ξ )) ≥ 1 2 ṡ ( h 2π), where ps is the charge carrier momentum, h is Planck’s constant and the inequality sign “ <” is reserved for the dissipation-free flow.

Studies on N-Acetyltransferase (NAT2) Genotype Relationships in Emiratis: Confirmation of the Existence of Phenotype Variation among Slow Acetylators.

PubMed

Al-Ahmad, Mohammad M; Amir, Naheed; Dhanasekaran, Subramanian; John, Anne; Abdulrazzaq, Yousef M; Ali, Bassam R; Bastaki, Salim

2017-09-01

Individuals with slow N-acetylation phenotype often experience toxicity from drugs such as isoniazid, sulfonamides, procainamide, and hydralazine, whereas rapid acetylators may not respond to these medications. The highly polymorphic N-acetyltransferase 2 enzyme encoded by the NAT2 gene is one of the N-acetylators in humans with a clear impact on the metabolism of a significant number of important drugs. However, there are limited studies on N-acetylation phenotypes and NAT2 genotypes among Emiratis, and thus this study was carried out to fill this gap. Five hundred seventy-six Emirati subjects were asked to consume a soft drink containing caffeine (a nontoxic and reliable probe for predicting the acetylation phenotype) and then provide a buccal swab along with a spot urine sample. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotype of each individual. Phenotyping was carried out by analyzing the caffeine metabolites using high-performance liquid chromatography (HPLC) analysis. We found that 78.5%, 19.1%, and 2.4% of the Emirati subjects were slow, intermediate, and rapid acetylators, respectively. In addition, we found that 77.4% of the subjects were homozygous or heterozygous for two nonreference alleles, whereas 18.4% and 4.2% were heterozygous or homozygous for the reference allele (NAT2*4), respectively. The most common genotypes found were NAT2*5B/*7B, NAT2*5B/*6A, NAT2*7B/*14B, and NAT2*4/*5B, with frequencies of 0.255, 0.135, 0.105, and 0.09, respectively. The degree of phenotype/genotype concordance was 96.2%. The NAT2*6A/*6A, NAT2*6A/*7B, NAT2*7B/*7B, and NAT2*5A/*5B genotypes were found to be associated with the lowest 5-acetylamino-6-formylamino-3-methyluracil/1-methylxanthine (AFMU/1X) ratios. There is a high percentage of slow acetylators among Emiratis, which correlates with the presence of nonreference alleles for the NAT2 gene. Individuals who carried NAT2*6A/*6A, NAT2*6A/*7B, NAT2*7B/*7B, or NAT2*5A/*5B genotypes might be at higher risk of toxicity with some drugs and some diseases compared to others, as these genotypes are associated with the slowest acetylation status. © 2017 John Wiley & Sons Ltd/University College London.

Recent progress in N-acetyltransferase research: 7th international workshop on N-acetyltransferases (NAT): workshop report.

PubMed

Lichter, Jutta; Golka, Klaus; Sim, Edith; Blömeke, Brunhilde

2017-07-01

The 7th International Workshop on N-Acetyltransferases (NAT), held from 18 to 20 June 2016, was hosted by Brunhilde Blömeke and her team at the Trier University (Germany). The workshop addressed important aspects and latest advancements in the fields of NAT enzymes, endogenous functions of NATs, NAT gene nomenclature, genetic polymorphisms, and their associations with diseases as well as their use in diagnosis. Representatives from the leading teams performing research on NATs presented their excellent work, discussed the latest results, and created new ideas in the field of N-acetyltransferase research.

Environmental Adaptations Improve Everyday Action in Schizophrenia.

PubMed

Kessler, Rachel K; Rhodes, Emma; Giovannetti, Tania

2015-05-01

Cognitive functioning, particularly executive functioning, is a strong predictor of functional outcomes in people with schizophrenia. Cognitive remediation has been shown to improve specific cognitive processes, but adjunctive interventions are required for meaningful gains in adaptive functioning, particularly in people with chronic illness. This study examined whether (and how) environmental adaptations, used without training, may circumvent cognitive difficulties and facilitate everyday task performance in individuals with chronic schizophrenia. Forty-two individuals with chronic schizophrenia/schizoaffective disorder were administered cognitive measures and two versions of the Naturalistic Action Test (NAT)-a standard version (ST-NAT), and a user-centered version (UC-NAT) that incorporated environmental adaptations designed to facilitate task performance. The NAT conditions were counterbalanced across participants. Analyses compared performance between the NAT versions and examined the cognitive correlates of each NAT condition. Individuals with schizophrenia made fewer errors on the UC-NAT as compared to the ST-NAT; this between-group difference was significant for all error types. Compared to the ST-NAT, the UC-NAT performance was not significantly associated with an executive function measure of planning. Environmental adaptations may be implemented without extensive training to improve everyday action in individuals with chronic schizophrenia. Environmental adaptations that reduce planning demands may be most effective in this population.

Cis-Natural Antisense Transcripts Are Mainly Co-expressed with Their Sense Transcripts and Primarily Related to Energy Metabolic Pathways during Muscle Development.

PubMed

Zhao, Yunxia; Hou, Ye; Zhao, Changzhi; Liu, Fei; Luan, Yu; Jing, Lu; Li, Xinyun; Zhu, Mengjin; Zhao, Shuhong

2016-01-01

Cis-natural antisense transcripts (cis-NATs) are a new class of RNAs identified in various species. However, the biological functions of cis-NATs are largely unknown. In this study, we investigated the transcriptional characteristics and functions of cis-NATs in the muscle tissue of lean Landrace and indigenous fatty Lantang pigs. In total, 3,306 cis-NATs of 2,469 annotated genes were identified in the muscle tissue of pigs. More than 1,300 cis-NATs correlated with their sense genes at the transcriptional level, and approximately 80% of them were co-expressed in the two breeds. Furthermore, over 1,200 differentially expressed cis-NATs were identified during muscle development. Function annotation showed that the cis-NATs participated in muscle development mainly by co-expressing with genes involved in energy metabolic pathways, including citrate cycle (TCA cycle), glycolysis or gluconeogenesis, mitochondrial activation and so on. Moreover, these cis-NATs and their sense genes abruptly increased at the transition from the late fetal stages to the early postnatal stages and then decreased along with muscle development. In conclusion, the cis-NATs in the muscle tissue of pigs were identified and determined to be mainly co-expressed with their sense genes. The co-expressed cis-NATs and their sense gene were primarily related to energy metabolic pathways during muscle development in pigs. Our results offered novel evidence on the roles of cis-NATs during the muscle development of pigs.

Codominant Expression of N-Acetylation and O-Acetylation Activities Catalyzed by N-Acetyltransferase 2 in Human Hepatocytes

PubMed Central

Doll, Mark A.; Zang, Yu; Moeller, Timothy

2010-01-01

Human populations exhibit genetic polymorphism in N-acetylation capacity, catalyzed by N-acetyltransferase 2 (NAT2). We investigated the relationship between NAT2 acetylator genotype and phenotype in cryopreserved human hepatocytes. NAT2 genotypes determined in 256 human samples were assigned as rapid (two rapid alleles), intermediate (one rapid and one slow allele), or slow (two slow alleles) acetylator phenotypes based on functional characterization of the NAT2 alleles reported previously in recombinant expression systems. A robust and significant relationship was observed between deduced NAT2 phenotype (rapid, intermediate, or slow) and N-acetyltransferase activity toward sulfamethazine (p < 0.0001) and 4-aminobiphenyl (p < 0.0001) and for O-acetyltransferase-catalyzed metabolic activation of N-hydroxy-4-aminobiphenyl (p < 0.0001), N-hydroxy-2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (p < 0.01), and N-hydroxy-2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (p < 0.0001). NAT2-specific protein levels also significantly associated with the rapid, intermediate, and slow NAT2 acetylator phenotypes (p < 0.0001). As a negative control, p-aminobenzoic acid (an N-acetyltransferase 1-selective substrate) N-acetyltransferase activities from the same samples did not correlate with the three NAT2 acetylator phenotypes (p > 0.05). These results clearly document codominant expression of human NAT2 alleles resulting in rapid, intermediate, and slow acetylator phenotypes. The three phenotypes reflect levels of NAT2 protein catalyzing both N- and O-acetylation. Our results suggest a significant role of NAT2 acetylation polymorphism in arylamine-induced cancers and are consistent with differential cancer risk and/or drug efficacy/toxicity in intermediate compared with rapid or slow NAT2 acetylator phenotypes. PMID:20430842

Arylamine N-Acetyltransferases in Mycobacteria

PubMed Central

Sim, Edith; Sandy, James; Evangelopoulos, Dimitrios; Fullam, Elizabeth; Bhakta, Sanjib; Westwood, Isaac; Krylova, Anna; Lack, Nathan; Noble, Martin

2008-01-01

Polymorphic Human arylamine N-acetyltransferase (NAT2) inactivates the anti-tubercular drug isoniazid by acetyltransfer from acetylCoA. There are active NAT proteins encoded by homologous genes in mycobacteria including M. tuberculosis, M. bovis BCG, M. smegmatis and M. marinum. Crystallographic structures of NATs from M. smegmatis and M. marinum, as native enzymes and with isoniazid bound share a similar fold with the first NAT structure, Salmonella typhimurium NAT. There are three approximately equal domains and an active site essential catalytic triad of cysteine, histidine and aspartate in the first two domains. An acetyl group from acetylCoA is transferred to cysteine and then to the acetyl acceptor e.g. isoniazid. M. marinum NAT binds CoA in a more open mode compared with CoA binding to human NAT2. The structure of mycobacterial NAT may promote its role in synthesis of cell wall lipids, identified through gene deletion studies. NAT protein is essential for survival of M. bovis BCG in macrophage as are the proteins encoded by other genes in the same gene cluster (hsaA-D). HsaA-D degrade cholesterol, essential for mycobacterial survival inside macrophage. Nat expression remains to be fully understood but is co-ordinated with hsaA-D and other stress response genes in mycobacteria. Amide synthase genes in the streptomyces are also nat homologues. The amide synthases are predicted to catalyse intramolecular amide bond formation and creation of cyclic molecules, e.g. geldanamycin. Lack of conservation of the CoA binding cleft residues of M. marinum NAT suggests the amide synthase reaction mechanism does not involve a soluble CoA intermediate during amide formation and ring closure. PMID:18680471

View northeast; interior structural detail Naval Base PhiladelphiaPhiladelphia Naval ...

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

View northeast; interior structural detail - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

21. Scrapping In Dry Dock #4. Naval Shipyard Philadelphia. February ...

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

21. Scrapping In Dry Dock #4. Naval Shipyard Philadelphia. February 18, 1946. Original Photograph In Collection of National Archives, Mid-Atlantic Regional Records Center, Philadelphia. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 4, Broad Street south of Government Avenue, Philadelphia, Philadelphia County, PA

View northwest; south and east facades Naval Base PhiladelphiaPhiladelphia ...

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

View northwest; south and east facades - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

View southwest; north and east facades Naval Base PhiladelphiaPhiladelphia ...

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

View southwest; north and east facades - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

Genetic and small molecule inhibition of arylamine N-acetyltransferase 1 reduces anchorage-independent growth in human breast cancer cell line MDA-MB-231.

PubMed

Stepp, Marcus W; Doll, Mark A; Carlisle, Samantha M; States, J Christopher; Hein, David W

2018-04-01

Arylamine N-acetyltransferase 1 (NAT1) expression is reported to affect proliferation, invasiveness, and growth of cancer cells. MDA-MB-231 breast cancer cells were engineered such that NAT1 expression was elevated or suppressed, or treated with a small molecule inhibitor of NAT1. The MDA-MB-231 human breast cancer cell lines were engineered with a scrambled shRNA, a NAT1 specific shRNA or a NAT1 overexpression cassette stably integrated into a single flippase recognition target (FRT) site facilitating incorporation of these different genetic elements into the same genomic location. NAT1-specific shRNA reduced NAT1 activity in vitro by 39%, increased endogenous acetyl coenzyme A levels by 35%, and reduced anchorage-independent growth (sevenfold) without significant effects on cell morphology, growth rates, anchorage-dependent colony formation, or invasiveness compared to the scrambled shRNA cell line. Despite 12-fold overexpression of NAT1 activity in the NAT1 overexpression cassette transfected MDA-MB-231 cell line, doubling time, anchorage-dependent cell growth, anchorage-independent cell growth, and relative invasiveness were not changed significantly when compared to the scrambled shRNA cell line. A small molecule (5E)-[5-(4-hydroxy-3,5-diiodobenzylidene)-2-thioxo-1,3-thiazolidin-4-one (5-HDST) was 25-fold more selective towards the inhibition of recombinant human NAT1 than N-acetyltransferase 2. Incubation of MDA-MB-231 cell line with 5-HDST resulted in 60% reduction in NAT1 activity and significant decreases in cell growth, anchorage-dependent growth, and anchorage-independent growth. In summary, inhibition of NAT1 activity by either shRNA or 5-HDST reduced anchorage-independent growth in the MDA-MB-231 human breast cancer cell line. These findings suggest that human NAT1 could serve as a target for the prevention and/or treatment of breast cancer. © 2018 Wiley Periodicals, Inc.

Xenobiotic-metabolizing enzymes in Bacillus anthracis: molecular and functional analysis of a truncated arylamine N-acetyltransferase isozyme.

PubMed

Kubiak, Xavier; Duval, Romain; Pluvinage, Benjamin; Chaffotte, Alain F; Dupret, Jean-Marie; Rodrigues-Lima, Fernando

2017-07-01

The arylamine N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes that play an important role in the detoxification and/or bioactivation of arylamine drugs and xenobiotics. In bacteria, NATs may contribute to the resistance against antibiotics such as isoniazid or sulfamides through their acetylation, which makes this enzyme family a possible drug target. Bacillus anthracis, a bacterial species of clinical significance, expresses three NAT isozymes with distinct structural and enzymatic properties, including an inactive isozyme ((BACAN)NAT3). (BACAN)NAT3 features both a non-canonical Glu residue in its catalytic triad and a truncated C-terminus domain. However, the role these unusual characteristics play in the lack of activity of the (BACAN)NAT3 isozyme remains unclear. Protein engineering, recombinant expression, enzymatic analyses with aromatic amine substrates and phylogenetic analysis approaches were conducted. The deletion of guanine 580 (G580) in the nat3 gene was shown to be responsible for the expression of a truncated (BACAN)NAT3 isozyme. Artificial re-introduction of G580 in the nat3 gene led to a functional enzyme able to acetylate several arylamine drugs displaying structural characteristics comparable with its functional Bacillus cereus homologue ((BACCR)NAT3). Phylogenetic analysis of the nat3 gene in the B. cereus group further indicated that nat3 may constitute a pseudogene of the B. anthracis species. The existence of NATs with distinct properties and evolution in Bacillus species may account for their adaptation to their diverse chemical environments. A better understanding of these isozymes is of importance for their possible use as drug targets. This article is part of a themed section on Drug Metabolism and Antibiotic Resistance in Micro-organisms. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.14/issuetoc. © 2016 The British Pharmacological Society.

A pilot study on screening blood donors with individual-donation nucleic acid testing in China

PubMed Central

Dong, Jie; Wu, Yaling; Zhu, Hong; Li, Gan; Lv, Mengen; Wu, Daxiao; Li, Xiaotao; Zhu, Faming; Lv, Hangjun

2014-01-01

Background Nucleic acid amplification testing (NAT) is not yet obligatory in China for blood donor screening and the risk of enzyme immunoassay (EIA)-negative, NAT-reactive donations in Chinese blood donors has rarely been reported. The aim of this study was to screen a population of Chinese blood donors using a triplex individual-donation (ID)-NAT assay and assess the safety benefits of implementing NAT. Materials and methods Between 1st August, 2010 and 31st December, 2011 all donations at a Chinese blood centre were screened individually using the Procleix® Ultrio® assay, a multiplex NAT assay for the detection of hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) RNA and human immunodeficiency virus-1 (HIV-1) RNA. All donations were also screened for HBsAg, anti-HIV and anti-HCV using two different EIA for each marker. Samples with discordant results between NAT and EIA were further tested with an alternative NAT assay (Cobas® TaqMan®). Potential yield cases (serologically negative/NAT-reactive donors) were further evaluated when possible. Results During the study period a total of 178,447 donations were screened by NAT and EIA, among which 169 HBV NAT yield cases (0.095%) were detected. No N AT yield cases were found for HIV-1 or HCV. For the HBV NAT yield cases, follow-up results showed that 11 (6.51%) were probable or confirmed HBV window period infections, 5 (2.96%) were chronic HBV carriers and 153 (90.53%) were probable or confirmed occult HBV infections. There was a statistically significant difference between the NAT-positive rates for first-time vs repeat donations (0.472% vs 0.146%, respectively; P<0.001). Discussion Our data demonstrate that the potential HBV yield rate was 1:1,056 for blood donations in the Zhejiang province of China. Implementation of NAT will provide a significant increment in safety relative to serological screening alone. PMID:24333061

View westsouthwest of marine railway at reserve basin of Philadelphia ...

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

View west-southwest of marine railway at reserve basin of Philadelphia Naval Shipyard. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Reserve Basin & Marine Railway, League Island, Philadelphia, Philadelphia County, PA

20. Zoo Substation. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP ...

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

20. Zoo Substation. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 87.25. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

28. Poquessing Creek Bridge. Philadelphia, Philadelphia Co., PA. Sec. 1101, ...

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

28. Poquessing Creek Bridge. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 74.20. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

7. B & O RAILROAD BRIDGE. PHILADELPHIA, PHILADELPHIA CO., PA. ...

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

7. B & O RAILROAD BRIDGE. PHILADELPHIA, PHILADELPHIA CO., PA. Sec. 1101, MP 3.11. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

22. Schuylkill River Bridge. Philadelphia, Philadelphia Co., PA. Sec. 1101, ...

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

22. Schuylkill River Bridge. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 87.14. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

6. B & O RAILROAD BRIDGE. PHILADELPHIA, PHILADELPHIA CO., PA. ...

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

6. B & O RAILROAD BRIDGE. PHILADELPHIA, PHILADELPHIA CO., PA. Sec. 1101, MP 3.11. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

27. Pennypack Creek Bridge. Philadelphia, Philadelphia Co., PA. Sec. 1101, ...

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

27. Pennypack Creek Bridge. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 76.70. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

21. Schuylkill River Bridge. Philadelphia, Philadelphia Co., PA. Sec. 1101, ...

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

21. Schuylkill River Bridge. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 87.14. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

N-acetyltransferase 2 activity and folate levels

PubMed Central

Cao, Wen; Strnatka, Diana; McQueen, Charlene A.; Hunter, Robert J.; Erickson, Robert P.

2010-01-01

Aims To determine whether increased N-acetyltransferase (NAT) activity might have a toxic effect during development and an influence on folate levels since previous work has shown that only low levels of exogenous NAT can be achieved in constitutionally transgenic mice (Cao, et al, 2005) Main Methods A human NAT1 tet-inducible construct was used that would not be expressed until the inducer was delivered. Human NAT1 cDNA was cloned into pTRE2 and injected into mouse oocytes. Two transgenic lines were crossed to mouse line TgN(rtTahCMV)4Uh containing the CMV promoted “teton.”Measurements of red blood cell folate levels in inbred strains of mice were performed. Key findings Only low levels of human NAT1 could be achieved in kidney (highly responsive in other studies) whether the inducer, doxycycline, was given by gavage or in drinking water.An inverse correlation of folate levels with Nat2 enzyme activity was found. Significance Since increasing NAT1 activity decrease folate in at least one tissue, the detrimental effect of expression of human NAT1 in combination with endogenous mouse Nat2 may be a consequence of increased catabolism of folate. PMID:19932120

Gene cloning and characterization of arylamine N-acetyltransferase from Bacillus cereus strain 10-L-2.

PubMed

Takenaka, Shinji; Cheng, Minyi; Mulyono; Koshiya, Atsushi; Murakami, Shuichiro; Aoki, Kenji

2009-01-01

Bacillus cereus strain 10-L-2 synthesizes two arylamine N-acetyltransferases (Nat-a and Nat-b) with broad substrate specificities toward aniline and its derivatives. In southern blot analysis using probes encoding the NH2-terminus of Nat-b and a conserved region of N-acetyltransferases, digested total DNA of strain 10-L-2 showed one positive band. We cloned and sequenced the gene encoding Nat-b. The NH2-terminal amino acid sequence predicted from the open reading frame (768 base pairs) corresponded to that of purified Nat-b. The cloned Nat-b gene was expressed in Escherichia coli. The expressed enzyme (BcNAT) from the recombinant strain was partially purified and characterized. Nat-b from strain 10-L-2 and BcNAT from the recombinant strain were slightly different from each others in substrate specificity and thermo-stability. We examined the biotransformations of 2-aminophenols and phenylenediamines by the whole cells of the recombinant strain. The cells converted these compounds into their corresponding acetanilides. Only one amino group of phenylenediamines was acetylated. The cells utilized 4-nitroacetanilide as an acetyl donor instead of acetyl-CoA. 4-Aminoacetanilide was produced and 4-nitroaniline was released almost stoichiometrically.

18. Pennsylvania Railroad: Brick Arch Viaduct. Philadelphia, Philadelphia Co., PA. ...

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

18. Pennsylvania Railroad: Brick Arch Viaduct. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 87.44. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

24. Elevated SEPTA subway Bridge crossing NEC. Philadelphia, Philadelphia Co., ...

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

24. Elevated SEPTA subway Bridge crossing NEC. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 81.69. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

19. Pennsylvania Railroad: Brick Arch Viaduct. Philadelphia, Philadelphia Co., PA. ...

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

19. Pennsylvania Railroad: Brick Arch Viaduct. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 87.44. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

26. Elevated SEPTA subway Bridge crossing NEC. Philadelphia, Philadelphia Co., ...

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

26. Elevated SEPTA subway Bridge crossing NEC. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 81.69. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

25. Elevated SEPTA subway Bridge crossing NEC. Philadelphia, Philadelphia Co., ...

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

25. Elevated SEPTA subway Bridge crossing NEC. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 81.69. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

20. Scrapping C112 U.S.S. Marblehead. Naval Shipyard Philadelphia. January 10, ...

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

20. Scrapping C1-12 U.S.S. Marblehead. Naval Shipyard Philadelphia. January 10, 1946. Original Photograph In Collection of National Archives, Mid-Atlantic Regional Records Center, Philadelphia. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 4, Broad Street south of Government Avenue, Philadelphia, Philadelphia County, PA

Proton and deuteron induced reactions on natGa: Experimental and calculated excitation functions

NASA Astrophysics Data System (ADS)

Hermanne, A.; Adam-Rebeles, R.; Tárkányi, F.; Takács, S.; Ditrói, F.

2015-09-01

Cross-sections for reactions on natGa, induced by protons (up to 65 MeV) and deuterons (up to 50 MeV), producing γ-emitting radionuclides with half-lives longer than 1 h were measured in a stacked-foil irradiation using thin Ga-Ni alloy (70-30%) targets electroplated on Cu or Au backings. Excitation functions for generation of 68,69Ge, 66,67,68,72Ga and 65,69mZn on natGa are discussed, relative to the monitor reactions natAl(d,x)24,22Na, natAl(p,x)24,22Na, natCu(p,x)62Zn and natNi(p,x)57Ni. The results are compared to our earlier measurements, the scarce literature values and to the results of the code TALYS 1.6 (online database TENDL-2014).

11. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. ...

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

11. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 88.10. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

12. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. ...

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

12. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 88.10. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

8. Pennsylvania Railroad: 30th Street Station Powerhouse. Philadelphia, Philadelphia Co., ...

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

8. Pennsylvania Railroad: 30th Street Station Powerhouse. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 88.11. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

16. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. ...

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

16. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 88.10. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

9. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. ...

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

9. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 88.10. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

10. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. ...

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

10. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 88.10. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

14. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. ...

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

14. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 88.10. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

15. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. ...

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

15. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 88.10. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

13. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. ...

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

13. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 88.10. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

17. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. ...

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

17. Pennsylvania Railroad: 30th Street Station. Philadelphia, Philadelphia Co., PA. Sec. 1101, MP 88.10. - Northeast Railroad Corridor, Amtrak route between Delaware-Pennsylvania & Pennsylvania-New Jersey state lines, Philadelphia, Philadelphia County, PA

Comparative investigation of the xenobiotic metabolizing arylamine N-acetyltransferase enzyme family among fungi

USDA-ARS?s Scientific Manuscript database

Arylamine N-acetyltransferases (NATs) are xenobiotic metabolizing enzymes well-characterized in several bacteria and higher eukaryotes. The role of NATs in fungal biology has only recently been investigated. The NAT1 gene of Gibberella moniliformis was the first NAT cloned and characterized from fun...

Phylogenetic and biological investigation of the xenobiotic metabolizing arylamine N-acetyltransferase enzyme family among fungi

USDA-ARS?s Scientific Manuscript database

Arylamine N-acetyltransferases (NATs) are xenobiotic metabolizing enzymes well-characterized in several bacteria and eukaryotic organisms. The role of NATs in fungal biology has only recently been investigated. The NAT1 (FDB2) gene of Fusarium verticillioides was the first NAT cloned and character...

Greening of the Sahara - a paleo perspective on the history of water in the Middle East and North Africa

NASA Astrophysics Data System (ADS)

Bar-Matthews, M.

2012-04-01

The Middle-East, mostly at its southern edge together with North Africa, the northern edge of the Sahara Desert, are located at the boundary between high- to-mid latitude and tropical-subtropical climate systems. The geographical duality of desert adjacent to Mediterranean-type climate regions played and still plays a major role on the water availability. Thanks to the number of important paleoclimate studies that been made on accurate dating of cave speleothems in Southern Arabia and Oman (Fleitmann et al., 2011) and in the northeast Sahara, the Negev Desert Israel (Vaks et al., 2010) and the study of sapropels in Eastern and central Mediterranean (Almogi-Labin et al., 2009; Osborne et al, 2008), it is clear that the region was graced with water during peak interglacials when the African monsoon and westerly storm/rainfall systems intensified. Northward penetration of the Inter Tropical Convergence Zone over the Arabian and African continents resulted in increased discharge of the Nile River and rivers that emerged from central Sahara into the Eastern Mediterranean Sea. Correspondingly, enhanced westerly wind activity led to an increase in rainfall from Atlantic-Mediterranean sources over the entire Mediterranean basin, which even penetrated south into the north-east corner of the Sahara Desert. The Saharo-Arabian Desert became narrower and climatic "windows" opened for the dispersal of hominids and animals out of the African continent at 250-239, 210-193, 138-120, 108-98, 87-84 and 10-6.5 ka BP, with severe dry conditions in between. Greening of the Sahara Desert at these intervals is supported also by various marine and terrestrial records, such as corals, lakes, tufa deposits and archeological findings. Dry conditions prevailed in the Sahara desert during glacials. This is in contrast to the climatic conditions in the Eastern Mediterranean coastal region and the Jordan Rift Valley (Bar-Matthews et al., 2003; Lisker et al., 2010), where water was available for humans and animals who enjoyed a variety of ecological niches for living (Frumkin et al., 2011). Almogi-Labin, A. et a.l (2009) Quat. Sci. Rev. 28, 2882-2896. Bar-Matthews, M. et al (2003 Geochim. Cosmochim. Acta 67, 3181-99. Fleitmann, D. et al. (2011). Quat. Sci. Rev. 30, 783-787. Frumkin, et al. A. (2011). Jour. Human Evol. 60, 437-451 Lisker et al, (2010). Quat. Sci. Rev 29, 1201-1211. Osborne A.H. et al. (2008). Proc. Nat. Acad. Sci. 105, 16444-16447 Vaks et al. (2010). Quat. Sci. Rev. 29, 2647-2662.

Numerical modelling of volatiles in the deep mantle

NASA Astrophysics Data System (ADS)

Eichheimer, Philipp; Thielmann, Marcel; Golabek, Gregor J.

2017-04-01

The transport and storage of water in the mantle significantly affects several material properties of mantle rocks and thus water plays a key role in a variety of geodynamical processes (tectonics, magmatism etc.). The processes driving transport and circulation of H2O in subduction zones remain a debated topic. Geological and seismological observations suggest different inflow mechanisms of water e.g. slab bending, thermal cracking and serpentinization (Faccenda et al., 2009; Korenaga, 2017), followed by dehydration of the slab. On Earth both shallow and steep subduction can be observed (Li et al., 2011). However most previous models (van Keken et al., 2008; Wilson et al., 2014) did not take different dip angles and subduction velocities of slabs into account. To which extent these parameters and processes influence the inflow of water still remains unclear. We present 2D numerical models simulating the influence of the various water inflow mechanisms on the mantle with changing dip angle and subduction velocity of the slab over time. The results are used to make predictions regarding the rheological behavior of the mantle wedge, dehydration regimes and volcanism at the surface. References: van Keken, P. E., et al. A community benchmark for subduction zone modeling. Phys. Earth Planet. Int. 171, 187-197 (2008). Faccenda, M., T.V. Gerya, and L. Burlini. Deep slab hydration induced by bending-related variations in tectonic pressure. Nat. Geosci. 2, 790-793 (2009). Korenaga, J. On the extent of mantle hydration caused by plate bending. Earth Planet. Sci. Lett. 457, 1-9 (2017). Wilson, C. R., et al. Fluid flow in subduction zones: The role of solid rheology and compaction pressure. Earth Planet. Sci. Lett. 401, 261-274 (2014). Li, Z. H., Z. Q. Xu, and T. V. Gerya. Flat versus steep subduction: Contrasting modes for the formation and exhumation of high- to ultrahigh-pressure rocks in continental collision zones. Earth Planet. Sci. Lett. 301, 65-77 (2011).

On the Chemical Emergence of Phosphate-Based Biochemistry

NASA Astrophysics Data System (ADS)

Kee, Terence

Contemporary organisms use orthophosphate derivatives (PO43-) in their cell biochemistry,1 yet questions remain as to how Nature was able to accumulate, activate and exploit the or-thophosphate group from geological sources with both poorly solubility and low chemical activ-ity.2 Gulick argued3 a central role for reduced oxidation state phosphorus (P) oxyacids such as H-phosphonates (H2PO3-) and especially H-phosphinates (H2PO2-) in prebiotic chemistry on account of the greater water solubility of their metal salts and, with the presence of P-H bonds, a different reactivity profile to that expected of orthophosphate. The recent demonstration that hydrothermal corrosion of P-rich mineral phases such as schreibersite (Fe,Ni)3P within iron meteorites leads to production of various P-oxyacids including H-phosphonic (H3PO3)4 and H-phosphinic5 acids as well as orthophosphate has reignited interest in reduced oxida-tion state P chemistry in prebiotic environments. We are examining the prebiotic potential of reduced oxidation state P-chemistry through reactions with carbonyl substrates with rea-sonable prebiotic provenance including formaldehyde glycolaldehyde, both intimately involved in the formose reaction for sugar synthesis6 and pyruvic acid,7 a product of glycolysis and feed-stock for the citric acid cycle, a fundamental cellular metablic process whose heritage is considered an ancient one. In this contribution we present some of our latest results on the H-phosphinate-pyruvate system. References: [1] Lodish H et al. (2000) Molecular Cell Biology, 4th Ed., W. H. Freeman Co., New York. [2] Gulick A. (1955) Am. Sci., 43, 479. [3] Gulick A. (1957) Ann. N. Y. Acad. Sci. 69, 309. [4] Pasek M. A. (2008) Proc. Nat. Acad. Sci. USA, 105, 853. [5] Bryant D. E.and Kee T. P. (2006) Chem. Commun. 2344. [6] Weber A. L. (2000) Origins of Life and Evol. Biosph., 30, 33. [7] Cody G. D. et. al. (2000) Science 289, 1337.

Experimental study of the energy dependence of the total cross section for the 6He + natSi and 9Li + natSi reactions

NASA Astrophysics Data System (ADS)

Sobolev, Yu. G.; Penionzhkevich, Yu. E.; Aznabaev, D.; Zemlyanaya, E. V.; Ivanov, M. P.; Kabdrakhimova, G. D.; Kabyshev, A. M.; Knyazev, A. G.; Kugler, A.; Lashmanov, N. A.; Lukyanov, K. V.; Maj, A.; Maslov, V. A.; Mendibayev, K.; Skobelev, N. K.; Slepnev, R. S.; Smirnov, V. V.; Testov, D.

2017-11-01

New experimental measurements of the total reaction cross sections for the 6He + natSi and 9Li + natSi processes in the energy range of 5 to 40 A MeV are presented. A modified transmission method based on high-efficiency detection of prompt n-γ radiation has been used in the experiment. A bump is observed for the first time in the energy dependence σR( E) at E ˜ 10-30 A MeV for the 9Li + natSi reaction, and existence of the bump in σR( E) at E ˜ 10-20 A MeV first observed in the standard transmission experiments is experimentally confirmed for the 6He + natSi reaction. Theoretical analysis of the measured 6He + natSi and 9Li + natSi reaction cross sections is performed within the microscopic double folding model. Disagreement is observed between the experimental and theoretical cross sections in the region of the bump at the energies of 10 to 20 A MeV, which requires further study.

Structure-activity relationships and colorimetric properties of specific probes for the putative cancer biomarker human arylamine N-acetyltransferase 1.

PubMed

Egleton, James E; Thinnes, Cyrille C; Seden, Peter T; Laurieri, Nicola; Lee, Siu Po; Hadavizadeh, Kate S; Measures, Angelina R; Jones, Alan M; Thompson, Sam; Varney, Amy; Wynne, Graham M; Ryan, Ali; Sim, Edith; Russell, Angela J

2014-06-01

A naphthoquinone inhibitor of human arylamine N-acetyltransferase 1 (hNAT1), a potential cancer biomarker and therapeutic target, has been reported which undergoes a distinctive concomitant color change from red to blue upon binding to the enzyme. Here we describe the use of in silico modeling alongside structure-activity relationship studies to advance the hit compound towards a potential probe to quantify hNAT1 levels in tissues. Derivatives with both a fifty-fold higher potency against hNAT1 and a two-fold greater absorption coefficient compared to the initial hit have been synthesized; these compounds retain specificity for hNAT1 and its murine homologue mNat2 over the isoenzyme hNAT2. A relationship between pKa, inhibitor potency and colorimetric properties has also been uncovered. The high potency of representative examples against hNAT1 in ZR-75-1 cell extracts also paves the way for the development of inhibitors with improved intrinsic sensitivity which could enable detection of hNAT1 in tissue samples and potentially act as tools for elucidating the unknown role hNAT1 plays in ER+ breast cancer; this could in turn lead to a therapeutic use for such inhibitors. Copyright © 2014. Published by Elsevier Ltd.

Effectiveness of a flow-based device using riboflavin photochemistry in damaging blood-borne viral nucleic acids.

PubMed

Zhu, Liguo; Tong, Hongli; Wang, Shufang; Yu, Yang; Liu, Zhong; Li, Changqing; Wang, Deqing

2018-05-03

Effectiveness of a flow-based treatment device using riboflavin photochemistry was demonstrated by cytopathic effect method using indicator viruses. However, inactivation efficacy against real blood-borne viruses needs to be evaluated, especially at nucleic acid level. Special plasma samples with varying concentrations of blood-borne virus were selected using a strict blood selection procedure and were treated with device treatment (DT). Nucleic acid test (NAT) using polymerase chain reaction fluorescence method was used to detect virus copies. The NAT value of 4325 in plasma with high Hepatitis B Virus (HBV) concentrations decreased to 1330 with DT. After 100-fold dilution, the NAT value was below the NAT detection limits with DT compared with 23.0 that without DT. The NAT value of 61.9 in plasma with medium HBV concentrations decreased to 37.8 with DT, and after 10-fold dilution, the NAT value was below the NAT detection limits with DT compared with below 20 that without DT. The Ct values of plasma with low concentrations of blood-borne viruses were below the NAT detection limits with DT. There was a dose effect with DT which was effective in blood-borne viruses damaging nucleic acids to a level below the NAT detection limits. Copyright © 2018 Elsevier B.V. All rights reserved.

Functional effects of single nucleotide polymorphisms in the coding region of human N-acetyltransferase 1

PubMed Central

Zhu, Yuanqi; Hein, David W.

2007-01-01

Genetic variants of human N-acetyltransferase 1 (NAT1) are associated with cancer and birth defects. N- and O-acetyltransferase catalytic activities, Michaelis-Menten kinetic constants (Km & Vmax), and steady state expression levels of NAT1-specific mRNA and protein were determined for the reference NAT1*4 and variant human NAT1 haplotypes possessing single nucleotide polymorphisms (SNPs) in the open reading frame. Although none of the SNPs caused a significant effect on steady state levels of NAT1-specific mRNA, C97T(R33stop), C190T(R64W), C559T (R187stop) and A752T(D251V) each reduced NAT1 protein level and/or N- and O-acetyltransferase catalytic activities to levels below detection. G560A(R187Q) substantially reduced NAT1 protein level and catalytic activities and increased substrate Km. The G445A(V149I), G459A(synonymous) and T640G(S214A) haplotype present in NAT1*11 significantly (p<0.05) increased NAT1 protein level and catalytic activity. Neither T21G(synonymous), T402C(synonymous), A613G(M205V), T777C(synonymous), G781A(E261K), or A787G(I263V) significantly affected Km, catalytic activity, mRNA or protein level. These results suggest heterogeneity among slow NAT1 acetylator phenotypes. PMID:17909564

4-Aminobiphenyl Downregulation of NAT2 Acetylator Genotype–Dependent N- and O-acetylation of Aromatic and Heterocyclic Amine Carcinogens in Primary Mammary Epithelial Cell Cultures from Rapid and Slow Acetylator Rats

PubMed Central

Jefferson, Felicia A.; Xiao, Gong H.; Hein, David W.

2009-01-01

Aromatic and heterocyclic amine carcinogens present in the diet and in cigarette smoke induce breast tumors in rats. N-acetyltransferase 1 (NAT1) and N-acetyltransferase 2 (NAT2) enzymes have important roles in their metabolic activation and deactivation. Human epidemiological studies suggest that genetic polymorphisms in NAT1 and/or NAT2 modify breast cancer risk in women exposed to these carcinogens. p-Aminobenzoic acid (selective for rat NAT2) and sulfamethazine (SMZ; selective for rat NAT1) N-acetyltransferase catalytic activities were both expressed in primary cultures of rat mammary epithelial cells. PABA, 2-aminofluorene, and 4-aminobiphenyl N-acetyltransferase and N-hydroxy-2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine and N-hydroxy-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline O-acetyltransferase activities were two- to threefold higher in mammary epithelial cell cultures from rapid than slow acetylator rats. In contrast, SMZ (a rat NAT1-selective substrate) N-acetyltransferase activity did not differ between rapid and slow acetylators. Rat mammary cells cultured in the medium supplemented 24 h with 10μM ABP showed downregulation in the N-and O-acetylation of all substrates tested except for the NAT1-selective substrate SMZ. This downregulation was comparable in rapid and slow NAT2 acetylators. These studies clearly show NAT2 acetylator genotype–dependent N- and O-acetylation of aromatic and heterocyclic amine carcinogens in rat mammary epithelial cell cultures to be subject to downregulation by the arylamine carcinogen ABP. PMID:18842621

FUNCTIONAL CHARACTERIZATION OF THE A411T (L137F) and G364A (D122N) GENETIC POLYMORPHISMS IN HUMAN N-ACETYLTRANSFERASE 2

PubMed Central

Zang, Yu; Zhao, Shuang; Doll, Mark A.; States, J Christopher; Hein, David W.

2007-01-01

Human N-acetyltransferase 2 (NAT2) genetic polymorphisms may modify drug efficacy and toxicity and individual cancer susceptibility from carcinogen exposure. A411T (L137F) and G364A (D122N) are two single nucleotide polymorphisms (SNPs) that coexist with other SNPs in human NAT2 alleles NAT2*5I and NAT2*12D, respectively. Cloning and expression in COS-1 cells showed that both A411T and G364A reduced NAT2 immunoreactive protein to an undetectable level without causing changes in mRNA level. Missense mutants displayed different effects on sulfamethazine N-acetylation activity for both L137 (wild-type: 70.2±5.2; L137F: 1.34±0.03; L137W: non-detectable; L137I: 34.2±2.0; L137G: 0.52±0.04 nmol/min/mg) and D122 (wildtype: 70.2±5.2; D122R: non-detectable; D122Q: non-detectable; D122E: 1.72±0.24 nmol/min/mg). To further test our hypothesis that A411T (L137F) and G364A (D122N) accelerate protein degradation, various NAT2 alleles were cloned and expressed in E. coli, which does not possess the ubiquitin-mediated degradation pathway. In contrast to the expression in mammalian cells, recombinant NAT2 possessing either of these two SNPs showed no reduction in immunoreactive NAT2 level when expressed in E. coli. These findings suggest that both A411T (L137F) and G364A (D122N) enhance NAT2 degradation, resulting in reduced NAT2 protein and catalytic activity for NAT2 5I and NAT2 12D. PMID:17264801

N-Acetyltransferase-2 Genotypes Among Patients with Rheumatoid Arthritis Attending Jordan University Hospital

PubMed Central

Oqal, Muna K.; Mustafa, Khader N.

2012-01-01

Aim: To determine the frequency of major N-acetyltransferase (NAT2) alleles and genotypes among Jordanian patients with rheumatoid arthritis (RA). Methods: The study was approved by the IRB of the Jordan University Hospital. An informed consent was signed by every patient. DNA samples from 150 healthy volunteers and 108 patients with RA were analyzed by polymerase chain reaction followed by a restriction fragment length polymorphism assay (PCR-RFLP) to determine the frequency of four major alleles: NAT2*4, NAT2*5, NAT2*6, and NAT2*7. Results: The most prevalent genotypes are those that encode the slow acetylation phenotype. About 59.3% of the patients with RA carried the slow, 33.3% the intermediate, and 7.4% the fast-encoding genotypes. The frequency of NAT2 alleles was 0.241 (95% confidence interval [CI] 0.184–0.298) for NAT2*4, 0.449 (95% CI 0.383–0.515) for NAT2*5, 0.273 (95% CI 0.214–0.332) for NAT2*6, and 0.037 (95% CI 0.012–0.062) for NAT2*7 allele. The overall frequency of the slow acetylation genotype in patients with RA is similar to that in healthy Jordanian volunteers. However, the NAT2*5/7 genotype was found in seven patients (6.5%) with RA and was absent in Jordanian volunteers, and the z test revealed that the difference was statistically significant. This genotype constituted 10.9% of the genotypes encoding slow acetylation. Conclusion: The overall acetylator genotype in RA is similar to that in healthy volunteers. The overall slow acetylator genotypes do not seem to be a genetic risk factor for RA among Jordanians. However, the NAT2*5/7 genotype seems to be related to RA. The nature of this relationship needs further clarification. PMID:22731637

The Shift From Sentinel Lymph Node Biopsy Performed Either Before or After Neoadjuvant Systemic Therapy in the Clinical Negative Nodes of Breast Cancer Patients. Results, and the Advantages and Disadvantages of Both Procedures.

PubMed

Fernandez-Gonzalez, Sergi; Falo, Catalina; Pla, Maria Jesus; Pernas, Sonia; Bajen, Maite; Soler, Teresa; Ortega, Raul; Quetglas, Cecilia; Perez-Martin, Xavier; Fernandez Montoli, Maria Eulalia; Campos, Miriam; Varela-Rodriguez, Mar; Ponce, Jordi; Garcia-Tejedor, Amparo

2018-02-01

In patients with breast cancer who are candidates for neoadjuvant therapy (NAT), the timing of when to perform sentinel lymph node biopsy (SLNB) remains under discussion. The aim of this study was to compare the advantages and disadvantages of SLNB performed before and after NAT. One hundred seventy-two patients, T1c to T3 and N0 (clinically and according to ultrasound) candidates for NAT were included. We compared the outcomes of 2 groups: (1) 122 patients of whom SLNB was performed before NAT (pre-NAT) from December 2006 to April 2014; and (2) 50 patients with SLNB performed after NAT (post-NAT) from May 2014 to July 2016. Both groups were homogeneous in baseline patient characteristics. The SLNB was positive in 50 patients [41.7%] (33 macrometastases [66%] and 17 micrometastases [34%]) versus 6 patients [12%] (5 macrometastases [83.3%] and 1 micrometastases [16.7%]) in pre- and post-NAT groups, respectively. The lymphadenectomy was performed in 34 patients [28.3%] versus 4 patients [8%], with an odds ratio of 3.48 (95% confidence interval, 1.3-9.3). The recurrences in the pre-NAT group after a median follow-up of 62 months were 12 systemic, 2 local and systemic, and none axillary. In the post-NAT group were no recurrences after a median follow-up of 16 months. Finally, SLNB after NAT reduces the delay in starting NAT from 24 to 14 days (medians; P < .001) and the identification of the SLNB was in 122 patients [100%] versus 49 patients [98%]. SLNB performed after NAT significantly reduces the rate of lymphadenectomies without any increase in recurrences at early follow-up. Furthermore, it allows systemic treatment to be started earlier without interfering in the SLNB identification rate. Copyright © 2017 Elsevier Inc. All rights reserved.

General elevation, 1941, drawn by Waddell and Hardesty, New York, ...

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

General elevation, 1941, drawn by Waddell and Hardesty, New York, New York. Drawing in collection of Caretaker Site Office, Philadelphia Naval Business Center, Philadelphia, Pennsylvania. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Lift Bridge, Mouth of Reserve Basin, League Island, Philadelphia, Philadelphia County, PA

Detection of HCV and HIV-1 antibody negative infections in Scottish and Northern Ireland blood donations by nucleic acid amplification testing.

PubMed

Jarvis, L M; Dow, B C; Cleland, A; Davidson, F; Lycett, C; Morris, K; Webb, B; Jordan, A; Petrik, J

2005-10-01

To reduce the risk of transfusion-transmissible viruses entering the blood supply, the nucleic acid amplification testing (NAT) was implemented to screen Scottish and Northern Irish blood donations in minipools. After 5 years of NAT for hepatitis C virus (HCV) and 2 years for human immunodeficiency virus-1 (HIV-1), the yield of serologically negative, nucleic acid positive 'window donations' and cost-benefit of NAT is under review. When the Scottish National Blood Transfusion Service (SNBTS) implemented NAT in 1999, a fully automated 'black box' system was not available. Therefore, an 'in-house' assimilated NAT assay was developed, validated and implemented. The system is flexible and allows testing for additional viral markers to be introduced with relative ease. The HCV and HIV NAT assays have 95% detection levels of 7.25 IU/ml and 39.8 IU/ml, respectively, as determined by probit analysis. One HCV (1 in 1.9 million) and one HIV (1 in 0.77 million) window donation have been detected in 5 and 2 years, respectively, of NAT. The SNBTS NAT assays are robust and have performed consistently over the last 5 years. The design of the in-house system allowed HIV NAT to be added in 2003 at a relatively small additional cost per sample, although for both assays, the royalty fee far exceeds the cost of the test itself. Clearly NAT has a benefit in improving the safety of the blood supply although the risks of transfusion-transmitted viral infections, as reported in the Serious Hazards of Transfusion (SHOT) report, are extremely low. Also, in UK the yield of HCV antibody negative, NAT positive donations is far lower than predicted although the early detection of an HIV window period donation and the increase of HIV in the blood donor and general populations may provide a stronger case for HIV NAT. SUMMARY SENTENCE: The yield of HCV and HIV NAT in UK is significantly less than that anticipated from statistical models.

77 FR 72873 - Notice of Revocation of Customs Broker Licenses

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-06

... Philadelphia. Aries Global Logistics, Inc 22742 Philadelphia. Coxson Charles R 15760 Philadelphia. Semel Dana L... Madonna M 13219 Philadelphia. Caiazza John L 16868 Philadelphia. Myers Ronald W 15479 Philadelphia.... Ferguson Anthony R 10934 Washington, DC. Brown Charles L 12112 Washington, DC. Bucher Jane Linnea 12388...

General drawing, section 1941, drawn by Waddell and Hardesty, New ...

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

General drawing, section 1941, drawn by Waddell and Hardesty, New York, New York. Drawing in collection of Caretaker Site Office, Philadelphia Naval Business Center, Philadelphia, Pennsylvania. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Lift Bridge, Mouth of Reserve Basin, League Island, Philadelphia, Philadelphia County, PA

Tower machinery house elevations, 1941, drawn by Waddell and Hardesty, ...

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

Tower machinery house elevations, 1941, drawn by Waddell and Hardesty, New York, New York. Drawing in collection of Caretaker Site Office, Philadelphia Naval Business Center, Philadelphia, Pennsylvania. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Lift Bridge, Mouth of Reserve Basin, League Island, Philadelphia, Philadelphia County, PA

General plan and elevation, 1941, drawn by Waddell and Hardesty, ...

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

General plan and elevation, 1941, drawn by Waddell and Hardesty, New York, New York. Drawing in collection of Caretaker Site Office, Philadelphia Naval Business Center, Philadelphia, Pennsylvania. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Lift Bridge, Mouth of Reserve Basin, League Island, Philadelphia, Philadelphia County, PA

Lift span trusses; plans, sections and elevations, 1941, drawn by ...

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

Lift span trusses; plans, sections and elevations, 1941, drawn by Waddell and Hardesty, New York, New York. Drawing in collection of Caretaker Site Office, Philadelphia Naval Business Center, Philadelphia, Pennsylvania. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Lift Bridge, Mouth of Reserve Basin, League Island, Philadelphia, Philadelphia County, PA

Mean field study of a propagation-turnover lattice model for the dynamics of histone marking

NASA Astrophysics Data System (ADS)

Yao, Fan; Li, FangTing; Li, TieJun

2017-02-01

We present a mean field study of a propagation-turnover lattice model, which was proposed by Hodges and Crabtree [Proc. Nat. Acad. Sci. 109, 13296 (2012)] for understanding how posttranslational histone marks modulate gene expression in mammalian cells. The kinetics of the lattice model consists of nucleation, propagation and turnover mechanisms, and exhibits second-order phase transition for the histone marking domain. We showed rigorously that the dynamics essentially depends on a non-dimensional parameter κ = k +/ k -, the ratio between the propagation and turnover rates, which has been observed in the simulations. We then studied the lowest order mean field approximation, and observed the phase transition with an analytically obtained critical parameter. The boundary layer analysis was utilized to investigate the structure of the decay profile of the mark density. We also studied the higher order mean field approximation to achieve sharper estimate of the critical transition parameter and more detailed features. The comparison between the simulation and theoretical results shows the validity of our theory.

Structural and functional characterization of an arylamine N-acetyltransferase from the pathogen Mycobacterium abscessus: differences from other mycobacterial isoforms and implications for selective inhibition.

PubMed

Cocaign, Angélique; Kubiak, Xavier; Xu, Ximing; Garnier, Guillaume; Li de la Sierra-Gallay, Inès; Chi-Bui, Linh; Dairou, Julien; Busi, Florent; Abuhammad, Areej; Haouz, Ahmed; Dupret, Jean Marie; Herrmann, Jean Louis; Rodrigues-Lima, Fernando

2014-11-01

Mycobacterium abscessus is the most pathogenic rapid-growing mycobacterium and is one of the most resistant organisms to chemotherapeutic agents. However, structural and functional studies of M. abscessus proteins that could modify/inactivate antibiotics remain nonexistent. Here, the structural and functional characterization of an arylamine N-acetyltransferase (NAT) from M. abscessus [(MYCAB)NAT1] are reported. This novel prokaryotic NAT displays significant N-acetyltransferase activity towards aromatic substrates, including antibiotics such as isoniazid and p-aminosalicylate. The enzyme is endogenously expressed and functional in both the rough and smooth M. abscessus morphotypes. The crystal structure of (MYCAB)NAT1 at 1.8 Å resolution reveals that it is more closely related to Nocardia farcinica NAT than to mycobacterial isoforms. In particular, structural and physicochemical differences from other mycobacterial NATs were found in the active site. Peculiarities of (MYCAB)NAT1 were further supported by kinetic and docking studies showing that the enzyme was poorly inhibited by the piperidinol inhibitor of mycobacterial NATs. This study describes the first structure of an antibiotic-modifying enzyme from M. abscessus and provides bases to better understand the substrate/inhibitor-binding specificities among mycobacterial NATs and to identify/optimize specific inhibitors. These data should also contribute to the understanding of the mechanisms that are responsible for the pathogenicity and extensive chemotherapeutic resistance of M. abscessus.

2. Photocopy of the fountain in front of Philadelphia Museum ...

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

2. Photocopy of the fountain in front of Philadelphia Museum of Art, ca. 1928, courtesy of Philadelphia Museum of Art - Fountain of the Sea Horses, Aquarium Lane, Philadelphia, Philadelphia County, PA

75 FR 22814 - Guidance for Industry: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-30

... Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus (HCV): Testing, Product Disposition, and Donor Deferral... Industry: Nucleic Acid Testing (NAT) for Human Immunodeficiency Virus Type 1 (HIV-1) and Hepatitis C Virus... Acid Test (NAT) and Hepatitis C Virus (HCV) NAT, on testing individual samples or pooled samples from...

Analysis of protein function in clinical C. albicans isolates

PubMed Central

Gerami-Nejad, Maryam; Forche, Anja; McClellan, Mark; Berman, Judith

2012-01-01

Clinical isolates are prototrophic and hence are not amenable to genetic manipulation using nutritional markers. Here we describe a new set of plasmids carrying the NAT1 (nourseothricin) drug resistance marker (Shen et al., 2005) that can be used both in clinical isolates and in laboratory strains. We constructed novel plasmids containing HA-NAT1 or MYC-NAT1 cassettes to facilitate PCR-mediated construction of strains with C-terminal epitope-tagged proteins and a NAT1-pMet3-GFP plasmid to enable conditional expression of proteins with or without the green fluorescent protein fused at the N-terminus. Furthermore, for proteins that require both the endogenous N- and C-termini for function, we have constructed a GF-NAT1-FP cassette carrying truncated alleles that facilitate insertion of an intact, single copy of GFP internal to the coding sequence. In addition, GFP-NAT1, RFP-NAT1, and M-Cherry-NAT1 plasmids were constructed expressing two differently labeled gene products for the study of protein co-expression and co-localization in vivo. Together, these vectors provide a useful set of genetic tools for studying diverse aspects of gene function in C. albicans clinical as well as laboratory strains. PMID:22777821

Crystal Structure of the Golgi-Associated Human Nα-Acetyltransferase 60 Reveals the Molecular Determinants for Substrate-Specific Acetylation.

PubMed

Støve, Svein Isungset; Magin, Robert S; Foyn, Håvard; Haug, Bengt Erik; Marmorstein, Ronen; Arnesen, Thomas

2016-07-06

N-Terminal acetylation is a common and important protein modification catalyzed by N-terminal acetyltransferases (NATs). Six human NATs (NatA-NatF) contain one catalytic subunit each, Naa10 to Naa60, respectively. In contrast to the ribosome-associated NatA to NatE, NatF/Naa60 specifically associates with Golgi membranes and acetylates transmembrane proteins. To gain insight into the molecular basis for the function of Naa60, we developed an Naa60 bisubstrate CoA-peptide conjugate inhibitor, determined its X-ray structure when bound to CoA and inhibitor, and carried out biochemical experiments. We show that Naa60 adapts an overall fold similar to that of the catalytic subunits of ribosome-associated NATs, but with the addition of two novel elongated loops that play important roles in substrate-specific binding. One of these loops mediates a dimer to monomer transition upon substrate-specific binding. Naa60 employs a catalytic mechanism most similar to Naa50. Collectively, these data reveal the molecular basis for Naa60-specific acetyltransferase activity with implications for its Golgi-specific functions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Paper-based sample-to-answer molecular diagnostic platform for point-of-care diagnostics.

PubMed

Choi, Jane Ru; Tang, Ruihua; Wang, ShuQi; Wan Abas, Wan Abu Bakar; Pingguan-Murphy, Belinda; Xu, Feng

2015-12-15

Nucleic acid testing (NAT), as a molecular diagnostic technique, including nucleic acid extraction, amplification and detection, plays a fundamental role in medical diagnosis for timely medical treatment. However, current NAT technologies require relatively high-end instrumentation, skilled personnel, and are time-consuming. These drawbacks mean conventional NAT becomes impractical in many resource-limited disease-endemic settings, leading to an urgent need to develop a fast and portable NAT diagnostic tool. Paper-based devices are typically robust, cost-effective and user-friendly, holding a great potential for NAT at the point of care. In view of the escalating demand for the low cost diagnostic devices, we highlight the beneficial use of paper as a platform for NAT, the current state of its development, and the existing challenges preventing its widespread use. We suggest a strategy involving integrating all three steps of NAT into one single paper-based sample-to-answer diagnostic device for rapid medical diagnostics in the near future. Copyright © 2015 Elsevier B.V. All rights reserved.

Preventing disease transmission by deceased tissue donors by testing blood for viral nucleic acid.

PubMed

Strong, D Michael; Nelson, Karen; Pierce, Marge; Stramer, Susan L

2005-01-01

Nucleic acid testing (NAT) has reduced the risk of transmitting infectious disease through blood transfusion. Currently NAT for HIV-1 and HCV are FDA licensed and performed by nearly all blood collection facilities, but HBV NAT is performed under an investigational study protocol. Residual risk estimates indicate that NAT could potentially reduce disease transmission through transplanted tissue. However, tissue donor samples obtained post-mortem have the potential to produce an invalid NAT result due to inhibition of amplification reactions by hemolysis and other factors. The studies reported here summarize the development of protocols to allow NAT of deceased donor samples with reduced rates of invalid results. Using these protocols, inventories from two tissue centers were tested with greater than 99% of samples producing a valid test result.

5. Photocopy of 1915 photograph showing a view of the ...

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

5. Photocopy of 1915 photograph showing a view of the building (the tallest building), courtesy of Philadelphia City Archives, City Hall, Philadelphia, Pennsylvania - Reliance Insurance Company of Philadelphia, 429 Walnut Street, Philadelphia, Philadelphia County, PA

Comparison of receptor affinity of natSc-DOTA-TATE versus natGa-DOTA-TATE.

PubMed

Koumarianou, Eftychia; Pawlak, Dariusz; Korsak, Agnieszka; Mikolajczak, Renata

2011-01-01

44Sc as a positron emitter can be an interesting alternative to 68Ga (T½=67.71 min) due to its longer half-life (T½=3.97 h). Moreover, the b-emitter 47Sc can be used for therapy when attached to the same biomolecule vectors. DOTA as a chelating agent has been proven suitable for the radiolabelling of peptides recognising tumour cell receptors in vivo with M3+ radiometals. DOTA-derivatized peptides have been successfully labelled with 90Y and 177Lu for therapy, and with 68Ga for PET imaging. However, published data on 44Sc-labelled DOTA-biomolecules as potential PET radiotracers are still very limited. The aim of this study was to compare the affinity of natGa- and natSc-labelled DOTA-TATE to somatostatin receptors subtype 2 expressed in rat pancreatic cancer cell line AR42J. The cold complexes of DOTA-TATE with natGa and natSc were synthesized and identified by HPLC and MS analysis and evaluated in vitro for competitive binding to cancer cell line AR42J expressing somatostatin receptors subtype 2 (sstr2). The IC50 values calculated from the displacement curve of {125I-Tyr11}-SST-14 were: 0.20±0.18, 0.70±0.20, 0.64±0.22 and 0.67±0.12 for natGa-DOTA-TATE, natSc-DOTA-TATE, DOTA-TATE, and {Tyr11}-SST-14 complexes, respectively, with the affinity lowering in the decreasing order: natGa-DOTA-TATE>DOTA-TATE>Tyr11-SST-14>natSc-DOTA-TATE. The binding affinity of natGa-DOTA-TATE appeared higher than that of natSc-DOTA-TATE. Further in vitro and in vivo studies are needed to verify the influence of the chelated metal on the affinity and uptake of the respective radiolabelled compounds. This information might be crucial when the in vivo applications of peptides labelled with 68Ga and 44Sc for PET, as well as the use of 47Sc for radiotherapy are considered.

3. Photocopy of May 2, 1908 photograph showing a general ...

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

3. Photocopy of May 2, 1908 photograph showing a general view of the bridge, courtesy of Philadelphia City Archives, Philadelphia City Hall, Philadelphia, Pa. - Strawberry Mansion Bridge, Ford Road & East River Drive, Philadelphia, Philadelphia County, PA

Accuracy of various human NAT2 SNP genotyping panels to infer rapid, intermediate and slow acetylator phenotypes

PubMed Central

Hein, David W; Doll, Mark A

2012-01-01

Aim Humans exhibit genetic polymorphism in NAT2 resulting in rapid, intermediate and slow acetylator phenotypes. Over 65 NAT2 variants possessing one or more SNPs in the 870-bp NAT2 coding region have been reported. The seven most frequent SNPs are rs1801279 (191G>A), rs1041983 (282C>T), rs1801280 (341T>C), rs1799929 (481C>T), rs1799930 (590G>A), rs1208 (803A>G) and rs1799931 (857G>A). The majority of studies investigate the NAT2 genotype assay for three SNPs: 481C>T, 590G>A and 857G>A. A tag-SNP (rs1495741) recently identified in a genome-wide association study has also been proposed as a biomarker for the NAT2 phenotype. Materials & methods Sulfamethazine N-acetyltransferase catalytic activities were measured in cryopreserved human hepatocytes from a convenience sample of individuals in the USA with an ethnic frequency similar to the 2010 US population census. These activities were segregated by the tag-SNP rs1495741 and each of the seven SNPs described above. We assessed the accuracy of the tag-SNP and various two-, three-, four- and seven-SNP genotyping panels for their ability to accurately infer NAT2 phenotype. Results The accuracy of the various NAT2 SNP genotype panels to infer NAT2 phenotype were as follows: seven-SNP: 98.4%; tag-SNP: 77.7%; two-SNP: 96.1%; three-SNP: 92.2%; and four-SNP: 98.4%. Conclusion A NAT2 four-SNP genotype panel of rs1801279 (191G>A), rs1801280 (341T>C), rs1799930 (590G>A) and rs1799931 (857G>A) infers NAT2 acetylator phenotype with high accuracy, and is recommended over the tag-, two-, three- and (for economy of scale) the seven-SNP genotyping panels, particularly in populations of non-European ancestry. PMID:22092036

N-acetyltransferase genotypes and the pharmacokinetics and tolerability of para-aminosalicylic acid in patients with drug-resistant pulmonary tuberculosis.

PubMed

Sy, Sherwin K B; de Kock, Lizanne; Diacon, Andreas H; Werely, Cedric J; Xia, Huiming; Rosenkranz, Bernd; van der Merwe, Lize; Donald, Peter R

2015-07-01

The aim of this study was to examine the relationships between N-acetyltransferase genotypes, pharmacokinetics, and tolerability of granular slow-release para-aminosalicylic acid (GSR-PAS) in tuberculosis patients. The study was a randomized, two-period, open-label, crossover design wherein each patient received 4 g GSR-PAS twice daily or 8 g once daily alternately. The PAS concentration-time profiles were modeled by a one-compartment disposition model with three transit compartments in series to describe its absorption. Patients' NAT1 and NAT2 genotypes were determined by sequencing and restriction enzyme analysis, respectively. The number of daily vomits was modeled by a Poisson probability mass function. Comparisons of other tolerability measures by regimens, gender, and genotypes were evaluated by a linear mixed-effects model. The covariate effects associated with efavirenz, gender, and NAT1*3, NAT1*14, and NAT2*5 alleles corresponded to 25, 37, -17, -48, and -27% changes, respectively, in oral clearance of PAS. The NAT1*10 allele did not influence drug clearance. The time above the MIC of 1 mg/liter was significantly different between the two regimens but not influenced by the NAT1 or NAT2 genotypes. The occurrence and intensity of intolerance differed little between regimens. Four grams of GSR-PAS twice daily but not 8 g once daily ensured concentrations exceeding the MIC (1 mg/liter) throughout the dosing interval; PAS intolerance was not related to maximum PAS concentrations over the doses studied and was not more frequent after once-daily dosing. We confirm that the slow phenotype conferred by the NAT1*14 and NAT1*3 alleles resulted in higher PAS exposure but found no evidence of increased activity of the NAT1*10 allele. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Nat1 promotes translation of specific proteins that induce differentiation of mouse embryonic stem cells.

PubMed

Sugiyama, Hayami; Takahashi, Kazutoshi; Yamamoto, Takuya; Iwasaki, Mio; Narita, Megumi; Nakamura, Masahiro; Rand, Tim A; Nakagawa, Masato; Watanabe, Akira; Yamanaka, Shinya

2017-01-10

Novel APOBEC1 target 1 (Nat1) (also known as "p97," "Dap5," and "Eif4g2") is a ubiquitously expressed cytoplasmic protein that is homologous to the C-terminal two thirds of eukaryotic translation initiation factor 4G (Eif4g1). We previously showed that Nat1-null mouse embryonic stem cells (mES cells) are resistant to differentiation. In the current study, we found that NAT1 and eIF4G1 share many binding proteins, such as the eukaryotic translation initiation factors eIF3 and eIF4A and ribosomal proteins. However, NAT1 did not bind to eIF4E or poly(A)-binding proteins, which are critical for cap-dependent translation initiation. In contrast, compared with eIF4G1, NAT1 preferentially interacted with eIF2, fragile X mental retardation proteins (FMR), and related proteins and especially with members of the proline-rich and coiled-coil-containing protein 2 (PRRC2) family. We also found that Nat1-null mES cells possess a transcriptional profile similar, although not identical, to the ground state, which is established in wild-type mES cells when treated with inhibitors of the ERK and glycogen synthase kinase 3 (GSK3) signaling pathways. In Nat1-null mES cells, the ERK pathway is suppressed even without inhibitors. Ribosome profiling revealed that translation of mitogen-activated protein kinase kinase kinase 3 (Map3k3) and son of sevenless homolog 1 (Sos1) is suppressed in the absence of Nat1 Forced expression of Map3k3 induced differentiation of Nat1-null mES cells. These data collectively show that Nat1 is involved in the translation of proteins that are required for cell differentiation.

Piperidinols That Show Anti-Tubercular Activity as Inhibitors of Arylamine N-Acetyltransferase: An Essential Enzyme for Mycobacterial Survival Inside Macrophages

PubMed Central

Abuhammad, Areej; Fullam, Elizabeth; Lowe, Edward D.; Staunton, David; Kawamura, Akane; Westwood, Isaac M.; Bhakta, Sanjib; Garner, Alun Christopher; Wilson, David L.; Seden, Peter T.; Davies, Stephen G.; Russell, Angela J.; Garman, Elspeth F.; Sim, Edith

2012-01-01

Latent M. tuberculosis infection presents one of the major obstacles in the global eradication of tuberculosis (TB). Cholesterol plays a critical role in the persistence of M. tuberculosis within the macrophage during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids. Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the cholesterol sterol-ring degradation and is essential for intracellular survival. The ability of the NAT from M. tuberculosis (TBNAT) to utilise propionyl-CoA links it to the cholesterol-catabolism pathway. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. TBNAT has been investigated as a potential target for TB therapies. From a previous high-throughput screen, 3-benzoyl-4-phenyl-1-methylpiperidinol was identified as a selective inhibitor of prokaryotic NAT that exhibited antimycobacterial activity. The compound resulted in time-dependent irreversible inhibition of the NAT activity when tested against NAT from M. marinum (MMNAT). To further evaluate the antimycobacterial activity and the NAT inhibition of this compound, four piperidinol analogues were tested. All five compounds exert potent antimycobacterial activity against M. tuberculosis with MIC values of 2.3–16.9 µM. Treatment of the MMNAT enzyme with this set of inhibitors resulted in an irreversible time-dependent inhibition of NAT activity. Here we investigate the mechanism of NAT inhibition by studying protein-ligand interactions using mass spectrometry in combination with enzyme analysis and structure determination. We propose a covalent mechanism of NAT inhibition that involves the formation of a reactive intermediate and selective cysteine residue modification. These piperidinols present a unique class of antimycobacterial compounds that have a novel mode of action different from known anti-tubercular drugs. PMID:23285185

N-acetyltransferase (nat) is a critical conjunct of photoperiodism between the circadian system and endocrine axis in Antheraea pernyi.

PubMed

Mohamed, Ahmed A M; Wang, Qiushi; Bembenek, Jadwiga; Ichihara, Naoyuki; Hiragaki, Susumu; Suzuki, Takeshi; Takeda, Makio

2014-01-01

Since its discovery in 1923, the biology of photoperiodism remains a mystery in many ways. We sought the link connecting the circadian system to an endocrine switch, using Antheraea pernyi. PER-, CLK- and CYC-ir were co-expressed in two pairs of dorsolateral neurons of the protocerebrum, suggesting that these are the circadian neurons that also express melatonin-, NAT- and HIOMT-ir. The results suggest that a melatonin pathway is present in the circadian neurons. Melatonin receptor (MT2 or MEL-1B-R)-ir in PTTH-ir neurons juxtaposing clock neurons suggests that melatonin gates PTTH release. RIA showed a melatonin rhythm with a peak four hours after lights off in adult brain both under LD16:8 (LD) and LD12:12 (SD), and both the peak and the baseline levels were higher under LD than SD, suggesting a photoperiodic influence. When pupae in diapause were exposed to 10 cycles of LD, or stored at 4 °C for 4 months under constant darkness, an increase of NAT activity was observed when PTTH released ecdysone. DNA sequence upstream of nat contained E-boxes to which CYC/CLK could bind, and nat transcription was turned off by clk or cyc dsRNA. dsRNA(NAT) caused dysfunction of photoperiodism. dsRNA(PER) upregulated nat transcription as anticipated, based on findings in the Drosophila melanogaster circadian system. Transcription of nat, cyc and clk peaked at ZT12. RIA showed that dsRNA(NAT) decreased melatonin while dsRNA(PER) increased melatonin. Thus nat, a clock controlled gene, is the critical link between the circadian clock and endocrine switch. MT-binding may release PTTH, resulting in termination of diapause. This study thus examined all of the basic functional units from the clock: a photoperiodic counter as an accumulator of mRNA(NAT), to endocrine switch for photoperiodism in A. pernyi showing this system is self-complete without additional device especially for photoperiodism.

N-Acetyltransferase 2 (NAT2) genetic variation and the susceptibility to noncardiac gastric adenocarcinoma in Taiwan.

PubMed

Chang, Chih-Hao; Huang, Yi-Shin; Perng, Chin-Lin; Lin, Han-Chieh

2016-03-01

N-Acetyltransferase (NAT) is an important enzyme with the capacity to metabolize carcinogenic aromatic amines. However, it remains controversial whether the encoded functional NAT2 genetic polymorphism is related to the risk of gastric adenocarcinoma (GA). The aim of this study was to evaluate the association between NAT2 genetic variation and gastric adenocarcinoma (GA), with special reference to the gastric noncardiac adenocarcinoma (GNA). Peripheral white blood cell DNA from 368 GA patients and 368 age- and sex-matched controls were genotyped for NAT2 by a polymerase chain reaction method. The lifestyle habits of the participants were assessed using a semiquantitative food-frequency questionnaire. NAT2 genotype, interaction with lifestyle habits, and the risk of GA and GNA were analyzed by logistic regression. GA patients were more likely to have a smoking habit, ate more salted foods, and consumed more well-done meat than the controls. There was no association between the NAT2 genotypes and susceptibility to GA. However, if patients with gastric cardiac adenocarcinoma (GCA; n = 42) were excluded, the NAT2 slow acetylators (without rapid acetylator allele) had a higher risk of GA than intermediate and rapid acetylators (odds ratio = 1.53; 95% confidence interval, 1.05-2.23, p = 0.027). In addition, there was a synergic effect of NAT2 slow acetylator and well-done meat intake to the development of GNA (odds ratio = 3.83; 95% confidence interval, 1.68-8.76, p = 0.001). NAT2 slow acetylators have a higher risk of GNA than intermediate and rapid acetylators have in a Taiwanese population. The intake of well-done meat, an additive to the acetylator status, may contribute to the incidence of gastric carcinogenesis. Copyright © 2015. Published by Elsevier Taiwan LLC.

Cost projections for implementation of safety interventions to prevent transfusion-transmitted Zika virus infection in the United States

PubMed Central

Ellingson, Katherine D.; Sapiano, Mathew R.P.; Haass, Kathryn A.; Savinkina, Alexandra A.; Baker, Misha L.; Henry, Richard A.; Berger, James J.; Kuehnert, Matthew J.; Basavaraju, Sridhar V.

2017-01-01

BACKGROUND In August 2016, the Food and Drug Administration advised US blood centers to screen all whole blood and apheresis donations for Zika virus (ZIKV) with an individual-donor nucleic acid test (ID-NAT) or to use approved pathogen reduction technology (PRT). The cost of implementing this guidance nationally has not been assessed. STUDY DESIGN AND METHODS Scenarios were constructed to characterize approaches to ZIKV screening, including universal ID-NAT, risk-based seasonal allowance of minipool (MP) NAT by state, and universal MP-NAT. Data from the 2015 National Blood Collection and Utilization Survey (NBCUS) were used to characterize the number of donations nationally and by state. For each scenario, the estimated cost per donor ($3–$9 for MP-NAT, $7–$13 for ID-NAT) was multiplied by the estimated number of relevant donations from the NBCUS. Cost of PRT was calculated by multiplying the cost per unit ($50–$125) by the number of units approved for PRT. Prediction intervals for costs were generated using Monte Carlo simulation methods. RESULTS Screening all donations in the 50 states and DC for ZIKV by ID-NAT would cost $137 million (95% confidence interval [CI], $109–$167) annually. Allowing seasonal MP-NAT in states with lower ZIKV risk could reduce NAT screening costs by 18% to 25%. Application of PRT to all platelet (PLT) and plasma units would cost $213 million (95% CI, $156–$304). CONCLUSION Universal ID-NAT screening for ZIKV will cost US blood centers more than $100 million annually. The high cost of PRT for apheresis PLTs and plasma could be mitigated if, once validated, testing for transfusion transmissible pathogens could be eliminated. PMID:28591470

Rapid and sensitive approach to simultaneous detection of genomes of hepatitis A, B, C, D and E viruses.

PubMed

Kodani, Maja; Mixson-Hayden, Tonya; Drobeniuc, Jan; Kamili, Saleem

2014-10-01

Five viruses have been etiologically associated with viral hepatitis. Nucleic acid testing (NAT) remains the gold standard for diagnosis of viremic stages of infection. NAT methodologies have been developed for all hepatitis viruses; however, a NAT-based assay that can simultaneously detect all five viruses is not available. We designed TaqMan card-based assays for detection of HAV RNA, HBV DNA, HCV RNA, HDV RNA and HEV RNA. The performances of individual assays were evaluated on TaqMan Array Cards (TAC) for detecting five viral genomes simultaneously. Sensitivity and specificity were determined by testing 329 NAT-tested clinical specimens. All NAT-positive samples for HCV (n = 32), HDV (n = 28) and HEV (n = 14) were also found positive in TAC (sensitivity, 100%). Forty-three of 46 HAV-NAT positive samples were also positive in TAC (sensitivity, 94%), while 36 of 39 HBV-NAT positive samples were positive (sensitivity, 92%). No false-positives were detected for HBV (n = 32), HCV (n = 36), HDV (n = 30), and HEV (n = 31) NAT-negative samples (specificity 100%), while 38 of 41 HAV-NAT negative samples were negative by TAC (specificity 93%). TAC assay was concordant with corresponding individual NATs for hepatitis A-E viral genomes and can be used for their detection simultaneously. The TAC assay has potential for use in hepatitis surveillance, for screening of donor specimens and in outbreak situations. Wider availability of TAC-ready assays may allow for customized assays, for improving acute jaundice surveillance and for other purposes for which there is need to identify multiple pathogens rapidly. Published by Elsevier B.V.

Interaction between Red Meat Intake and NAT2 Genotype in Increasing the Risk of Colorectal Cancer in Japanese and African Americans

PubMed Central

Wang, Hansong; Iwasaki, Motoki; Haiman, Christopher A.; Kono, Suminori; Wilkens, Lynne R.; Keku, Temitope O.; Berndt, Sonja I.; Tsugane, Shoichiro; Le Marchand, Loïc

2015-01-01

Heterocyclic aromatic amines formed in cooked meat may be an underlying mechanism for the red meat-colorectal cancer (CRC) association. These compounds require bioactivaction by N-acetyltransferase 2 (NAT2). An interaction effect between red meat consumption and NAT2 in increasing CRC risk has been inconsistently reported in whites. We investigated this interaction in two populations in which the high-activity rapid NAT2 phenotype is 10- and 2-fold more common than in whites. We meta-analyzed four studies of Japanese (2,217 cases, 3,788 controls) and three studies of African Americans (527 cases, 4,527 controls). NAT2 phenotype was inferred from an optimized seven-SNP genotyping panel. Processed and total red meat intakes were associated with an increased CRC risk in Japanese and in both ethnic groups combined (P’s ≤ 0.002). We observed an interaction between processed meat intake and NAT2 in Japanese (P = 0.04), African Americans (P = 0.02), and in both groups combined (P = 0.006). The association of processed meat with CRC was strongest among individuals with the rapid NAT2 phenotype (combined analysis, OR for highest vs. lowest quartile: 1.62, 95% CI: 1.28–2.05; Ptrend = 8.0×10−5), intermediate among those with the intermediate NAT2 phenotype (1.29, 95% CI: 1.05–1.59; Ptrend = 0.05) and null among those with the slow phenotype (Ptrend = 0.45). A similar interaction was found for NAT2 and total red meat (Pinteraction = 0.03). Our findings support a role for NAT2 in modifying the association between red meat consumption and CRC in Japanese and African Americans. PMID:26683305

Foundations of Nuclear Geophysics

NASA Astrophysics Data System (ADS)

Herndon, J. M.; Hollenbach, D. F.

2002-05-01

Herndon suggested that the inner core of the Earth consists, not of partially crystallized iron metal, but of nickel silicide. He has shown by fundamental mass ratios that i) the Earth as a whole, especially the inner 82%, has a state of oxidation like primitive enstatite chondrites, and ii) the lower mantle and core are similar in composition to the Abee enstatite chondrite. By analogy with Abee data, CaS and MgS precipitates from the core are expected to collect at the core-mantle boundary and, significantly, a major fraction of the actinides are expected to precipitate from the core and to collect at the center of the Earth. Herndon demonstrated the feasibility of a nuclear fission reactor at the center of the Earth as the energy source for the geomagnetic field and described a natural mechanism that would lead to variations in energy production and thus variations in the geomagnetic field. Hollenbach and Herndon produced numerical simulations of the operation of the geo-reactor over the lifetime of the Earth using the state-of-the-art, validated, industry standard SCALE code package developed at Oak Ridge National Laboratory. The results clearly demonstrate that such a geo-reactor would i) function as a fast-neutron breeder reactor; ii) under appropriate conditions, operate over the entire period of geologic time; iii) function in such a manner as to yield variable and/or intermittent output; iv) generate energy at levels in the range generally accepted by the geophysics community; and, v) produce He-3 and He-4 in ratios that are in the range observed from deep-mantle sources. Deep-source He-3, the authors submit, is evidence of in-core sustained nuclear fission, rather than the out-gassing of primordial He-3; which in turn is evidence of large amounts of uranium residing in the Earth's core; which in turn is evidence that the core has a state of oxidation like the corresponding matter in primitive enstatite chondrites. The factors affecting He-3/He-4 ratios, their causes and implications, will be discussed in the presentation. Also, the current state of investigations into additional deep-Earth nuclear fission signatures will be presented. References: J. M. Herndon, Proc. R. Roc. London, Ser. A, 368 (1979) 495; J. Geomagn. Geoelectr. 45 (1993) 423; Proc. R. Soc. London, Ser. A, 445 (1994) 453; Proc. Nat. Acad. Sci. (USA) 93 (1996) 646. Hollenbach, D. F. and J. M. Herndon, Proc. Nat. Acad. Sci. (USA) 98 (2001) 11085.

Antarctic NAT PSC Belt of June 2003: Observational Validation of the Mountain Wave Seeding Hypothesis

NASA Technical Reports Server (NTRS)

Eckermann, S. D.; Hoffmann, L.; Hoepfner, M.; Wu, D. L.; Alexander, M. J.

2009-01-01

Satellite observations of polar stratospheric clouds (PSCs) over Antarctica in June 2003 revealed small nitric acid trihydrate (NAT) particles forming suddenly along the vortex edge. Models suggest the trigger was mountain waves over the Antarctic Peninsula (AP) forming ice for NAT nucleation. We test this hypothesis by analyzing perturbations in stratospheric radiances from the Atmospheric Infrared Sounder (AIRS). AIRS data show mountain waves over the AP on 10-14 June, with no resolved wave activity before or after. Peak wave temperature amplitudes derived from independent 40 hPa channels all return values of 10-12 K, in agreement with values used to model this NAT event. These observations support a NAT wake from a small region of mountain wave activity over the AP as the source of this circumpolar NAT outbreak.

NAT10, a nucleolar protein, localizes to the midbody and regulates cytokinesis and acetylation of microtubules

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

Shen, Qi; Zheng, Xingzheng; McNutt, Michael A.

2009-06-10

The midbody is a structural organelle formed in late phase mitosis which is responsible for completion of cytokinesis. Although various kinds of proteins have been found to distribute or immigrate to this organelle, their functions have still not been completely worked out. In this study, we demonstrated that NAT10 (N-acetyltransferase 10, NAT10) is not only predominantly distributed in the nucleolus in interphase, but is also concentrated in the mitotic midbody during telophase. The domain in N-terminal residues 549-834 of NAT10 specifically mediated its subcellular localization. Treatment with genotoxic agents or irradiation increased concentration of NAT10 in both the nucleolus andmore » midbody. Moreover, DNA damage induced increase of NAT10 in the midbody apparently accompanied by in situ elevation of the level of acetylated {alpha}-tubulin, suggesting that it plays a role in maintaining or enhancing stability of {alpha}-tubulin. The depletion of NAT10 induced defects in nucleolar assembly, cytokinesis and decreased acetylated {alpha}-tubulin, leading to G2/M cell cycle arrest or delay of mitotic exit. In addition, over-expression of NAT10 was found in a variety of soft tissue sarcomas, and correlated with tumor histological grading. These results indicate that NAT10 may play an important role in cell division through facilitating reformation of the nucleolus and midbody in the late phase of cell mitosis, and stabilization of microtubules.« less

Identification and validation of N-acetyltransferase 2 as an insulin sensitivity gene.

PubMed

Knowles, Joshua W; Xie, Weijia; Zhang, Zhongyang; Chennamsetty, Indumathi; Chennemsetty, Indumathi; Assimes, Themistocles L; Paananen, Jussi; Hansson, Ola; Pankow, James; Goodarzi, Mark O; Carcamo-Orive, Ivan; Morris, Andrew P; Chen, Yii-Der I; Mäkinen, Ville-Petteri; Ganna, Andrea; Mahajan, Anubha; Guo, Xiuqing; Abbasi, Fahim; Greenawalt, Danielle M; Lum, Pek; Molony, Cliona; Lind, Lars; Lindgren, Cecilia; Raffel, Leslie J; Tsao, Philip S; Schadt, Eric E; Rotter, Jerome I; Sinaiko, Alan; Reaven, Gerald; Yang, Xia; Hsiung, Chao A; Groop, Leif; Cordell, Heather J; Laakso, Markku; Hao, Ke; Ingelsson, Erik; Frayling, Timothy M; Weedon, Michael N; Walker, Mark; Quertermous, Thomas

2015-04-01

Decreased insulin sensitivity, also referred to as insulin resistance (IR), is a fundamental abnormality in patients with type 2 diabetes and a risk factor for cardiovascular disease. While IR predisposition is heritable, the genetic basis remains largely unknown. The GENEticS of Insulin Sensitivity consortium conducted a genome-wide association study (GWAS) for direct measures of insulin sensitivity, such as euglycemic clamp or insulin suppression test, in 2,764 European individuals, with replication in an additional 2,860 individuals. The presence of a nonsynonymous variant of N-acetyltransferase 2 (NAT2) [rs1208 (803A>G, K268R)] was strongly associated with decreased insulin sensitivity that was independent of BMI. The rs1208 "A" allele was nominally associated with IR-related traits, including increased fasting glucose, hemoglobin A1C, total and LDL cholesterol, triglycerides, and coronary artery disease. NAT2 acetylates arylamine and hydrazine drugs and carcinogens, but predicted acetylator NAT2 phenotypes were not associated with insulin sensitivity. In a murine adipocyte cell line, silencing of NAT2 ortholog Nat1 decreased insulin-mediated glucose uptake, increased basal and isoproterenol-stimulated lipolysis, and decreased adipocyte differentiation, while Nat1 overexpression produced opposite effects. Nat1-deficient mice had elevations in fasting blood glucose, insulin, and triglycerides and decreased insulin sensitivity, as measured by glucose and insulin tolerance tests, with intermediate effects in Nat1 heterozygote mice. Our results support a role for NAT2 in insulin sensitivity.

Nucleic Acid Amplification Test For Detection Of West Nile Virus Infection In Pakistani Blood Donors.

PubMed

Niazi, Saifullah Khan; Alam, Maqbool; Yazdani, Muhammad Sajid; Ghani, Eijaz; Rathore, Muhammad Ali

2017-01-01

The study was planned to determine the presence of West Nile Virus (WNV) infection in Pakistani blood donors, using Nucleic Acid Amplification Test (NAT). The blood donors for study were selected on the basis of the standard questionnaire and routine screening results. Six donors were pooled using an automated pipettor and NAT for WNV was performed on Roche Cobas s 201 NAT system. The reactive pools were resolved in Individual Donation-NAT (ID-NAT) format and a sample from FFP bags of reactive donations was retrieved. NAT was again performed on retrieved plasma bag (RPB) sample to confirm the reactive donations. The donors were also recalled and interviewed about history of illness related to recent WNV infection. After serological screening of 1929 donors during the study period, 1860 donors were selected for NAT test for WNV detection. The mean age of the donors was 28±8.77 (range: 18-57 years). 1847 (99.3%) donors were male and 13 (0.7%) were female. NAT for WNV identified six initially reactive pools (0.32%). On follow-up testing with RPB samples, 4 donors (0.21%) were found confirmed reactive for WNV RNA (NAT yield of 1 in 465 blood donors). WNV is a threat to safety of blood products in Pakistan. A screening strategy can be implemented after a large-scale study and financial considerations. One of the reduced cost screening strategies is seasonal screening of blood donors for WNV, with pooling of samples.

Service building no. 620. Typical wall sections (Dry Dock Associates, ...

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

Service building no. 620. Typical wall sections (Dry Dock Associates, November 7, 1941). In files of Cushman & Wakefield Building (no. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Service Building, Dry Docks No. 4 & 5, League Island, Philadelphia, Philadelphia County, PA

In vitro effects of 5-hydroxytryptophan, indoleamines and leptin on arylalkylamine N-acetyltransferase (AA-NAT) activity in pineal organ of the fish, Clarias gariepinus (Burchell, 1822) during different phases of the breeding cycle.

PubMed

Gupta, B B P; Yanthan, L; Singh, Ksh Manisana

2010-08-01

Arylalkylamine N-acetyltransferase (AA-NAT) is the rate-limiting enzyme of melatonin biosynthetic pathway. In vitro effects of 5-hydroxytryptophan (5-HTP) and indoleamines (serotonin, N-acetylserotonin and melatonin) were studied on AA-NAT activity in the pineal organ of the fish, C. gariepinus during different phases of its annual breeding cycle. Further, in vitro effects of leptin on AA-NAT activity in the pineal organ were studied in fed and fasted fishes during summer and winter seasons. Treatments with 5-HTP and indoleamines invariably stimulated pineal AA-NAT activity in a dose-dependent manner during all the phases. However, leptin increased AA-NAT activity in a dose-dependent manner only in the pineal organ of the fed fishes, but not of the fasted fishes irrespective of the seasons.

13. Dry Dock No. 4. Plan. Subdivision IV (Frederic R. ...

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

13. Dry Dock No. 4. Plan. Subdivision IV (Frederic R. Harris, Inc., January 10, 1941). In Files of Cushman & Wakefield, Building No. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 4, Broad Street south of Government Avenue, Philadelphia, Philadelphia County, PA

10. Dry Dock No. 4. Plan. Subdivision I (Frederic R. ...

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

10. Dry Dock No. 4. Plan. Subdivision I (Frederic R. Harris, Inc., January 10, 1941). In Files of Cushman & Wakefield, Building No. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 4, Broad Street south of Government Avenue, Philadelphia, Philadelphia County, PA

Photograph of elevation and details of structure 841, used for ...

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

Photograph of elevation and details of structure 841, used for repair project, dated 1973. Drawing in collection of Caretaker Site Office, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Structure No. 841, Delaware Avenue between East Fourth Street & Webster Avenue, League Island, Philadelphia, Philadelphia County, PA

12. Dry Dock No. 4. Plan. Subdivision III (Frederic R. ...

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

12. Dry Dock No. 4. Plan. Subdivision III (Frederic R. Harris, Inc., January 10, 1941). In Files of Cushman & Wakefield, Building No. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 4, Broad Street south of Government Avenue, Philadelphia, Philadelphia County, PA

9. Dry Dock No. 4. Typical CrossSections (Frederic R. Harris, ...

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

9. Dry Dock No. 4. Typical Cross-Sections (Frederic R. Harris, Inc., January 10, 1941). In Files of Cushman & Wakefield, Building No. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 4, Broad Street south of Government Avenue, Philadelphia, Philadelphia County, PA

11. Dry Dock No. 4. Plan. Subdivision II (Frederic R. ...

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

11. Dry Dock No. 4. Plan. Subdivision II (Frederic R. Harris, Inc., January 10, 1941). In Files of Cushman & Wakefield, Building No. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 4, Broad Street south of Government Avenue, Philadelphia, Philadelphia County, PA

18. Dry Dock No. 4. Entrance Details (Frederic R. Harris, ...

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

18. Dry Dock No. 4. Entrance Details (Frederic R. Harris, Inc., January 10, 1941). In Files of Cushman & Wakefield, Building No. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 4, Broad Street south of Government Avenue, Philadelphia, Philadelphia County, PA

Trefoil knot timescales for reconnection and helicity

NASA Astrophysics Data System (ADS)

Kerr, Robert M.

2018-02-01

Three-dimensional images of evolving numerical trefoil vortex knots are used to study the growth and decay of the enstrophy and helicity. Negative helicity density (h< 0) plays several roles. First, during anti-parallel reconnection, sheets of oppositely signed helicity dissipation of equal magnitude on either side of the maximum of the enstrophy dissipation allow the global helicity { H } to be preserved through the first reconnection, as suggested theoretically (Laing et al 2015 Sci. Rep. 5 9224) and observed experimentally (Scheeler et al 2014a Proc. Natl Acad. Sci. 111 15350-5). Next, to maintain the growth of the enstrophy and positive helicity within the trefoil while { H } is preserved, h< 0 forms in the outer parts of the trefoil so long as the periodic boundaries do not interfere. To prevent that, the domain size {\\ell } is increased as the viscosity ν \\to 0. Combined, this allows two sets of trefoils to form a new scaling regime with linearly decreasing {(\\sqrt{ν }Z(t))}-1/2 up to common ν-independent times t x that the graphics show is when the first reconnection ends. During this phase there is good correspondence between the evolution of the simulated vortices and the reconnecting experimental trefoil of Kleckner and Irvine (2017 Nat. Phys. 9 253-8) when time is scaled by their respective nonlinear timescales t f . The timescales t f are based upon by the radii r f of the trefoils and their circulations Γ, so long as the strong camber of the experimental hydrofoil models is used to correct the published experimental circulations Γ that use only the flat-plate approximation.

Crustal stress, seismicity, acoustic emission (AE), and tectonics: the Kefallinì;a (Greece) case study

NASA Astrophysics Data System (ADS)

Gregori, G. P.; Poscolieri, M.; Paparo, G.; Ventrice, G.; de Simone, S.; Rafanelli, C.

2009-04-01

New inferences - confirming previous results (see references)- are presented dealing with a few years Acoustic Emission (AE) records collected at Kefallinìa (Ionian Islands, Greece). A physical distinction between HF (high frequency) vs. LF (low frequency) AE is required. Step-wise changes of the AE underground conductivity are evidenced, and can be suitably handled. "Smooth" results concern (i) the annual variation, (ii) some long-lasting stress "solitons" crossing through the area, and (iii) tidal effects. In particular, every AE station can be operated like a monitoring station both for Earth's tides and for the free oscillations of the Earth. In addition, Kefallinìa exhibits a much peculiar groundwater circulation, in which conduit flow is dominant, that originates a specific (and unique) AE effect. By means of AE time-series analysis, "extreme" or "catastrophic" events can be also monitored and possibly related to relevant tectonic occurrences (either earthquakes, or maybe other occasional phenomena). They can be investigated, and have a regional - rather than local - character. Therefore, every interpretation based on a single station record - being biased by some arbitrariness - can only result indicative. A standardized procedure and software is proposed for routine AE data handling and analysis. References.: Lagios et al., 2004. In Proc. SCI 2004 (The 8th World Multi-Conference on Systemics, Cybernetics and Informatic), Orlando, Florida, July 1004, 6 pp. Poscolieri et al., 2006. In. G. Cello and B. D. Malamud, (eds), 2006. Geol. Soc. London, Special Publ., 261, 63-78. Poscolieri et al., 2006a. Nat. Hazards Earth Syst. Sci., 6, 961-971.

Management engineering (building no. 4), looking west along Porter Avenue. ...

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

Management engineering (building no. 4), looking west along Porter Avenue. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Management Engineering, League Island, Philadelphia, Philadelphia County, PA

Excitation function of alpha-particle-induced reactions on natNi from threshold to 44 MeV

NASA Astrophysics Data System (ADS)

Uddin, M. S.; Kim, K. S.; Nadeem, M.; Sudár, S.; Kim, G. N.

2017-05-01

Excitation functions of the natNi(α,x)62,63,65Zn, natNi(α,x)56,57Ni and natNi(α,x)56,57,58m+gCo reactions were measured from the respective thresholds to 44MeV using the stacked-foil activation technique. The tests for the beam characterization are described. The radioactivity was measured using HPGe γ-ray detectors. Theoretical calculations on α-particles-induced reactions on natNi were performed using the nuclear model code TALYS-1.8. A few results are new, the others strengthen the database. Our experimental data were compared with results of nuclear model calculations and described the reaction mechanism.

Diverse point mutations in the human gene for polymorphic N-acetyltransferase

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

Vatsis, K.P.; Martell, K.J.; Weber, W.W.

1991-07-15

Classification of humans as rapid or slow acetylators is based on hereditary differences in rates of N-acetylation of therapeutic and carcinogenic agents, but N-acetylation of certain arylamine drugs displays no genetic variation. Two highly homologous human genes for N-acetyltransferase NAT1 and NAT2, presumably code for the genetically invariant and variant NAT proteins, respectively. In the present investigation, 1.9-kilobase human genomic EcoRI fragments encoding NAT2 were generated by the polymerase chain reaction with liver and leukocyte DNA from seven subjects phenotyped as homozygous and heterozygous acetylators. Direct sequencing revealed multiple point mutations in the coding region of two distinct NAT2 variants.more » One of these was derived from leukocytes of a slow acetylator and was distinguished by a silent mutation (coden 94) and a separate G {r arrow} A transition (position 590) leading to replacement of Arg-197 by Gln; the mutated guanine was part of a CpG dinucleotide and a Taq I site. The second NAT2 variant originated from liver with low N-acetylation activity. It was characterized by three nucleotide transitions giving rise to a silent mutation (codon 161), accompanied by obliteration of the sole Kpn I site, and two amino acid substitutions. The results show conclusively that the genetically variant NAT is encoded by NAT2.« less

Priority needs and wisdom strategy for blood transfusion safety in developing low-resource countries.

PubMed

Abdelrazik, Abeer Mohamed; Ezzat Ahmed, Ghada M

2016-02-01

To evaluate the implementation of alternative safety measures that reduce the risk of transfusion transmissible infections as an affordable measure in low resource countries. It is still difficult in developing countries with limited resources to mandate nucleic acid testing due to its high cost. Although NAT reduces the window period of infection, the developing countries are still in need of an efficient and effective transfusion programme before implementing the complex high cost NAT. Two thousand eight hundred eighty sero-negative first-time and repeat donations from Fayoum University Hospital blood bank were individually analysed by NAT for HIV, HBV and HCV. Only discriminatory-positive NAT were classified comparing the non-remunerated and family replacement donations. Significant discriminatory-positive differences were observed for HBV NAT results, 2 remunerated donations compared to 0 non-remunerated sero-negative donations. The discriminatory positive differences were also significant for HCV NAT results, 4 remunerated donations compared to 1 non-remunerated sero-negative donation. No sero-negative, discriminatory-positive NAT HIV case was found. Seven out of 8 discriminatory positive cases were from first time donations. In order to ensure blood safety, the recruitment and retention of voluntary, non-remunerated repeat donors should be a major commitment for low resource countries in which NAT implementation is costly and not feasible. Copyright © 2016 Elsevier Ltd. All rights reserved.

Measurement of activation cross sections of alpha particle induced reactions on iridium up to an energy of 50 MeV.

PubMed

Takács, S; Ditrói, F; Szűcs, Z; Aikawa, M; Haba, H; Komori, Y; Saito, M

2018-06-01

Cross sections of alpha particle induced nuclear reactions on iridium were investigated using a 51.2-MeV alpha particle beam. The standard stacked-foil target technique and the activation method were applied. The activity of the reaction products was assessed without chemical separation using high resolution gamma-ray spectrometry. Excitation functions for production of gold, platinum and iridium isotopes ( 196m2 Au, 196m,g Au, 195m,g Au, 194 Au, 193 m,g Au, 192 Au, 191m,g Au, 191 Pt, 195m Pt, 194g Ir, 194m Ir, 192g Ir, 190g Ir and 189 Ir) were determined and compared with available earlier measured experimental data and results of theoretical calculations using TALYS code system. Cross section data were reported for the first time for the nat Ir(α,x) 196m2 Au, nat Ir(α,x) 196m,g Au, nat Ir(α,x) 191 Pt, nat Ir(α,x) 195m Pt, nat Ir(α,x) 194g Ir, nat Ir(α,x) 194m Ir, nat Ir(α,x) 190g Ir and nat Ir(α,x) 189 Ir processes. A possible production route for 195m Pt, the potentially important radionuclide in nuclear medicine, is discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

NAT1/DAP5/p97 and Atypical Translational Control in the Drosophila Circadian Oscillator

PubMed Central

Bradley, Sean; Narayanan, Siddhartha; Rosbash, Michael

2012-01-01

Circadian rhythms are driven by gene expression feedback loops in metazoans. Based on the success of genetic screens for circadian mutants in Drosophila melanogaster, we undertook a targeted RNAi screen to study the impact of translation control genes on circadian locomotor activity rhythms in flies. Knockdown of vital translation factors in timeless protein-positive circadian neurons caused a range of effects including lethality. Knockdown of the atypical translation factor NAT1 had the strongest effect and lengthened circadian period. It also dramatically reduced PER protein levels in pigment dispersing factor (PDF) neurons. BELLE (BEL) protein was also reduced by the NAT1 knockdown, presumably reflecting a role of NAT1 in belle mRNA translation. belle and NAT1 are also targets of the key circadian transcription factor Clock (CLK). Further evidence for a role of NAT1 is that inhibition of the target of rapamycin (TOR) kinase increased oscillator activity in cultured wings, which is absent under conditions of NAT1 knockdown. Moreover, the per 5′- and 3′-UTRs may function together to facilitate cap-independent translation under conditions of TOR inhibition. We suggest that NAT1 and cap-independent translation are important for per mRNA translation, which is also important for the circadian oscillator. A circadian translation program may be especially important in fly pacemaker cells. PMID:22904033

N-acetyltransferase 1 and 2 polymorphisms and risk of diabetes mellitus type 2 in a Saudi population.

PubMed

Al-Shaqha, Waleed M; Alkharfy, Khalid M; Al-Daghri, Nasser M; Mohammed, Abdul Khader

2015-01-01

There have been inconsistent reports on N-acetyltransferase (NAT) gene polymorphism in type 2 diabetes mellitus (T2DM), and data is particularly limited in the Arab population. Therefore, the main objective of this study was to identify whether the genetic polymorphisms of NAT1 and NAT2 play a role in susceptibility to T2DM in the Saudi population. A population-based, prospective genetic association case-control study on a Saudi population. Whole blood, anthropometric measurements and biochemistry data were collected from 369 Saudi individuals (186 T2DM patients and 183 healthy controls). DNA was isolated from the blood. Polymorphism of NAT1 and NAT2 SNPs [NAT2*7B, rs1041983(C > T); NAT2*7, rs1799931(G > A); NAT2*6A, rs1799930(G > A); NAT2*5A, rs1799929(C > T); and NAT1*11A, rs4986988(C > T)] were evaluated by allelic discrimination using real-time PCR. Subjects with T2DM had a significantly increased body mass index (BMI), waist circumference, sys.tolic and diastolic blood pressure, glucose, triglycerides, and LDL-cholesterol compared with healthy controls (P < .05). The rs1799931(G > A) genotype was detected in the control population but not in the T2DM population (P < .001). The wild type (G) allele frequency was higher in T2DM than controls (P=.038). The mutant allele (A) in rs1799931(G > A) had a protective effect for T2DM (OR 0.32, 95% CI 0.16-0.62; P=.001). Regression analysis showed that BMI, systolic BP and triglycerides are potential risk factors for T2DM. The genotypes as well as the individual alleles of rs1799931(G > A) differed significantly be.tween the case and control populations. The variation in the data reported so far suggest that polymorphism of the NAT gene may vary among different geographical areas. Environmental or dietary factors may also contribute to disease manifestation.

26. Photographic copy of Second Floor Plan (The Ballinger Company, ...

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

26. Photographic copy of Second Floor Plan (The Ballinger Company, April 12, 1955), In files of the City of Philadelphia. Division of Aviation, Terminal E. Philadelphia International Airport. Reprinted with permission of Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

25. Photographic copy of First Floor Plan (The Ballinger Company, ...

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

25. Photographic copy of First Floor Plan (The Ballinger Company, April 12, 1955). In files of the City of Philadelphia, Division of Aviation, Terminal E, Philadelphia International Airport. Reprinted with permission of the Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

28. Photographic copy of North, South, East Elevation (The Ballinger ...

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

28. Photographic copy of North, South, East Elevation (The Ballinger Company, April 12, 1955). In files of the City of Philadelphia. Division of Aviation, Terminal E, Philadelphia International Airport. Reprinted with permission of the Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

30. Photographic copy of Wall Sections and Details (The Ballinger ...

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

30. Photographic copy of Wall Sections and Details (The Ballinger Company, April 12, 1955). In files of the City of Philadelphia, Division of Aviation, Terminal E. Philadelphia International Airport Reprinted with permission of the Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

4. Photocopy of photograph of Reliance Insurance Company in its ...

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

4. Photocopy of photograph of Reliance Insurance Company in its original appearance. View photocopied from George W. Engelhart's book, Philadelphia, Penna., The Book of its Bourse and Cooperating Bodies, published in Philadelphia in 1898-99. The page number is 193. - Reliance Insurance Company of Philadelphia, 429 Walnut Street, Philadelphia, Philadelphia County, PA

Service building no. 620. Details of ramps in south end ...

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

Service building no. 620. Details of ramps in south end of service building (Dry Dock Associates, November 7, 1941). In files of Cushman & Wakefiled, building no. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Service Building, Dry Docks No. 4 & 5, League Island, Philadelphia, Philadelphia County, PA

17. Dry Dock No. 4. Longitudinal Section. Subdivision V and ...

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

17. Dry Dock No. 4. Longitudinal Section. Subdivision V and Stair Details (Frederic R. Harris, Inc., January 10, 1941). In Files of Cushman & Wakefield, Building No. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 4, Broad Street south of Government Avenue, Philadelphia, Philadelphia County, PA

Photograph of drawing building 523 and 100,000gallon water tank above ...

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

Photograph of drawing building 523 and 100,000-gallon water tank above it, dated 1979. Drawing in collection of Caretaker Site Office, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Building No. 523, Delaware Avenue between East Fourth Street & Webster Avenue, League Island, Philadelphia, Philadelphia County, PA

Dry dock no. 4. Service Building between dry docks 4 ...

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

Dry dock no. 4. Service Building between dry docks 4 and 5. Floor plans (Navy Yard Public Works Office 1941). In files of Cushman & Wakefield, building 501. Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Service Building, Dry Docks No. 4 & 5, League Island, Philadelphia, Philadelphia County, PA

15. Dry Dock No. 4. Longitudinal Section. Subdivision Nos. I ...

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

15. Dry Dock No. 4. Longitudinal Section. Subdivision Nos. I and II (Frederic R. Harris, Inc., January 10, 1941). In Files of Cushman & Wakefield, Building no. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 4, Broad Street south of Government Avenue, Philadelphia, Philadelphia County, PA

16. Dry Dock No. 4. Longitudinal Section. Subdivision Nos. III ...

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

16. Dry Dock No. 4. Longitudinal Section. Subdivision Nos. III and IV (Frederic R. Harris, Inc., January 10, 1941). In Files of Cushman & Wakefield, Building no. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 4, Broad Street south of Government Avenue, Philadelphia, Philadelphia County, PA

19. Dry Dock No. 4. Details of Drainage and Filling ...

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

19. Dry Dock No. 4. Details of Drainage and Filling Culverts (Frederic R. Harris, Inc., November 1, 1941). In Files of Cushman & Wakefield, Building No. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 4, Broad Street south of Government Avenue, Philadelphia, Philadelphia County, PA

14. Dry Dock No. 4. Plan of subdivision V and ...

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

14. Dry Dock No. 4. Plan of subdivision V and Welding Set Platform Details (Frederick R. Harris, Inc., January 10, 1941). In Files of Cushman & Wakefield, Building No. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 4, Broad Street south of Government Avenue, Philadelphia, Philadelphia County, PA

76 FR 19518 - Notice of Intent to Rule on Request To Release Airport Property at the Northeast Philadelphia...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-07

... To Release Airport Property at the Northeast Philadelphia Airport (PNE), Philadelphia, PA AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of request to release airport property. SUMMARY... Philadelphia Airport, Philadelphia, Pennsylvania under the provisions of Section 47125(a) of Title 49 United...

5. Photocopy of old exterior photo showing Western Saving Fund ...

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

5. Photocopy of old exterior photo showing Western Saving Fund Society before the addition of ca. 1910 building. Original photo, late 19th century, is at the Philadelphia Free Library, Philadelphia Collection, Print and Picture Department. - Western Saving Fund Society of Philadelphia, 1000-1008 Walnut Street, Philadelphia, Philadelphia County, PA

North Atlantic (NAT) aided inertial navigation system simulation volume I. : technical results

DOT National Transportation Integrated Search

1973-07-01

Current air traffic operations over the North ATlantic (NAT) and the application of hybrid navigation systems to obtain more accurate performance on these NAT routes are reviewed. A digital computer simulation program (NATNAV - North ATlantic NAVigat...

View south of sail loft mid loft area. Note ...

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

View south of sail loft - mid- loft area. Note inflatable boats undergoing pressure testing. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Structure Shop, League Island, Philadelphia, Philadelphia County, PA

NorthEast view; Platform, canopy, and freight elevator North Philadelphia ...

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

North-East view; Platform, canopy, and freight elevator - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

Simulations of the Vertical Redistribution of HNO3 by NAT or NAD PSCs: The Sensitivity to the Number of Cloud Particles Formed and the Cloud Lifetime

NASA Technical Reports Server (NTRS)

Jensen, Eric J.; Tabazadeh, Azadeh; Drdla, Katja; Toon, Owen B.; Gore, Warren J. (Technical Monitor)

2000-01-01

Recent satellite and in situ measurements have indicated that limited denitrification can occur in the Arctic stratosphere. In situ measurements from the SOLVE campaign indicate polar stratospheric clouds (PSCs) composed of small numbers (about 3 x 10^ -4 cm^-3) of 10-20 micron particles (probably NAT or NAD). These observations raise the issue of whether low number density NAT PSCs can substantially denitrify the air with reasonable cloud lifetimes. In this study, we use a one dimensional cloud model to investigate the verticle redistribution of HNO3 by NAT/NAD PSCs. The cloud formation is driven by a temperature oscillation which drops the temperature below the NAT/NAD formation threshold (about 195 K) for a few days. We assume that a small fraction of the available aerosols act as NAT nuclei when the saturation ratio of HNO3 over NAT(NAD) exceeds 10(l.5). The result is a cloud between about 16 and 20 km in the model, with NAT/NAD particle effective radii as large as about 10 microns (in agreement with the SOLVE data). We find that for typical cloud lifetimes of 2-3 days or less, the net depletion of HNO3 is no more than 1-2 ppbv, regardless of the NAT or NAD particle number density. Repeated passes of the air column through the cold pool build up the denitrification to 3-4 ppbv, and the cloud altitude steadily decreases due to the downward transport of nitric acid. Increasing the cloud lifetime results in considerably more effective denitrification, even with very low cloud particle number densities. As expected, the degree of denitrification by NAT clouds is much larger than that by NAD Clouds. Significant denitrification by NAD Clouds is only possible if the cloud lifetime is several days or more. The clouds also cause a local maximum HNO3 mixing ratio at cloud base where the cloud particles sublimate.

Treatment of Rats with Apocynin Has Considerable Inhibitory Effects on Arylamine N-Acetyltransferase Activity in the Liver.

PubMed

Francis, Sheena; Laurieri, Nicola; Nwokocha, Chukwuemeka; Delgoda, Rupika

2016-05-31

The effect of apocynin on the activity of arylamine N-acetyltransferases (NATs) in excised liver samples was examined using eighteen Sprague-Dawley rats. Three groups of six animals each were fed a normal diet alone or a treatment of 50 or 100 mg/kg/day of apocynin via gavages for eight (8) weeks. Chronic in vivo administration of apocynin led to significant (p < 0.001) reduction of in vitro liver NAT activity up to 93% as compared with untreated rats (18.80 ± 2.10 μmols p-anisidine/min/μg liver protein). In vitro exposure of untreated liver homogenates to apocynin led to a dose-dependent inhibition of NAT activity with IC50 = 0.69 ± 0.02 mM. In silico modelling of apocynin tautomers and radical species into human NAT crystal structures supported the hypothesis that thiol functionalities in NAT enzymes may be crucial in apocynin binding. The involvement of human NAT enzymes in different pathological conditions, such as cancer, has encouraged the research for selective NAT inhibitors in both humans and animal models with possible chemopreventive properties.

Occult HBV infection in HIV-infected adults and evaluation of pooled NAT for HBV.

PubMed

Dinesha, T R; Boobalan, J; Sivamalar, S; Subashini, D; Solomon, S S; Murugavel, K G; Balakrishnan, P; Smith, D M; Saravanan, S

2018-06-01

The study aimed to determine the prevalence of occult hepatitis B virus infection among HIV-infected persons and to evaluate the use of a pooling strategy to detect occult HBV infection in the setting of HIV infection. Five hundred and two HIV-positive individuals were tested for HBV, occult HBV and hepatitis C and D with serologic and nucleic acid testing (NAT). We also evaluated a pooled NAT strategy for screening occult HBV infection among the HIV-positive individuals. The prevalence of HBV infection among HIV-positive individuals was 32 (6.4%), and occult HBV prevalence was 10%. The pooling HBV NAT had a sensitivity of 66.7% and specificity of 100%, compared to HBV DNA NAT of individual samples. In conclusion, this study found a high prevalence of occult HBV infection among our HIV-infected population. We also demonstrated that pooled HBV NAT is highly specific, moderately sensitive and cost-effective. As conventional HBV viral load assays are expensive in resource-limited settings such as India, pooled HBV DNA NAT might be a good way for detecting occult HBV infection and will reduce HBV-associated complications. © 2018 John Wiley & Sons Ltd.

Effectiveness of Nateglinide on In Vitro Insulin Secretion from Rat Pancreatic Islets Desensitized to Sulfonylureas

PubMed Central

Wang, Shuya; Dunning, Beth E.

2001-01-01

Chronic exposure of pancreatic islets to sulfonylureas (SUs) is known to impair the ability of islets to respond to subsequent acute stimulation by SUs or glucose. Nateglinide (NAT) is a novel insulinotropic agent with a primarily site of action at β-cell KATP channels, which is common to the structurally diverse drugs like repaglinide (REP) and the SUs. Earlier studies on the kinetics, glucosedependence and sensitivity to metabolic inhibitors of the interaction between NAT and KATP channels suggested a distinct signaling pathways with NAT compared to REP, glyburide (GLY) or glimepiride (GLI). To obtain further evidence for this concept, the present study compared the insulin secretion in vitro from rat islets stimulated acutely by NAT, GLY, GLI or REP at equipotent concentrations during 1-hr static incubation following overnight treatment with GLY or tolbutamide (TOL). The islets fully retained the responsiveness to NAT stimulation after prolonged pretreatment with both SUs, while their acute response to REP, GLY, and GLI was markedly attenuated, confirming the desensitization of islets. The insulinotropic efficacy of NAT in islets desensitized to SUs may result from a distinct receptor/effector mechanism, which contributes to the unique pharmacological profile of NAT. PMID:12369729

Impact of stratospheric aircraft on calculations of nitric acid trihydrate cloud surface area densities using NMC temperatures and 2D model constituent distributions

NASA Technical Reports Server (NTRS)

Considine, David B.; Douglass, Anne R.

1994-01-01

A parameterization of NAT (nitric acid trihydrate) clouds is developed for use in 2D models of the stratosphere. The parameterization uses model distributions of HNO3 and H2O to determine critical temperatures for NAT formation as a function of latitude and pressure. National Meteorological Center temperature fields are then used to determine monthly temperature frequency distributions, also as a function of latitude and pressure. The fractions of these distributions which fall below the critical temperatures for NAT formation are then used to determine the NAT cloud surface area density for each location in the model grid. By specifying heterogeneous reaction rates as functions of the surface area density, it is then possible to assess the effects of the NAT clouds on model constituent distributions. We also consider the increase in the NAT cloud formation in the presence of a fleet of stratospheric aircraft. The stratospheric aircraft NO(x) and H2O perturbations result in increased HNO3 as well as H2O. This increases the probability of NAT formation substantially, especially if it is assumed that the aircraft perturbations are confined to a corridor region.

19. Historic American Buildings Survey, 1932 measured drawing from old ...

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

19. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, photocopy courtesy of the Free Library of Philadelphia DETAILS: MAIN STAIRS. - Woodford, Philadelphia, Philadelphia County, PA

16. Historic American Buildings Survey, 1932 measured drawing from old ...

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

16. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, photocopy courtesy of the Free Library of Philadelphia MAIN ENTRANCE DETAILS. - Woodford, Philadelphia, Philadelphia County, PA

22. Historic American Buildings Survey, 1932 measured drawing from old ...

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

22. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, photocopy courtesy of the Free Library of Philadelphia DETAILS: PALLADIAN WINDOW. - Woodford, Philadelphia, Philadelphia County, PA

24. Historic American Buildings Survey, 1932 measured drawing from old ...

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

24. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, photocopy courtesy of the Free Library of Philadelphia DETAILS: ENTRANCE HALL. - Woodford, Philadelphia, Philadelphia County, PA

Interior view; Street Car Waiting House North Philadelphia Station, ...

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

Interior view; Street Car Waiting House - North Philadelphia Station, Street Car Waiting House, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

View east; interior view of south bay Naval Base ...

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

View east; interior view of south bay - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

View east; interior view of central bay Naval Base ...

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

View east; interior view of central bay - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

View west; interior view of south bay Naval Base ...

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

View west; interior view of south bay - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

View west; interior view of central bay Naval Base ...

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

View west; interior view of central bay - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

Contextual view of building no. 541, looking northeast. Structure no. ...

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

Contextual view of building no. 541, looking northeast. Structure no. 1043 in foreground. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Structural Assembly Shop, League Island, Philadelphia, Philadelphia County, PA

13. WEST END, LOOKING NE, PHILADELPHIA ZOO LION SCULPTURE IN ...

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

13. WEST END, LOOKING NE, PHILADELPHIA ZOO LION SCULPTURE IN FOREGROUND. - Connecting Railway, Schuylkill River Bridge, Spanning Schuylkill River, north of Girard Avenue Bridge, Philadelphia, Philadelphia County, PA

View of building 18 section looking southeast. Jet Lowe, Haer ...

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

View of building 18 section looking southeast. Jet Lowe, Haer staff photographer, summer 1995. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Machine Shops, League Island, Philadelphia, Philadelphia County, PA

Role of Increased n-acetylaspartate Levels in Cancer

PubMed Central

Zand, Behrouz; Previs, Rebecca A.; Zacharias, Niki M.; Rupaimoole, Rajesha; Mitamura, Takashi; Nagaraja, Archana Sidalaghatta; Guindani, Michele; Dalton, Heather J.; Yang, Lifeng; Baddour, Joelle; Achreja, Abhinav; Hu, Wei; Pecot, Chad V.; Ivan, Cristina; Wu, Sherry Y.; McCullough, Christopher R.; Gharpure, Kshipra M.; Shoshan, Einav; Pradeep, Sunila; Mangala, Lingegowda S.; Rodriguez-Aguayo, Cristian; Wang, Ying; Nick, Alpa M.; Davies, Michael A.; Armaiz-Pena, Guillermo; Liu, Jinsong; Lutgendorf, Susan K.; Baggerly, Keith A.; Eli, Menashe Bar; Lopez-Berestein, Gabriel; Nagrath, Deepak; Bhattacharya, Pratip K.

2016-01-01

Background: The clinical and biological effects of metabolic alterations in cancer are not fully understood. Methods: In high-grade serous ovarian cancer (HGSOC) samples (n = 101), over 170 metabolites were profiled and compared with normal ovarian tissues (n = 15). To determine NAT8L gene expression across different cancer types, we analyzed the RNA expression of cancer types using RNASeqV2 data available from the open access The Cancer Genome Atlas (TCGA) website (http://www.cbioportal.org/public-portal/). Using NAT8L siRNA, molecular techniques and histological analysis, we determined cancer cell viability, proliferation, apoptosis, and tumor growth in in vitro and in vivo (n = 6–10 mice/group) settings. Data were analyzed with the Student’s t test and Kaplan-Meier analysis. Statistical tests were two-sided. Results: Patients with high levels of tumoral NAA and its biosynthetic enzyme, aspartate N-acetyltransferase (NAT8L), had worse overall survival than patients with low levels of NAA and NAT8L. The overall survival duration of patients with higher-than-median NAA levels (3.6 years) was lower than that of patients with lower-than-median NAA levels (5.1 years, P = .03). High NAT8L gene expression in other cancers (melanoma, renal cell, breast, colon, and uterine cancers) was associated with worse overall survival. NAT8L silencing reduced cancer cell viability (HEYA8: control siRNA 90.61%±2.53, NAT8L siRNA 39.43%±3.00, P < .001; A2780: control siRNA 90.59%±2.53, NAT8L siRNA 7.44%±1.71, P < .001) and proliferation (HEYA8: control siRNA 74.83%±0.92, NAT8L siRNA 55.70%±1.54, P < .001; A2780: control siRNA 50.17%±4.13, NAT8L siRNA 26.52%±3.70, P < .001), which was rescued by addition of NAA. In orthotopic mouse models (ovarian cancer and melanoma), NAT8L silencing reduced tumor growth statistically significantly (A2780: control siRNA 0.52 g±0.15, NAT8L siRNA 0.08 g±0.17, P < .001; HEYA8: control siRNA 0.79 g±0.42, NAT8L siRNA 0.24 g±0.18, P = .008, A375-SM: control siRNA 0.55 g±0.22, NAT8L siRNA 0.21 g±0.17g, P = .001). NAT8L silencing downregulated the anti-apoptotic pathway, which was mediated through FOXM1. Conclusion: These findings indicate that the NAA pathway has a prominent role in promoting tumor growth and represents a valuable target for anticancer therapy. Altered energy metabolism is a hallmark of cancer (1). Proliferating cancer cells have much greater metabolic requirements than nonproliferating differentiated cells (2,3). Moreover, altered cancer metabolism elevates unique metabolic intermediates, which can promote cancer survival and progression (4,5). Furthermore, emerging evidence suggests that proliferating cancer cells exploit alternative metabolic pathways to meet their high demand for energy and to accumulate biomass (6–8). PMID:26819345

35. Photographic copy of Hangar Door Canopy Details (Ammann and ...

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

35. Photographic copy of Hangar Door Canopy Details (Ammann and Whitney and The Ballinger Company. April 12, 1955). In files of the City of Philadelphia, Division of Aviation, Terminal E. Philadelphia International Airport. Reprinted with permission of the Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

32. Photographic copy of Hangar Roof Framing Plan (Ammann and ...

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

32. Photographic copy of Hangar Roof Framing Plan (Ammann and Whitney and The Ballinger Company, April 12, 1955). In files of the City of Philadelphia, Division of Aviation, Terminal E, Philadelphia International Airport. Reprinted with permission of the Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

27. Photographic copy of Mezzanine Plan, Roof Plan and Details ...

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

27. Photographic copy of Mezzanine Plan, Roof Plan and Details (The Ballinger Company, April 12, 1955). In files of the City of Philadelphia, Division of Aviation, Terminal E, Philadelphia International Airport. Reprinted with permission of the Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

29. Photographic copy of West Elevation and Sections Through Building ...

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

29. Photographic copy of West Elevation and Sections Through Building (The Ballinger Company, April 12, 1955). In files of the City of Philadelphia. Division of Aviation. Terminal E. Philadelphia International Airport. Reprinted with permission of the Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

Service building. Cross section thru dry dock nos. 4 & ...

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

Service building. Cross section thru dry dock nos. 4 & 5 showing service bldg & 20-75-150 ton cranes (dry dock associates, May 23, 1941). In files of Cushman & Wakefield, building no. 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Service Building, Dry Docks No. 4 & 5, League Island, Philadelphia, Philadelphia County, PA

34. Photographic copy of Hangar Doors (Ammann and Whitney and ...

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

34. Photographic copy of Hangar Doors (Ammann and Whitney and The Ballinger Company, April 12, 1955). In files of the City of Philadelphia, Division of Aviaiton, Terminal E, Philadelphia International Airport. Reprinted with permission of the Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

33. Photographic copy of Main Roof Girder Details (Ammann and ...

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

33. Photographic copy of Main Roof Girder Details (Ammann and Whitney and The Ballinger Company, April 12, 1955). In files of the City of Philadelphia, Division of Aviation, Terminal E, Philadelphia International Airport. Reprinted with permission of the Division of Aviaiton. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

26. Historic American Buildings Survey, 1932 measured drawing from old ...

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

26. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, photocopy courtesy of the Free Library of Philadelphia DETAILS: FIRST FLOOR WINDOW. - Woodford, Philadelphia, Philadelphia County, PA

20. Historic American Buildings Survey, 1932 measured drawing from old ...

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

20. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, photocopy courtesy of the Free Library of Philadelphia FURTHER DETAILS: MAIN STAIRS. - Woodford, Philadelphia, Philadelphia County, PA

23. Historic American Buildings Survey, 1932 measured drawing from old ...

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

23. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, photocopy courtesy of the Free Library of Philadelphia FURTHER DETAILS: LIVING ROOM. - Woodford, Philadelphia, Philadelphia County, PA

14. Historic American Buildings Survey, 1932 measured drawing from old ...

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

14. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, photocopy courtesy of the Free Library of Philadelphia DETAIL OF EAST ELEVATION. - Woodford, Philadelphia, Philadelphia County, PA

View northwest; south and east facades and context Naval ...

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

View northwest; south and east facades and context - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

View northwest from floor of drydock no. 2; foundry/propeller shop ...

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

View northwest from floor of drydock no. 2; foundry/propeller shop in background. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Drydock No. 2, League Island, Philadelphia, Philadelphia County, PA

View southeast; west and north facades and context Naval ...

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

View southeast; west and north facades and context - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

44. Storehouse of Philadelphia Signal Depot, U.S. Army Corps of ...

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

44. Storehouse of Philadelphia Signal Depot, U.S. Army Corps of Engineers, War Department (1942) - Atwater Kent Manufacturing Company, North Plant, 5000 Wissahickon Avenue, Philadelphia, Philadelphia County, PA

N-Acetyltransferase Polymorphism and Risk of Colorectal Adenoma and Cancer: A Pooled Analysis of Variations from 59 Studies

PubMed Central

Wang, Xiaoxue; Chen, Yizhi; Li, Rong; Zhang, Ying; Luo, Rongcheng

2012-01-01

Background There have been an increasing number of studies with evidence suggesting that the N-acetyltransferase 1 (NAT1) and N-acetyltransferase 2 (NAT2) genotypes may be implicated in the development of colorectal cancer (CRC) and colorectal adenoma (CRA). So far the published data on this association has remained controversial, however. We performed a meta-analysis of case-cohort and case-control studies using a subset of the published data, with an aim to derive a better understanding of the underlying relationship. Methods/Principal Findings A literature search was performed using Medline database for relevant studies published through October 31, 2011. A total of 39 publications were selected for this meta-analysis, including 11,724 cases and 16,215 controls for CRC, and 3,701 cases and 5,149 controls for CRA. In our pooled analysis of all these studies, the results of our meta-analysis suggested that the NAT1 genotype was not significantly associated with an elevated CRC risk (OR 0.99, 95% CI 0.91–1.07). We also found that individuals with the rapid NAT2 genotype did have an elevated risk of CRC (OR 1.07, 95% CI 1.01–1.13). There was no evidence for an association between the NAT1 and 2 rapid genotype and an elevated CRA risk (NAT1: OR 1.14, 95% CI 0.99–1.29; NAT2: OR 0.94, 95% CI 0.86–1.03). Conclusion This meta-analysis suggests that individuals with NAT2 genotype had an elevated risk of CRC. There was no evidence for the association between NAT1 and 2 rapid genotype and CRA risk. PMID:22905173

In vivo evaluation of a cancer therapy strategy combining HSV1716-mediated oncolysis with gene transfer and targeted radiotherapy.

PubMed

Sorensen, Annette; Mairs, Robert J; Braidwood, Lynne; Joyce, Craig; Conner, Joe; Pimlott, Sally; Brown, Moira; Boyd, Marie

2012-04-01

Oncolytic herpes viruses show promise for cancer treatment. However, it is unlikely that they will fulfill their therapeutic potential when used as monotherapies. An alternative strategy is to use these viruses not only as oncolytic agents but also as a delivery mechanism of therapeutic transgenes to enhance tumor cell killing. The herpes simplex virus 1 deletion mutant HSV1716 is a conditionally replicating oncolytic virus that selectively replicates in and lyses dividing tumor cells. It has a proven safety profile in clinical trials and has demonstrated efficacy as a gene-delivery vehicle. To enhance its therapeutic potential, we have engineered HSV1716 to convey the noradrenaline transporter (NAT) gene (HSV1716/NAT), whose expression endows infected cells with the capacity to accumulate the noradrenaline analog metaiodobenzylguanidine (MIBG). Thus, the NAT gene-infected cells are susceptible to targeted radiotherapy using radiolabeled (131)I-MIBG, a strategy that has already shown promise for combined targeted radiotherapy-gene therapy in cancer cells after plasmid-mediated transfection. We used HSV1716/NAT as a dual cell lysis-gene delivery vehicle for targeting the NAT transgene to human tumor xenografts in vivo. In tumor xenografts that did not express NAT, intratumoral or intravenous injection of HSV1716/NAT induced the capacity for active uptake of (131)I-MIBG. Administration of HSV1716/NAT and (131)I-MIBG resulted in decreased tumor growth and enhanced survival relative to injection of either agent alone. Efficacy was dependent on the scheduling of delivery of the 2 agents. These findings support a role for combination radiotherapy-gene therapy for cancer using HSV1716 expressing the NAT transgene and targeted radionuclide therapy.

3. Photocopy of drawing (from Moses King, Philadelphia and Notable ...

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

3. Photocopy of drawing (from Moses King, Philadelphia and Notable Philadelphians, 1902) MAIN BUILDING WITH ADDITION - New York Mutual Life Insurance Company Building, 1001-1005 Chestnut Street, Philadelphia, Philadelphia County, PA

13. Historic American Buildings Survey, 1932 measured drawing from old ...

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

13. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, photocopy courtesy of the Free Library of Philadelphia DETAILS: EXTERIOR CORNICES AND DORMER WINDOWS. - Woodford, Philadelphia, Philadelphia County, PA

12. Historic American Buildings Survey, 1932 measured drawing from old ...

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

12. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, photocopy courtesy of the Free Library of Philadelphia WEST ELEVATION AND NORTH ELEVATION. - Woodford, Philadelphia, Philadelphia County, PA

11. Historic American Buildings Survey, 1932 measured drawing from old ...

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

11. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, photocopy courtesy of the Free Library of Philadelphia EAST ELEVATION AND SOUTH ELEVATION. - Woodford, Philadelphia, Philadelphia County, PA

15. Historic American Buildings Survey, 1932 measured drawing from old ...

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

15. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, photocopy courtesy of the Free Library of Philadelphia CROSS SECTION AND LONGITUDINAL SECTION. - Woodford, Philadelphia, Philadelphia County, PA

10. VIEW SOUTHSOUTHEAST IN DRYDOCK SHOWING STERN OF JFK; NOTE ...

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

10. VIEW SOUTH-SOUTHEAST IN DRYDOCK SHOWING STERN OF JFK; NOTE PROP SHAFTS AND RUDDER. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 5, League Island, Philadelphia, Philadelphia County, PA

9. VIEW SOUTHSOUTHEAST STERN OF JFK, SCAFFOLDING SET UP FOR ...

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

9. VIEW SOUTH-SOUTHEAST STERN OF JFK, SCAFFOLDING SET UP FOR REMOUNTING OF PROPELLERS. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 5, League Island, Philadelphia, Philadelphia County, PA

View northeast of mould loft and plating cutting shop in ...

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

View northeast of mould loft and plating cutting shop in structural assembly shop (building no. 541) - Naval Base Philadelphia-Philadelphia Naval Shipyard, Structural Assembly Shop, League Island, Philadelphia, Philadelphia County, PA

View from west sharp perspective, foundry/propeller shop. Naval Base ...

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

View from west sharp perspective, foundry/propeller shop. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

11. SOUTH (REAR) ELEVATION OF THE PHILADELPHIA SAVING FUND SOCIETY ...

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

11. SOUTH (REAR) ELEVATION OF THE PHILADELPHIA SAVING FUND SOCIETY (PSFS) BUILDING WITH MEETING HOUSE CORNICE IN FOREGROUND. - Twelfth Street Meeting House, 20 South Twelfth Street, Philadelphia, Philadelphia County, PA

Rapid identification of the NAT2 genotype in tuberculosis patients by multicolor melting curve analysis.

PubMed

Hu, Yanjie; Chen, Suting; Yu, Xia; Dai, Guangming; Dong, Lingling; Li, Yunxu; Zhao, Liping; Huang, Hairong

2016-07-01

NAT2 genotype is an indicator for isoniazid dosage adjusting for tuberculosis treatment. Multicolor melting curve analysis (MMCA) was evaluated as a potential method for NAT2 genotyping. 352 blood samples were analyzed by MMCA kit (Zeesan Biotech Co., Xiamen, China) targeting NAT2 SNPs at T341C, C481T, G590A and G857A, and direct sequencing was used as control. The sensitivity, specificity and accuracy of the MMCA assay for rapid NAT2 genotype detection were 97.9, 99.6 and 99.1% respectively, whereas for intermediate genotypes the values were 99.5, 98.7 and 99.1%, respectively, and for slow genotypes the values were 100% for the three aspects. The 24 saliva and blood for the control samples were also successfully analyzed using the MMCA assay, both produced uniform outcomes. The MMCA assay described in our study is very promising for the efficient determination of NAT2 genotype, and can facilitate the personalized dosing of isoniazid.

Strategies to identify natural antisense transcripts.

PubMed

Sun, Yulong; Li, Dijie; Zhang, Ru; Peng, Shang; Zhang, Ge; Yang, Tuanmin; Qian, Airong

2017-01-01

Natural antisense transcripts, originally considered as transcriptional noises arising from so-called "junk DNA″, are recently recognized as important modulators for gene regulation. They are prevalent in nearly all realms of life and have been found to modulate gene expression positively or negatively. By affecting almost all stages of gene expression range from pre-transcriptional, transcriptional and post-transcriptional to translation, NATs are fundamentally involved in various biological processes. However, compared to increasing huge data from transcriptional analysis especially high-throughput sequencing technologies (such as RNA-seq), limited functional NATs (around 70) are so far reported, which hinder our advanced comprehensive understanding for this field. Hence, efficient strategies for identifying NATs are urgently desired. In this review, we discussed the current strategies for identifying NATs, with a focus on the advantages, disadvantages, and applications of methods isolating functional NATs. Moreover, publicly available databases for NATs were also discussed. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

31. Photographic copy of Leanto Roof Framing Plan & Bent ...

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

31. Photographic copy of Leanto Roof Framing Plan & Bent Details (Ammann and Whitney and The Balinger Company, April 12, 1955). In files of the City of Philadelphia, Division of Aviation, Terminal E, Philadelphia International Airport. Reprinted with permission of the Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

27. Historic American Buildings Survey, 1932 measured drawing from old ...

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

27. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, photocopy courtesy of the Free Library of Philadelphia ELEVATION AND DETAILS: PANELLED WALL, SECOND FLOOR BEDROOM. - Woodford, Philadelphia, Philadelphia County, PA

18. Historic American Buildings Survey, 1932 measured drawing from old ...

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

18. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, photocopy courtesy of the Free Library of Philadelphia BASEMENT FLOOR PLAN AND THIRD FLOOR PLAN. - Woodford, Philadelphia, Philadelphia County, PA

25. Historic American Buildings Survey, 1932 measured drawing from old ...

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

25. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, photocopy courtesy of the Free Library of Philadelphia DETAILS: MISCELLANEOUS CORNICES, CHAIR RAILS, AND BASES. - Woodford, Philadelphia, Philadelphia County, PA

21. Historic American Buildings Survey, 1932 measured drawing from old ...

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

21. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, photocopy courtesy of the Free Library of Philadelphia DETAILS: LIVING ROOM, INTERIOR ELEVATIONS, NORTH AND WEST. - Woodford, Philadelphia, Philadelphia County, PA

17. Historic American Buildings Survey, 1932 measured drawing from old ...

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

17. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, photocopy courtesy of the Free Library of Philadelphia FIRST FLOOR PLAN AND SECOND FLOOR PLAN. - Woodford, Philadelphia, Philadelphia County, PA

2. VIEW NORTH OF BOW OF JFK IN DRYDOCK NO. ...

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

2. VIEW NORTH OF BOW OF JFK IN DRYDOCK NO. 5; NOTE BOW ANCHOR AT TOP CENTER. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 5, League Island, Philadelphia, Philadelphia County, PA

View of foundry/propeller shop (building no. 20) looking northeast. ...

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

View of foundry/propeller shop (building no. 20) looking northeast. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

View south; detail view of column A13, south bay ...

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

View south; detail view of column A13, south bay - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

6. BRIDGE OF CARRIER JFK SURROUNDED BY SCAFFOLDING FOR REHABILITATION ...

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

6. BRIDGE OF CARRIER JFK SURROUNDED BY SCAFFOLDING FOR REHABILITATION UNDER SERVICE LIFE EXTENSION PROGRAM (SLEP). - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 5, League Island, Philadelphia, Philadelphia County, PA

View southsouthwest of drydock no. 2 caisson with receiving ship ...

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

View south-southwest of drydock no. 2 caisson with receiving ship and ship FS 2 in background. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Drydock No. 2, League Island, Philadelphia, Philadelphia County, PA

Detail view of bracket, arched window and eagle from building ...

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

Detail view of bracket, arched window and eagle from building 18 section. Jet Lowe, Haer staff photographer, summer 1995 - Naval Base Philadelphia-Philadelphia Naval Shipyard, Machine Shops, League Island, Philadelphia, Philadelphia County, PA

View of west elevation of building 18 section of machine ...

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

View of west elevation of building 18 section of machine shops. Jet Lowe, Haer staff photographer, summer 1995. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Machine Shops, League Island, Philadelphia, Philadelphia County, PA

2. Photocopy of aerial view of the museum, taken October ...

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

2. Photocopy of aerial view of the museum, taken October 26, 1966. Original photo in possession of the Philadelphia Museum of Art. - Philadelphia Museum of Art, Benjamin Franklin Parkway, Philadelphia, Philadelphia County, PA

Arylamine N-acetyltransferase activity in bronchial epithelial cells and its inhibition by cellular oxidants

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

Dairou, Julien; Petit, Emile; Ragunathan, Nilusha

2009-05-01

Bronchial epithelial cells express xenobiotic-metabolizing enzymes (XMEs) that are involved in the biotransformation of inhaled toxic compounds. The activities of these XMEs in the lung may modulate respiratory toxicity and have been linked to several diseases of the airways. Arylamine N-acetyltransferases (NAT) are conjugating XMEs that play a key role in the biotransformation of aromatic amine pollutants such as the tobacco-smoke carcinogens 4-aminobiphenyl (4-ABP) and {beta}-naphthylamine ({beta}-NA). We show here that functional human NAT1 or its murine counterpart Nat2 are present in different lung epithelial cells i.e. Clara cells, type II alveolar cells and bronchial epithelial cells, thus indicating thatmore » inhaled aromatic amines may undergo NAT-dependent biotransformation in lung epithelium. Exposure of these cells to pathophysiologically relevant amounts of oxidants known to contribute to lung dysfunction, such as H{sub 2}O{sub 2} or peroxynitrite, was found to impair the NAT1/Nat2-dependent cellular biotransformation of aromatic amines. Genetic and non genetic impairment of intracellular NAT enzyme activities has been suggested to compromise the important detoxification pathway of aromatic amine N-acetylation and subsequently to contribute to an exacerbation of untoward effects of these pollutants on health. Our study suggests that oxidative/nitroxidative stress in lung epithelial cells, due to air pollution and/or inflammation, could contribute to local and/or systemic dysfunctions through the alteration of the functions of pulmonary NAT enzymes.« less

Genetic Variation at the N-acetyltransferase (NAT) Genes in Global Populations

EPA Science Inventory

Functional variability at the N-acetyltransferase (NAT) genes is associated with adverse drug reactions and cancer susceptibility in humans. Previous studies of small sets of ethnic groups have indicated that the NAT genes have high levels of amino acid variation that differ in f...

3. Photocopy of circa 1910 photograph showing a general view ...

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

3. Photocopy of circa 1910 photograph showing a general view of the building, published in a 1911 book, Stanley's Views of Philadelphia. - Philadelphia Trust, Safe Deposit & Insurance Company, 415 Chestnut Street, Philadelphia, Philadelphia County, PA

View southeast; detail of north façade with crane rail ...

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

View southeast; detail of north façade with crane rail - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

View south; interior structural detail at column A13 south bay ...

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

View south; interior structural detail at column A13 south bay - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

3. Photocopy of BUILDING WITH ORIGINAL ROOF BALUSTRADE, taken ca. ...

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

3. Photocopy of BUILDING WITH ORIGINAL ROOF BALUSTRADE, taken ca. 1860, from A History of the Philadelphia Saving Fund Society 1816-1916, page 64. - Philadelphia Saving Fund Society, 306 Walnut Street, Philadelphia, Philadelphia County, PA

21. Photocopy of 1897 measured drawing showing details of Solitude. ...

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

21. Photocopy of 1897 measured drawing showing details of Solitude. Delineators: Charles L. Hillman and John McClintock. Original at the Free Library of Philadelphia, Philadelphia, Pa. - Solitude, Zoo grounds, Philadelphia, Philadelphia County, PA

22. Photocopy of 1897 measured drawing showing details of Solitude. ...

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

22. Photocopy of 1897 measured drawing showing details of Solitude. Delineators: Charles L. Hillman and John McClintock. Original at the Free Library of Philadelphia, Philadelphia, Pa. - Solitude, Zoo grounds, Philadelphia, Philadelphia County, PA

Service Building No. 620. Detail of north elevation and entrance ...

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

Service Building No. 620. Detail of north elevation and entrance to substation & windowns in top of elevator shafts no. 2 & stair no. 1 & section thru substation (dry dock associates, June 12, 1941). In files of Cushman & Wakefield, building 501, Philadelphia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Service Building, Dry Docks No. 4 & 5, League Island, Philadelphia, Philadelphia County, PA

3. VIEW NORTHEAST OF PORT BOW OF JFK IN DRYDOCK ...

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

3. VIEW NORTHEAST OF PORT BOW OF JFK IN DRYDOCK NO. 5; PAINTERS WORKING APPLYING ANTI-FOULING PAINT BELOW WATER LINE. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 5, League Island, Philadelphia, Philadelphia County, PA

View north at north end of drydock no. 2 with ...

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

View north at north end of drydock no. 2 with the foundry/propeller shop (Haer no. Pa-387-O), in background. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Drydock No. 2, League Island, Philadelphia, Philadelphia County, PA

View northeast; detail of southwest corner showing damage to façade ...

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

View northeast; detail of southwest corner showing damage to façade - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

View north detail of south façade showing damage to wall ...

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

View north detail of south façade showing damage to wall - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

1. VIEW NORTHNORTHEAST OF CARRIER JOHN F. KENNEDY (JFK) IN ...

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

1. VIEW NORTH-NORTHEAST OF CARRIER JOHN F. KENNEDY (JFK) IN DRYDOCK NO. 5 FOR SERVICE LIFE EXTENSION PROGRAM (SLEP). - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 5, League Island, Philadelphia, Philadelphia County, PA

Looking east along Porter Avenue, management engineering in foreground; supply ...

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

Looking east along Porter Avenue, management engineering in foreground; supply department storehouse (building no. 5) (Haer no. PA-387-1) to left. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Management Engineering, League Island, Philadelphia, Philadelphia County, PA

Contextual view of building no. 541, looking southwest. Structure no. ...

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

Contextual view of building no. 541, looking southwest. Structure no. 1051 in left foreground and structure no. 1045 in right foreground. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Structural Assembly Shop, League Island, Philadelphia, Philadelphia County, PA

20. Photocopy of 1897 measured drawing showing elevations and plans ...

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

20. Photocopy of 1897 measured drawing showing elevations and plans of Soliture. Delineators: Charles L. Hillman and John McClintock. Original at the Free Library of Philadelphia, Philadelphia, Pa. - Solitude, Zoo grounds, Philadelphia, Philadelphia County, PA

77 FR 9681 - Federal Property Suitable as Facilities To Assist the Homeless

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-17

... Property-Duk Property Olympic Nat'l Park Clallam WA 98326 Landholding Agency: Interior Property Number.../environmental elements Lake Quinault Lapham Olympic Nat'l Park Quinault WA 98575 Landholding Agency: Interior.../environmental elements House 574-Ozettee Ranger Resid Olympic Nat'l Park Clallam WA 98326 Landholding Agency...

No Association Between Variant N-acetyltransferase Genes, Cigarette Smoking and Prostate Cancer Susceptibility Among Men of African Descent

PubMed Central

Kidd, La Creis Renee; VanCleave, Tiva T.; Doll, Mark A.; Srivastava, Daya S.; Thacker, Brandon; Komolafe, Oyeyemi; Pihur, Vasyl; Brock, Guy N.; Hein, David W.

2011-01-01

Objective We evaluated the individual and combination effects of NAT1, NAT2 and tobacco smoking in a case-control study of 219 incident prostate cancer (PCa) cases and 555 disease-free men. Methods Allelic discriminations for 15 NAT1 and NAT2 loci were detected in germ-line DNA samples using Taqman polymerase chain reaction (PCR) assays. Single gene, gene-gene and gene-smoking interactions were analyzed using logistic regression models and multi-factor dimensionality reduction (MDR) adjusted for age and subpopulation stratification. MDR involves a rigorous algorithm that has ample statistical power to assess and visualize gene-gene and gene-environment interactions using relatively small samples sizes (i.e., 200 cases and 200 controls). Results Despite the relatively high prevalence of NAT1*10/*10 (40.1%), NAT2 slow (30.6%), and NAT2 very slow acetylator genotypes (10.1%) among our study participants, these putative risk factors did not individually or jointly increase PCa risk among all subjects or a subset analysis restricted to tobacco smokers. Conclusion Our data do not support the use of N-acetyltransferase genetic susceptibilities as PCa risk factors among men of African descent; however, subsequent studies in larger sample populations are needed to confirm this finding. PMID:21709725

Aromatic amine metabolism: immunochemical relationships of N-acetyltransferase and N,O-acyltransferase

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

Land, S.; Allaben, W.T.; King, C.M.

1986-05-01

Mutagenic and carcinogenic aromatic amines are acetylated in most organisms. Acetyl CoA and arylhydroxamic acids can serve as acetyl donors for N-Acetylation of amines to yield stable amides, or by O-acetylation of hydroxylamine derivatives to produce reactive metabolites that can react covalently with nucleic acid. Polyclonal antibodies against rat arylhydroxamic acid, N,O-acyltransferase (AHAT) have been compared for their abilities to react with this enzyme and the acetyl CoA-dependent N-acetyltransferase (NAT) of the rat, rabbit, hamster, mouse and human. Liver cytosols were treated with increasing quantities of antibodies from immune or control rabbits. Immune complexes were removed by treatment with proteinmore » A-Sepharose before assay of nucleic acid adduct formation by AHAT activation of N-hydroxy-2-acetylaminofluorene and the acetylation of 2-aminofluorene by NAT. Both rat activities, the AHAT of the hamster and the NAT of the mouse and human were removed by this treatment. No decrease in NAT activity of hamster, or of either rabbit cytosol activity was observed. Neither mouse nor human liver has appreciable AHAT activity. These data support the idea that AHAT and NAT of rat, AHAT of hamster and NAT of mouse and human liver are immunochemically related, but that NAT of the hamster is an immunochemically distinct peptide.« less

Insights into the O-Acetylation Reaction of Hydroxylated Heterocyclic Amines by Human Arylamine N-Acetyltransferases: A Computational Study

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

Lau, E Y; Felton, J S; Lightstone, F C

2006-06-06

A computational study was performed to better understand the differences between human arylamine N-acetyltransferase (NAT) 1 and 2. Homology models were constructed from available crystal structures and comparisons of the active site residues 125, 127, and 129 for these two enzymes provide insight into observed substrate differences. The NAT2 model provided a basis for understanding how some of the common mutations may affect the structure of the protein. Molecular dynamics simulations of the human NAT models and the template structure (NAT from Mycobacterium smegmatis) were performed and showed the models to be stable and reasonable. Docking studies of hydroxylated heterocyclicmore » amines in the models of NAT1 and NAT2 probed the differences exhibited by these two proteins with mutagenic agents. The hydroxylated heterocyclic amines were only able to fit into the NAT2 active site, and an alternative binding site by the P-loop was found using our models and will be discussed. Additionally, quantum mechanical calculations were performed to study the O-acetylation reaction of the hydroxylated heterocyclic amines N-OH MeIQx and N-OH PhIP. This study has given us insight into why there are substrate differences among isoenzymes and explains some of the polymorphic activity differences.« less

2. Photocopy of April 28, 1915 photograph showing a general ...

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

2. Photocopy of April 28, 1915 photograph showing a general view of the building (right-hand side), courtesy of Philadelphia City Archives, City Hall, Philadelphia, Pennsylvania - Spring Garden Insurance Company Building, 431 Walnut Street, Philadelphia, Philadelphia County, PA

Drydock no. 2, view north from caisson; foundry/propeller shop (Haer ...

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

Drydock no. 2, view north from caisson; foundry/propeller shop (Haer no. Pa-387-O) in backgound and crane AL138 at left. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Drydock No. 2, League Island, Philadelphia, Philadelphia County, PA

View south; detail view of south façade at column A13 ...

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

View south; detail view of south façade at column A13 - Naval Base Philadelphia-Philadelphia Naval Shipyard, Foundry-Propeller Shop, North of Porter Avenue, west of Third Street West, Philadelphia, Philadelphia County, PA

6. 1831 engraving by Fenner, Sears and Company, Philadelphia. After ...

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

6. 1831 engraving by Fenner, Sears and Company, Philadelphia. After drawing by Charles Burton (see HABS No. PA-1487-7); probably not published until circa 1840-45. - Walnut Street Theater, 829-833 Walnut Street, Philadelphia, Philadelphia County, PA

View north of building 16 section (left) and pipe coppersmith ...

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

View north of building 16 section (left) and pipe coppersmith shop (Haer no. Pa-387-T) (right). Jet Lowe, Haer staff photographer, summer 1995 - Naval Base Philadelphia-Philadelphia Naval Shipyard, Machine Shops, League Island, Philadelphia, Philadelphia County, PA

29. Historic American Buildings Survey, 1932 measured drawing from old ...

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

29. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, 1897 measured drawing by C. L. Hillman and John McClintock, photocopy courtesy of the Free Library of Philadelphia ELEVATIONS: NORTH AND SOUTH. - Woodford, Philadelphia, Philadelphia County, PA

28. Historic American Buildings Survey, 1932 measured drawing from old ...

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

28. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, 1897 measured drawing by C. L. Hillman and John McClintock, photocopy courtesy of the Free Library of Philadelphia EAST ELEVATION AND DETAILS. - Woodford, Philadelphia, Philadelphia County, PA

Photocopy of photograph (from NBPPNSY, CSF530663) photographer unknown, June 16, ...

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

Photocopy of photograph (from NBP-PNSY, CSF-530-6-63) photographer unknown, June 16, 1963 view of a blade for a variable-pitch propeller positioned for finish machining. - Naval Base Philadelphia-Philadelphia Naval Shipyard, League Island, Philadelphia, Philadelphia County, PA

View southeast of caps for blocks for JFK; blocks are ...

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

View southeast of caps for blocks for JFK; blocks are used to support ship when it is repositioned to paint inaccessible areas masked by original support blocks. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Carpentry Shop, League Island, Philadelphia, Philadelphia County, PA

View northwest of building 19 area used for pattern shop ...

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

View northwest of building 19 area used for pattern shop storage (foreground), building 17 section of structure on left. This structure consists of two formerly separate buildings. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Machine Shops, League Island, Philadelphia, Philadelphia County, PA

Service building no. 620. Elevations (dry dock associates, June 12, ...

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

Service building no. 620. Elevations (dry dock associates, June 12, 1941). In files of Cushman & Wakefield, building 501, Philadephia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Service Building, Dry Docks No. 4 & 5, League Island, Philadelphia, Philadelphia County, PA

Structure of Mesorhizobium loti arylamine N-acetyltransferase 1

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

Holton, Simon J.; Dairou, Julien; Sandy, James

2005-01-01

The crystal structure of a M. loti arylamine N-acetyltransferase 1 has been determined at 2.0 Å resolution. The arylamine N-acetyltransferase (NAT) enzymes have been found in a broad range of both eukaryotic and prokaryotic organisms. The NAT enzymes catalyse the transfer of an acetyl group from acetyl Co-enzyme A onto the terminal nitrogen of a range of arylamine, hydrazine and arylhydrazine compounds. Recently, several NAT structures have been reported from different prokaryotic sources including Salmonella typhimurium, Mycobacterium smegmatis and Pseudomonas aeruginosa. Bioinformatics analysis of the Mesorhizobium loti genome revealed two NAT paralogues, the first example of multiple NAT isoenzymes inmore » a eubacterial organism. The M. loti NAT 1 enzyme was recombinantly expressed and purified for X-ray crystallographic studies. The purified enzyme was crystallized in 0.5 M Ca(OAc){sub 2}, 16% PEG 3350, 0.1 M Tris–HCl pH 8.5 using the sitting-drop vapour-diffusion method. A data set diffracting to 2.0 Å was collected from a single crystal at 100 K. The crystal belongs to the orthorhombic spacegroup P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 53.2, b = 97.3, c = 114.3 Å. The structure was refined to a final free-R factor of 24.8%. The structure reveals that despite low sequence homology, M. loti NAT1 shares the common fold as reported in previous NAT structures and exhibits the same catalytic triad of residues (Cys-His-Asp) in the active site.« less

Heterogeneous Formation of Polar Stratospheric Clouds- Part 1: Nucleation of Nitric Acid Trihydrate (NAT)

NASA Technical Reports Server (NTRS)

Hoyle, C. R.; Engel, I.; Luo, B. P.; Pitts, M. C.; Poole, L. R.; Grooss, J.-U.; Peter, T.

2013-01-01

Satellite-based observations during the Arctic winter of 2009/2010 provide firm evidence that, in contrast to the current understanding, the nucleation of nitric acid trihydrate (NAT) in the polar stratosphere does not only occur on preexisting ice particles. In order to explain the NAT clouds observed over the Arctic in mid-December 2009, a heterogeneous nucleation mechanism is required, occurring via immersion freezing on the surface of solid particles, likely of meteoritic origin. For the first time, a detailed microphysical modelling of this NAT formation pathway has been carried out. Heterogeneous NAT formation was calculated along more than sixty thousand trajectories, ending at Cloud Aerosol Lidar with Orthogonal Polarization (CALIOP) observation points. Comparing the optical properties of the modelled NAT with these observations enabled a thorough validation of a newly developed NAT nucleation parameterisation, which has been built into the Zurich Optical and Microphysical box Model (ZOMM). The parameterisation is based on active site theory, is simple to implement in models and provides substantial advantages over previous approaches which involved a constant rate of NAT nucleation in a given volume of air. It is shown that the new method is capable of reproducing observed polar stratospheric clouds (PSCs) very well, despite the varied conditions experienced by air parcels travelling along the different trajectories. In a companion paper, ZOMM is applied to a later period of the winter, when ice PSCs are also present, and it is shown that the observed PSCs are also represented extremely well under these conditions.

[Disappearance of a Philadelphia chromosome-positive clone and appearance of a -negative clone following treatment with imatinib mesylate in acute myelomonocytic leukemia].

PubMed

Takahashi, Wataru; Arai, Yukihiro; Tadokoro, Jiro; Takeuchi, Kengo; Yamagata, Tetsuya; Mitani, Kinuko

2006-02-01

A 63-year-old female was diagnosed as having Philadelphia chromosome-positive acute myelomonocytic leukemia in June 2002. The patient received monotherapy with imatinib mesylate or combination therapy with DCM and idarubicin/cytarabine, both of which failed in attaining disease remission. However, the second imatinib administration plus CAG therapy resulted in disappearance of the Philadelphia chromosome-positive clone and increase of Philadelphia chromosome-negative cells. During a therapy-withholding period due to fungal infection, the Philadelphia chromosome-positive clone expanded and the patient died of cerebral hemorrhage in February 2003. The transient suppression of the Philadelphia chromosome-positive clone may have brought about amplification of the Philadelphia chromosome-negative cells after the secondary imatinib treatment.

VizieR Online Data Catalog: Swift UVOT light curves of ASASSN-15lh (Margutti+, 2017)

NASA Astrophysics Data System (ADS)

Margutti, R.; Metzger, B. D.; Chornock, R.; Milisavljevic, D.; Berger, E.; Blanchard, P. K.; Guidorzi, C.; Migliori, G.; Kamble, A.; Lunnan, R.; Nicholl, M.; Coppejans, D. L.; Dall'Osso, S.; Drout, M. R.; Perna, R.; Sbarufatti, B.

2017-09-01

We obtained four epochs of deep X-ray observations of ASASSN-15lh with the Chandra X-ray Observatory (CXO) on 2015 November 12 (exposure of 10ks), 2015 December 13 (10ks), 2016 February 20 (40ks), and 2016 August 19 (30 ks, PI Margutti), corresponding to δt=129.4d, δt=154.6, δt=210.5d, and δt=357.8d rest-frame since optical maximum light, which occurred on 2015 June 5. We reprocessed all the X-ray data collected by the Swift-XRT and all the Swift-UVOT observations obtained from 2015 June 24 until 2016 July 22. A partial collection of the Swift-UVOT photometry of ASASSN-15lh has already been presented by Dong+ (2016Sci...351..257D), Godoy-Rivera+ (2017MNRAS.466.1428G), Brown+ (2016, J/ApJ/828/3), and Leloudas+ (2016NatAs...1E...2L). Here we update the observations and focus on the presence of significant temporal variability that appears at the time of the rebrightening. (1 data file).

Structure of a Unimolecular Dendritic Reverse Micelle in Dense CO2 Via Small Angle Scattering

NASA Astrophysics Data System (ADS)

Lin, J. S.

1997-03-01

Dilute solutions in dense CO2 (5Kpsi and 25 degC) of a unimolecular reverse micelle were studied via small angle x ray scattering (SAXS). The unimolecular micelle was based on a fourth generation poly(propylene imine) dendrimer, functionalized with perfluoropolyether acid fluoride chains. A value of 26 added chains per dendrimer was obtained from other characterization techniques, and this number of chains was fixed in the fitting of the SAXS data to an f-arm star model. The molecular weight ( 33.5K g mol-1) agreed well with estimates from other techniques. The observed negative second virial coefficient, A2 = -1.2 x 10-4 cm^3 g-2 mol, correlates with prior observations, as does the observed radius of gyration, Rg = 32ÅSponsors: Div. of Mat. Sci., Basic Energy Sc., USDOE, contract DE-AC05-96OR22464, Oak Ridge Nat. Lab., managed by Lockheed Martin Energy Research Corp.; The Royal Commission for the Exhibition of 1851; National Science Foundation; Consortium for the Sythesis and Processing of Polymeric Materials in Carbon Dioxide.

Comparative genomic, phylogenetic, and functional investigation of the xenobiotic metabolizing arylamine N-acetyltransferase enzyme family among fungi

USDA-ARS?s Scientific Manuscript database

Arylamine N-acetyltransferases (NATs) are xenobiotic metabolizing enzymes well-characterized in several bacteria and higher eukaryotes. The role of NATs in fungal biology has only recently been investigated (Glenn and Bacon, 2009; Glenn et al., 2010). The NAT1 gene of Gibberella moniliformis was the...

14. LION SCULPTURE, AT THE PHILADELPHIA MUSEUM OF ART, MOVED ...

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

14. LION SCULPTURE, AT THE PHILADELPHIA MUSEUM OF ART, MOVED FROM MERCHANTS' EXCHANGE, WHERE IT RESTED ON THE STAIR WALL OF SIDE ENTRANCE STAIRS. (A REPLACEMENT LION HAS BEEN PLACED IN THE ORIGINAL SITE, AS DID ANOTHER REPLACEMENT IN THE OTHER SIDE OF THE BUILDING. FOR THIS LATTER REPLACEMENT SEE PA-1028-15). A VIEW OF THE MUSEUM IS IN THE BACKGROUND - Philadelphia Exchange Company, 143 South Third Street, Philadelphia, Philadelphia County, PA

The human serotonin N-acetyltransferase (EC 2.3.1.87) gene (AANAT): Structure, chromosomal localization, and tissue expression

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

Coon, S.L.; Bernard, M.; Roseboom, P.H.

Serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AA-NAT, HGMW-approved symbol AANAT;EC 2.3.1.87) is the penultimate enzyme in melatonin synthesis and controls the night/day rhythm in melatonin production in the vertebrate pineal gland. We have found that the human AA-NAT gene spans {approx}2.5 kb, contains four exons, and is located at chromosome 17q25. The open reading frame encodes a 23.2-kDa protein that is {approx}80% identical to sheep and rat AA-NAT. The AA-NAT transcript ({approx}1 kb) is highly abundant in the pineal gland and is expressed at lower levels in the retina and in the Y79 retinoblastoma cell line. AA-NAT mRNA is also detectable atmore » low levels in several brain regions and the pituitary gland, but not in several peripheral tissues examined. Brain and pituitary AA-NAT could modulate serotonin-dependent aspects of human behavior and pituitary function. 31 refs., 5 figs.« less

Asymmetric localization of natural antisense RNA of neuropeptide sensorin in Aplysia sensory neurons during aging and activity.

PubMed

Kadakkuzha, Beena M; Liu, Xin-An; Narvaez, Maria; Kaye, Alexandra; Akhmedov, Komolitdin; Puthanveettil, Sathyanarayanan V

2014-01-01

Despite the advances in our understanding of transcriptome, regulation and function of its non-coding components continue to be poorly understood. Here we searched for natural antisense transcript for sensorin (NAT-SRN), a neuropeptide expressed in the presynaptic sensory neurons of gill-withdrawal reflex of the marine snail Aplysia californica. Sensorin (SRN) has a key role in learning and long-term memory storage in Aplysia. We have now identified NAT-SRN in the central nervous system (CNS) and have confirmed its expression by northern blotting and fluorescent RNA in situ hybridization. Quantitative analysis of NAT-SRN in micro-dissected cell bodies and processes of sensory neurons suggest that NAT-SRN is present in the distal neuronal processes along with sense transcripts. Importantly, aging is associated with reduction in levels of NAT-SRN in sensory neuron processes. Furthermore, we find that forskolin, an activator of CREB signaling, differentially alters the distribution of SRN and NAT-SRN. These studies reveal novel insights into physiological regulation of natural antisense RNAs.

2. GENERAL VIEW, CENTER BUILDING, WITH SIGN SAYING '1855 JEFFERSON ...

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

2. GENERAL VIEW, CENTER BUILDING, WITH SIGN SAYING '1855 JEFFERSON 1907 INSURANCE BUILDING' Photocopy of April 28, 1915 photograph on file at City Archives of Philadelphia, located at Philadelphia City Hall - Jefferson Fire Insurance Company, 425 Walnut Street, Philadelphia, Philadelphia County, PA

3. Photocopy of old 19th century photo showing a nonsteam ...

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

3. Photocopy of old 19th century photo showing a non-steam engine. Original photo in files of Insurance Company of North America, Philadelphia, Pa. Exact date not known. - Philadelphia Hose Company No. 1, Seventh & Filbert Streets, Philadelphia, Philadelphia County, PA

View north of west gallery of inside machine shop 36; ...

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

View north of west gallery of inside machine shop 36; the gallery housed turret, engine and toolroom lathes, small milling machines and drill presses used for machining small parts. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Structure Shop, League Island, Philadelphia, Philadelphia County, PA

Photocopy of photograph (from NBPPNSY) photographer unknown, 1988 view east ...

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

Photocopy of photograph (from NBP-PNSY) photographer unknown, 1988 view east of marine railway (Haer no. Pa-387-W). The railway was being dismantled at the time this photograph was taken. - Naval Base Philadelphia-Philadelphia Naval Shipyard, League Island, Philadelphia, Philadelphia County, PA

Steel storehouse in foreground. Streetscape looking eastsoutheast shows heavy material ...

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

Steel storehouse in foreground. Streetscape looking east-southeast shows heavy material storehouse (building no. 544), and main supply warehouse (building no. 624) (Haer no. Pa-387-V) to left. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Steel Storehouse, League Island, Philadelphia, Philadelphia County, PA

Performance analysis for wireless networks: an analytical approach by multifarious Sym Teredo.

PubMed

Punithavathani, D Shalini; Radley, Sheryl

2014-01-01

IPv4-IPv6 transition rolls out numerous challenges to the world of Internet as the Internet is drifting from IPv4 to IPv6. IETF recommends few transition techniques which includes dual stack and translation and tunneling. By means of tunneling the IPv6 packets over IPv4 UDP, Teredo maintains IPv4/IPv6 dual stack node in isolated IPv4 networks behindhand network address translation (NAT). However, the proposed tunneling protocol works with the symmetric and asymmetric NATs. In order to make a Teredo support several symmetric NATs along with several asymmetric NATs, we propose multifarious Sym Teredo (MTS), which is an extension of Teredo with a capability of navigating through several symmetric NATs. The work preserves the Teredo architecture and also offers a backward compatibility with the original Teredo protocol.

Performance Analysis for Wireless Networks: An Analytical Approach by Multifarious Sym Teredo

PubMed Central

Punithavathani, D. Shalini; Radley, Sheryl

2014-01-01

IPv4-IPv6 transition rolls out numerous challenges to the world of Internet as the Internet is drifting from IPv4 to IPv6. IETF recommends few transition techniques which includes dual stack and translation and tunneling. By means of tunneling the IPv6 packets over IPv4 UDP, Teredo maintains IPv4/IPv6 dual stack node in isolated IPv4 networks behindhand network address translation (NAT). However, the proposed tunneling protocol works with the symmetric and asymmetric NATs. In order to make a Teredo support several symmetric NATs along with several asymmetric NATs, we propose multifarious Sym Teredo (MTS), which is an extension of Teredo with a capability of navigating through several symmetric NATs. The work preserves the Teredo architecture and also offers a backward compatibility with the original Teredo protocol. PMID:25506611

Reliability of a science admission test (HAM-Nat) at Hamburg medical school.

PubMed

Hissbach, Johanna; Klusmann, Dietrich; Hampe, Wolfgang

2011-01-01

The University Hospital in Hamburg (UKE) started to develop a test of knowledge in natural sciences for admission to medical school in 2005 (Hamburger Auswahlverfahren für Medizinische Studiengänge, Naturwissenschaftsteil, HAM-Nat). This study is a step towards establishing the HAM-Nat. We are investigating parallel forms reliability, the effect of a crash course in chemistry on test results, and correlations of HAM-Nat test results with a test of scientific reasoning (similar to a subtest of the "Test for Medical Studies", TMS). 316 first-year students participated in the study in 2007. They completed different versions of the HAM-Nat test which consisted of items that had already been used (HN2006) and new items (HN2007). Four weeks later half of the participants were tested on the HN2007 version of the HAM-Nat again, while the other half completed the test of scientific reasoning. Within this four week interval students were offered a five day chemistry course. Parallel forms reliability for four different test versions ranged from r(tt)=.53 to r(tt)=.67. The retest reliabilities of the HN2007 halves were r(tt)=.54 and r(tt )=.61. Correlations of the two HAM-Nat versions with the test of scientific reasoning were r=.34 und r=.21. The crash course in chemistry had no effect on HAM-Nat scores. The results suggest that further versions of the test of natural sciences will not easily conform to the standards of internal consistency, parallel-forms reliability and retest reliability. Much care has to be taken in order to assemble items which could be used interchangeably for the construction of new test versions. The test of scientific reasoning and the HAM-Nat are tapping different constructs. Participation in a chemistry course did not improve students' achievement, probably because the content of the course was not coordinated with the test and many students lacked of motivation to do well in the second test.

Reliability of a science admission test (HAM-Nat) at Hamburg medical school

PubMed Central

Hissbach, Johanna; Klusmann, Dietrich; Hampe, Wolfgang

2011-01-01

Objective: The University Hospital in Hamburg (UKE) started to develop a test of knowledge in natural sciences for admission to medical school in 2005 (Hamburger Auswahlverfahren für Medizinische Studiengänge, Naturwissenschaftsteil, HAM-Nat). This study is a step towards establishing the HAM-Nat. We are investigating parallel forms reliability, the effect of a crash course in chemistry on test results, and correlations of HAM-Nat test results with a test of scientific reasoning (similar to a subtest of the "Test for Medical Studies", TMS). Methods: 316 first-year students participated in the study in 2007. They completed different versions of the HAM-Nat test which consisted of items that had already been used (HN2006) and new items (HN2007). Four weeks later half of the participants were tested on the HN2007 version of the HAM-Nat again, while the other half completed the test of scientific reasoning. Within this four week interval students were offered a five day chemistry course. Results: Parallel forms reliability for four different test versions ranged from rtt=.53 to rtt=.67. The retest reliabilities of the HN2007 halves were rtt=.54 and rtt =.61. Correlations of the two HAM-Nat versions with the test of scientific reasoning were r=.34 und r=.21. The crash course in chemistry had no effect on HAM-Nat scores. Conclusions: The results suggest that further versions of the test of natural sciences will not easily conform to the standards of internal consistency, parallel-forms reliability and retest reliability. Much care has to be taken in order to assemble items which could be used interchangeably for the construction of new test versions. The test of scientific reasoning and the HAM-Nat are tapping different constructs. Participation in a chemistry course did not improve students’ achievement, probably because the content of the course was not coordinated with the test and many students lacked of motivation to do well in the second test. PMID:21866246

Comparison of CYP1A2 and NAT2 Phenotypes between Black and White Smokers

PubMed Central

Muscat, Joshua E.; Pittman, Brian; Kleinman, Wayne; Lazarus, Philip; Stellman, Steven D.; Richie, John P.

2008-01-01

The lower incidence rate of transitional cell carcinoma of the urinary bladder in blacks than in whites may be due to racial differences in the catalytic activity of enzymes that metabolize carcinogenic arylamines in tobacco smoke. To examine this, we compared cytochrome P4501A2 (CYP1A2) and N-acetyltransferase-2 activities (NAT2) in black and white smokers using urinary caffeine metabolites as a probe for enzyme activity in a community-based study of 165 black and 183 white cigarette smokers. The paraxanthine (1,7-dimethylxanthine, 17X)/caffeine (trimethylxanthine, 137X) ratio or [17X + 1,7-dimethyluric acid (17U)]/137X ratio was used as an indicator of CYP1A2 activity. The 5-acetyl-amino-6-formylamino-3-methyluracil (AFMU)/1-methylxanthine (1X) ratio indicated NAT2 activity. The odds ratio for the slow NAT2 phenotype associated with black race was 0.4; 95% confidence intervals 0.2–0.7. The putative combined low risk phenotype (slow CYP1A2/rapid NAT2) was more common in blacks than in whites (25% vs. 15%, P<0.02). There were no significant racial differences in slow and rapid CYP1A2 phenotypes, and in the combined slow NAT2/rapid CYP1A2 phenotype. Age, education, cigarette smoking amount, body mass index, GSTM1 and GSTM3 genotypes were unrelated to CYP1A2 and NAT2 activity. Intake of cruciferous vegetables (primarily broccoli), red meat, carrots, grapefruit and onions predicted CYP1A2 activity either for all subjects or in race-specific analyses. Carrot and grapefruit consumption was related to NAT2 activity. Collectively, these results indicated that phenotypic differences in NAT2 alone or in combination with CYP1A2 might help explain the higher incidence rates of transitional cell bladder cancer in whites. PMID:18703023

The results of nucleic acid testing in remunerated and non-remunerated blood donors in Lithuania

PubMed Central

Kalibatas, Vytenis; Kalibatienė, Lina

2014-01-01

Background In Lithuania, governmentally covered remuneration for whole blood donations prevails. Donors may choose to accept or reject the remuneration. The purpose of this study was to compare the rate of nucleic acid testing (NAT) discriminatory-positive markers for human immunodeficiency virus-1 (HIV-1), hepatitis B virus (HBV) and hepatitis C virus (HCV) in seronegative, first-time and repeat, remunerated and non-remunerated donations at the National Blood Centre in Lithuania during the period from 2005 to 2010. Materials and methods All seronegative whole blood and blood component donations were individually analysed by NAT for HIV-1, HBV and HCV. Only discriminatory-positive NAT were classified. The prevalence of discriminatory-positive NAT per 100,000 donations in the donor groups and the odds ratios comparing the remunerated and non-remunerated donations were determined. Results Significant differences were observed for HBV NAT results: 47.42 and 26.29 per 100,000 remunerated first-time and repeat donations, respectively, compared to 10.6 and 3.58 per 100,000 non-remunerated first-time and repeat, seronegative donations, respectively. The differences were also significant for HCV NAT results: 47.42 and 51.99 for remunerated first-time and repeat donations, respectively, compared to 2.12 and 0 per 100,000 non-remunerated first-time and repeat, seronegative donations, respectively. No seronegative, discriminatory-positive NAT HIV case was found. The odds of discriminatory HBV and HCV NAT positive results were statistically significantly higher for both first-time and repeat remunerated donations compared to first-time and repeat non-remunerated donations. Discussion First-time and repeat remunerated seronegative donations were associated with a statistically significantly higher prevalence and odds for discriminatory-positive HBV and HCV NAT results compared to first-time and repeat non-remunerated donations at the National Blood Centre in Lithuania. PMID:24120587

Structural Evaluation of 5,5'-Bis(naphth-2-yl)-2,2'-bithiophene in Organic Field-Effect Transistors with n-Octadecyltrichlorosilane Coated SiO2 Gate Dielectric.

PubMed

Lauritzen, Andreas E; Torkkeli, Mika; Bikondoa, Oier; Linnet, Jes; Tavares, Luciana; Kjelstrup-Hansen, Jakob; Knaapila, Matti

2018-05-25

We report on the structure and morphology of 5,5'-bis(naphth-2-yl)-2,2'-bithiophene (NaT2) films in bottom-contact organic field-effect transistors (OFETs) with octadecyltrichlorosilane (OTS) coated SiO 2 gate dielectric, characterized by atomic force microscopy (AFM), grazing-incidence X-ray diffraction (GIXRD), and electrical transport measurements. Three types of devices were investigated with the NaT2 thin-film deposited either on (1) pristine SiO 2 (corresponding to higher surface energy, 47 mJ/m 2 ) or on OTS deposited on SiO 2 under (2) anhydrous or (3) humid conditions (corresponding to lower surface energies, 20-25 mJ/m 2 ). NaT2 films grown on pristine SiO 2 form nearly featureless three-dimensional islands. NaT2 films grown on OTS/SiO 2 deposited under anhydrous conditions form staggered pyramid islands where the interlayer spacing corresponds to the size of the NaT2 unit cell. At the same time, the grain size measured by AFM increases from hundreds of nanometers to micrometers and the crystal size measured by GIXRD from 30 nm to more than 100 nm. NaT2 on OTS/SiO 2 deposited under humid conditions also promotes staggered pyramids but with smaller crystals 30-80 nm. The NaT2 unit cell parameters in OFETs differ 1-2% from those in bulk. Carrier mobilities tend to be higher for NaT2 layers on SiO 2 (2-3 × 10 -4 cm 2 /(V s)) compared to NaT2 on OTS (2 × 10 -5 -1 × 10 -4 cm 2 /(V s)). An applied voltage does not influence the unit cell parameters when probed by GIXRD in operando.

Clinical Outcomes in International Federation of Gynecology and Obstetrics Stage IA Endometrial Cancer With Myometrial Invasion Treated With or Without Postoperative Vaginal Brachytherapy

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

Diavolitsis, V.; Rademaker, A.; Lurain, J.

2012-10-01

Purpose: To assess the clinical outcomes of patients with Stage IA endometrial cancer with myometrial invasion treated with postoperative vaginal brachytherapy (VBT) with those who received no adjuvant therapy (NAT). Methods and Materials: All patients treated with hysterectomy for endometrial cancer at Northwestern Memorial Hospital between 1978 and 2005 were identified. Those patients with Stage IA disease with myometrial invasion who were treated with VBT alone or NAT were identified and included in the present analysis. Results: Of 252 patients with Stage IA endometrial cancer with superficial (<50%) myometrial invasion who met the inclusion criteria, 169 underwent VBT and 83more » received NAT. The median follow-up in the VBT and NAT groups was 103 and 61 months, respectively. In the VBT group, 56.8% had Grade 1, 37.9% had Grade 2, and 5.3% had Grade 3 tumors. In the NAT group, 75.9%, 20.5%, and 3.6% had Grade 1, 2, and 3 tumors, respectively. Lymphatic or vascular space invasion was noted in 12.4% of the VBT patients and 5.6% of the NAT patients. The 5-year overall survival rate was 95.5%. The 5-year recurrence-free survival rate was 92.4% for all patients, 94.4% for the VBT group, and 87.4% for the NAT group (p = NS). Of the 169 VBT patients and 83 NAT patients, 8 (4.7%) and 6 (7.2%) developed recurrent disease. One vaginal recurrence occurred in the VBT group (0.6%) and three in the NAT group (3.8%). Recurrences developed 2-102 months after surgical treatment. Two of the four vaginal recurrences were salvaged. No Grade 3 or higher acute or late radiation toxicity was noted. Conclusions: The use of postoperative VBT in patients with Stage I endometrial cancer with <50% myometrial invasion yielded excellent vaginal disease control and disease-free survival, with minimal toxicity.« less

4. Photocopy of old 19th century photo showing a steam ...

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

4. Photocopy of old 19th century photo showing a steam engine in active use. Original photo in files of Insurance Company of North America, Philadelphia, Pa. Exact date not known. - Philadelphia Hose Company No. 1, Seventh & Filbert Streets, Philadelphia, Philadelphia County, PA

View of hammer nameplate (Chambersburg Engineering Company, Chambersburg, Penna USA) ...

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

View of hammer nameplate (Chambersburg Engineering Company, Chambersburg, Penna USA) and view north of Tony Talotta (heavy forger), Paul Azcharka (hammer operator), and Morty Hoffman (hammer operator helper) forging eyebolts. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Structure Shop, League Island, Philadelphia, Philadelphia County, PA

View southwest of machine shops, building 18 section visible in ...

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

View southwest of machine shops, building 18 section visible in foreground; building 16 section on left. This structure consists of two formerly separate buildings. Jet Lowe, Haer staff photographer, summer 1995. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Machine Shops, League Island, Philadelphia, Philadelphia County, PA

Evaluation of the Procleix Ultrio Elite Assay and the Panther-System for Individual NAT Screening of Blood, Hematopoietic Stem Cell, Tissue and Organ Donors.

PubMed

Heim, Albert

2016-05-01

The performance of the multiplex Procleix Ultrio Elite assay as individual donor nucleic acid test (ID-NAT) for the detection of HIV-1, HIV-2, HCV, and HBV was evaluated in a retrospective, single center study. ID-NAT results of 21,181 blood donors, 984 tissue donors, 293 hematopoietic stem cell donors and 4 organ donors were reviewed in synopsis with results of serological screening and additional discriminatory and repetitive NAT in case of positive donors. Specificity of the initial Procleix Ultrio Elite assay was 99.98% and after discriminatory testing 100.00%. Initially invalid results were observed in 75 of 21,181 blood donors (0.35%) but 16 of 984 tissue donors (1.62%, p < 0.001) which included non-heart-beating ('cadaveric') donors. All these had valid negative ID-NAT results after repeated testing or testing of 1:5 diluted specimens in case of tissue donors. Occult hepatitis B (defined here as HBV DNAemia without HBsAg detection) was demonstrated by ID-NAT in two anti-HBc-positive tissue donors and suspected in two other tissue donors, where a definite diagnosis was not achieved due to the insufficient sample volumes available. The Procleix Ultrio Elite assay proved to be specific, robust and rapid. Therefore, routine ID-NAT may also be feasible for organ and granulocyte donors.

Methamphetamine-induced neuronal protein NAT8L is the NAA biosynthetic enzyme: implications for specialized acetyl coenzyme A metabolism in the CNS.

PubMed

Ariyannur, Prasanth S; Moffett, John R; Manickam, Pachiappan; Pattabiraman, Nagarajan; Arun, Peethambaran; Nitta, Atsumi; Nabeshima, Toshitaka; Madhavarao, Chikkathur N; Namboodiri, Aryan M A

2010-06-04

N-acetylaspartate (NAA) is a concentrated, neuron-specific brain metabolite routinely used as a magnetic resonance spectroscopy marker for brain injury and disease. Despite decades of research, the functional roles of NAA remain unclear. Biochemical investigations over several decades have associated NAA with myelin lipid synthesis and energy metabolism. However, studies have been hampered by an inability to identify the gene for the NAA biosynthetic enzyme aspartate N-acetyltransferase (Asp-NAT). A very recent report has identified Nat8l as the gene encoding Asp-NAT and confirmed that the only child diagnosed with a lack of NAA on brain magnetic resonance spectrograms has a 19-bp deletion in this gene. Based on in vitro Nat8l expression studies the researchers concluded that many previous biochemical investigations have been technically flawed and that NAA may not be associated with brain energy or lipid metabolism. In studies done concurrently in our laboratory we have demonstrated via cloning, expression, specificity for acetylation of aspartate, responsiveness to methamphetamine treatment, molecular modeling and comparative immunolocalization that NAT8L is the NAA biosynthetic enzyme Asp-NAT. We conclude that NAA is a major storage and transport form of acetyl coenzyme A specific to the nervous system, thus linking it to both lipid synthesis and energy metabolism. Published by Elsevier B.V.

30. Historic American Buildings Survey, 1932 measured drawing from old ...

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

30. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, 1897 measured drawing by C. L. Hillman and John McClintock, photocopy courtesy of the Free Library of Philadelphia MISCELLANEOUS DETAILS: INTERIOR DOORS, STAIRS, SOUTH ROOM CHIMNEY-PIECE, ENTRANCE HALL. - Woodford, Philadelphia, Philadelphia County, PA

38. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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38. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

27. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

27. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

25. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

25. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

30. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

30. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

11. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

11. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

18. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

18. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

6. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

6. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

13. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

13. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

34. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

34. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

7. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

7. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

36. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

36. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

8. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

8. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

33. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

33. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

21. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

21. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

16. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

16. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

10. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

10. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

37. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

37. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

17. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

17. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

24. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

24. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

31. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

31. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

28. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

28. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

26. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

26. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

39. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

39. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

3. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

3. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

19. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

19. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

1. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

1. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

12. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

12. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

20. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

20. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

14. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

14. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

15. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

15. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

29. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

29. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

2. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

2. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

23. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

23. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

5. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

5. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

35. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

35. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

32. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

32. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

22. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

22. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

9. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

9. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

4. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ...

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

4. PHOTOCOPIES OF TITLE PAGE, BOOKPLATE, MEMBERSHIP CERTIFICATE AND PLATES ILLUSTRATING EXAMPLES OF CARPENTERS' WORK PUBLISHED IN ARTICLES OF THE CARPENTERS' COMPANY OF PHILADELPHIA AND THEIR RULES FOR MEASURING AND VALUING HOUSE CARPENTERS' WORK (Philadelphia: Hall and Sellars, 1786). - Carpenters' Company, Rule Book (carpentry manual), Philadelphia, Philadelphia County, PA

Cultural Participation in the Philadelphia Area.

ERIC Educational Resources Information Center

Hanford, Terry; And Others

Described are the results of two separate surveys of cross-sections of the Philadelphia public concerning their cultural behavior, attitudes, and perceptions. The more recent survey was conducted in 1984 with a random telephone sample of 404 Philadelphia residents. The other survey consisted of a subset of approximately 400 Philadelphia area…

Photocopy of photograph (from NBPPNSY) Replogle, Photographers, April 21, 1920 ...

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

Photocopy of photograph (from NBP-PNSY) Replogle, Photographers, April 21, 1920 View of boat shop showing the variety of small boats made by the shipyard; whaleboats, sailboats, lifeboats, crew barges, naptha launches and dorys. - Naval Base Philadelphia-Philadelphia Naval Shipyard, League Island, Philadelphia, Philadelphia County, PA

Proper regulation of a sperm-specific cis-nat-siRNA is essential for double fertilization in Arabidopsis

USDA-ARS?s Scientific Manuscript database

/Cis/-nat-siRNAs are a recently characterized class of small regulatory RNAs that are widespread in eukaryotes. Despite their abundance the importance of their regulatory activity is largely unknown. The only functional role for eukaryotic /cis/-nat-siRNAs that has been described to date is in envir...

First principles study of iron-bearing MgO under ultrahigh pressure

NASA Astrophysics Data System (ADS)

Umemoto, K.; Hsu, H.

2017-12-01

Understanding of minerals under ultrahigh pressure is essential to model interiors of super-Earths. Chemical compositions of the super-Earths are expected to be similar to those of the Earth. Computational studies on Mg-Si-O ternary systems under ultrahigh pressures, which are difficult to be achieved by diamond-anvil-cell experiments, have been intensively performed (e.g., [1] for MgO, [2,3] for SiO2, and [4,5] for MgSiO3). However, as far as we know, these studies have been restricted to pure Mg-Si-O systems. In the mantles of super-Earths, we expect that there should be impurities as in the Earth's mantle. Among candidates of impurities, iron is especially important to model interiors of super-Earths. Here, we investigate iron-bearing MgO under ultrahigh pressures by first principles. We clarify effects of iron on the phase transition of MgO and thermodynamic quantities by first principles. The role of the 3d electrons will be elucidated. [1] Z. Wu, R. M. Wentzcovitch, K. Umemoto, B. Li, K. Hirose, and J. C. Zheng, J. Geophys. Res. 113, B06204 (2008). [2] S. Q. Wu, K. Umemoto, M. Ji, C. Z. Wang, K. M. Ho, and R. M. Wentzcovitch, Phys. Rev. B 83, 184102 (2011). [3] T. Tsuchiya and J. Tsuchiya, Proc. Nat. Acad. Sci. 108, 1252 (2011) [4] S. Q. Wu, M. Ji, C. Z. Wang, M. C. Nguye, X. Zhao, K. Umemoto, R. M. Wentzcovitch, and K. M. Ho, J. Phys.: Condens. Matter 26, 035402 (2014). [5] H. Niu, A. R. Oganov, X.-C. Chen, and D. Li, Sci. Rep. 5, 18347 (2015).

Heterogeneous kinetics of H2O, HNO3 and HCl on HNO3 hydrates (α-NAT, β-NAT, NAD) in the range 175-200 K

NASA Astrophysics Data System (ADS)

Iannarelli, Riccardo; Rossi, Michel J.

2016-09-01

Experiments on the title compounds have been performed using a multidiagnostic stirred-flow reactor (SFR) in which the gas phase as well as the condensed phase has been simultaneously investigated under stratospheric temperatures in the range 175-200 K. Wall interactions of the title compounds have been taken into account using Langmuir adsorption isotherms in order to close the mass balance between deposited and desorbed (recovered) compounds. Thin solid films at 1 µm typical thickness have been used as a proxy for atmospheric ice particles and have been deposited on a Si window of the cryostat, with the optical element being the only cold point in the deposition chamber. Fourier transform infrared (FTIR) absorption spectroscopy in transmission as well as partial and total pressure measurement using residual gas mass spectrometry (MS) and sensitive pressure gauges have been employed in order to monitor growth and evaporation processes as a function of temperature using both pulsed and continuous gas admission and monitoring under SFR conditions. Thin solid H2O ice films were used as the starting point throughout, with the initial spontaneous formation of α-NAT (nitric acid trihydrate) followed by the gradual transformation of α- to β-NAT at T > 185 K. Nitric acid dihydrate (NAD) was spontaneously formed at somewhat larger partial pressures of HNO3 deposited on pure H2O ice. In contrast to published reports, the formation of α-NAT proceeded without prior formation of an amorphous HNO3 / H2O layer and always resulted in β-NAT. For α- and β-NAT, the temperature-dependent accommodation coefficient α(H2O) and α(HNO3), the evaporation flux Jev(H2O) and Jev(HNO3) and the resulting saturation vapor pressure Peq(H2O) and Peq(HNO3) were measured and compared to binary phase diagrams of HNO3 / H2O in order to afford a thermochemical check of the kinetic parameters. The resulting kinetic and thermodynamic parameters of activation energies for evaporation (Eev) and standard heats of evaporation ΔHev0 of H2O and HNO3 for α- and β-NAT, respectively, led to an estimate for the relative standard enthalpy difference between α- and β-NAT of -6.0 ± 20 kJ mol-1 in favor of β-NAT, as expected, despite a significantly larger value of Eev for HNO3 in α-NAT. This in turn implies a substantial activation energy for HNO3 accommodation in α- compared to β-NAT where Eacc(HNO3) is essentially zero. The kinetic (α(HCl), Jev(HCl)) and thermodynamic (Peq(HCl)) parameters of HCl-doped α- and β-NAT have been determined under the assumption that HCl adsorption did not significantly affect α(H2O) and α(HNO3) as well as the evaporation flux Jev(H2O). Jev(HCl) and Peq(HCl) on both α- and β-NAT are larger than the corresponding values for HNO3 across the investigated temperature range but significantly smaller than the values for pure H2O ice at T < 200 K.

N-acetyltransferase 2 (NAT2) gene polymorphism as a predisposing factor for phenytoin intoxication in tuberculous meningitis or tuberculoma patients having seizures - A pilot study.

PubMed

Adole, Prashant S; Kharbanda, Parampreet S; Sharma, Sadhna

2016-05-01

Simultaneous administration of phenytoin and isoniazid (INH) in tuberculous meningitis (TBM) or tuberculoma patients with seizures results in higher plasma phenytoin level and thus phenytoin intoxication. N-acetyltransferase 2 (NAT2) enzyme catalyses two acetylation reactions in INH metabolism and NAT2 gene polymorphism leads to slow and rapid acetylators. The present study was aimed to evaluate the effect of allelic variants of N-acetyltransferase 2 (NAT2) gene as a predisposing factor for phenytoin toxicity in patients with TBM or tuberculoma having seizures, and taking INH and phenytoin simultaneously. Sixty patients with TBM or tuberculoma with seizures and taking INH and phenytoin simultaneously for a minimum period of seven days were included in study. Plasma phenytoin was measured by high performance liquid chromatography. NAT2 gene polymorphism was studied using restriction fragment length polymorphism and allele specific PCR. The patients were grouped into those having phenytoin intoxication and those with normal phenytoin level, and also classified as rapid or slow acetylators by NAT2 genotyping. Genotypic analysis showed that of the seven SNPs (single nucleotide polymorphisms) of NAT2 gene studied, six mutations were found to be associated with phenytoin intoxication. For rs1041983 (C282T), rs1799929 (C481T), rs1799931 (G857A), rs1799930 (G590A), rs1208 (A803G) and rs1801280 (T341C) allelic variants, the proportion of homozygous mutant was higher in phenytoin intoxicated group than in phenytoin non-intoxicated group. Homozygous mutant allele of NAT2 gene at 481site may act as a predisposing factor for phenytoin intoxication among TBM or tuberculoma patients having seizures.

Effects of human arylamine N-acetyltransferase I knockdown in triple-negative breast cancer cell lines

PubMed Central

Tiang, Jacky M; Butcher, Neville J; Minchin, Rodney F

2015-01-01

Expression of human arylamine N-acetyltransferase I (NAT1) has been associated with various cancer subtypes and inhibition of this enzyme with small molecule inhibitors or siRNA affects cell growth and survival. Here, we have investigated the role of NAT1 in the invasiveness of breast cancer cells both in vitro and in vivo. We knocked down NAT1 using a lentivirus-based shRNA approach and observed marked changes in cell morphology in the triple-negative breast cancer cell lines MDA-MB-231, MDA-MB-436, and BT-549. Most notable was a reduction in the number and size of the filopodia protrusions on the surface of the cells. The loss of filopodia could be rescued by the reintroduction of NAT1 into the knockdown cells. NAT1 expression was localized to the lamellipodia and extended into the filopodia protrusions. In vitro invasion through Geltrex was significantly inhibited in both the MDA cell lines but not in the BT-549 cells. The expression of Snail increased when NAT1 was knocked down, while other genes associated with mesenchymal to epithelial transition (vimentin, cytokeratin-18, and Twist) did not show any changes. By contrast, both N-cadherin and β-catenin were significantly reduced. When MDA-MB-231 cells expressing shRNA were injected in vivo into BALB/c nu/nu nude mice, a significant reduction in the number of colonies that formed in the lungs was observed. Taken together, the results show that NAT1 can alter the invasion and metastatic properties of some triple-negative breast cancer cells but not all. The study suggests that NAT1 may be a novel therapeutic target in a subset of breast cancers. PMID:25627111

Effects of human arylamine N-acetyltransferase I knockdown in triple-negative breast cancer cell lines.

PubMed

Tiang, Jacky M; Butcher, Neville J; Minchin, Rodney F

2015-04-01

Expression of human arylamine N-acetyltransferase I (NAT1) has been associated with various cancer subtypes and inhibition of this enzyme with small molecule inhibitors or siRNA affects cell growth and survival. Here, we have investigated the role of NAT1 in the invasiveness of breast cancer cells both in vitro and in vivo. We knocked down NAT1 using a lentivirus-based shRNA approach and observed marked changes in cell morphology in the triple-negative breast cancer cell lines MDA-MB-231, MDA-MB-436, and BT-549. Most notable was a reduction in the number and size of the filopodia protrusions on the surface of the cells. The loss of filopodia could be rescued by the reintroduction of NAT1 into the knockdown cells. NAT1 expression was localized to the lamellipodia and extended into the filopodia protrusions. In vitro invasion through Geltrex was significantly inhibited in both the MDA cell lines but not in the BT-549 cells. The expression of Snail increased when NAT1 was knocked down, while other genes associated with mesenchymal to epithelial transition (vimentin, cytokeratin-18, and Twist) did not show any changes. By contrast, both N-cadherin and β-catenin were significantly reduced. When MDA-MB-231 cells expressing shRNA were injected in vivo into BALB/c nu/nu nude mice, a significant reduction in the number of colonies that formed in the lungs was observed. Taken together, the results show that NAT1 can alter the invasion and metastatic properties of some triple-negative breast cancer cells but not all. The study suggests that NAT1 may be a novel therapeutic target in a subset of breast cancers. © 2015 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Brachial artery endothelial function is stable across a menstrual and oral contraceptive pill cycle, but lower in premenopausal women than age-matched men.

PubMed

Shenouda, Ninette; Priest, Stacey E; Rizzuto, Vanessa I; MacDonald, Maureen J

2018-05-04

Sex hormone concentrations differ between men, premenopausal women with natural menstrual cycles (NAT), and premenopausal women using oral contraceptive pills (OCP), as well as across menstrual or OCP phases. This study sought to investigate how differences in sex hormones, particularly estradiol, between men and women and across cycle phases, may influence brachial artery endothelial function. Fifty-three healthy adults (22{plus minus}3 yrs; 20 men, 15 NAT, 18 second, third or fourth generation OCP) underwent assessments of sex hormones and endothelial (flow-mediated dilation test, FMD) and smooth muscle (nitroglycerin test, NTG) function. Men were tested three times at one-week intervals, and women were tested three times throughout a single menstrual or OCP cycle (NAT: menstrual, mid-follicular, luteal; OCP: placebo/no pill, 'early' and 'late' active pill). Endogenous estradiol concentration was comparable between men and women in their NAT menstrual or OCP placebo phase (p=0.36) but increased throughout a NAT cycle (p<0.001). Allometrically scaled FMD did not change across a NAT or OCP cycle but was lower in both groups of women than men (p=0.005), whereas scaled NTG was lower only in NAT women (p=0.001). Changes in estradiol across a NAT cycle were not associated with changes in relative FMD (r2=0.01, p=0.62) or NTG (r2=0.09, p=0.13). Duration of OCP use was negatively associated with the average relative FMD for second generation OCP users only (r=-0.65, p=0.04). Our findings suggest that brachial endothelial function is unaffected by cyclic hormonal changes in premenopausal women but may be negatively impacted by longer term use of second generation OCPs.

Rapid, Fully Automated Digital Immunoassay for p24 Protein with the Sensitivity of Nucleic Acid Amplification for Detecting Acute HIV Infection.

PubMed

Cabrera, Carlos; Chang, Lei; Stone, Mars; Busch, Michael; Wilson, David H

2015-11-01

Nucleic acid testing (NAT) has become the standard for high sensitivity in detecting low levels of virus. However, adoption of NAT can be cost prohibitive in low-resource settings where access to extreme sensitivity could be clinically advantageous for early detection of infection. We report development and preliminary validation of a simple, low-cost, fully automated digital p24 antigen immunoassay with the sensitivity of quantitative NAT viral load (NAT-VL) methods for detection of acute HIV infection. We developed an investigational 69-min immunoassay for p24 capsid protein for use on a novel digital analyzer on the basis of single-molecule-array technology. We evaluated the assay for sensitivity by dilution of standardized preparations of p24, cultured HIV, and preseroconversion samples. We characterized analytical performance and concordance with 2 NAT-VL methods and 2 contemporary p24 Ag/Ab combination immunoassays with dilutions of viral isolates and samples from the earliest stages of HIV infection. Analytical sensitivity was 0.0025 ng/L p24, equivalent to 60 HIV RNA copies/mL. The limit of quantification was 0.0076 ng/L, and imprecision across 10 runs was <10% for samples as low as 0.09 ng/L. Clinical specificity was 95.1%. Sensitivity concordance vs NAT-VL on dilutions of preseroconversion samples and Group M viral isolates was 100%. The digital immunoassay exhibited >4000-fold greater sensitivity than contemporary immunoassays for p24 and sensitivity equivalent to that of NAT methods for early detection of HIV. The data indicate that NAT-level sensitivity for acute HIV infection is possible with a simple, low-cost digital immunoassay. © 2015 American Association for Clinical Chemistry.

Infectivity of HBV DNA positive donations identified in look-back studies in Hyogo-Prefecture, Japan.

PubMed

Bouike, Y; Imoto, S; Mabuchi, O; Kokubunji, A; Kai, S; Okada, M; Taniguchi, R; Momose, S; Uchida, S; Nishio, H

2011-04-01

To clarify transfusion incidence of hepatitis B virus (HBV) infected blood negative for mini pool-nucleic acid amplification testing (MP-NAT). Japanese Red Cross (JRC) blood centres screen donated blood to avoid contamination with HBV. However, a low copy number of HBV may be overlooked. In Hyogo-Prefecture, JRC blood centres screened 787 695 donations for HBV from April 2005 to March 2009. Of these, 685 844 were donations from the repeat donors. To detect the donors with HBV, serological tests, MP-NAT and/or individual donation (ID)-NAT were performed. To detect the recipients with transfusion-transmitted HBV infection (TTHBI), serological analysis and/or ID-NAT were performed. In this study, 265 of the 685 844 repeat donations were serologically and/or MP-NAT positive for HBV. Their repository samples from the previous donation were examined in a look-back study; 13 of the 265 repository samples proved ID-NAT positive. Twelve recipients were transfused with HBV-infected blood components derived from 10 of the 13 HBV-infected donors. Only 1 of the 12 recipients was identified as TTHBI case. Seven of the 12 recipients escaped from our follow-up study and 4 recipients were negative for HBV during the observation period. On the basis of the look-back study among the repeat donors in Hyogo-Prefecture, Japan, donations with HBV-infected blood negative for MP-NAT occurred with a frequency of 13 in 685 844 donations (∼1/53 000 donations). However, more than half of the recipients transfused with HBV-infected blood negative for MP-NAT could not be followed up. It is necessary to establish a more cautious follow-up system. © 2010 The Authors. Transfusion Medicine © 2010 British Blood Transfusion Society.

N-acetyltransferase 2 (NAT2) gene polymorphism as a predisposing factor for phenytoin intoxication in tuberculous meningitis or tuberculoma patients having seizures - A pilot study

PubMed Central

Adole, Prashant S.; Kharbanda, Parampreet S.; Sharma, Sadhna

2016-01-01

Background & objectives: Simultaneous administration of phenytoin and isoniazid (INH) in tuberculous meningitis (TBM) or tuberculoma patients with seizures results in higher plasma phenytoin level and thus phenytoin intoxication. N-acetyltransferase 2 (NAT2) enzyme catalyses two acetylation reactions in INH metabolism and NAT2 gene polymorphism leads to slow and rapid acetylators. The present study was aimed to evaluate the effect of allelic variants of N-acetyltransferase 2 (NAT2) gene as a predisposing factor for phenytoin toxicity in patients with TBM or tuberculoma having seizures, and taking INH and phenytoin simultaneously. Methods: Sixty patients with TBM or tuberculoma with seizures and taking INH and phenytoin simultaneously for a minimum period of seven days were included in study. Plasma phenytoin was measured by high performance liquid chromatography. NAT2 gene polymorphism was studied using restriction fragment length polymorphism and allele specific PCR. Results: The patients were grouped into those having phenytoin intoxication and those with normal phenytoin level, and also classified as rapid or slow acetylators by NAT2 genotyping. Genotypic analysis showed that of the seven SNPs (single nucleotide polymorphisms) of NAT2 gene studied, six mutations were found to be associated with phenytoin intoxication. For rs1041983 (C282T), rs1799929 (C481T), rs1799931 (G857A), rs1799930 (G590A), rs1208 (A803G) and rs1801280 (T341C) allelic variants, the proportion of homozygous mutant was higher in phenytoin intoxicated group than in phenytoin non-intoxicated group. Interpretation & conclusions: Homozygous mutant allele of NAT2 gene at 481site may act as a predisposing factor for phenytoin intoxication among TBM or tuberculoma patients having seizures. PMID:27488001

Structural determinants and cellular environment define processed actin as the sole substrate of the N-terminal acetyltransferase NAA80.

PubMed

Goris, Marianne; Magin, Robert S; Foyn, Håvard; Myklebust, Line M; Varland, Sylvia; Ree, Rasmus; Drazic, Adrian; Bhambra, Parminder; Støve, Svein I; Baumann, Markus; Haug, Bengt Erik; Marmorstein, Ronen; Arnesen, Thomas

2018-04-24

N-terminal (Nt) acetylation is a major protein modification catalyzed by N-terminal acetyltransferases (NATs). Methionine acidic N termini, including actin, are cotranslationally Nt acetylated by NatB in all eukaryotes, but animal actins containing acidic N termini, are additionally posttranslationally Nt acetylated by NAA80. Actin Nt acetylation was found to regulate cytoskeletal dynamics and motility, thus making NAA80 a potential target for cell migration regulation. In this work, we developed potent and selective bisubstrate inhibitors for NAA80 and determined the crystal structure of NAA80 in complex with such an inhibitor, revealing that NAA80 adopts a fold similar to other NAT enzymes but with a more open substrate binding region. Furthermore, in contrast to most other NATs, the substrate specificity of NAA80 is mainly derived through interactions between the enzyme and the acidic amino acids at positions 2 and 3 of the actin substrate and not residues 1 and 2. A yeast model revealed that ectopic expression of NAA80 in a strain lacking NatB activity partially restored Nt acetylation of NatB substrates, including yeast actin. Thus, NAA80 holds intrinsic capacity to posttranslationally Nt acetylate NatB-type substrates in vivo. In sum, the presence of a dominant cotranslational NatB in all eukaryotes, the specific posttranslational actin methionine removal in animals, and finally, the unique structural features of NAA80 leave only the processed actins as in vivo substrates of NAA80. Together, this study reveals the molecular and cellular basis of NAA80 Nt acetylation and provides a scaffold for development of inhibitors for the regulation of cytoskeletal properties. Copyright © 2018 the Author(s). Published by PNAS.

NAT2, meat consumption and colorectal cancer incidence: an ecological study among 27 countries.

PubMed

Ognjanovic, Simona; Yamamoto, Jennifer; Maskarinec, Gertraud; Le Marchand, Loïc

2006-11-01

The polymorphic gene NAT2 is a major determinant of N-acetyltransferase activity and, thus, may be responsible for differences in one's ability to bioactivate heterocyclic amines, a class of procarcinogens in cooked meat. An unusually marked geographic variation in enzyme activity has been described for NAT2. The present study re-examines the international direct correlation reported for meat intake and colorectal cancer (CRC) incidence, and evaluates the potential modifying effects of NAT2 phenotype and other lifestyle factors on this correlation. Country-specific CRC incidence data, per capita consumption data for meat and other dietary factors, prevalence of the rapid/intermediate NAT2 phenotype, and prevalence of smoking for 27 countries were used. Multiple linear regression models were fit and partial correlation coefficients (PCCs) were computed for men and women separately. Inclusion of the rapid/intermediate NAT2 phenotype with meat consumption improved the fit of the regression model for CRC incidence in both sexes (males-R (2) = 0.78, compared to 0.70 for meat alone; p for difference in model fit-0.009; females-R (2) = 0.76 compared to 0.69 for meat alone; p = 0.02). Vegetable consumption (inversely and in both sexes) and fish consumption (directly and in men only) were also weakly correlated with CRC, whereas smoking prevalence and alcohol consumption had no effects on the models. The PCC between NAT2 and CRC incidence was 0.46 in males and 0.48 in females when meat consumption was included in the model, compared to 0.14 and 0.15, respectively, when it was not. These data suggest that, in combination with meat intake, some proportion of the international variability in CRC incidence may be attributable to genetic susceptibility to heterocyclic amines, as determined by NAT2 genotype.

Cosmology with negative absolute temperatures

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

Vieira, J.P.P.; Byrnes, Christian T.; Lewis, Antony, E-mail: J.Pinto-Vieira@sussex.ac.uk, E-mail: ctb22@sussex.ac.uk, E-mail: antony@cosmologist.info

Negative absolute temperatures (NAT) are an exotic thermodynamical consequence of quantum physics which has been known since the 1950's (having been achieved in the lab on a number of occasions). Recently, the work of Braun et al. [1] has rekindled interest in negative temperatures and hinted at a possibility of using NAT systems in the lab as dark energy analogues. This paper goes one step further, looking into the cosmological consequences of the existence of a NAT component in the Universe. NAT-dominated expanding Universes experience a borderline phantom expansion ( w < -1) with no Big Rip, and their contractingmore » counterparts are forced to bounce after the energy density becomes sufficiently large. Both scenarios might be used to solve horizon and flatness problems analogously to standard inflation and bouncing cosmologies. We discuss the difficulties in obtaining and ending a NAT-dominated epoch, and possible ways of obtaining density perturbations with an acceptable spectrum.« less

Arylamine N-acetyltransferase 2 genotype-dependent N-acetylation of isoniazid in cryopreserved human hepatocytes.

PubMed

Doll, Mark A; Salazar-González, Raúl A; Bodduluri, Srineil; Hein, David W

2017-07-01

Cryopreserved human hepatocytes were used to investigate the role of arylamine N -acetyltransferase 2 (NAT2; EC 2.3.1.5) polymorphism on the N -acetylation of isoniazid (INH). NAT2 genotype was determined by Taqman allelic discrimination assay and INH N -acetylation was measured by high performance liquid chromatography. INH N -acetylation rates in vitro exhibited a robust and highly significant ( P <0.005) NAT2 phenotype-dependent metabolism. N -acetylation rates in situ were INH concentration- and time-dependent. Following incubation for 24 h with 12.5 or 100 µmol/L INH, acetyl-INH concentrations varied significantly ( P = 0.0023 and P = 0.0002) across cryopreserved human hepatocytes samples from rapid, intermediate, and slow acetylators, respectively. The clear association between NAT2 genotype and phenotype supports use of NAT2 genotype to guide INH dosing strategies in the treatment and prevention of tuberculosis.

Excitation functions of nuclear reactions induced by alpha particles up to 42 MeV on natTi for monitoring purposes and TLA

NASA Astrophysics Data System (ADS)

Hermanne, A.; Sonck, M.; Takács, S.; Szelecsényi, F.; Tárkányi, F.

1999-05-01

Excitation functions for the reactions induced by alpha particles on natTi foils and leading to the formation of 44m,44g,46,47,48Sc; 48,51Cr and 48V were determined using the stacked foil technique for energies from the respective reaction thresholds up to 42 MeV. The new experimental values are compared to earlier literature values and generally good accordance is found. It appears that the natTi(α,x) 51Cr reaction is particularly useful for monitoring α-beams in the 10-20 MeV region while for energies above 20 MeV the natTi(α,x) 47Sc reaction or the natTi(α,x) 48V reaction are more suited. The excitation functions established can be used to determine calibration curves for thin layer activation (TLA) as well.

Structure of Multi-component Basaltic Glasses under Static and Dynamic Compression: Implications for Mantle Melting and Impact Processes on Planetary Surfaces

NASA Astrophysics Data System (ADS)

Lee, S.; Mosenfelder, J. L.; Tschauner, O. D.; Asimow, P. D.; Park, S.; Kim, H.

2012-12-01

The structures of basaltic melts under both static and dynamic compression are essential to understand the changes in the corresponding melt properties and to provide atomistic insights into impact-induced events in Earth's crust and planetary surfaces. Despite the importance, structural changes in basaltic glasses due both to dynamic and static compression have not been well understood. The advances in multi-nuclear NMR and multi-edge inelastic x-ray scattering allow us to obtain details of the pressure-induced changes in the degree of melt polymerization and cation coordination number in multi-component melts under static and dynamic compression (e.g. Lee, Proc. Nat. Aca. Sci. 2011, 108, 6847; Sol. St. NMR. 2010, 38, 45; Lee et al. Geophys. Res. Letts. 39 5306; Proc. Nat. Aca. Sci. 2008, 105, 7925). Here, we explore the structures of shock compressed silicate glass with a diopside-anorthite eutectic composition (Di64An36), a common Fe-free model basaltic composition, using oxygen K-edge X-ray Raman scattering and high- resolution Al-27 solid-state NMR spectroscopy and report details of shock-induced changes in the atomic configurations. A topologically driven densification of the Di64An36 glass is indicated by the increase in oxygen K-edge energy for the glass upon shock compression with peak pressure up to 20 GPa. The first experimental evidence of the increase in the fraction of highly coordinated Al in shock compressed glass is found in the Al-27 NMR spectra. This result provides atomistic insights into shock compression in basaltic glasses and allows us to microscopically constrain the magnitude of impact events or relevant processes involving natural basalts on Earth and planetary surfaces. We also report the first high pressure multi-nuclear NMR spectrum for basaltic glass up to 5 GPa. While [4]Al species is dominant at 1atm, the significant fraction of [5,6]Al in the glass is apparent, leading to changes in oxygen connectivity in the multi-component. The prevalence of highly coordinated Al and high energy oxygen cluster in the basaltic melts at 5 GPa implies that thermodynamic properties (e.g. element portioning coefficient between melts and crystal) of primary mantle melts formed at mid-ocean ridge (~150 km in depth) should be largely different from what can be predicted for silicate melts at 1 atm. The structural transitions in model basaltic glass at high pressure provide atomistic origins of anomalous mantle composition based on MORB at 1atm that is different from the prediction from chondritic meteorite (e.g. missing Si content in the primitive mantle).

Early Earth evolution: new insight from Sm and Nd isotopes in meteoritic inclusions

NASA Astrophysics Data System (ADS)

Bouvier, A.; Boyet, M.

2014-12-01

The interpretation of Sm-Nd systematics for the early Earth relies on knowing the composition of the silicate Earth and the 146Sm decay constant. We have measured both 146Sm-142Nd and 147Sm-143Nd internal systematics of four individual Calcium, Aluminum-rich Inclusions (CAIs), the first solids formed in the Solar System [1], from 3 different carbonaceous chondrites from the CV3 group: Allende, Northwest Africa (NWA) 2364 and NWA 6991. Results obtained on NWA 6991 plot on a well-defined mineral and bulk isochron with a Solar System initial 146Sm/144Sm ratio of 0.0070 ±0.0024. This ratio is more consistent with the ratio defined from internal isochrons of differentiated meteorites using the half-life of 103 Ma for 146Sm [2], instead of the value obtained considering the half-life of 68 Ma [3]. On the basis of nucleosynthethic anomalies in Sm and Nd isotopes [4], the ordinary (O) and enstatite (E) chondrites remain potential candidates for the Earth's building blocks. OC have an average deficit of -18±3 ppm relative to modern terrestrial 142Nd/144Nd, whereas EC range from the OC to the terrestrial values [4-6]. Sm stable isotope compositions of the analyzed CAIs indicate that galactic cosmic rays did not affect the 142Nd/144Nd compositions, but deficits are found in the pure p-process 144Sm nuclide (-240 to -290 ppm/ standard). These deficits may translate to 142Nd deficits of a few ppm. NWA 6991 CAI 146Sm-142Nd internal isochron passes through a 142Nd/144Nd ratio of -6 ±6 ppm relative to the terrestrial standard at a chondritic 147Sm/144Nd of 0.1960. We note that this value is identical to the enstatite chondrite average and the 142Nd/144Nd ratio of the lunar mantle, as defined recently by [7] using a chondritic Sm/Nd and Lu/Hf for the bulk Moon. While the determination of the Sm-Nd reference parameters for the bulk Earth is still contentious, the difference in 142Nd/144Nd between modern terrestrial rocks and meteorites analyzed so far is <10ppm. [1] Bouvier and Wadhwa (2010) Nat. Geosc. 3, 637. [2] Boyet et al. (2010) Earth Planet. Sci. Lett. 291, 172. [3] Kinoshita et al. (2012) Science 335, 1614. [4] Carlson et al. (2007) Science 316, 1175. [5] Boyet and Carlson (2005) Science 309, 576. [6] Gannoun et al. (2011) Proc. Nat. Acad. Sc. 108, 7693. [7] Sprung et al. (2013) Earth Planet. Sci. Lett. 380, 77.

18. Photographic copy of photograph of south and east elevations ...

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

18. Photographic copy of photograph of south and east elevations taken on March 22, 1957. Photographer unknown. Original photograph property of the City of Philadelphia, Division of Aviation. Reprinted with permission of the Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

17. Photographic copy of photograph of north elevation taken on ...

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

17. Photographic copy of photograph of north elevation taken on March 22, 1957, photographer unknown. Original photograph property of the City of Philadelphia. Division of Aviation. Reprinted with permission of the Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

22. Photographic copy of photograph of interior of hangar looking ...

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

22. Photographic copy of photograph of interior of hangar looking west taken on March 22, 1957. Photographer unknown. Original photograph property of the City of Philadelphia, Division of Aviation. Reprinted with permission of the Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

21. Photographic copy of photograph of interior of hangar looking ...

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

21. Photographic copy of photograph of interior of hangar looking east taken on March 22, 1957. Photographer unknown. Original photograph property of the City of Philadelphia, Division of Aviation. Reprinted with permission of the Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

23. Photographic copy of photograph of interior of hangar looking ...

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

23. Photographic copy of photograph of interior of hangar looking south taken on March 22, 1957. Photographer unknown. Original photograph property of the City of Philadelphia, Division of Aviation. Reprinted with permission of the Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

20. Photographic copy of photograph of roof suspender system taken ...

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

20. Photographic copy of photograph of roof suspender system taken on March 22, 1957. Photographer unknown. Original photograph property of the City of Philadelphia, Division of Aviation. Reprinted with permission of the Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

24. Photographic copy of photograph of mezzanine, interior of hangar, ...

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

24. Photographic copy of photograph of mezzanine, interior of hangar, taken on March 22, 1957. Photographer unknown. Original photograph property of the City of Philadelphia, Division of Aviation. Reprinted with permission of the Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

31. Historic American Buildings Survey, 1932 measured drawing from old ...

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

31. Historic American Buildings Survey, 1932 measured drawing from old Philadelphia Survey, 1897 measured drawing by C. L. Hillman and John McClintock, photocopy courtesy of the Free Library of Philadelphia ELEVATIONS AND PROFILES, PALLADIAN WINDOW, EAST END OF HALL, SECOND STORY; PLAN AND CORNICE DETAILS, FIRST FLOOR. - Woodford, Philadelphia, Philadelphia County, PA

(Dis)empowerment: The Implementation of Corrective Mathematics in Philadelphia Empowerment Schools

ERIC Educational Resources Information Center

Connor, Hannah

2011-01-01

The need to improve math education around the country has been well documented, especially in urban school systems like Philadelphia. In Spring 2010, only 56.6% of students in Philadelphia Public schools scored proficient or advanced on the Pennsylvania State Standardized Assessment (PSSA). In Philadelphia Empowerment Schools, the 107 lowest…

View north of tube bending shop in boilermakers department located ...

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

View north of tube bending shop in boilermakers department located in southeast corner of the structural shop building (building 57). The computer controlled tube bender can be programmed to bend boiler tubing to nearly any required configuration - Naval Base Philadelphia-Philadelphia Naval Shipyard, Structure Shop, League Island, Philadelphia, Philadelphia County, PA

1. CONTEXTUAL VIEW OF DRY DOCK NO. 4, LOOKING NORTHEAST ...

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

1. CONTEXTUAL VIEW OF DRY DOCK NO. 4, LOOKING NORTHEAST FROM ROOF OF BUILDING NO. 620. NOTE OVERHEAD CRANE (STRUCTURE NO. 1043) AND STRUCTURAL ASSEMBLY SHOP (BUILDING NO. 541) IN LEFT BACKGROUND. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Dry Dock No. 4, Broad Street south of Government Avenue, Philadelphia, Philadelphia County, PA

African Diaspora Movement Arts in Philadelphia: A Beginning Resource List. Philadelphia Folklore Project Working Papers #10.

ERIC Educational Resources Information Center

Brown-Danquah, Benita Binta

This guide provides history, format, contact names, addresses, and phone numbers of some African dance and African American marching units in Philadelphia (Pennsylvania). The working papers are divided into two categories. "Part One: Movements of African Dance in Philadelphia" begins with a sensitive, detailed explanation of the…

Service building no. 620. Details of of Toilet & Wash ...

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

Service building no. 620. Details of of Toilet & Wash rooms at South end of building (Dry Dock Associates, June 12, 1941). In files of Cushman & Wakefield, building no. 501, Philadephia Naval Business Center. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Service Building, Dry Docks No. 4 & 5, League Island, Philadelphia, Philadelphia County, PA

Excitation functions of the natCr(p,x)44Ti, 56Fe(p,x)44Ti, natNi(p,x)44Ti and 93Nb(p,x)44Ti reactions at energies up to 2.6 GeV

NASA Astrophysics Data System (ADS)

Titarenko, Yu. E.; Batyaev, V. F.; Pavlov, K. V.; Titarenko, A. Yu.; Zhivun, V. M.; Chauzova, M. V.; Balyuk, S. A.; Bebenin, P. V.; Ignatyuk, A. V.; Mashnik, S. G.; Leray, S.; Boudard, A.; David, J. C.; Mancusi, D.; Cugnon, J.; Yariv, Y.; Nishihara, K.; Matsuda, N.; Kumawat, H.; Stankovskiy, A. Yu.

2016-06-01

The paper presents the measured cumulative yields of 44Ti for natCr, 56Fe, natNi and 93Nb samples irradiated by protons at the energy range 0.04-2.6 GeV. The obtained excitation functions are compared with calculations of the well-known codes: ISABEL, Bertini, INCL4.2+ABLA, INCL4.5+ABLA07, PHITS, CASCADE07 and CEM03.02. The predictive power of these codes regarding the studied nuclides is analyzed.

The expression of xenobiotic-metabolizing enzymes in human prostate and in prostate epithelial cells (PECs) derived from primary cultures.

PubMed

Al-Buheissi, S Z; Cole, K J; Hewer, A; Kumar, V; Bryan, R L; Hudson, D L; Patel, H R; Nathan, S; Miller, R A; Phillips, D H

2006-06-01

Dietary heterocyclic amines (HCAs) are carcinogenic in rodent prostate requiring activation by enzymes such as cytochrome P450 (CYP) and N-acetyltransferase (NAT). We investigated by Western blotting and immunohistochemistry the expression of CYP1A1, CYP1A2, and NAT1 in human prostate and in prostate epithelial cells (PECs) derived from primary cultures and tested their ability to activate the dietary carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and its N-hydroxy metabolite (N-OH-IQ) to DNA-damaging moieties. Western blotting identified CYP1A1, CYP1A2, and NAT1. Immunohistochemistry localized NAT1 to the cytoplasm of PECs. Inter-individual variation was observed in the expression levels of CYP1A1, 1A2, and NAT1 (11, 75, and 35-fold, respectively). PECs expressed CYP1A1 and NAT1 but not CYP1A2. When incubated with IQ or N-OH-IQ, PECs formed DNA adducts indicating their ability to metabolically activate these compounds. Prostate cells possess the capacity to activate dietary carcinogens. PECs may provide a useful model system to study their role in prostate carcinogenesis.

The Neighborhood Auditing Tool: a hybrid interface for auditing the UMLS.

PubMed

Morrey, C Paul; Geller, James; Halper, Michael; Perl, Yehoshua

2009-06-01

The UMLS's integration of more than 100 source vocabularies, not necessarily consistent with one another, causes some inconsistencies. The purpose of auditing the UMLS is to detect such inconsistencies and to suggest how to resolve them while observing the requirement of fully representing the content of each source in the UMLS. A software tool, called the Neighborhood Auditing Tool (NAT), that facilitates UMLS auditing is presented. The NAT supports "neighborhood-based" auditing, where, at any given time, an auditor concentrates on a single-focus concept and one of a variety of neighborhoods of its closely related concepts. Typical diagrammatic displays of concept networks have a number of shortcomings, so the NAT utilizes a hybrid diagram/text interface that features stylized neighborhood views which retain some of the best features of both the diagrammatic layouts and text windows while avoiding the shortcomings. The NAT allows an auditor to display knowledge from both the Metathesaurus (concept) level and the Semantic Network (semantic type) level. Various additional features of the NAT that support the auditing process are described. The usefulness of the NAT is demonstrated through a group of case studies. Its impact is tested with a study involving a select group of auditors.

Evaluation of the Procleix Ultrio Elite Assay and the Panther-System for Individual NAT Screening of Blood, Hematopoietic Stem Cell, Tissue and Organ Donors

PubMed Central

Heim, Albert

2016-01-01

Summary Background The performance of the multiplex Procleix Ultrio Elite assay as individual donor nucleic acid test (ID-NAT) for the detection of HIV-1, HIV-2, HCV, and HBV was evaluated in a retrospective, single center study. Methods ID-NAT results of 21,181 blood donors, 984 tissue donors, 293 hematopoietic stem cell donors and 4 organ donors were reviewed in synopsis with results of serological screening and additional discriminatory and repetitive NAT in case of positive donors. Results Specificity of the initial Procleix Ultrio Elite assay was 99.98% and after discriminatory testing 100.00%. Initially invalid results were observed in 75 of 21,181 blood donors (0.35%) but 16 of 984 tissue donors (1.62%, p < 0.001) which included non-heart-beating (‘cadaveric’) donors. All these had valid negative ID-NAT results after repeated testing or testing of 1:5 diluted specimens in case of tissue donors. Occult hepatitis B (defined here as HBV DNAemia without HBsAg detection) was demonstrated by ID-NAT in two anti-HBc-positive tissue donors and suspected in two other tissue donors, where a definite diagnosis was not achieved due to the insufficient sample volumes available. Conclusion The Procleix Ultrio Elite assay proved to be specific, robust and rapid. Therefore, routine ID-NAT may also be feasible for organ and granulocyte donors. PMID:27403089

Role for human arylamine N-acetyltransferase 1 in the methionine salvage pathway.

PubMed

Witham, Katey L; Minchin, Rodney F; Butcher, Neville J

2017-02-01

The Phase II drug metabolizing enzyme arylamine N-acetyltransferase 1 (NAT1) has been implicated in the growth and survival of cancer cells, although the mechanisms that underlies these effects are unknown. Here, a focused metabolomics approach was used to identify changes in folate catabolism as well as the S-adenosylmethionine (SAM) cycle following NAT1 knockdown with shRNA. Although acetylation of the folate catabolite p-aminobenzoylglutamate (pABG) was significantly decreased, there were no changes in intracellular pABG or the various components of the SAM cycle. By contrast, the flux of homocysteine in the medium was different following NAT1 knockdown after the methionine content was exhausted suggesting a need for this metabolite in methionine synthesis. Analysis of the growth of various cancer cells in methylthioadenosine-supplemented medium showed that NAT1 knockdown inhibited the methionine salvage pathway in HT-29 cells but not in HeLa or MDA-MB-436 cells. The cause of this was a low level of expression of the isomerase MRI-1 in the HT-29 cells. Knocking down both NAT1 and MRI-1 in HeLa cells with siRNA further demonstrated a redundancy between these 2 enzymes, although direct isomerase activity by NAT1 could not be demonstrated. The present study has identified a novel endogenous role for human NAT1 that might explain some of its effects in cancer cell growth and survival. Copyright © 2016 Elsevier Inc. All rights reserved.

Solid-state NMR study of various mono- and divalent cation forms of the natural zeolite natrolite.

PubMed

Park, Min Bum; Vicente, Aurélie; Fernandez, Christian; Hong, Suk Bong

2013-05-28

Here we present the one-dimensional (29)Si and (27)Al MAS NMR and two-dimensional (27)Al MQMAS and DQF-STMAS NMR spectra of the monovalent (Na(+), K(+), Rb(+), Cs(+) and NH4(+)) and divalent (Ca(2+), Sr(2+) and Ba(2+)) cation forms of the natural zeolite natrolite (framework type NAT) with complete Si-Al ordering over the crystallographically distinct tetrahedral sites and with the same hydration state (hydrated, partially dehydrated or fully dehydrated). In the case of monovalent cation-exchanged natrolites, the differences in their crystal symmetry evidenced by (29)Si MAS NMR were found to be in good agreement with those determined by crystallographic analyses. However, (27)Al DQF-STMAS NMR spectroscopy shows the presence of two distinct Al sites in dehydrated K-NAT, Rb-NAT and NH4-NAT, suggesting that their actual crystal symmetry is lower than the reported one (i.e., orthorhombic Fdd2). The MAS NMR results also show that the space group of hydrated Ca-NAT is lower than that (monoclinic F1d1) of hydrated scolecite, the natural calcium counterpart of natrolite, which is also the case with hydrated Sr-NAT and Ba-NAT. We believe that the unexpected diversity in the crystal symmetry of natrolite caused by exchange of various mono- and divalent ions, as well as by dehydration, may be inherently due to the high framework flexibility of this natural zeolite.

SP-100 GES/NAT radiation shielding systems design and development testing

NASA Astrophysics Data System (ADS)

Disney, Richard K.; Kulikowski, Henry D.; McGinnis, Cynthia A.; Reese, James C.; Thomas, Kevin; Wiltshire, Frank

1991-01-01

Advanced Energy Systems (AES) of Westinghouse Electric Corporation is under subcontract to the General Electric Company to supply nuclear radiation shielding components for the SP-100 Ground Engineering System (GES) Nuclear Assembly Test to be conducted at Westinghouse Hanford Company at Richland, Washington. The radiation shielding components are integral to the Nuclear Assembly Test (NAT) assembly and include prototypic and non-prototypic radiation shielding components which provide prototypic test conditions for the SP-100 reactor subsystem and reactor control subsystem components during the GES/NAT operations. W-AES is designing three radiation shield components for the NAT assembly; a prototypic Generic Flight System (GFS) shield, the Lower Internal Facility Shield (LIFS), and the Upper Internal Facility Shield (UIFS). This paper describes the design approach and development testing to support the design, fabrication, and assembly of these three shield components for use within the vacuum vessel of the GES/NAT. The GES/NAT shields must be designed to operate in a high vacuum which simulates space operations. The GFS shield and LIFS must provide prototypic radiation/thermal environments and mechanical interfaces for reactor system components. The NAT shields, in combination with the test facility shielding, must provide adequate radiation attenuation for overall test operations. Special design considerations account for the ground test facility effects on the prototypic GFS shield. Validation of the GFS shield design and performance will be based on detailed Monte Carlo analyses and developmental testing of design features. Full scale prototype testing of the shield subsystems is not planned.

West Nile virus blood transfusion-related infection despite nucleic acid testing.

PubMed

Macedo de Oliveira, Alexandre; Beecham, Brady D; Montgomery, Susan P; Lanciotti, Robert S; Linnen, Jeffrey M; Giachetti, Cristina; Pietrelli, Larry A; Stramer, Susan L; Safranek, Thomas J

2004-12-01

A case of West Nile virus (WNV) encephalitis associated with transfusion of blood that did not react when tested for WNV by minipool (MP) nucleic acid testing (NAT) is described. A Nebraska man developed clinical encephalitis 13 days after surgery and transfusion of 26 blood components. Antibody testing confirmed WNV infection. An investigation was initiated to determine the source of this infection. The patient's family members were interviewed to identify risk factors for WNV infection. Residual samples were retested for WNV RNA using transcription-mediated amplification (TMA) assay and two polymerase chain reaction (PCR) assays. Blood donors' follow-up serum samples were collected. All samples were tested for WNV-specific immunoglobulin M antibodies. The patient's family denied recent mosquito exposure. The 20 blood components collected after July 2003 did not react when tested for WNV in a six-member MP-NAT at the time of donation. Retrospective individual testing identified one sample as WNV-reactive by the TMA assay and one of the PCR assays. Seroconversion was demonstrated in the donor associated with this sample. WNV RNA detection by individual donation NAT demonstrates viremic blood escaping MP-NAT and supports transfusion-related WNV transmission. MP-NAT may not detect all WNV-infected blood donors, allowing WNV transmission to continue at low levels. WNV NAT assays might vary in sensitivity and pooling donations could further impact test performance. Understanding MP NAT limitations can improve strategies to maintain safety of the blood supply in the United States.

Strengthening Career and Technical Education and 21st Century Skills in Philadelphia

ERIC Educational Resources Information Center

Philadelphia Youth Network, 2009

2009-01-01

In Spring 2007, the John S. and James L. Knight Foundation awarded funds to the Philadelphia Youth Network (PYN) to undertake an analysis of Career and Technical Education (CTE) in Philadelphia, and to make recommendations on how CTE and other forms of career-connected education could better align with Philadelphia standards for college and career…

Blended Learning: Lessons from Best Practice Sites and the Philadelphia Context. PERC Research Brief

ERIC Educational Resources Information Center

Beaver, Jessica K.; Hallar, Brittan; Westmaas, Lucas; Englander, Katie

2015-01-01

The Philadelphia Education Research Consortium--or PERC--was launched in August 2014 as an innovative partnership designed to provide research and analyses on some of the city's most pressing education issues. This partnership was forged among the School District of Philadelphia, Philadelphia's charter school sector, and Research for Action (RFA).…

Coccolith calcite time capsules preserve a molecule-specific record of pCO2

NASA Astrophysics Data System (ADS)

McClelland, H. L. O.; Pearson, A.; Hermoso, M.; Wilkes, E.; Lee, R. B. Y.; Rickaby, R. E. M.

2017-12-01

Coccolithophores are single-celled phytoplankton that have contributed organic matter and calcite to marine sediments since the Late Triassic. The carbon isotopic compositions of both the calcite, and the organic matter, constitute valuable archives of information about the interaction between these organisms and the environments in which they lived. The isotopic composition of alkenone lipids, a recalcitrant component of coccolithophore organic carbon produced by a single family of coccolithophores, has been widely used to reconstruct pCO2 in the geological past. However, the robustness of this approach has remained controversial, due in part to the difficulties associated with reproducing pCO2 changes across periods of known pCO2 change, and uncertainties in relevant physiological variables such as growth rate and cell size. Meanwhile the calcite, produced in the form of plates called coccoliths, and which has had limited utility in paleoclimate reconstructions due to its large and variable departures from the isotopic composition of abiogenic calcite, has garnered increasing attention in recent years for the environmental and physiological information it contains. Here we show that polysaccharides preserved within the calcite crystal lattice of near monospecific fractions of fossil coccoliths constitute an ancient pristine source of organic carbon that unlike alkenones is unambiguously associated with the coccolith1. The isotopic composition of these polysaccharides, in tandem with that of the host coccolith calcite, and morphometrics from the same coccoliths2, can be used simultaneously constrain a recently published cellular carbon isotope flux model3, embedded in a more complex nutrient limitation model, in a powerful new approach to simultaneously predict cellular parameters and pCO2. We demonstrate the validity of this approach across a glacial / interglacial cycle. Lee, R. B. Y., et al,, Nat. Commun. 7, 13144 (2016). McClelland, H. L. O. et al. Sci. Rep. 6, 34263 (2016). McClelland, H. L. O. et al., Nat. Commun. 8, 1-16 (2017)

North view; Station Building south (front) elevation North ...

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

North view; Station Building - south (front) elevation - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

8. Photocopy of circa 1892 construction photograph, courtesy of Reading ...

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

8. Photocopy of circa 1892 construction photograph, courtesy of Reading Company Archives - Philadelphia & Reading Railroad, Terminal Station, 1115-1141 Market Street, Philadelphia, Philadelphia County, PA

West view; Station Building south and east elevations ...

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

West view; Station Building - south and east elevations - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

19. Photographic copy of photograph of portion of east elevation ...

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

19. Photographic copy of photograph of portion of east elevation taken on March 22, 1957 showing door beam and ladder to building roof. Photographer unknown. Original photograph property of the City of Philadelphia. Division of Aviation. Reprinted with permission of the Division of Aviation. - TWA Maintenance Hangar, South side of Tinicum Island Road, Philadelphia International Airport, Philadelphia, Philadelphia County, PA

View north of inside machine shop 36; shop floor accommodates ...

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

View north of inside machine shop 36; shop floor accommodates lathes capable of machining a cylinder 60 inches in diameter and 75 feet long; other equipment includes horizontal and vertical jig borders, hydraulic tube straighteners and other equipment for precision machining of large ship components. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Structure Shop, League Island, Philadelphia, Philadelphia County, PA

View south of hydraulic hammer in boilermakers shop (probably the ...

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

View south of hydraulic hammer in boilermakers shop (probably the oldest piece of equipment in the yard, originally powered by steam) nameplate: United Engineers and FDRY. Co. Pittsburgh, Pa, USA Davy Brothers LTD. Patents - Aug 1, 1905, Feb, 1901, Sept 8, 1908 - 10000 lbs. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Structure Shop, League Island, Philadelphia, Philadelphia County, PA

SouthWest view; Station Building north elevation, oblique North ...

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

South-West view; Station Building - north elevation, oblique - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

Attic floor; view west showing roof structural system North ...

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

Attic floor; view west showing roof structural system - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

SouthEast view; Station Building north elevation, oblique North ...

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

South-East view; Station Building - north elevation, oblique - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

Genetic polymorphisms of N-acetyltransferase 2 & susceptibility to antituberculosis drug-induced hepatotoxicity.

PubMed

Sharma, Surendra K; Jha, Brajesh Kumar; Sharma, Abhishek; Sreenivas, V; Upadhyay, Vishwanath; Jaisinghani, Chandrita; Singla, Rohit; Mishra, Hemant Kumar; Soneja, Manish

2016-12-01

The N-acetyltransferase 2 (NAT2) gene encodes an enzyme which both activates and deactivates arylamine and other drugs and carcinogens. This study was aimed to investigate the role of NAT2 gene polymorphism in anti-tuberculosis drug-induced hepatotoxicity (DIH). In this prospective study, polymerase chain reaction-restriction fragment length polymorphism results for NAT2 gene were compared between 185 tuberculosis patients who did not develop DIH and 105 tuberculosis patients who developed DIH while on anti-tuberculosis drugs. Frequency of slow-acetylator genotype was commonly encountered and was not significantly different between DIH (82.8%) and non-DIH (77.2%) patients. However, the genotypic distribution of variant NAT2FNx015/FNx017 amongst slow-acetylator genotypes was significantly higher in DIH (56%) group as compared to non-DIH (39%) group (odds ratio 2.02; P=0.006). The present study demonstrated no association between NAT2 genotype and DIH in the north Indian patients with tuberculosis.

The Hamburg Selection Procedure for Dental Students – Introduction of the HAM-Nat as subject-specific test for study aptitude

PubMed Central

Kothe, Christian; Hissbach, Johanna; Hampe, Wolfgang

2013-01-01

Introduction: The present study examines the question whether the selection of dental students should be based solely on average school-leaving grades (GPA) or whether it could be improved by using a subject-specific aptitude test. Methods: The HAM-Nat Natural Sciences Test was piloted with freshmen during their first study week in 2006 and 2007. In 2009 and 2010 it was used in the dental student selection process. The sample size in the regression models varies between 32 and 55 students. Results: Used as a supplement to the German GPA, the HAM-Nat test explained up to 12% of the variance in preclinical examination performance. We confirmed the prognostic validity of GPA reported in earlier studies in some, but not all of the individual preclinical examination results. Conclusion: The HAM-Nat test is a reliable selection tool for dental students. Use of the HAM-Nat yielded a significant improvement in prediction of preclinical academic success in dentistry. PMID:24282449

Measurement of the natHf(d,x)177Ta cross section and impact of erroneous gamma-ray intensities

NASA Astrophysics Data System (ADS)

Simonelli, F.; Abbas, K.; Bulgheroni, A.; Pommé, S.; Altzitzoglou, T.; Suliman, G.

2012-08-01

In this work, excitation functions for deuteron-induced reactions on natural hafnium have been measured in the energy range 7-17 MeV, using the stacked-foil technique. Particular attention has been paid to the reaction natHf(d,x)177Ta, because reported γ-ray intensities have been found to be in disagreement with previously published data. This discrepancy is due to an error in the 2003 ENSDF absolute γ-ray intensities of 177Hf following the decay of 177Ta, which are about a factor of three higher compared to other available data. As a consquence, some peer reviewed papers reporting on natHf(d,x)177Ta, and also on natHf(p,x) 177Ta and natW(p,x) 177Ta, need to be reviewed. An upcoming re-evaluation of the 177Ta decay data shows new significant changes in the absolute γ-ray intensities, which in turn will affect again the 177Ta producing cross sections.

North view; Canopy detail and platformlevel freight elevator North ...

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

North view; Canopy detail and platform-level freight elevator - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

NorthWest view; Station Building south (front) elevation, oblique ...

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

North-West view; Station Building - south (front) elevation, oblique - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

NorthEast view; Station Building south (front) elevation, oblique ...

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

North-East view; Station Building - south (front) elevation, oblique - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

Toxicokinetics of novel psychoactive substances: characterization of N-acetyltransferase (NAT) isoenzymes involved in the phase II metabolism of 2C designer drugs.

PubMed

Meyer, Markus R; Robert, Anja; Maurer, Hans H

2014-06-05

The 2,5-dimethoxyphenethylamine-derived designer drugs (so-called "2Cs") recently became of great importance on the illicit drug market as stimulating hallucinogens. They are distributed and consumed as "novel psychoactive substances" (NPS) without any safety testing at the forefront. As previous studies have shown, the 2Cs are mainly metabolized by O-demethylation, N-acetylation, or deamination. Therefore, the aim of this study was to elucidate the role of the recombinant human N-acetyltransferase (NAT) isoforms 1 and 2 in the phase II metabolism of 2Cs. For these studies, cDNA-expressed recombinant human NATs were used and formation of metabolites after incubation was measured using GC-MS. NAT2 could be shown to be the only isoform catalyzing the reaction in vitro, hence it should be the only relevant enzyme for in vivo acetylation. In general, all metabolite formation reactions followed classic Michaelis-Menten kinetics and the affinity to human NAT2 was increasing with the volume of the 4-substituent. In consequence, a slow acetylator phenotype or inhibition of NAT2 could lead to decreased N-acetylation and might lead to an increased risk of side effects caused by these novel psychoactive substances. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Crystal structure of bacillus subtilis YdaF protein : a putative ribosomal N-acetyltransferase.

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

Brunzelle, J. S.; Wu, R.; Korolev, S. V.

2004-12-01

Comparative sequence analysis suggests that the ydaF gene encodes a protein (YdaF) that functions as an N-acetyltransferase, more specifically, a ribosomal N-acetyltransferase. Sequence analysis using basic local alignment search tool (BLAST) suggests that YdaF belongs to a large family of proteins (199 proteins found in 88 unique species of bacteria, archaea, and eukaryotes). YdaF also belongs to the COG1670, which includes the Escherichia coli RimL protein that is known to acetylate ribosomal protein L12. N-acetylation (NAT) has been found in all kingdoms. NAT enzymes catalyze the transfer of an acetyl group from acetyl-CoA (AcCoA) to a primary amino group. Formore » example, NATs can acetylate the N-terminal {alpha}-amino group, the {epsilon}-amino group of lysine residues, aminoglycoside antibiotics, spermine/speridine, or arylalkylamines such as serotonin. The crystal structure of the alleged ribosomal NAT protein, YdaF, from Bacillus subtilis presented here was determined as a part of the Midwest Center for Structural Genomics. The structure maintains the conserved tertiary structure of other known NATs and a high sequence similarity in the presumed AcCoA binding pocket in spite of a very low overall level of sequence identity to other NATs of known structure.« less

The Neighborhood Auditing Tool: A Hybrid Interface for Auditing the UMLS

PubMed Central

Morrey, C. Paul; Geller, James; Halper, Michael; Perl, Yehoshua

2009-01-01

The UMLS’s integration of more than 100 source vocabularies, not necessarily consistent with one another, causes some inconsistencies. The purpose of auditing the UMLS is to detect such inconsistencies and to suggest how to resolve them while observing the requirement of fully representing the content of each source in the UMLS. A software tool, called the Neighborhood Auditing Tool (NAT), that facilitates UMLS auditing is presented. The NAT supports “neighborhood-based” auditing, where, at any given time, an auditor concentrates on a single focus concept and one of a variety of neighborhoods of its closely related concepts. Typical diagrammatic displays of concept networks have a number of shortcomings, so the NAT utilizes a hybrid diagram/text interface that features stylized neighborhood views which retain some of the best features of both the diagrammatic layouts and text windows while avoiding the shortcomings. The NAT allows an auditor to display knowledge from both the Metathesaurus (concept) level and the Semantic Network (semantic type) level. Various additional features of the NAT that support the auditing process are described. The usefulness of the NAT is demonstrated through a group of case studies. Its impact is tested with a study involving a select group of auditors. PMID:19475725

A new approach to the characterization of subtle errors in everyday action: implications for mild cognitive impairment.

PubMed

Seligman, Sarah C; Giovannetti, Tania; Sestito, John; Libon, David J

2014-01-01

Mild functional difficulties have been associated with early cognitive decline in older adults and increased risk for conversion to dementia in mild cognitive impairment, but our understanding of this decline has been limited by a dearth of objective methods. This study evaluated the reliability and validity of a new system to code subtle errors on an established performance-based measure of everyday action and described preliminary findings within the context of a theoretical model of action disruption. Here 45 older adults completed the Naturalistic Action Test (NAT) and neuropsychological measures. NAT performance was coded for overt errors, and subtle action difficulties were scored using a novel coding system. An inter-rater reliability coefficient was calculated. Validity of the coding system was assessed using a repeated-measures ANOVA with NAT task (simple versus complex) and error type (overt versus subtle) as within-group factors. Correlation/regression analyses were conducted among overt NAT errors, subtle NAT errors, and neuropsychological variables. The coding of subtle action errors was reliable and valid, and episodic memory breakdown predicted subtle action disruption. Results suggest that the NAT can be useful in objectively assessing subtle functional decline. Treatments targeting episodic memory may be most effective in addressing early functional impairment in older age.

The importance of surgeon involvement in the evaluation of non-accidental trauma patients.

PubMed

Larimer, Emily L; Fallon, Sara C; Westfall, Jaimee; Frost, Mary; Wesson, David E; Naik-Mathuria, Bindi J

2013-06-01

Non-Accidental Trauma (NAT) is a significant cause of childhood morbidity and mortality, causing 50% of trauma-related deaths at our institution. Our purpose was to evaluate the necessity of primary surgical evaluation and admission to the trauma service for children presenting with NAT. We reviewed all NAT patients from 2007-2011. Injury types, demographic data, and hospitalization information were collected. Comparisons to accidental trauma (AT) patients were made using Wilcoxon rank sum and Student's t tests. We identified 267 NAT patients presenting with 473 acute injuries. Injuries in NAT patients were more severe than in AT patients, and Injury Severity Scores, ICU admission rates, and mortality were all significantly (p<0.001) higher. The majority suffered from polytrauma. Multiple areas of injury were seen in patients with closed head injuries (72%), extremity fractures (51%), rib fractures (82%), and abdominal/thoracic trauma (80%). Despite these complex injury patterns, only 56% received surgical consults, resulting in potential delays in diagnosis, as 24% of abdominal CT scans were obtained >12 hours after hospitalization. Given the high incidence of polytrauma in NAT patients, prompt surgical evaluation is necessary to determine the scope of injury. Admission to the trauma service and a thorough tertiary survey should be considered for all patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Non-accidental Trauma Injury Patterns and Outcomes: A Single Institutional Experience.

PubMed

Ward, Austin; Iocono, Joseph A; Brown, Samuel; Ashley, Phillip; Draus, John M

2015-09-01

Non-accidental trauma (NAT) victims account for a significant percentage of our pediatric trauma population. We sought to better understand the injury patterns and outcomes of NAT victims who were treated at our level I pediatric trauma center. Trauma registry data were used to identify NAT victims between January 2008 and December 2012. Demographic data, injury severity, hospital course, and outcomes were evaluated. One hundred and eighty-eight cases of suspected NAT were identified. Children were mostly male and white. The median age was 1.1 years; the median Injury Severity Score was 9. Traumatic brain injuries, lower extremity fractures, and skull fractures were the most common injuries. Twenty-seven per cent required medical procedures; most were performed by orthopedic surgery. Twenty-four per cent required admission to the pediatric intensive care unit. The median length of stay was two days. The mortality rate was 9.6 per cent. We generated a hot spot map of our catchment area and identified areas of our state where NAT occurs at increased rates. NAT victims sustain significant morbidity and mortality. Due to the severity of injuries, pediatric trauma surgeons should be involved in the evaluation and management of these children. Much work is needed to prevent the death and disability incurred by victims of child abuse.

3. Photocopy of 1932 photograph showing another general view of ...

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

3. Photocopy of 1932 photograph showing another general view of the mansion, looking northwest. Original photograph at the Philadelphia Museum of Art. - Strawberry Mansion, Philadelphia, Philadelphia County, PA

WEST CORRIDOR (ORIGINALLY KNOWN AS LIBRARY OF CONGRESS CARD CATALOG) ...

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

WEST CORRIDOR (ORIGINALLY KNOWN AS LIBRARY OF CONGRESS CARD CATALOG) ON FIRST FLOOR, LOOKING EAST - Free Library of Philadelphia, Central Library, 1901 Vine Street, Philadelphia, Philadelphia County, PA

EDUCATION, PHILOSOPHY, AND RELIGION DEPARTMENT, DETAIL OF ORIGINAL ALLMETAL TABLE, ...

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

EDUCATION, PHILOSOPHY, AND RELIGION DEPARTMENT, DETAIL OF ORIGINAL ALL-METAL TABLE, LAMP, AND WINDSOR CHAIR - Free Library of Philadelphia, Central Library, 1901 Vine Street, Philadelphia, Philadelphia County, PA

12. VIEW OF MERCHANTS' HOTEL IN MID 19th CENTURY, 'FOURTH ...

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

12. VIEW OF MERCHANTS' HOTEL IN MID- 19th CENTURY, 'FOURTH STREET, PHILA., WEST SIDE, FROM MARKET TO ARCH', as it appeared in The Baxter Panoramic Business Directory, Est. 1857 which is available for viewing at the Free Library of Philadelphia, in the Castner Collection, Philadelphia Vol. No. 12, 'Streets 1'. - Merchants' Hotel, 40-50 North Fourth Street, Philadelphia, Philadelphia County, PA

The Philadelphia Education Longitudinal Study (PELS): Report on the Transition to High School in the School District of Philadelphia.

ERIC Educational Resources Information Center

Neild, Ruth Curran; Weiss, Christopher C.

The Philadelphia Education Longitudinal Study (PELS) on the transition to ninth grade in Philadelphia highlights the high school choice process, course failure rates during ninth grade, and parents' responses to the transition to high school. The PELS study followed a city-wide random sample of public school students from the summer after eighth…

An Acetyltransferase Conferring Tolerance to Toxic Aromatic Amine Chemicals

PubMed Central

Martins, Marta; Rodrigues-Lima, Fernando; Dairou, Julien; Lamouri, Aazdine; Malagnac, Fabienne; Silar, Philippe; Dupret, Jean-Marie

2009-01-01

Aromatic amines (AA) are a major class of environmental pollutants that have been shown to have genotoxic and cytotoxic potentials toward most living organisms. Fungi are able to tolerate a diverse range of chemical compounds including certain AA and have long been used as models to understand general biological processes. Deciphering the mechanisms underlying this tolerance may improve our understanding of the adaptation of organisms to stressful environments and pave the way for novel pharmaceutical and/or biotechnological applications. We have identified and characterized two arylamine N-acetyltransferase (NAT) enzymes (PaNAT1 and PaNAT2) from the model fungus Podospora anserina that acetylate a wide range of AA. Targeted gene disruption experiments revealed that PaNAT2 was required for the growth and survival of the fungus in the presence of toxic AA. Functional studies using the knock-out strains and chemically acetylated AA indicated that tolerance of P. anserina to toxic AA was due to the N-acetylation of these chemicals by PaNAT2. Moreover, we provide proof-of-concept remediation experiments where P. anserina, through its PaNAT2 enzyme, is able to detoxify the highly toxic pesticide residue 3,4-dichloroaniline in experimentally contaminated soil samples. Overall, our data show that a single xenobiotic-metabolizing enzyme can mediate tolerance to a major class of pollutants in a eukaryotic species. These findings expand the understanding of the role of xenobiotic-metabolizing enzyme and in particular of NATs in the adaptation of organisms to their chemical environment and provide a basis for new systems for the bioremediation of contaminated soils. PMID:19416981

Acute murine colitis reduces colonic 5-aminosalicylic acid metabolism by regulation of N-acetyltransferase-2

PubMed Central

Ramírez-Alcántara, Verónica

2014-01-01

Pharmacotherapy based on 5-aminosalicylic acid (5-ASA) is a preferred treatment for ulcerative colitis, but variable patient response to this therapy is observed. Inflammation can affect therapeutic outcomes by regulating the expression and activity of drug-metabolizing enzymes; its effect on 5-ASA metabolism by the colonic arylamine N-acetyltransferase (NAT) enzyme isoforms is not firmly established. We examined if inflammation affects the capacity for colonic 5-ASA metabolism and NAT enzyme expression. 5-ASA metabolism by colonic mucosal homogenates was directly measured with a novel fluorimetric rate assay. 5-ASA metabolism reported by the assay was dependent on Ac-CoA, inhibited by alternative NAT substrates (isoniazid, p-aminobenzoylglutamate), and saturable with Km (5-ASA) = 5.8 μM. A mouse model of acute dextran sulfate sodium (DSS) colitis caused pronounced inflammation in central and distal colon, and modest inflammation of proximal colon, defined by myeloperoxidase activity and histology. DSS colitis reduced capacity for 5-ASA metabolism in central and distal colon segments by 52 and 51%, respectively. Use of selective substrates of NAT isoforms to inhibit 5-ASA metabolism suggested that mNAT2 mediated 5-ASA metabolism in normal and colitis conditions. Western blot and real-time RT-PCR identified that proximal and distal mucosa had a decreased mNAT2 protein-to-mRNA ratio after DSS. In conclusion, an acute colonic inflammation impairs the expression and function of mNAT2 enzyme, thereby diminishing the capacity for 5-ASA metabolism by colonic mucosa. PMID:24742986

SP-100 GES/NAT radiation shielding systems design and development testing

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

Disney, R.K.; Kulikowski, H.D.; McGinnis, C.A.

1991-01-10

Advanced Energy Systems (AES) of Westinghouse Electric Corporation is under subcontract to the General Electric Company to supply nuclear radiation shielding components for the SP-100 Ground Engineering System (GES) Nuclear Assembly Test to be conducted at Westinghouse Hanford Company at Richland, Washington. The radiation shielding components are integral to the Nuclear Assembly Test (NAT) assembly and include prototypic and non-prototypic radiation shielding components which provide prototypic test conditions for the SP-100 reactor subsystem and reactor control subsystem components during the GES/NAT operations. W-AES is designing three radiation shield components for the NAT assembly; a prototypic Generic Flight System (GFS) shield,more » the Lower Internal Facility Shield (LIFS), and the Upper Internal Facility Shield (UIFS). This paper describes the design approach and development testing to support the design, fabrication, and assembly of these three shield components for use within the vacuum vessel of the GES/NAT. The GES/NAT shields must be designed to operate in a high vacuum which simulates space operations. The GFS shield and LIFS must provide prototypic radiation/thermal environments and mechanical interfaces for reactor system components. The NAT shields, in combination with the test facility shielding, must provide adequate radiation attenuation for overall test operations. Special design considerations account for the ground test facility effects on the prototypic GFS shield. Validation of the GFS shield design and performance will be based on detailed Monte Carlo analyses and developmental testing of design features. Full scale prototype testing of the shield subsystems is not planned.« less

NAT2 genotype guided regimen reduces isoniazid-induced liver injury and early treatment failure in the 6-month four-drug standard treatment of tuberculosis: a randomized controlled trial for pharmacogenetics-based therapy.

PubMed

Azuma, Junichi; Ohno, Masako; Kubota, Ryuji; Yokota, Soichiro; Nagai, Takayuki; Tsuyuguchi, Kazunari; Okuda, Yasuhisa; Takashima, Tetsuya; Kamimura, Sayaka; Fujio, Yasushi; Kawase, Ichiro

2013-05-01

This study is a pharmacogenetic clinical trial designed to clarify whether the N-acetyltransferase 2 gene (NAT2) genotype-guided dosing of isoniazid improves the tolerability and efficacy of the 6-month four-drug standard regimen for newly diagnosed pulmonary tuberculosis. In a multicenter, parallel, randomized, and controlled trial with a PROBE design, patients were assigned to either conventional standard treatment (STD-treatment: approx. 5 mg/kg of isoniazid for all) or NAT2 genotype-guided treatment (PGx-treatment: approx. 7.5 mg/kg for patients homozygous for NAT2 4: rapid acetylators; 5 mg/kg, patients heterozygous for NAT2 4: intermediate acetylators; 2.5 mg/kg, patients without NAT2 4: slow acetylators). The primary outcome included incidences of 1) isoniazid-related liver injury (INH-DILI) during the first 8 weeks of therapy, and 2) early treatment failure as indicated by a persistent positive culture or no improvement in chest radiographs at the 8th week. One hundred and seventy-two Japanese patients (slow acetylators, 9.3 %; rapid acetylators, 53.5 %) were enrolled in this trial. In the intention-to-treat (ITT) analysis, INH-DILI occurred in 78 % of the slow acetylators in the STD-treatment, while none of the slow acetylators in the PGx-treatment experienced either INH-DILI or early treatment failure. Among the rapid acetylators, early treatment failure was observed with a significantly lower incidence rate in the PGx-treatment than in the STD-treatment (15.0 % vs. 38 %). Thus, the NAT2 genotype-guided regimen resulted in much lower incidences of unfavorable events, INH-DILI or early treatment failure, than the conventional standard regimen. Our results clearly indicate a great potential of the NAT2 genotype-guided dosing stratification of isoniazid in chemotherapy for tuberculosis.

N-acetyltransferase (nat) Is a Critical Conjunct of Photoperiodism between the Circadian System and Endocrine Axis in Antheraea pernyi

PubMed Central

Bembenek, Jadwiga; Hiragaki, Susumu; Suzuki, Takeshi; Takeda, Makio

2014-01-01

Since its discovery in 1923, the biology of photoperiodism remains a mystery in many ways. We sought the link connecting the circadian system to an endocrine switch, using Antheraea pernyi. PER-, CLK- and CYC-ir were co-expressed in two pairs of dorsolateral neurons of the protocerebrum, suggesting that these are the circadian neurons that also express melatonin-, NAT- and HIOMT-ir. The results suggest that a melatonin pathway is present in the circadian neurons. Melatonin receptor (MT2 or MEL-1B-R)-ir in PTTH-ir neurons juxtaposing clock neurons suggests that melatonin gates PTTH release. RIA showed a melatonin rhythm with a peak four hours after lights off in adult brain both under LD16∶8 (LD) and LD12∶12 (SD), and both the peak and the baseline levels were higher under LD than SD, suggesting a photoperiodic influence. When pupae in diapause were exposed to 10 cycles of LD, or stored at 4°C for 4 months under constant darkness, an increase of NAT activity was observed when PTTH released ecdysone. DNA sequence upstream of nat contained E-boxes to which CYC/CLK could bind, and nat transcription was turned off by clk or cyc dsRNA. dsRNANAT caused dysfunction of photoperiodism. dsRNAPER upregulated nat transcription as anticipated, based on findings in the Drosophila melanogaster circadian system. Transcription of nat, cyc and clk peaked at ZT12. RIA showed that dsRNANAT decreased melatonin while dsRNAPER increased melatonin. Thus nat, a clock controlled gene, is the critical link between the circadian clock and endocrine switch. MT-binding may release PTTH, resulting in termination of diapause. This study thus examined all of the basic functional units from the clock: a photoperiodic counter as an accumulator of mRNANAT, to endocrine switch for photoperiodism in A. pernyi showing this system is self-complete without additional device especially for photoperiodism. PMID:24667367

Arylamine N-Acetyltransferase 2 (NAT2) Genetic Diversity and Traditional Subsistence: A Worldwide Population Survey

PubMed Central

Sabbagh, Audrey; Darlu, Pierre; Crouau-Roy, Brigitte; Poloni, Estella S.

2011-01-01

Arylamine N-acetyltransferase 2 (NAT2) is involved in human physiological responses to a variety of xenobiotic compounds, including common therapeutic drugs and exogenous chemicals present in the diet and the environment. Many questions remain about the evolutionary mechanisms that have led to the high prevalence of slow acetylators in the human species. Evidence from recent surveys of NAT2 gene variation suggests that NAT2 slow-causing variants might have become targets of positive selection as a consequence of the shift in modes of subsistence and lifestyle in human populations in the last 10,000 years. We aimed to test more extensively the hypothesis that slow acetylation prevalence in humans is related to the subsistence strategy adopted by the past populations. To this end, published frequency data on the most relevant genetic variants of NAT2 were collected from 128 population samples (14,679 individuals) representing different subsistence modes and dietary habits, allowing a thorough analysis at both a worldwide and continent scale. A significantly higher prevalence of the slow acetylation phenotype was observed in populations practicing farming (45.4%) and herding (48.2%) as compared to populations mostly relying on hunting and gathering (22.4%) (P = 0.0007). This was closely mirrored by the frequency of the slow 590A variant that was found to occur at a three-fold higher frequency in food producers (25%) as compared to hunter-gatherers (8%). These findings are consistent with the hypothesis that the Neolithic transition to subsistence economies based on agricultural and pastoral resources modified the selective regime affecting the NAT2 acetylation pathway. Furthermore, the vast amount of data collected enabled us to provide a comprehensive and up-to-date description of NAT2 worldwide genetic diversity, thus building up a useful resource of frequency data for further studies interested in epidemiological or anthropological research questions involving NAT2. PMID:21494681

PERSPECTIVE VIEW OF LIBRARY IN ENVIRONMENT CONTEXT, LOOKING NORTHEAST FROM ...

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

PERSPECTIVE VIEW OF LIBRARY IN ENVIRONMENT CONTEXT, LOOKING NORTHEAST FROM THE ROOF OF THE FRANKLIN INSTITUTE - Free Library of Philadelphia, Central Library, 1901 Vine Street, Philadelphia, Philadelphia County, PA

Detail; south (front) elevation, second floor, center portal of loggia ...

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

Detail; south (front) elevation, second floor, center portal of loggia - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

22. SOUTHWEST CORNER OF BANKING ROOM, FROM EAST, SHOWING CLOCK ...

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

22. SOUTHWEST CORNER OF BANKING ROOM, FROM EAST, SHOWING CLOCK ON SOUTH WALL AND TWO MEZZANINES BEYOND COLUMNS - Philadelphia Saving Fund Society, Twelfth & Market Streets, Philadelphia, Philadelphia County, PA

2. Photocopy of 1932 photograph showing a general view and ...

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

2. Photocopy of 1932 photograph showing a general view and east (front) facade of the mansion. Original photograph at the Philadelphia Museum of Art - Strawberry Mansion, Philadelphia, Philadelphia County, PA

5. Photocopy of 1963 photograph showing parlor in the center ...

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

5. Photocopy of 1963 photograph showing parlor in the center (18th century) section of the mansion. Original photograph at the Philadelphia Museum of Art. - Strawberry Mansion, Philadelphia, Philadelphia County, PA

4. VIEW RECONSTRUCTED TOWER, LOOKING NNE. Philadelphia & Reading ...

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

4. VIEW RECONSTRUCTED TOWER, LOOKING NNE. - Philadelphia & Reading Railroad, Pedestrian Suspension Bridge, Foot of Sixth Street at Schuylkill River (formerly spanned Philadelphia & Reading main line at Reading Depot), Reading, Berks County, PA

1. 3/4 VIEW, LOOKING NE. Philadelphia & Reading Railroad, ...

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

1. 3/4 VIEW, LOOKING NE. - Philadelphia & Reading Railroad, Pedestrian Suspension Bridge, Foot of Sixth Street at Schuylkill River (formerly spanned Philadelphia & Reading main line at Reading Depot), Reading, Berks County, PA

11. Photocopy of circa 1948 photograph showing detail view of ...

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

11. Photocopy of circa 1948 photograph showing detail view of Waiting Room ceiling, courtesy of Reading Company Archives - Philadelphia & Reading Railroad, Terminal Station, 1115-1141 Market Street, Philadelphia, Philadelphia County, PA

3. DETAIL OF WEST TOWER, LOOKING NE. Philadelphia & ...

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

3. DETAIL OF WEST TOWER, LOOKING NE. - Philadelphia & Reading Railroad, Pedestrian Suspension Bridge, Foot of Sixth Street at Schuylkill River (formerly spanned Philadelphia & Reading main line at Reading Depot), Reading, Berks County, PA

2. Photocopy of photograph (from Reading Co. Archives) Photographer unknown ...

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

2. Photocopy of photograph (from Reading Co. Archives) Photographer unknown ca. 1937 NORTHEAST FRONT AND SOUTHEAST SIDE - Philadelphia & Reading Railroad, Terminal Station, 1115-1141 Market Street, Philadelphia, Philadelphia County, PA

Detail; Street Car Waiting House window, north wall North ...

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

Detail; Street Car Waiting House window, north wall - North Philadelphia Station, Street Car Waiting House, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

North view; Street Car Waiting House, south (front) elevation ...

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

North view; Street Car Waiting House, south (front) elevation - North Philadelphia Station, Street Car Waiting House, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

West view; Street Car Waiting House, east elevation North ...

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

West view; Street Car Waiting House, east elevation - North Philadelphia Station, Street Car Waiting House, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

76 FR 409 - Philadelphia International Airport, Capacity Enhancement Program, Environmental Impact Statement...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-04

... in the Philadelphia Metropolitan Area during all weather conditions. This ROD sets forth FAA's final... current and future aviation demand in the Philadelphia Metropolitan Area during all weather conditions...

North view; Station Building south (front) elevations, portion of ...

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

North view; Station Building - south (front) elevations, portion of covered ramp at left - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

West view, general; Station Building, covered ramp, and Street Car ...

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

West view, general; Station Building, covered ramp, and Street Car Waiting House - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

SouthEast view; Platform, canopy, and Station Building north elevation ...

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

South-East view; Platform, canopy, and Station Building - north elevation (obscured) - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

PERSPECTIVE VIEW OF NORTH SIDE AND WEST REAR, LOOKING SOUTHEAST ...

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

PERSPECTIVE VIEW OF NORTH SIDE AND WEST REAR, LOOKING SOUTHEAST TOWARDS CORNER LECTURE HALL ENTRANCE - Free Library of Philadelphia, Oak Lane Branch, 6614 North 12th Street, Philadelphia, Philadelphia County, PA

1. PHOTOCOPY OF RENDERING OF PSFS BUILDING BY D.E. SUTTON. ...

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

1. PHOTOCOPY OF RENDERING OF PSFS BUILDING BY D.E. SUTTON. Date possibly 1929 or 1930, when construction started. - Philadelphia Saving Fund Society, Twelfth & Market Streets, Philadelphia, Philadelphia County, PA

33. SOLARIUM AND TERRACE IN EXECUTIVE SUITE LOOKING NORTH PAST ...

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

33. SOLARIUM AND TERRACE IN EXECUTIVE SUITE LOOKING NORTH PAST SLIDING GLASS WALL THAT DIVIDES SOLARIUM FROM EXECUTIVE DINING ROOM - Philadelphia Saving Fund Society, Twelfth & Market Streets, Philadelphia, Philadelphia County, PA

DETAIL VIEW OF BRICK WALKWAY ON SOUTHEAST SIDE SHOWING NAMES ...

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

DETAIL VIEW OF BRICK WALKWAY ON SOUTHEAST SIDE SHOWING NAMES OF DONORS TO RECENT RENOVATION - Free Library of Philadelphia, Falls of Schuylkill Branch, 3501 Midvale Avenue, Philadelphia, Philadelphia County, PA

2. Photocopy of old 2 1/8' X 3' photograph by ...

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

2. Photocopy of old 2 1/8' X 3' photograph by F. Gutekunst mounted on 2 3/8' X 4' card marked in script on rear: 'Bought at the Sanitary Fair Phila June 8th 1864'. Also printed on rear: 'F. Gutekunst, photographer 704 & 706 Arch St Philadelphia'. Photocopied by Jack E. Boucher in November 1959. - Union League of Philadelphia, 140 South Broad Street, Philadelphia, Philadelphia County, PA

Measurement of activation cross-section of long-lived products in deuteron induced nuclear reactions on palladium in the 30-50MeV energy range.

PubMed

Ditrói, F; Tárkányi, F; Takács, S; Hermanne, A; Ignatyuk, A V

2017-10-01

Excitation functions were measured in the 31-49.2MeV energy range for the nat Pd(d,xn) 111,110m,106m,105,104g,103 Ag, nat Pd(d,x) 111m,109,101,100 Pd, nat Pd(d,x), 105,102m,102g,101m,101g,100,99m,99g Rh and nat Pd(d,x) 103,97 Ru nuclear reactions by using the stacked foil irradiation technique. The experimental results are compared with our previous results and with the theoretical predictions calculated with the ALICE-D, EMPIRE-D and TALYS (TENDL libraries) codes. Copyright © 2017 Elsevier Ltd. All rights reserved.

2. LOOKING NW, WITH READING DEPOT IN BACKGROUND. Philadelphia ...

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

2. LOOKING NW, WITH READING DEPOT IN BACKGROUND. - Philadelphia & Reading Railroad, Pedestrian Suspension Bridge, Foot of Sixth Street at Schuylkill River (formerly spanned Philadelphia & Reading main line at Reading Depot), Reading, Berks County, PA

Detail; Street Car Waiting House, support for exterior light fixture ...

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

Detail; Street Car Waiting House, support for exterior light fixture - North Philadelphia Station, Street Car Waiting House, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

133. PARTIAL PLAN AND ELEVATION OF MILL HOUSE & MAP ...

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

133. PARTIAL PLAN AND ELEVATION OF MILL HOUSE & MAP OF RESERVOIRS, From Annual Report of 1851, Water Department of Philadelphia - Fairmount Waterworks, East bank of Schuylkill River, Aquarium Drive, Philadelphia, Philadelphia County, PA

Second floor; view northeast down entrance lobby (loggia of south ...

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

Second floor; view north-east down entrance lobby (loggia of south - front - elevation) - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

SouthWest view; Main passenger tunnel entrance and new (1991) Amtrak ...

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

South-West view; Main passenger tunnel entrance and new (1991) Amtrak Station - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

15. Photocopy of unexecuted competition drawing signed 'John Notman, Architect, ...

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

15. Photocopy of unexecuted competition drawing signed 'John Notman, Architect, Philadelphia', circa 1854, from Historical Society of Pennsylvania), EAST ELEVATION - American Academy of Music, 232-246 South Broad Street, Philadelphia, Philadelphia County, PA

20. BANKING ROOM, LOOKING SOUTH FROM NORTHWEST CORNER, SHOWING ESCALATOR ...

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

20. BANKING ROOM, LOOKING SOUTH FROM NORTHWEST CORNER, SHOWING ESCALATOR ENTRANCE FROM STREET ON RIGHT AND BALCONY EDGES OF TWO MEZZANINES BEYOND - Philadelphia Saving Fund Society, Twelfth & Market Streets, Philadelphia, Philadelphia County, PA

1. GENERAL VIEW, (the one with the woman at the ...

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

1. GENERAL VIEW, (the one with the woman at the front door). Photocopy of December 1957 photo on file at Philadelphia Historical Commission - James Keen House, 946 South Front Street, Philadelphia, Philadelphia County, PA

10. Photocopy of circa 1948 photograph showing a view of ...

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

10. Photocopy of circa 1948 photograph showing a view of the Waiting Room Access of Train Shed, courtesy of Reading Company Archives - Philadelphia & Reading Railroad, Terminal Station, 1115-1141 Market Street, Philadelphia, Philadelphia County, PA

SouthWest view, Street Car Waiting House, north and east elevations ...

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

South-West view, Street Car Waiting House, north and east elevations - North Philadelphia Station, Street Car Waiting House, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

East view general left to right; Platform, trackage, canopies, ...

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

East view - general left to right; Platform, trackage, canopies, and roof of Station Building at right - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

SouthWest view; Platform, canopy, and Station Building east and ...

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

South-West view; Platform, canopy, and Station Building - east and north elevations - right to left - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

South view; Interior view of covered ramp to Street Car ...

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

South view; Interior view of covered ramp to Street Car Waiting House from Station Building - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

North view; Interior view of covered ramp to Station Building ...

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

North view; Interior view of covered ramp to Station Building from Street Car Waiting House - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

West view, general; Station Building, covered ramp, and Street Car ...

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

West view, general; Station Building, covered ramp, and Street Car Waiting House, right to left - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

32. DETAIL OF BOARD ROOM CHAIR WITH SILVER PLATE LISTING ...

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

32. DETAIL OF BOARD ROOM CHAIR WITH SILVER PLATE LISTING NAMES AND DATES OF PAST OCCUPANTS AND PLATE WITH NAME OF CURRENT OCCUPANT - Philadelphia Saving Fund Society, Twelfth & Market Streets, Philadelphia, Philadelphia County, PA

Photocopy of photograph. Photographer unknown. Typical suggestion award photograph from ...

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

Photocopy of photograph. Photographer unknown. Typical suggestion award photograph from the World War II period. Useful suggestions were awarded a $ 50 bond and usually a photo in the shipyard newspaper, the beacon. This photo shows an improved bilge block template layout table left to right: Stuart S. Sanders, Rosalie Moschella, Eddie Ormond, Lt. CDR. J.M. Ballinger, and A.A. Goldman. - Naval Base Philadelphia-Philadelphia Naval Shipyard, League Island, Philadelphia, Philadelphia County, PA

View southwest of 350ton crane, showing one of four castings ...

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

View southwest of 350-ton crane, showing one of four castings which support a stationary, tapered steel girder structure called a "tower". This tower is located within an outer rotating framework designated as the "pintle" of the 350-ton crane. The whole crane pivots around bearing at the top of this tapered support tower. - Naval Base Philadelphia-Philadelphia Naval Shipyard, 350-Ton Hammerhead Crane, League Island, Philadelphia, Philadelphia County, PA

Detection of occult hepatitis B and window period infection among blood donors by individual donation nucleic acid testing in a tertiary care center in South India.

PubMed

Keechilot, Cinzia S; Shenoy, Veena; Kumar, Anil; Biswas, Lalitha; Vijayrajratnam, Sukhithasri; Dinesh, Kavitha; Nair, Prem

With the introduction of highly sensitive hepatitis B surface antigen immunoassay, transfusion associated HBV infection have reduced drastically but they still tend to occur due to blood donors with occult hepatitis B infection (OBI) and window period (WP) infection. Sera from, 24338 healthy voluntary blood donors were screened for HBsAg, HIV and HCV antibody using Vitros Enhanced Chemiluminescent Immunoassay. The median age of the donor population was 30 (range 18-54) with male preponderance (98%). All serologically negative samples were screened by nucleic acid testing (NAT) for viral DNA and RNA. NAT-positive samples were subjected to discriminatory NAT for HBV, HCV, and HIV and all samples positive for HBV DNA were tested for anti-HBc, anti-HBs, HBeAg. Viral load was determined using artus HBV RG PCR Kit. Of the 24,338 donors screened, 99.81% (24292/24338) were HBsAg negative of which NAT was positive for HBV DNA in 0.0205% (5/24292) donors. Four NAT positive donors had viral load of <200 IU/ml making them true cases of OBI. One NAT positive donor was negative for all antibodies making it a case of WP infection. Among OBI donors, 75% (3/4) were immune and all were negative for HBeAg. Precise HBV viral load could not be determined in all (5/5) NAT positive donors due to viral loads below the detection limit of the artus HBV RG PCR Kit. The overall incidence of OBI and WP infections was found to be low at 1 in 6503 and 1 in 24214 donations, respectively. More studies are needed to determine the actual burden of WP infections in Indian blood donors.

Association Between N-acetyltransferase 2 Polymorphism and Bladder Cancer Risk: Results From Studies of the Past Decade and a Meta-Analysis.

PubMed

Wu, Haoran; Wang, Xugang; Zhang, Liang; Mo, Naixin; Lv, Zhong

2016-04-01

Numerous studies have identified that the slow acetylation status of N-acetyltransferase 2 (NAT2) is associated with an elevated bladder cancer risk. However, the results remain inconclusive. The aim of our study was to evaluate the effect of NAT2 acetylation status in patients with bladder cancer. Electronic databases were searched to retrieve related studies published in the past decade. The pooled odds ratio (OR) with its 95% confidence interval (CI) was used to calculate the strength of this relationship. Overall, a total of 18 studies were selected for the analysis, which included 4473 bladder cancer cases and 7204 matched controls. Our result showed that the NAT2 slow acetylation phenotypes were significantly associated with an increased risk of bladder cancer compared with the rapid phenotypes (OR, 1.56; 95% CI, 1.33-1.82; P < .00001) in a random-effect model. This significant association was also found in a subgroup analysis of ethnicity (P < .05). Furthermore, the NAT2 slow phenotypes also significantly increased the risk of bladder cancer in smokers (OR, 0.75; 95% CI, 0.62-0.90; P = .002). However, no correlation was found between the combined effect of NAT2 slow phenotypes and gender with bladder cancer risk (OR, 0.89; 95% CI, 0.28-2.78; P = .84). In conclusion, our results suggest that the NAT2 slow acetylator, in particular, the NAT2 slow acetylator combined with smoking, are associated with an increased bladder cancer risk. Future well-designed studies with large populations and more ethnicities are needed to clarify this association further. Copyright © 2016 Elsevier Inc. All rights reserved.

Molecular Characterization of a Novel N-Acetyltransferase from Chryseobacterium sp.

PubMed Central

Yoshida, Kenji; Tanaka, Kosei; Yoshida, Ken-ichi

2014-01-01

N-Acetyltransferase from Chryseobacterium sp. strain 5-3B is an acetyl coenzyme A (acetyl-CoA)-dependent enzyme that catalyzes the enantioselective transfer of an acetyl group from acetyl-CoA to the amino group of l-2-phenylglycine to produce (2S)-2-acetylamino-2-phenylacetic acid. We purified the enzyme from strain 5-3B and deduced the N-terminal amino acid sequence. The gene, designated natA, was cloned with two other hypothetical protein genes; the three genes probably form a 2.5-kb operon. The deduced amino acid sequence of NatA showed high levels of identity to sequences of putative N-acetyltransferases of Chryseobacterium spp. but not to other known arylamine and arylalkylamine N-acetyltransferases. Phylogenetic analysis indicated that NatA forms a distinct lineage from known N-acetyltransferases. We heterologously expressed recombinant NatA (rNatA) in Escherichia coli and purified it. rNatA showed high activity for l-2-phenylglycine and its chloro- and hydroxyl-derivatives. The Km and Vmax values for l-2-phenylglycine were 0.145 ± 0.026 mM and 43.6 ± 2.39 μmol · min−1 · mg protein−1, respectively. The enzyme showed low activity for 5-aminosalicylic acid and 5-hydroxytryptamine, which are reported as good substrates of a known arylamine N-acetyltransferase and an arylalkylamine N-acetyltransferase. rNatA had a comparatively broad acyl donor specificity, transferring acyl groups to l-2-phenylglycine and producing the corresponding 2-acetylamino-2-phenylacetic acids (relative activity with acetyl donors acetyl-CoA, propanoyl-CoA, butanoyl-CoA, pentanoyl-CoA, and hexanoyl-CoA, 100:108:122:10:<1). PMID:24375143

Risks on N-acetyltransferase 2 and bladder cancer: a meta-analysis.

PubMed

Zhu, Zongheng; Zhang, Jinshan; Jiang, Wei; Zhang, Xianjue; Li, Youkong; Xu, Xiaoming

2015-01-01

It is known that bladder cancer disease is closely related to aromatic amine compounds, which could cause cancer by regulating of N-acetylation and N-acetyltransferase 1 and 2 (NAT1 and NAT2). The NAT2 slowed acetylation and would increase the risk of bladder cancer, with tobacco smoke being regarded as a risk factor for this increased risk. However, the relationship between NAT2 slow acetylation and bladder cancer is still debatable at present. This study aims to explore preliminarily correlation of NAT2 slow acetylation and the risk of bladder cancer. The articles were searched from PubMed, Cochran, McGrane English databases, CBM, CNKI, and other databases. The extraction of bladder cancer patients and a control group related with the NAT2 gene were detected by the state, and the referenced articles and publications were also used for data retrieval. Using a random effects model, the model assumes that the studies included in the analysis cases belong to the overall population in the study of random sampling, and considering the variables within and between studies. Data were analyzed using STATA Version 6.0 software, using the META module. According to the inclusion and exclusion criteria of the literature study, 20 independent studies are included in this meta-analysis. The results showed that the individual differences of bladder cancer susceptibility might be part of the metabolism of carcinogens. Slow acetylation status of bladder cancer associated with the pooled odds ratio was 1.31 (95% confidence interval: 1.11-1.55). The status of NAT2 slow N-acetylation is associated with bladder cancer risks, and may increase the risk of bladder cancer.

An assessment of differences in costs and health benefits of serology and NAT screening of donations for blood transfusion in different Western countries.

PubMed

Janssen, M P; van Hulst, M; Custer, B

2017-08-01

The cost-utility of safety interventions is becoming increasingly important as a driver of implementation decisions. The aim of this study was to compare the cost-utility of different blood screening strategies in various settings, and to analyse the extent and cause of differences in health economic results. For eight Western countries (Australia, Canada, Denmark, Finland, France, The Netherlands, UK and the United States of America), data were collected on donor and recipient populations, blood products, screening tests, and on patient treatment practices and costs. An existing ISBT web-tool model was used to assess the cost-utility of various strategies for HIV, HCV and HBV screening. The cost-utility ratio of serology screening for these eight countries ranges between -11 000 and 92 000 US$ per QALY, and for NAT between -12 000 and 113 000 US$ per QALY when compared to no screening. Combined serology and NAT ranges between 600 and 217 000 US$ per QALY. The incremental cost-utility of NAT after implementation of serology screening ranges from 2 231 000 to 15 778 000 US$ per QALY. There are substantial differences in costs per QALY between countries for various HIV, HBV and HCV screening strategies. These differences are primarily caused by costs of screening tests and infection rates in the donor population. Within each country, similar cost per QALY results for serology and NAT compared to no screening, coupled with evidence of limited value of serology and NAT together prompts the need for further discussion on the acceptability of parallel testing by serology and NAT. © 2017 International Society of Blood Transfusion.

Regulation of an antisense RNA with the transition of neonatal to IIb myosin heavy chain during postnatal development and hypothyroidism in rat skeletal muscle

PubMed Central

Jiang, Weihua; Qin, Anqi X.; Bodell, Paul W.; Baldwin, Kenneth M.; Haddad, Fadia

2012-01-01

Postnatal development of fast skeletal muscle is characterized by a transition in expression of myosin heavy chain (MHC) isoforms, from primarily neonatal MHC at birth to primarily IIb MHC in adults, in a tightly coordinated manner. These isoforms are encoded by distinct genes, which are separated by ∼17 kb on rat chromosome 10. The neonatal-to-IIb MHC transition is inhibited by a hypothyroid state. We examined RNA products [mRNA, pre-mRNA, and natural antisense transcript (NAT)] of developmental and adult-expressed MHC genes (embryonic, neonatal, I, IIa, IIx, and IIb) at 2, 10, 20, and 40 days after birth in normal and thyroid-deficient rat neonates treated with propylthiouracil. We found that a long noncoding antisense-oriented RNA transcript, termed bII NAT, is transcribed from a site within the IIb-Neo intergenic region and across most of the IIb MHC gene. NATs have previously been shown to mediate transcriptional repression of sense-oriented counterparts. The bII NAT is transcriptionally regulated during postnatal development and in response to hypothyroidism. Evidence for a regulatory mechanism is suggested by an inverse relationship between IIb MHC and bII NAT in normal and hypothyroid-treated muscle. Neonatal MHC transcription is coordinately expressed with bII NAT. A comparative phylogenetic analysis also suggests that bII NAT-mediated regulation has been a conserved trait of placental mammals for most of the eutherian evolutionary history. The evidence in support of the regulatory model implicates long noncoding antisense RNA as a mechanism to coordinate the transition between neonatal and IIb MHC during postnatal development. PMID:22262309

Regulation of an antisense RNA with the transition of neonatal to IIb myosin heavy chain during postnatal development and hypothyroidism in rat skeletal muscle.

PubMed

Pandorf, Clay E; Jiang, Weihua; Qin, Anqi X; Bodell, Paul W; Baldwin, Kenneth M; Haddad, Fadia

2012-04-01

Postnatal development of fast skeletal muscle is characterized by a transition in expression of myosin heavy chain (MHC) isoforms, from primarily neonatal MHC at birth to primarily IIb MHC in adults, in a tightly coordinated manner. These isoforms are encoded by distinct genes, which are separated by ∼17 kb on rat chromosome 10. The neonatal-to-IIb MHC transition is inhibited by a hypothyroid state. We examined RNA products [mRNA, pre-mRNA, and natural antisense transcript (NAT)] of developmental and adult-expressed MHC genes (embryonic, neonatal, I, IIa, IIx, and IIb) at 2, 10, 20, and 40 days after birth in normal and thyroid-deficient rat neonates treated with propylthiouracil. We found that a long noncoding antisense-oriented RNA transcript, termed bII NAT, is transcribed from a site within the IIb-Neo intergenic region and across most of the IIb MHC gene. NATs have previously been shown to mediate transcriptional repression of sense-oriented counterparts. The bII NAT is transcriptionally regulated during postnatal development and in response to hypothyroidism. Evidence for a regulatory mechanism is suggested by an inverse relationship between IIb MHC and bII NAT in normal and hypothyroid-treated muscle. Neonatal MHC transcription is coordinately expressed with bII NAT. A comparative phylogenetic analysis also suggests that bII NAT-mediated regulation has been a conserved trait of placental mammals for most of the eutherian evolutionary history. The evidence in support of the regulatory model implicates long noncoding antisense RNA as a mechanism to coordinate the transition between neonatal and IIb MHC during postnatal development.

Identification of N-Acetyltaurine as a Novel Metabolite of Ethanol through Metabolomics-guided Biochemical Analysis*

PubMed Central

Shi, Xiaolei; Yao, Dan; Chen, Chi

2012-01-01

The influence of ethanol on the small molecule metabolome and the role of CYP2E1 in ethanol-induced hepatotoxicity were investigated using liquid chromatography-mass spectrometry (LC-MS)-based metabolomics platform and Cyp2e1-null mouse model. Histological and biochemical examinations of ethanol-exposed mice indicated that the Cyp2e1-null mice were more resistant to ethanol-induced hepatic steatosis and transaminase leakage than the wild-type mice, suggesting CYP2E1 contributes to ethanol-induced toxicity. Metabolomic analysis of urinary metabolites revealed time- and dose-dependent changes in the chemical composition of urine. Along with ethyl glucuronide and ethyl sulfate, N-acetyltaurine (NAT) was identified as a urinary metabolite that is highly responsive to ethanol exposure and is correlated with the presence of CYP2E1. Subsequent stable isotope labeling analysis using deuterated ethanol determined that NAT is a novel metabolite of ethanol. Among three possible substrates of NAT biosynthesis (taurine, acetyl-CoA, and acetate), the level of taurine was significantly reduced, whereas the levels of acetyl-CoA and acetate were dramatically increased after ethanol exposure. In vitro incubation assays suggested that acetate is the main precursor of NAT, which was further confirmed by the stable isotope labeling analysis using deuterated acetate. The incubations of tissues and cellular fractions with taurine and acetate indicated that the kidney has the highest NAT synthase activity among the tested organs, whereas the cytosol is the main site of NAT biosynthesis inside the cell. Overall, the combination of biochemical and metabolomic analysis revealed NAT is a novel metabolite of ethanol and a potential biomarker of hyperacetatemia. PMID:22228769

Red meat intake, NAT2, and risk of colorectal cancer: A pooled analysis of 11 studies

PubMed Central

Ananthakrishnan, Ashwin N.; Du, Mengmeng; Berndt, Sonja I.; Brenner, Hermann; Caan, Bette J.; Casey, Graham; Chang-Claude, Jenny; Duggan, David; Fuchs, Charles S.; Gallinger, Steven; Giovannucci, Edward L.; Harrison, Tabitha A.; Hayes, Richard B.; Hoffmeister, Michael; Hopper, John L.; Hou, Lifang; Hsu, Li; Jenkins, Mark A.; Kraft, Peter; Ma, Jing; Nan, Hongmei; Newcomb, Polly A.; Ogino, Shuji; Potter, John D.; Seminara, Daniela; Slattery, Martha L.; Thornquist, Mark; White, Emily; Wu, Kana; Peters, Ulrike; Chan, Andrew T.

2014-01-01

Background Red meat intake has been associated with risk of colorectal cancer (CRC), potentially mediated through heterocyclic amines. The metabolic efficiency of N-acetyltransferase 2 (NAT2) required for the metabolic activation of such amines is influenced by genetic variation. The interaction between red meat intake, NAT2 genotype, and CRC has been inconsistently reported. Methods We used pooled individual-level data from the Colon Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Red meat intake was collected by each study. We inferred NAT2 phenotype based on polymorphism at rs1495741, highly predictive of enzyme activity. Interaction was assessed using multiplicative interaction terms in multivariate-adjusted models. Results From 11 studies, 8,290 CRC cases and 9,115 controls were included. The highest quartile of red meat intake was associated with increased risk of CRC compared to the lowest quartile (OR 1.41, 95%CI 1.29 – 1.55). However, a significant association was observed only for studies with retrospective diet data, not for studies with diet prospectively assessed before cancer diagnosis. Combining all studies, high red meat intake was similarly associated with CRC in those with a rapid/intermediate NAT2 genotype (OR 1.38, 95%CI 1.20 – 1.59) as with a slow genotype (OR 1.43, 95%CI 1.28 – 1.61) (p- interaction=0.9). Conclusion We found that high red meat intake was associated with increased risk of CRC only from retrospective case-control studies and not modified by NAT2 enzyme activity. Impact Our results suggest no interaction between NAT2 genotype and red-meat intake in mediating risk of CRC. PMID:25342387

NorthEast view; Street Car Waiting House, south (front) and west ...

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

North-East view; Street Car Waiting House, south (front) and west elevations - North Philadelphia Station, Street Car Waiting House, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

North view general left to right; Mechanical Building, roof ...

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

North view - general left to right; Mechanical Building, roof of Station Building, covered ramp, and Street Car Waiting House - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

NorthEast view; Interior view of stair enclosure and stair from ...

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

North-East view; Interior view of stair enclosure and stair from platform to main passenger terminal - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

North view; Station Building south (front) elevation, portions of ...

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

North view; Station Building - south (front) elevation, portions of covered ramp and Street Car Waiting House at near left - North Philadelphia Station, 2900 North Broad Street, on northwest corner of Broad Street & Glenwood Avenue, Philadelphia, Philadelphia County, PA

Reduced 4-Aminobiphenyl-Induced Liver Tumorigenicity but not DNA Damage in Arylamine N-Acetyltransferase Null Mice

PubMed Central

Sugamori, Kim S.; Brenneman, Debbie; Sanchez, Otto; Doll, Mark A.; Hein, David W.; Pierce, William M.; Grant, Denis M.

2012-01-01

The aromatic amine 4-aminobiphenyl (ABP) is a liver procarcinogen in mice, requiring enzymatic bioactivation to exert its tumorigenic effect. To assess the role of arylamine N-acetyltransferase (NAT)-dependent acetylation capacity in the risk for ABP-induced liver tumors, we compared 1-year liver tumor incidence following the postnatal exposure of wild-type and NAT-deficient Nat1/2(−/−) mice to ABP. At an ABP exposure of 1200 nmoles, male Nat1/2(−/−) mice had a liver tumor incidence of 36% compared to 69% in wild-type males, and at 600 nmoles there was a complete absence of tumors compared to 60% in wild-type mice. Only one female wild-type mouse had a tumor using this exposure protocol. However, levels of N-deoxyguanosin-8-yl-ABP-DNA adducts did not correlate with either the strain or sex differences in tumor incidence. These results suggest that female sex and NAT deficiency reduce risk for ABP-induced liver tumors, but by mechanisms unrelated to differences in DNA-damaging events. PMID:22193722

Photocopy of photograph (from NBPPNSY, CSF35891264) Replogle, photographer, September 23, ...

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

Photocopy of photograph (from NBP-PNSY, CSF-3589-12-64) Replogle, photographer, September 23, 1921 View northeast from 350-ton crane (Haer no. PA-387-F) of Philadelphia Navy Yard. Drydock no. 1 (Haer no. Pa-387-A) is at center. This is the original timber drydock constructed 1889-1891 under the supervision of Robert E. Perry, explorer of the north pole. The riggers/sign shop (building no. 25) is above the drydock. Built in 1904, it is an example of renaissance revival industrial architecture at the time the photograph was taken it was used for a sheet metal, tool and inside shipfitters shop. - Naval Base Philadelphia-Philadelphia Naval Shipyard, League Island, Philadelphia, Philadelphia County, PA

Overall interior view of structures shop (11 shop) located on ...

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

Overall interior view of structures shop (11 shop) located on west side of building 57 - looking north; the south end of the structures shop was devoted to welding heavy plate foundations and ship components; the floor is fabricated of case steel and features a grillwork of 1 1/2 fabricated holes which are used as sockets for gripping position pins. - Naval Base Philadelphia-Philadelphia Naval Shipyard, Structure Shop, League Island, Philadelphia, Philadelphia County, PA

Ab initio Study of Transition metal binding to the Prion Protein

NASA Astrophysics Data System (ADS)

Cox, Daniel L.; Singh, Rajiv R. P.; Pan, Jianping

2004-03-01

Fundamental understanding of the prion protein (PrP) is of critical public health importance in view of mad cow and chronic wasting diseases. In recent years, it has been shown that the normal form (PrP^c) binds copper^1), and the structure of the copper binding domain has been elaborated. Hypotheses about toxicity associated with binding of other metals (notably manganese) have been put forward, Accordingly, using the ab initio SIESTA density functional theory code^2), we calculated the binding energy E_B(M) of M-(PrP) complexes relative to initially uncomplexed M ions, with M=Cu,Ni,Zn,Mn and (PrP)^* the minimal binding domain. The binding energy trend is E_B(Ni)>E_B(Cu)>E_B(Zn)>E_B(Mn), consistent with recent experiments apart from the surprising stability of Ni. We will also present preliminary results for binding of initially complexed M ions. *-Supported by U.S. DOE, Office of Basic Energy Sciences, Division of Materials Research 1) G.S. Jackson et al., Proc. Nat. Acad. Sci. (USA) 98, 8531 (2001). 2) P. Ordejón, et al., Phys. Rev. B53, R10441 (1996); J.M. Soler et al., J. Phys. Cond. Matt. 14, 2745 (2002).

Information content versus word length in random typing

NASA Astrophysics Data System (ADS)

Ferrer-i-Cancho, Ramon; Moscoso del Prado Martín, Fermín

2011-12-01

Recently, it has been claimed that a linear relationship between a measure of information content and word length is expected from word length optimization and it has been shown that this linearity is supported by a strong correlation between information content and word length in many languages (Piantadosi et al 2011 Proc. Nat. Acad. Sci. 108 3825). Here, we study in detail some connections between this measure and standard information theory. The relationship between the measure and word length is studied for the popular random typing process where a text is constructed by pressing keys at random from a keyboard containing letters and a space behaving as a word delimiter. Although this random process does not optimize word lengths according to information content, it exhibits a linear relationship between information content and word length. The exact slope and intercept are presented for three major variants of the random typing process. A strong correlation between information content and word length can simply arise from the units making a word (e.g., letters) and not necessarily from the interplay between a word and its context as proposed by Piantadosi and co-workers. In itself, the linear relation does not entail the results of any optimization process.

Nuclear relaxation and critical fluctuations in membranes containing cholesterol

NASA Astrophysics Data System (ADS)

McConnell, Harden

2009-04-01

Nuclear resonance frequencies in bilayer membranes depend on lipid composition. Our calculations describe the combined effects of composition fluctuations and diffusion on nuclear relaxation near a miscibility critical point. Both tracer and gradient diffusion are included. The calculations involve correlation functions and a correlation length ξ =ξ0T/(T -Tc), where T -Tc is temperature above the critical temperature and ξ0 is a parameter of molecular length. Several correlation functions are examined, each of which is related in some degree to the Ising model correlation function. These correlation functions are used in the calculation of transverse deuterium relaxation rates in magic angle spinning and quadrupole echo experiments. The calculations are compared with experiments that report maxima in deuterium and proton nuclear relaxation rates at the critical temperature [Veatch et al., Proc. Nat. Acad. Sci. U.S.A. 104, 17650 (2007)]. One Ising-model-related correlation function yields a maximum 1/T2 relaxation rate at the critical temperature for both magic angle spinning and quadrupole echo experiments. The calculated rates at the critical temperature are close to the experimental rates. The rate maxima involve relatively rapid tracer diffusion in a static composition gradient over distances of up to 10-100 nm.

Susceptibility of N-acetyltransferase 2 slow acetylators to antituberculosis drug-induced liver injury: a meta-analysis.

PubMed

Shi, Jing; Xie, Min; Wang, Jianmiao; Xu, Yongjian; Liu, Xiansheng

2015-12-01

This study aimed to evaluate the association between N-acetyltransferase 2 (NAT2) gene polymorphisms and the risk of antituberculosis drug-induced liver injury (ATLI). A meta-analysis was performed including 27 studies with 1289 cases and 5462 controls. Odds ratio with 95% CI was used to evaluate the strength of association. Our meta-analysis found that NAT2 slow acetylators were associated with increased risk of ATLI compared with fast and intermediate acetylators when standard dose of isoniazid was administrated (odds ratio: 3.08; 95% CI: 2.29-4.15). Individuals with NAT2 slow acetylators may have increased risk of ATLI when standard dose of isoniazid was used. Detection of NAT2 genotype may benefit to the prevention of ATLI.

2. GENERAL VIEW OF INTERIOR. NOTE SKYLIGHTS ON VAULTED CEILING. ...

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

2. GENERAL VIEW OF INTERIOR. NOTE SKYLIGHTS ON VAULTED CEILING. Photocopy of circa 1910 photo published in a 1911 book, Stanley's Views of Philadelphia. - Pennsylvania Company for Insurances on Lives & Granting Annuities, 431 Chestnut Street, Philadelphia, Philadelphia County, PA

1. Photocopy of July 13, 1959 photograph, courtesy of Committee ...

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

1. Photocopy of July 13, 1959 photograph, courtesy of Committee of Public Property, Philadelphia, Pennsylvania. VIEW OF VAULTS (on sidewalk), LOOKING EAST TOWARD FRONT STREET - Granite Street Vaults, 100-112 & 101-127 Granite Street, Philadelphia, Philadelphia County, PA

78 FR 14359 - Verizon Business Networks Services, Inc., Specialist-Tech Customer Service, Philadelphia, PA...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-05

... Business Networks Services, Inc., Specialist-Tech Customer Service, Philadelphia, PA; Verizon Business Networks Services, Inc., Specialist-Tech Customer Service, Tampa, Florida; Amended Certification Regarding... Business Networks Services, Inc., Order Management Division, Philadelphia, Pennsylvania and Verizon...

South Philadelphia Passive Sampler Method project communication sheet

EPA Science Inventory

The Environmental Protection Agency, Office of Research and Development (EPA ORD), EPA Region 3, and the City of Philadelphia Air Measurements Services (AMS) are collaborating on research project in South Philadelphia starting in the spring of 2013. This project investigates how...