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Sample records for juhan judu aare

  1. Mutations in aarE, the ubiA homolog of Providencia stuartii, result in high-level aminoglycoside resistance and reduced expression of the chromosomal aminoglycoside 2'-N-acetyltransferase.

    PubMed

    Paradise, M R; Cook, G; Poole, R K; Rather, P N

    1998-04-01

    The aarE1 allele was identified on the basis of the resulting phenotype of increased aminoglycoside resistance. The aarE1 mutation also resulted in a small-colony phenotype and decreased levels of aac(2')-Ia mRNA. The deduced AarE gene product displayed 61% amino acid identity to the Escherichia coli UbiA protein, an octaprenyltransferase required for the second step of ubiquinone biosynthesis. Complementation experiments in both Providencia stuartii and E. coli demonstrated that aarE and ubiA are functionally equivalent.

  2. The Automated Aircraft Rework System (AARS): A system integration approach

    NASA Technical Reports Server (NTRS)

    Benoit, Michael J.

    1994-01-01

    The Mercer Engineering Research Center (MERC), under contract to the United States Air Force (USAF) since 1989, has been actively involved in providing the Warner Robins Air Logistics Center (WR-ALC) with a robotic workcell designed to perform rework automated defastening and hole location/transfer operations on F-15 wings. This paper describes the activities required to develop and implement this workcell, known as the Automated Aircraft Rework System (AARS). AARS is scheduled to be completely installed and in operation at WR-ALC by September 1994.

  3. High salt diet modulates vascular response in A2AAR (+/+) and A 2AAR (-/-) mice: role of sEH, PPARγ, and K ATP channels.

    PubMed

    Pradhan, Isha; Ledent, Catherine; Mustafa, S Jamal; Morisseau, Christophe; Nayeem, Mohammed A

    2015-06-01

    This study aims to investigate the signaling mechanism involved in HS-induced modulation of adenosine-mediated vascular tone in the presence or absence of adenosine A2A receptor (A2AAR). We hypothesized that HS-induced enhanced vascular relaxation through A2AAR and epoxyeicosatrienoic acid (EETs) is dependent on peroxisome proliferator-activated receptor gamma (PPARγ) and ATP-sensitive potassium channels (KATP channels) in A2AAR(+/+) mice, while HS-induced vascular contraction to adenosine is dependent on soluble epoxide hydrolase (sEH) that degrades EETs in A2AAR(-/-) mice. Organ bath and Western blot techniques were conducted in HS (4 % NaCl) and normal salt (NS, 0.45 % NaCl)-fed A2AAR(+/+) and A2AAR(-/-) mouse aorta. We found that enhanced vasodilation to A2AAR agonist, CGS 21680, in HS-fed A2AAR(+/+) mice was blocked by PPARγ antagonist (T0070907) and KATP channel blocker (Glibenclamide). Also, sEH inhibitor (AUDA)-dependent vascular relaxation was mitigated by PPARγ antagonist. PPARγ agonist (Rosiglitazone)-induced relaxation in HS-A2AAR(+/+) mice was attenuated by KATP channel blocker. Conversely, HS-induced contraction in A2AAR(-/-) mice was attenuated by sEH inhibitor. Overall, findings from this study that implicates the contribution of EETs, PPARγ and KATP channels downstream of A2AAR to mediate enhanced vascular relaxation in response to HS diet while, role of sEH in mediating vascular contraction in HS-fed A2AAR(-/-) mice.

  4. A novel AARS mutation in a family with dominant myeloneuropathy

    PubMed Central

    Motley, William W.; Griffin, Laurie B.; Mademan, Inès; Baets, Jonathan; De Vriendt, Els; De Jonghe, Peter; Antonellis, Anthony; Jordanova, Albena

    2015-01-01

    Objective: To determine the genetic cause of neurodegeneration in a family with myeloneuropathy. Methods: We studied 5 siblings in a family with a mild, dominantly inherited neuropathy by clinical examination and electrophysiology. One patient had a sural nerve biopsy. After ruling out common genetic causes of axonal Charcot-Marie-Tooth disease, we sequenced 3 tRNA synthetase genes associated with neuropathy. Results: All affected family members had a mild axonal neuropathy, and 3 of 4 had lower extremity hyperreflexia, evidence of a superimposed myelopathy. A nerve biopsy showed evidence of chronic axonal loss. All affected family members had a heterozygous missense mutation c.304G>C (p.Gly102Arg) in the alanyl-tRNA synthetase (AARS) gene; this allele was not identified in unaffected individuals or control samples. The equivalent change in the yeast ortholog failed to complement a strain of yeast lacking AARS function, suggesting that the mutation is damaging. Conclusion: A novel mutation in AARS causes a mild myeloneuropathy, a novel phenotype for patients with mutations in one of the tRNA synthetase genes. PMID:25904691

  5. FASD -- De Aar mums get beyond the 'tippling point'.

    PubMed

    Bateman, Chris

    2010-11-09

    When most of the low-income folk in the 'ghost train' town of De Aar began remonstrating with any pregnant mother who was boozing, excited campaigners thought they'd broken through the 'tippling point'. However, their research colleagues proved they'd gone even further -- the dedicated local platoon of social workers, nurses, therapists and volunteers had in three short years reduced the prevalence of fetal alcohol spectrum disorder (FASD) by 30%. This is in a town with the worst recorded FASD prevalence in any single community in the world, where 120 out of every 1 000 residents suffer from FASD (12%).

  6. Redefining the phenotype of ALSP and AARS2 mutation–related leukodystrophy

    PubMed Central

    Lakshmanan, Rahul; Adams, Matthew E.; Lynch, David S.; Kinsella, Justin A.; Phadke, Rahul; Schott, Jonathan M.; Murphy, Elaine; Rohrer, Jonathan D.; Chataway, Jeremy; Houlden, Henry; Fox, Nick C.

    2017-01-01

    Objective: To provide an overview of the phenotype of 2 clinically, radiologically, and pathologically similar leukodystrophies, adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and alanyl-transfer RNA synthetase 2 mutation–related leukodystrophy (AARS2-L), and highlight key differentiating features. Methods: ALSP and AARS2-L cases were identified from the adult-onset leukodystrophy database at our institution. In addition, cases with imaging findings were identified from a literature review. The phenotypic features were determined by combining published cases with those from our database. Results: A combined total of 74 cases of ALSP and 10 cases of AARS2-L with neuroimaging data were identified. The mean age at onset was 42 years in ALSP and 26 years in AARS2-L. Cognitive and motor symptoms were the most common symptoms overall in both. Ovarian failure was exclusive to AARS2-L, present in all known female cases. Both ALSP and AARS2-L showed a confluent, asymmetric, predominantly frontoparietal, periventricular pattern of white matter disease with subcortical U-fiber sparing; pyramidal tract and corpus callosum involvement; and diffusion changes in the white matter which we have termed “deep white matter diffusion dots.” Central atrophy and corpus callosal thinning were prominent in ALSP and disproportionately mild in AARS2-L when present. ALSP also occasionally showed ventricular abnormalities and calcifications in the frontal periventricular white matter, features not seen in AARS2-L. AARS2-L demonstrates white matter rarefaction which suppresses on fluid-attenuated inversion recovery MRI sequences, a feature not seen in ALSP. Conclusions: ALSP and AARS2-L share similar clinical, imaging, and pathologic characteristics with key differentiating features that we have highlighted. PMID:28243630

  7. A2A Adenosine Receptor (A2AAR) as a Therapeutic Target in Diabetic Retinopathy

    PubMed Central

    Ibrahim, Ahmed S.; El-shishtawy, Mamdouh M.; Zhang, Wenbo; Caldwell, Ruth B.; Liou, Gregory I.

    2011-01-01

    In diabetic retinopathy (DR), abnormalities in vascular and neuronal function are closely related to the local production of inflammatory mediators whose potential source is microglia. A2A adenosine receptor (A2AAR) has been shown to possess anti-inflammatory properties that have not been studied in DR. Here, we evaluate the role of A2AAR and its underlying signaling in retinal complications associated with diabetes. Initial studies in wild-type mice revealed that the treatment with the A2AAR agonist resulted in marked decreases in hyperglycemia-induced retinal cell death and tumor necrosis factor (TNF)-α release. To further assess the role of A2AAR in DR, we studied the effects of A2AAR ablation on diabetes-induced retinal abnormalities. Diabetic A2AAR−/− mice had significantly more terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells, TNF-α release, and intercellular adhesion molecule-1 expression compared with diabetic wild-type mice. To explore a potential mechanism by which A2AAR signaling regulates inflammation in DR, we performed additional studies using microglial cells treated with Amadori-glycated albumin, a risk factor in diabetic disorders. The results showed that activation of A2AAR attenuated Amadori-glycated albumin-induced TNF-α release in a cAMP/exchange protein directly activated by cAMP-dependent mechanism and significantly repressed the inflammatory cascade, C-Raf/extracellular signal-regulated kinase (ERK), in activated microglia. Collectively, this work provides pharmacological and genetic evidence for A2AAR signaling as a control point of cell death in DR and suggests that the retinal protective effect of A2AAR is mediated by abrogating the inflammatory response that occurs in microglia via interaction with C-Raf/ERK pathway. PMID:21514428

  8. Identification and analysis of aarP, a transcriptional activator of the 2'-N-acetyltransferase in Providencia stuartii.

    PubMed

    Macinga, D R; Parojcic, M M; Rather, P N

    1995-06-01

    The aarP gene has been identified in a search for activators of the 2-N-acetyltransferase [encoded by aac(2')-Ia] in Providencia stuartii. Introduction of aarP into P. stuartii on a multicopy plasmid resulted in a 9.9-fold increase in the accumulation of beta-galactosidase from an aac(2')-lacZ fusion. Northern (RNA) blot analysis demonstrated that this increased aac(2')-Ia expression occurred at the level of mRNA accumulation. The deduced AarP protein was 15,898 Da in size and exhibited significant homology to a number of transcriptional activators in the AraC/XyIS family, including TetD,Rob, MarA, and SoxS. The similarity of AarP to the MarA and SoxS proteins prompted an investigation to determine whether AarP is involved in activation of genes in either the multiple antibiotic resistance (Mar) phenotype or redox stress (SoxRS) system. Introduction of aarP on a multicopy plasmid into either P. stuartii or Escherichia coli conferred a Mar phenotype with higher levels of resistance to tetracycline, chloramphenicol, and ciprofloxacin. Multiple copies of aarP in E. coli also resulted in activation of the endonuclease IV gene (nfo), a gene in the SoxRS regulon of E. coli. The function of aarP in its single-copy state was addressed by using allelic replacement to construct an aarP::Cm disruption, which resulted in a fivefold reduction in the accumulation of aac(2')-Ia mRNA. Analysis of aarP regulation showed that aarP mRNA accumulation was slightly increased by exposure to tetracycline and dramatically increased in cells containing the aarB3 (aar3) mutation, which was previously shown to increase transcription of the aac(2')-Ia gene. (P.N. Rather, E. Oroz, K.J. Shaw, R. Hare, and G. Miller, J. Bacteriol. 175:6492-6498).

  9. IGFBP-1 hyperphosphorylation in response to leucine deprivation is mediated by the AAR pathway.

    PubMed

    Malkani, Niyati; Jansson, Thomas; Gupta, Madhulika B

    2015-09-05

    Insulin-like growth factor-1 (IGF-I) is the key regulator of fetal growth. IGF-I bioavailability is markedly diminished by IGF binding protein-1 (IGFBP-1) phosphorylation. Leucine deprivation strongly induces IGFBP-1 hyperphosphorylation, and plays an important role in fetal growth restriction (FGR). FGR is characterized by decreased amino acid availability, which activates the amino acid response (AAR) and inhibits the mechanistic target of rapamycin (mTOR) pathway. We investigated the role of AAR and mTOR in mediating IGFBP-1 secretion and phosphorylation in HepG2 cells in leucine deprivation. mTOR inhibition (rapamycin or raptor + rictor siRNA), or activation (DEPTOR siRNA) demonstrated a role of mTOR in leucine deprivation-induced IGFBP-1 secretion but not phosphorylation. When the AAR was blocked (U0126, or ERK/GCN2 siRNA), both IGFBP-1 secretion and hyperphosphorylation (pSer101/pSer119/pSer169) due to leucine deprivation were prevented. CK2 inhibition by TBB also attenuated IGFBP-1 phosphorylation in leucine deprivation. These results suggest that the AAR and mTOR independently regulate IGFBP-1 secretion and phosphorylation in response to decreased amino acid availability.

  10. Multi-Facet Multicultural School Assessment: Adapting and Norming the AARS/POSIT.

    ERIC Educational Resources Information Center

    French, Laurence; Picthall-French, Nancy

    The National Institute on Mental Health attempted to address the issue of providing a reliable baseline on alcohol-related problems among adolescents with the Adolescent Assessment Referral System (AARS). Part of this tool is the Problem Oriented Screening Instrument (POSIT), a 139-item questionnaire printed in English and Spanish. This…

  11. aarC, an essential gene involved in density-dependent regulation of the 2'-N-acetyltransferase in Providencia stuartii.

    PubMed

    Rather, P N; Solinsky, K A; Paradise, M R; Parojcic, M M

    1997-04-01

    The 2'-N-acetyltransferase [AAC(2')-Ia] in Providencia stuartii has a dual function where it is involved in the acetylation of peptidoglycan and certain aminoglycosides. A search for negative regulators of the aac(2')-Ia gene has resulted in the identification of aarC. A missense allele (aarC1) resulted in an 8.9-fold increase in beta-galactosidase accumulation from an aac(2')-lacZ transcriptional fusion. Northern blot analysis demonstrated an increase in aac(2')-Ia mRNA accumulation that was specific to cells at high density. In addition, the aarC1 allele also resulted in a substantial increase in the expression of aarP, a transcriptional activator of the aac(2')-Ia gene. The wild-type aarC gene was isolated by complementation and encodes a predicted protein of 365 amino acids with a molecular mass of 39,815 Da. The predicted AarC protein exhibited 88% amino acid homology to the previously identified GcpE protein of Escherichia coli and 86% homology to a gene product from Haemophilus influenzae. The E. coli gcpE gene was able to functionally complement the aarC1 allele in P. stuartii. The aarC1 allele was identified as a T to G transversion that resulted in a valine to glycine substitution at position 136 in the AarC protein. The aarC gene appears to be essential for cell viability as construction of a disrupted copy (aarC::lacZ) was possible only in cells that carried an episomal copy of aarC or gcpE.

  12. Alkali - Aggregate reaction (AAR) A brief history of discovery of tis basic chemistry

    SciTech Connect

    Leps, T.M.

    1995-12-31

    Alkali Aggregate Reaction (AAR), also variously known as Alkali Silica Reaction (ASR) and even Alkali Carbonate Reaction (ACR), has troubled and challenged those of us since the 1930`s who would have liked to think of portland cement concrete and aggregates as a simple, reliable, inert, enduring construction material. Its complex and not easily understood chemistry successfully defied the understanding of the engineering fraternity for many decades. After all, civil engineers, architects, and construction engineers are not chemists or petrographers, and are only minimally laboratory-oriented or trained. Furthermore, the almost infinite variety of minerals which Nature has provided in the form of rocks and aggregates indeed constituted a nearly insurmountable challenge to the ready development of a credible understanding of the chemistry of expanding concrete. Accordingly, although a few talented pioneers such as E.A. Stephenson in 1916, J.C. Pearson & G.F. Loughlin in 1923, Professor R.J. Holden in 1935, and F. M. Lea & C.H. Desch in 1935, nibbled at the edges of understanding how gels were formed in the alkali-aggregate interaction process, it was not until 1940 when an engineer, Thomas E. Stanton, dared to publish a preliminary but understandable view of what causes portland cement concrete to expand. The writer`s interest in AAR began as far back as 1946 when the importance of the problem was repeatedly brought to his attention by Ralph W. Spencer, then Chief Civil Engineer of Southern California Edison Company, who was the writer`s supervisor in planning, designing and contracting the construction of many major projects, including dams. Previously as well as subsequently, the writer`s interest was enhanced by friendships and association with pioneers of AAR such as Professor Roy Carlson, Professor R.E. Davis, Lewis H. Tuthill, R.F. Blanks, and Roger Rhoades. The writer regrets never having met Thomas E. Stanton and his chief chemist, G.H.P.

  13. Role of SspA in the density-dependent expression of the transcriptional activator AarP in Providencia stuartii.

    PubMed

    Ding, X; Baca-DeLancey, R R; Rather, P N

    2001-03-01

    The AarP protein in Providencia stuartii encodes a small transcriptional activator which activates the chromosomal aminoglycoside acetyltransferase aac(2')-Ia gene. In addition, AarP activates genes involved in a multiple antibiotic resistance (Mar) phenotype. Expression of an aarP-lacZ fusion increased in a density-dependent manner and reached peak levels at stationary phase. The expression of an aarP-lacZ fusion could be prematurely activated in cells at early to mid-exponential phase by the addition of spent culture supernatants from stationary phase cultures or by ethyl acetate extracts of these supernatants. Nutrient starvation had a negligible effect on aarP expression. In a search for mutations that block aarP activation at stationary phase, a mini-Tn5Cm insertion has been identified within a gene whose product was 77% identical to SspA, a regulatory protein involved in stationary phase gene expression and virulence. An unmarked sspA null allele (sspA2) was created by allelic replacement to further examine the role of sspA in P. stuartii. The sspA2 allele resulted in substantial decrease in aarP mRNA accumulation at various phases of growth. Furthermore, in an sspA mutant background, the aarP-lacZ fusion was no longer activated by an extracellular signal.

  14. A regulatory cascade involving AarG, a putative sensor kinase, controls the expression of the 2'-N-acetyltransferase and an intrinsic multiple antibiotic resistance (Mar) response in Providencia stuartii.

    PubMed

    Rather, P N; Paradise, M R; Parojcic, M M; Patel, S

    1998-06-01

    A recessive mutation, aarG1, has been identified that resulted in an 18-fold increase in the expression of beta-galactosidase from an aac(2')-lacZ fusion. Transcriptional fusions and Northern blot analysis demonstrated that the aarG1 allele also resulted in a large increase in the expression of aarP, a gene encoding a transcriptional activator of aac(2')-Ia. The effects of aarG1 on aac(2')-Ia expression were mediated by aarP-dependent and -independent mechanisms. The aarG1 allele also resulted in a multiple antibiotic resistance (Mar) phenotype, which included increased chloramphenicol, tetracycline and fluoroquinolone resistance. This Mar phenotype also resulted from aarP-dependent and -independent mechanisms. Sequence analysis of the aarG locus revealed the presence of two open reading frames, designated aarR and aarG, organized in tandem. The putative AarR protein displayed 75% amino acid identity to the response regulator PhoP, and the AarG protein displayed 57% amino acid identity to the sensor kinase PhoQ. The aarG1 mutation, a C to T substitution, resulted in a threonine to isoleucine substitution at position 279 (T279I) in the putative sensor kinase. The AarG product was functionally similar to PhoQ, as it was able to restore wild-type levels of maganin resistance to a Salmonella typhimurium phoQ mutant. However, expression of the aarP and aac(2')-Ia genes was not significantly affected by the levels of Mg2+ or Ca2+, suggesting that aarG senses a signal other than divalent cations.

  15. Use of after action reports (AARs) to promote organizational and systems learning in emergency preparedness.

    PubMed

    Savoia, Elena; Agboola, Foluso; Biddinger, Paul D

    2012-08-01

    Many public health and healthcare organizations use formal knowledge management practices to identify and disseminate the experiences gained over time. The "lessons-learned" approach is one such example of knowledge management practice applied to the wider concept of organizational learning. In the field of emergency preparedness, the lessons-learned approach stands on the assumption that learning from experience improves practice and minimizes avoidable deaths and negative economic and social consequences of disasters. In this project, we performed a structured review of AARs to analyze how lessons learned from the response to real-incidents may be used to maximize knowledge management and quality improvement practices such as the design of public health emergency preparedness (PHEP) exercises. We chose as a source of data the "Lessons Learned Information Sharing (LLIS.gov)" system, a joined program of the U.S. Department of Homeland Security DHS and FEMA that serves as the national, online repository of lessons learned, best practices, and innovative ideas. We identified recurring challenges reported by various states and local public health agencies in the response to different types of incidents. We also strove to identify the limitations of systematic learning that can be achieved due to existing weaknesses in the way AARs are developed.

  16. Responses to the AAR-Teagle White Paper: "The Religious Studies Major in a Post-9/11 World"

    ERIC Educational Resources Information Center

    Webster, Jane S.; Buckley, James J.; Jensen, Tim; Floyd-Thomas, Stacey

    2011-01-01

    In October 2008 The American Academy of Religion published the findings of an eighteen month study (conducted with funding from the Teagle Foundation) on "The Religious Studies Major in a Post-9/11 World: New Challenges, New Opportunities." Re-published here, this AAR-Teagle White Paper provides the opportunity for four respondents to…

  17. A NASA F/A-18, participating in the Automated Aerial Refueling (AAR) project, flies over the Dryden

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A NASA F/A-18 is participating in the Automated Aerial Refueling (AAR) project. The 300-gallon aerial refueling store seen on the belly of the aircraft carries fuel and a refueling drogue. This aircraft acts as a tanker in the study to develop an aerodynamic model for future automated aerial refueling, especially of unmanned vehicles.

  18. Genome analysis of Excretory/Secretory proteins in Taenia solium reveals their Abundance of Antigenic Regions (AAR).

    PubMed

    Gomez, Sandra; Adalid-Peralta, Laura; Palafox-Fonseca, Hector; Cantu-Robles, Vito Adrian; Soberón, Xavier; Sciutto, Edda; Fragoso, Gladis; Bobes, Raúl J; Laclette, Juan P; Yauner, Luis del Pozo; Ochoa-Leyva, Adrián

    2015-05-19

    Excretory/Secretory (ES) proteins play an important role in the host-parasite interactions. Experimental identification of ES proteins is time-consuming and expensive. Alternative bioinformatics approaches are cost-effective and can be used to prioritize the experimental analysis of therapeutic targets for parasitic diseases. Here we predicted and functionally annotated the ES proteins in T. solium genome using an integration of bioinformatics tools. Additionally, we developed a novel measurement to evaluate the potential antigenicity of T. solium secretome using sequence length and number of antigenic regions of ES proteins. This measurement was formalized as the Abundance of Antigenic Regions (AAR) value. AAR value for secretome showed a similar value to that obtained for a set of experimentally determined antigenic proteins and was different to the calculated value for the non-ES proteins of T. solium genome. Furthermore, we calculated the AAR values for known helminth secretomes and they were similar to that obtained for T. solium. The results reveal the utility of AAR value as a novel genomic measurement to evaluate the potential antigenicity of secretomes. This comprehensive analysis of T. solium secretome provides functional information for future experimental studies, including the identification of novel ES proteins of therapeutic, diagnosis and immunological interest.

  19. Halogen and trace element geochemistry in Mid-Ocean Ridge basalts from the Australian-Antarctic Ridge (AAR)

    NASA Astrophysics Data System (ADS)

    Yang, Y. S.; Seo, J. H.; Park, S. H.; Kim, T.

    2015-12-01

    Australian-Antarctic Ridge (AAR) is an extension of easternmost SE Indian Mid-Ocean Ridge (MOR).We collected volcanic glasses from the "in-axis" of the KR1 and KR2 MOR, and the overlapping zones of the KR1 MOR and the nearby seamounts ("KR1 mixing"). We determined trace and halogen elements in the glasses. Halogen concentrations and its ratios in the glasses are important to understand the mantle metasomatism and volatile recycling. 52 of the collected glasses are "primitive" (higher than 6 wt% MgO), while 3 of them have rather "evolved" composition (MgO wt% of 1.72, 2.95 and 4.15). K2O concentrations and Th/Sc ratios in the glasses show a negative correlation with its MgO concentration. Incompatible element ratios such as La/Sm are rather immobile during a magma differentiation so the ratios are important to understand mantle composition (Hofmann et al. 2003). La/Sm ratios in the glasses are 0.95 ~ 3.28 suggesting that the AAR basalts can be classified into T-MORB and E-MORB (Schilling et al., 1983). La/Sm ratios are well-correlated with incompatible elements such as U, Ba, Nb, and negatively correlated with compatible elements such as Sc, Eu2+, Mg. The AAR glasses contain detectable halogen elements. The "KR1 mixing" glasses in halogen elements are more abundant than "in-axis" the glasses. Cl is the least variable element compared to the other halogens such as Br and I in the AAR. The "KR1 mixing" glasses have the largest variations of Br/Cl ratios compared to the "in-axis" glasses. The Cl/Br and Th/Sc ratios in the "in-axis" glasses and in the "KR1 mixing" glasses show positive and negative correlations, respectively. The Br-rich glasses in the "KR1 mixing" zone might be explained by a recycled Br-rich oceanic slab of paleo-subduction or by a hydrothermal alteration in the AAR. I composition in the glasses does not show a correlation other trace elements. The K/Cl and K/Ti ratios in the AAR glasses are similar to the basalts from the Galapagos Spreading Center

  20. The Front of the Aar Massif: A Crustal-Scale Ramp Anticline?

    NASA Astrophysics Data System (ADS)

    Herwegh, Marco; Mock, Samuel; Wehrens, Philip; Baumberger, Roland; Berger, Alfons; Wangenheim, Cornelia; Glotzbach, Christoph; Kissling, Edi

    2015-04-01

    The front of the Aar Massif (Swiss Central Alps) is characterized by Paleozoic basement rocks exposed at altitudes of more than 4600m above sea level, followed by a steeply north dipping Mesozoic sedimentary cover and overlying Helvetic nappes. The sediments turn into subhorizontal orientations just few kilometers to the N, where the top of the basement is situated at depths of about 7000m below sea level. What is the origin of this vertical jump of about 12000m of the basement rocks over such short horizontal distances? Recent structural investigations at the Basement-Cover contact indicate a complex structural evolution involving reactivation of extensional faults and inversion of half-grabens during early compressional stages. In the internal parts of the Aar Massif a general steepening of the faults resulted with progressive compression. In the northern frontal part, however, a new spaced cleavage evolved, which is dipping with 20-30° to the SE. In places, the new cleavage in the basement rocks is intense and pervasive and correlates with a steepening of the basement-cover contact and its offsets of several tens to hundreds of meters. Hence strain is strongly partitioned in a large number of high strain zones, which cover a cumulative thickness of at least 2000m, eventually even much more considering subsurface continuation. The Mesozoic sediments affected by this large-scale deformation zone are either intensely ductile folded in the case of limestones or faulted and imbricated in the case of dolomites. These differences in deformation style result from the deformation conditions of about < 250-300°C, where calcite still deforms in a ductile manner, while dolomite and crystalline basement preferentially undergo brittle deformation in combination of dissolution-precipitation processes. In a large-scale point of view, we suggest that the high strain domain in the crystalline basement in fact represents a crustal-scale several kilometers wide shear zone, which

  1. A recurrent loss-of-function alanyl-tRNA synthetase (AARS) mutation in patients with Charcot-Marie-Tooth disease type 2N (CMT2N).

    PubMed

    McLaughlin, Heather M; Sakaguchi, Reiko; Giblin, William; Wilson, Thomas E; Biesecker, Leslie; Lupski, James R; Talbot, Kevin; Vance, Jeffery M; Züchner, Stephan; Lee, Yi-Chung; Kennerson, Marina; Hou, Ya-Ming; Nicholson, Garth; Antonellis, Anthony

    2012-01-01

    Charcot-Marie-Tooth (CMT) disease comprises a heterogeneous group of peripheral neuropathies characterized by muscle weakness and wasting, and impaired sensation in the extremities. Four genes encoding an aminoacyl-tRNA synthetase (ARS) have been implicated in CMT disease. ARSs are ubiquitously expressed, essential enzymes that ligate amino acids to cognate tRNA molecules. Recently, a p.Arg329His variant in the alanyl-tRNA synthetase (AARS) gene was found to segregate with dominant axonal CMT type 2N (CMT2N) in two French families; however, the functional consequence of this mutation has not been determined. To investigate the role of AARS in CMT, we performed a mutation screen of the AARS gene in patients with peripheral neuropathy. Our results showed that p.Arg329His AARS also segregated with CMT disease in a large Australian family. Aminoacylation and yeast viability assays showed that p.Arg329His AARS severely reduces enzyme activity. Genotyping analysis indicated that this mutation arose on three distinct haplotypes, and the results of bisulfite sequencing suggested that methylation-mediated deamination of a CpG dinucleotide gives rise to the recurrent p.Arg329His AARS mutation. Together, our data suggest that impaired tRNA charging plays a role in the molecular pathology of CMT2N, and that patients with CMT should be directly tested for the p.Arg329His AARS mutation.

  2. Rhomboid protease AarA mediates quorum-sensing in Providencia stuartii by activating TatA of the twin-arginine translocase.

    PubMed

    Stevenson, Lindsay G; Strisovsky, Kvido; Clemmer, Katy M; Bhatt, Shantanu; Freeman, Matthew; Rather, Philip N

    2007-01-16

    The Providencia stuartii AarA protein is a member of the rhomboid family of intramembrane serine proteases and is required for the production of an unknown quorum-sensing molecule. In a screen to identify rhomboid-encoding genes from Proteus mirabilis, tatA was identified as a multicopy suppressor and restored extracellular signal production as well as complementing all other phenotypes of a Prov. stuartii aarA mutant. TatA is a component of the twin-arginine translocase (Tat) protein secretion pathway and likely forms a secretion pore. By contrast, the native tatA gene of Prov. stuartii in multicopy did not suppress an aarA mutation. We find that TatA in Prov. stuartii has a short N-terminal extension that was atypical of TatA proteins from most other bacteria. This extension was proteolytically removed by AarA both in vivo and in vitro. A Prov. stuartii TatA protein missing the first 7 aa restored the ability to rescue the aarA-dependent phenotypes. To verify that loss of the Tat system was responsible for the various phenotypes exhibited by an aarA mutant, a tatC-null allele was constructed. The tatC mutant exhibited the same phenotypes as an aarA mutant and was epistatic to aarA. These data provide a molecular explanation for the requirement of AarA in quorum-sensing and uncover a function for the Tat protein export system in the production of secreted signaling molecules. Finally, TatA represents a validated natural substrate for a prokaryotic rhomboid protease.

  3. Activation of the 2'-N-acetyltransferase gene [aac(2')-Ia] in Providencia stuartii by an interaction of AarP with the promoter region.

    PubMed

    Macinga, D R; Paradise, M R; Parojcic, M M; Rather, P N

    1999-07-01

    The aac(2')-Ia gene in Providencia stuartii encodes a 2'-N-acetyltransferase capable of acetylating both peptidoglycan and certain aminoglycoside antibiotics. Regulation of the aac(2')-Ia gene is influenced in a positive manner by the product of the aarP gene, which encodes a small transcriptional activator of the AraC (XylS) family. In this study, we demonstrate the sequence requirements at the aac(2')-Ia promoter for AarP binding and activation.

  4. Functional characterization of Escherichia coli GlpG and additional rhomboid proteins using an aarA mutant of Providencia stuartii.

    PubMed

    Clemmer, Katy M; Sturgill, Gwen M; Veenstra, Alexander; Rather, Philip N

    2006-05-01

    The Providencia stuartii AarA protein is a member of the rhomboid family of intramembrane serine proteases and required for the production of an extracellular signaling molecule that regulates cellular functions including peptidoglycan acetylation, methionine transport, and cysteine biosynthesis. Additional aarA-dependent phenotypes include (i) loss of an extracellular yellow pigment, (ii) inability to grow on MacConkey agar, and (iii) abnormal cell division. Since these phenotypes are easily assayed, the P. stuartii aarA mutant serves as a useful host system to investigate rhomboid function. The Escherichia coli GlpG protein was shown to be functionally similar to AarA and rescued the above aarA-dependent phenotypes in P. stuartii. GlpG proteins containing single alanine substitutions at the highly conserved catalytic triad of asparagine (N154A), serine (S201A), or histidine (H254A) residues were nonfunctional. The P. stuartii aarA mutant was also used as a biosensor to demonstrate that proteins from a variety of diverse sources exhibited rhomboid activity. In an effort to further investigate the role of a rhomboid protein in cell physiology, a glpG mutant of E. coli was constructed. In phenotype microarray experiments, the glpG mutant exhibited a slight increase in resistance to the beta-lactam antibiotic cefotaxime.

  5. The first Japanese case of leukodystrophy with ovarian failure arising from novel compound heterozygous AARS2 mutations.

    PubMed

    Hamatani, Mio; Jingami, Naoto; Tsurusaki, Yoshinori; Shimada, Shino; Shimojima, Keiko; Asada-Utsugi, Megumi; Yoshinaga, Kenji; Uemura, Norihito; Yamashita, Hirofumi; Uemura, Kengo; Takahashi, Ryosuke; Matsumoto, Naomichi; Yamamoto, Toshiyuki

    2016-10-01

    Even now, only a portion of leukodystrophy patients are correctly diagnosed, though various causative genes have been identified. In the present report, we describe a case of adult-onset leukodystrophy in a woman with ovarian failure. By whole-exome sequencing, a compound heterozygous mutation consisting of NM_020745.3 (AARS2_v001):c.1145C>A and NM_020745.3 (AARS2_v001):c.2255+1G>A was identified. Neither of the mutations has been previously reported, and this is the first report of alanyl-transfer RNA synthetase 2 mutation in Asia. We anticipate that further studies of the molecular basis of leukodystrophy will provide insight into its pathogenesis and hopefully lead to sophisticated diagnostic and treatment strategies.

  6. A NASA F/A-18, participating in the Automated Aerial Refueling (AAR) project, flies over the Dryden

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A NASA F/A-18 flies over the Dryden Flight Research Center and Rogers Dry Lake on December 11, 2002. The aircraft is participating in the Automated Aerial Refueling (AAR) project. The 300-gallon aerial refueling store seen on the belly of the aircraft carries fuel and a refueling drogue. This aircraft acts as a tanker in the study to develop an aerodynamic model for future automated aerial refueling, especially of unmanned vehicles.

  7. Lgr4 promotes prostate tumorigenesis through the Jmjd2a/AR signaling pathway.

    PubMed

    Zhang, Jianwei; Li, Qi; Zhang, Shaojin; Xu, Quanquan; Wang, Tianen

    2016-11-15

    Lgr4 (leucine-rich repeat domain containing G protein-coupled receptor 4) is implicated in the transcriptional regulation of multiple histone demethylases in the progression of diverse cancers, but there are few reports concerning the molecular mechanism by which Lgr4 regulates histone demethylase activation in prostate cancer (PCa) progression. As Jmjd2a is a histone demethylase, in the current study, we investigated the relationship between interaction Lgr4 with Jmjd 2a and Jmjd2a/androgen receptor (AR) signaling pathway in PCa progression. Firstly, Lgr4 was overexpressed by transfecting pcDNA3.1(+)/Lgr4 plasmids into PCa (LNCaP and PC-3) cell lines. Next, we found that Lgr4 overexpression promoted Jmjd2a mRNA expression, reduced cell apoptosis and arrested cell cycle in the S phase, these effects were reversed by Jmjd2a silencing. Moreover, Lgr4 overexpression markedly elevated AR levels and its interaction with Jmjd2a, which was tested by co-immunoprecipitation and luciferase reporter assays. Furthermore, interaction AR with PSA promoter (containing an AR response element) was obviously improved by Lgr4 overexpression, and PSA silencing reduced Lgr4-induced cell apoptosis and cell cycle arrest in PCa cells. Taken together, Lgr4 may be a novel tumor marker providing new mechanistic insights into PCa progression. Lgr4 activates Jmjd2a/AR signaling pathway to promote interaction AR with PSA promoter, causing reduction of PCa apoptosis and cell cycle arrest.

  8. GAMMA DETECTOR RESPONSE/SOIL CONCENTRATION CORRELATION STUDY AT THE AAR MANUFACTURING, INC. SITE, LIVONIA, MICHIGAN

    SciTech Connect

    ALTIC, NICK A

    2013-03-22

    At the NRC's request, ORAU conducted surveys of the AAR Manufacturing site during the period of September 25 through September 27, 2012. The survey activities included walkover surveys and sampling activities. Once the survey team was onsite, the NRC personnel decided to forgo survey activities in the New Addition and the pickling area. Areas of the planned study boundary were inaccessible due to overgrowth/large pieces of concrete covering the soil surface; therefore, the study boundary was redefined. Gamma walkover scans of the site boundary and front yard identified multiple areas of elevated gamma radiation. As a result, two judgmental samples were collected. Sample results were above thorium background levels The answer to the PSQ relating to the relationship between thorium concentration in soil and NaI instrument response is Yes. NaI instrument response can be used as a predictor of Th-232 concentration in the 0 to 1 m layer. An R2 value of 0.79 was determined for the surface soil relationship, thus satisfying the DQOs. Moreover, the regression was cross-checked by comparing the predicted Th-232 soil core concentration to the average Th-232 concentration (Section 5.3.2). Based on the cross-check, the regression equation provides a reasonable estimate for the Th-232 concentration at the judgmental locations. Consideration must be given when applying this equation to other soil areas of the site. If the contamination was heterogeneously distributed, and not distributed in a discrete layer as it was in the study area, then using the regression equation to predict Th-232 concentration would not be applicable.

  9. Internal structure of the Aar Massif: What can we learn in terms of exploration for deep geothermal energy?

    NASA Astrophysics Data System (ADS)

    Herwegh, Marco; Baumberger, Roland; Wehrens, Philip; Schubert, Raphael; Berger, Alfons; Maeder, Urs; Spillmann, Thomas

    2014-05-01

    The successful use of deep geothermal energy requires 3D flow paths, which allow an efficient heat exchange between the surrounding host rocks and the circulating fluids. Recent attempts to exploit this energy resource clearly demonstrate that the new technology is facing sever problems. Some major problems are related to the prediction of permeability, the 3D structure of the flow paths and the mechanical responses during elevated fluid pressures at depths of several kilometers. Although seemingly new in a technical perspective, nature is facing and solving similar problems since the beginning of the Alpine orogeny. Based on detailed studies in the Hasli Valley (Aar Massif) we can demonstrate that deformation and fluid flow are strongly localized along mechanical anisotropies (e.g. lithological variations, brittle and ductile faults). Some of them already evolved during Variscan and post-Variscan times. Interestingly, these inherited structures are reactivated over and over again during the Alpine orogeny. Their reactivation occurred at depths of ~13-15 km with elevated temperatures (400-475°C) and involved both ductile and brittle deformation processes. Brittle deformation in form of hydrofracking was always present due to the circulating fluids. It is this process, which was and still is responsible for seismic activity. With progressive uplift and exhumation of the Aar Massif, ductile deformation structures became replaced by brittle cataclasites and fault gouges during fault activity at shallower crustal levels. Existing hydrotest data from the Grimsel Test Site (Nagra's underground research laboratory) indicate that these brittle successors of the ductile shear zones are domains of enhanced recent fluid percolation. Note that although being exposed today, the continuation of these fault structures are still active at depth in both brittle and ductile deformation modes, a fact that can be inferred from recent uplift rates and the active seismicity. On the

  10. Altitude of the upper boundary of AAR based on observations of ion beams in inverted-V structures: A case study

    NASA Astrophysics Data System (ADS)

    Cui, YanBo; Fu, SuiYan; Zong, QuiGang; Xie, Lun; Sun, WeiJie; Zhao, Duo; Wu, Tong; Parks, George

    2016-07-01

    Outflowing ion beams forming four successive inverted-V structures in the energy-time spectrograms of H+, He+, and O+ were observed at an altitude of 3.4 RE by Cluster satellites travelling above the auroral acceleration region (AAR) in the southern hemisphere on February 14, 2001. Energization by negative U-shaped potential structures in the AAR is believed to be responsible for the formation of these outflowing ion inverted-V structures. Thus, utilizing the different motion properties of the three ion species, the altitude of the upper boundary of the AAR is estimated to be 11100 km. Moreover, based on multi-satellite observations, each ofthese U-shaped potential structures involved in this event crosses the latitud in aldirection at 0.4°-1° invariant latitude (ILAT), moving poleward at an average speed of 0.2° ILAT per minute, before disappearing at 71.5° ILAT.

  11. Amino acid racemization analysis (AAR) as a successful tool for dating Holocene coastal sediments: Stratigraphy of a barrier island spit (Southern Sylt/North Sea)

    NASA Astrophysics Data System (ADS)

    Tillmann, Tanja; Ziehe, Daniel

    2014-05-01

    Dating of Holocene sediments in shallow coastal areas of the German North Sea by conventional techniques is commonly problematic. In particular the marine reservoir effect of radiocarbon means that radiocarbon dating cannot be applied to sediments younger than about 400 years. Amino acid racemization dating (AAR) is a viable alternative for dating young sediments. The method is based on the determination of ratios of D and L amino acid enantiomers in organic matrices of biogenic carbonates. In this study we use AAR as a tool for dating Holocene barrier islands sediments. Based on an AAR derived chronological framework we develop a model of barrier spit accretion which describes the interaction between extreme events, fair weather coastal processes and sedimentary development that constrains the major episodes of barrier island evolution. The stratigraphy was defined using ground-penetrating radar (GPR) surveys complemented by sedimentological coring data. The stratigraphy is then conceptualised in a AAR chronostratigraphic framework to define a chronological order and allow the development of a stratigraphic model of the evolution of Southern Sylt. The AAR data provide high temporal resolution and have been used for dating stages of barrier spit accretion. The time lines are marked as storm surge generated erosion unconformities in the stratigraphic profile. Individual shells and shell fragments of Cerastoderma edule, Mya arenaria, Mytilus edulis and Scrobicularia plana have been accumulated by short-term storm events as shell layers associated with the erosion unconformities and have been dated by AAR. Time lines reveal that the barrier spit accretion occurred episodically, and is dependant on the provided rate of sand delivery. The general trend is that sequences young to the. South. The AAR derived time lines have been verified and correlated by historic maps and sea charts. It is apparent that spit enlargement at this site increased significantly during the

  12. aarD, a Providencia stuartii homologue of cydD: role in 2'-N-acetyltransferase expression, cell morphology and growth in the presence of an extracellular factor.

    PubMed

    Macinga, D R; Rather, P N

    1996-02-01

    In a search for genes involved in regulation of the 2'-N-acetyltransferase in Providencia stuartii, a mini-Tn5Cm insertion has been isolated in a locus designated aarD. The aarD1::mini-Tn5Cm mutation resulted in a 4.7-fold increase in the levels of beta-galactosidase accumulation from an aac(2')-lacZ transcriptional fusion and a 32-fold increase in the levels of gentamicin resistance in P. stuartii. The wild-type aarD locus was cloned on a 5.0 kb Cla I fragment and complemented the aarD1 mutation. Nucleotide sequence analysis of this fragment identified two large open reading frames whose deduced products displayed significant amino acid identity, 64% and 64%, respectively, to the CydD and CydC proteins of Escherichia coli, which are involved in formation of the cytochrome d oxidase complex. Physical mapping indicated the aarD1::mini-Tn5Cm insertion was within the open reading homologous to CydD. The strain containing the aarD1 mutation was unable to grow in the presence of toluidine blue or on glycerol minimal media in the presence of zinc, suggesting that aarD is functionally equivalent to cydD. Additional phenotypes resulting from the aarD1 mutation included: altered cell morphology, a reduced growth rate and the inability of cells to grow beyond early log phase. Further examination of this phenomenon revealed that the aarD1 mutant was unable to grow in the presence of a self-produced extracellular factor(s). This novel phenotype was limited to P. stuartii as E. coli cydD and delta cydAB::kan mutants were also sensitive to a self-produced extracellular factor.

  13. Magnetic fabric (AMS, AAR) of the Santa Marta batholith (northern Colombia) and the shear deformation along the Caribbean Plate margin

    NASA Astrophysics Data System (ADS)

    Salazar, Carlos A.; Bustamante, Camilo; Archanjo, Carlos J.

    2016-10-01

    Anisotropy of low-field magnetic susceptibility (AMS) and anhysteretic remanence (AAR) were measured in the Santa Marta Batholith formed by subduction of the Caribbean Plate beneath the northern South America. The batholith, elongated in the N-S direction, records multiple pulses of quartzdiorite to tonalite and granodiorite magmas between 58 and 49 Ma. The high mean magnetic susceptibility (4 × 10-3 SI) combined with thermomagnetic and partial magnetic remanence measurements indicate that the magnetic susceptibility depends on Ti-poor magnetite. AMS is defined by ellipsoids that are dominantly oblate. The foliation was used to distinguish a narrow band of E-trending magnetic structures that separate the batholith in two lobes. The southern lobe is characterized by foliations that are broadly parallel to the contact with the wall rocks, while the northern lobe by foliations oblique to the batholith elongation. Late tonalitic magmas dated at c. 50 Ma record, in turn, a fabric apparently controlled by E-trending tectonic events. Partial AAR indicates that the subfabrics of magnetite with different grain sizes are nearly parallel to AMS, therefore discarding the possibility of superposed fabrics with different orientations. The magnetic fabric pattern is consistent with a magma emplaced in an arc setting deformed by a dextral shear. Synthetic extensional shear bands localize the magmatic deformation along East-trending corridors that probably were exploited to emplace the late magmatic pulses. Accretion of the Eocene batholith and the Late Cretaceous metasedimentary host-rocks to the South American continent defines a major strike-slip shear suture that resulted from the oblique convergence of the Caribbean Plate.

  14. Structural modeling of tissue-specific mitochondrial alanyl-tRNA synthetase (AARS2) defects predicts differential effects on aminoacylation.

    PubMed

    Euro, Liliya; Konovalova, Svetlana; Asin-Cayuela, Jorge; Tulinius, Már; Griffin, Helen; Horvath, Rita; Taylor, Robert W; Chinnery, Patrick F; Schara, Ulrike; Thorburn, David R; Suomalainen, Anu; Chihade, Joseph; Tyynismaa, Henna

    2015-01-01

    The accuracy of mitochondrial protein synthesis is dependent on the coordinated action of nuclear-encoded mitochondrial aminoacyl-tRNA synthetases (mtARSs) and the mitochondrial DNA-encoded tRNAs. The recent advances in whole-exome sequencing have revealed the importance of the mtARS proteins for mitochondrial pathophysiology since nearly every nuclear gene for mtARS (out of 19) is now recognized as a disease gene for mitochondrial disease. Typically, defects in each mtARS have been identified in one tissue-specific disease, most commonly affecting the brain, or in one syndrome. However, mutations in the AARS2 gene for mitochondrial alanyl-tRNA synthetase (mtAlaRS) have been reported both in patients with infantile-onset cardiomyopathy and in patients with childhood to adulthood-onset leukoencephalopathy. We present here an investigation of the effects of the described mutations on the structure of the synthetase, in an effort to understand the tissue-specific outcomes of the different mutations. The mtAlaRS differs from the other mtARSs because in addition to the aminoacylation domain, it has a conserved editing domain for deacylating tRNAs that have been mischarged with incorrect amino acids. We show that the cardiomyopathy phenotype results from a single allele, causing an amino acid change R592W in the editing domain of AARS2, whereas the leukodystrophy mutations are located in other domains of the synthetase. Nevertheless, our structural analysis predicts that all mutations reduce the aminoacylation activity of the synthetase, because all mtAlaRS domains contribute to tRNA binding for aminoacylation. According to our model, the cardiomyopathy mutations severely compromise aminoacylation whereas partial activity is retained by the mutation combinations found in the leukodystrophy patients. These predictions provide a hypothesis for the molecular basis of the distinct tissue-specific phenotypic outcomes.

  15. An attempt to validate the ultra-accelerated microbar and the concrete performance test with the degree of AAR-induced damage observed in concrete structures

    SciTech Connect

    Leemann, Andreas; Merz, Christine

    2013-07-15

    There is little knowledge about the relation between AAR-induced damage observed in structures and the expansion potential obtained with accelerated tests. In this study, aggregates used in structures damaged by AAR were tested with the microbar test (MBT/AFNOR XP 18-594) and the concrete performance test (CPT/AFNOR P18-454). After the tests, the samples were examined using optical and scanning electron microscopy. Based on the results, the significance of the microbar test has to be examined very critically. The agreement of measured expansion, reacted rock types and the composition of the reaction products between the on-site concrete and the reproduced concrete subjected to the CPT clearly indicates that the reaction mechanisms in the structure and in the concrete performance test are comparable. As such, the concrete performance test seems to be an appropriate tool to test the potential reactivity of specific concrete mixtures.

  16. Thermal properties of Central Aare granite for temperatures up to 500°C: Irreversible changes due to thermal crack formation

    NASA Astrophysics Data System (ADS)

    Kant, Michael A.; Ammann, Jens; Rossi, Edoardo; Madonna, Claudio; Höser, Dragana; Rudolf von Rohr, Philipp

    2017-01-01

    Thermal diffusivity, heat capacity, and thermal conductivity of Central Aare granite are reported in the temperature range from 25°C to 500°C. Each rock sample underwent three consecutive heating and cooling cycles. Significant irreversible changes in the properties due to thermal crack formation could be observed. After the first thermal cycle, both thermal diffusivity and conductivity dropped to about 75% of the initial value at room temperature, whereas the heat capacity did not show an irreversible decay. For subsequent thermal cycles, no further permanent changes of the investigated properties could be observed. From the conducted measurements, accurate correlations are derived, offering a platform for precise high-temperature experiments and other research on Central Aare granite and similar granitic rocks. The report shows that the assumption of constant thermal properties leads to significant inaccuracies at elevated temperatures, especially if thermal cycles are present.

  17. A one- and two-dimensional cross-section sensitivity and uncertainty path of the AARE (Advanced Analysis for Reactor Engineering) modular code system

    SciTech Connect

    Davidson, J.W.; Dudziak, D.J.; Higgs, C.E.; Stepanek, J.

    1988-01-01

    AARE, a code package to perform Advanced Analysis for Reactor Engineering, is a linked modular system for fission reactor core and shielding, as well as fusion blanket, analysis. Its cross-section sensitivity and uncertainty path presently includes the cross-section processing and reformatting code TRAMIX, cross-section homogenization and library reformatting code MIXIT, the 1-dimensional transport code ONEDANT, the 2-dimensional transport code TRISM, and the 1- and 2- dimensional cross-section sensitivity and uncertainty code SENSIBL. IN the present work, a short description of the whole AARE system is given, followed by a detailed description of the cross-section sensitivity and uncertainty path. 23 refs., 2 figs.

  18. Estimating the gas transfer velocity: a prerequisite for more accurate and higher resolution GHG fluxes (lower Aare River, Switzerland)

    NASA Astrophysics Data System (ADS)

    Sollberger, S.; Perez, K.; Schubert, C. J.; Eugster, W.; Wehrli, B.; Del Sontro, T.

    2013-12-01

    Currently, carbon dioxide (CO2) and methane (CH4) emissions from lakes, reservoirs and rivers are readily investigated due to the global warming potential of those gases and the role these inland waters play in the carbon cycle. However, there is a lack of high spatiotemporally-resolved emission estimates, and how to accurately assess the gas transfer velocity (K) remains controversial. In anthropogenically-impacted systems where run-of-river reservoirs disrupt the flow of sediments by increasing the erosion and load accumulation patterns, the resulting production of carbonic greenhouse gases (GH-C) is likely to be enhanced. The GH-C flux is thus counteracting the terrestrial carbon sink in these environments that act as net carbon emitters. The aim of this project was to determine the GH-C emissions from a medium-sized river heavily impacted by several impoundments and channelization through a densely-populated region of Switzerland. Estimating gas emission from rivers is not trivial and recently several models have been put forth to do so; therefore a second goal of this project was to compare the river emission models available with direct measurements. Finally, we further validated the modeled fluxes by using a combined approach with water sampling, chamber measurements, and highly temporal GH-C monitoring using an equilibrator. We conducted monthly surveys along the 120 km of the lower Aare River where we sampled for dissolved CH4 (';manual' sampling) at a 5-km sampling resolution, and measured gas emissions directly with chambers over a 35 km section. We calculated fluxes (F) via the boundary layer equation (F=K×(Cw-Ceq)) that uses the water-air GH-C concentration (C) gradient (Cw-Ceq) and K, which is the most sensitive parameter. K was estimated using 11 different models found in the literature with varying dependencies on: river hydrology (n=7), wind (2), heat exchange (1), and river width (1). We found that chamber fluxes were always higher than boundary

  19. Lake Biel sediment record during the last 7500 years and impact of the Aare river deviation in 1878 AD.

    NASA Astrophysics Data System (ADS)

    Jeannet, Alice; Corella, Juan Pablo; Reusch, Anna; Kremer, Katrina; Girardclos, Stéphanie

    2013-04-01

    Lake sediments are excellent archives of environmental and climate changes as well as human impact on lake- and river-systems. Lake Biel is a medium-sized peri-alpine lake (Switzerland) with a maximum depth of 74 m and lies at 429 m asl. Our study focuses on the south-west basin, where the lake sedimentation was naturally mainly controlled by autochthonous sedimentation, and is now, since the artificial Aare river deviation through the Hagneck canal in 1878 AD, under the strong influence of water and sediment input from its catchment. A 10.05-m-long composite sediment sequence, cored in 2011 at 52 m water depth, was built from two cores retrieved with an Uwitec system. The cored sedimentary sequence begins in 1975 and spans the last 7500 years, as dated by seven 14C analyses and 210Pb/137Cs activity profiles. Magnetic susceptibility and density were measured with a Geotek MSCL at 0.5 cm resolution, granulometry with a CILAS grain sizer every 10 cm and X-ray fluorescence measurements were carried out using an Avaatech core scanner at 1-cm resolution. Lake Biel sediment record is subdivided in four main units. The lowest Unit A (651-1005 cm; 7355 to 5075 BP), with dark greyish clayey silty laminated layers and sedimentation rates between 0.10 to 0.29 cm/yr, shows stable low values for almost all proxies, excepted for allochtonous elements which increase between 7000-6000 BP. By analogy with Unit C facies (see below), Unit A is interpreted as influenced by the Aare river which probably flew into the south-west basin at that time. Unit B1 (651-343 cm, 5075 to 2036 BP) has lower sedimentation rate (0.10 cm/yr), high Ca/Ti ratio, light sediment color, constant clayey silty grain size and varying elemental profiles which point to the dominant influence of autochtonous lake processes influenced by climate. From the beginning of Unit B2 (343-147 cm, 2036 to 1878 AD) sediment grain size increases which possibly reflects a human influence over the lake system. The greatest

  20. This NASA Dryden F/A-18 is participating in the Automated Aerial Refueling (AAR) project. F/A-18 (No

    NASA Technical Reports Server (NTRS)

    2002-01-01

    A NASA Dryden F/A-18 is participating in the Automated Aerial Refueling (AAR) project. F/A-18 (No. 847) is acting as an in-flight refueling tanker in the study to develop analytical models for an automated aerial refueling system for unmanned vehicles. A 300-gallon aerodynamic pod containing air-refueling equipment is seen beneath the fuselage. The hose and refueling basket are extended during an assessment of their dynamics on the F/A-18A.

  1. Identification and characterization of aarF, a locus required for production of ubiquinone in Providencia stuartii and Escherichia coli and for expression of 2'-N-acetyltransferase in P. stuartii.

    PubMed

    Macinga, D R; Cook, G M; Poole, R K; Rather, P N

    1998-01-01

    Providencia stuartii contains a chromosomal 2'-N-acetyltransferase [AAC(2')-Ia] involved in the O acetylation of peptidoglycan. The AAC(2')-Ia enzyme is also capable of acetylating and inactivating certain aminoglycosides and confers high-level resistance to these antibiotics when overexpressed. We report the identification of a locus in P. stuartii, designated aarF, that is required for the expression of AAC(2')-Ia. Northern (RNA) analysis demonstrated that aac(2')-Ia mRNA levels were dramatically decreased in a P. stuartii strain carrying an aarF::Cm disruption. The aarF::Cm disruption also resulted in a deficiency in the respiratory cofactor ubiquinone. The aarF locus encoded a protein that had a predicted molecular mass of 62,559 Da and that exhibited extensive amino acid similarity to the products of two adjacent open reading frames of unknown function (YigQ and YigR), located at 86 min on the Escherichia coli chromosome. An E. coli yigR::Kan mutant was also deficient in ubiquinone content. Complementation studies demonstrated that the aarF and the E. coli yigQR loci were functionally equivalent. The aarF or yigQR genes were unable to complement ubiD and ubiE mutations that are also present at 86 min on the E. coli chromosome. This result indicates that aarF (yigQR) represents a novel locus for ubiquinone production and reveals a previously unreported connection between ubiquinone biosynthesis and the regulation of gene expression.

  2. How is strain localized in a meta-granitoid, mid-crustal basement section? Spatial distribution of deformation in the central Aar massif (Switzerland)

    NASA Astrophysics Data System (ADS)

    Wehrens, P.; Baumberger, R.; Berger, A.; Herwegh, M.

    2017-01-01

    This study investigates strain distribution in granitoid rocks formerly in the middle crust in the Central Aar massif, Switzerland and places the deformation behavior in the tectonic framework of the Alpine orogeny. Strain is heterogeneously distributed in terms of strain partitioning forming several hundreds of closely spaced shear zones (SZ) (>80 SZ/km with SZ thicknesses <10 cm; about 10 SZ/km with SZ thicknesses of 0.5-10 m) separating 3D bodies of low to moderate background strain. Both the degree of background-strain intensity as well as the number of shear zones increases from granitic to granodioritic host rocks and is controlled by primary variations in the mica content between 10 and 15 vol% (granodiorite) and <8 vol% (granite). Shear zones evolved from ductile shearing in granodiorites, whereas they often nucleated from fractures in the stronger granites. The majority of the steep shear zones preferentially accommodated upward motion by the southern block leading to an increase in peak metamorphic conditions from 250 °C in the North to 450 °C in the South of the Aar massif. The shear zones initiated at about 18-20 km depths during a stage of crustal thickening (Handegg phase). Subsequent deformation reactivated some shear zones with a gradual transition from reverse dip-slip over oblique-slip to strike-slip shear zones under local transpressional conditions (Oberaar phase).

  3. A specialized citric acid cycle requiring succinyl-coenzyme A (CoA):acetate CoA-transferase (AarC) confers acetic acid resistance on the acidophile Acetobacter aceti.

    PubMed

    Mullins, Elwood A; Francois, Julie A; Kappock, T Joseph

    2008-07-01

    Microbes tailor macromolecules and metabolism to overcome specific environmental challenges. Acetic acid bacteria perform the aerobic oxidation of ethanol to acetic acid and are generally resistant to high levels of these two membrane-permeable poisons. The citric acid cycle (CAC) is linked to acetic acid resistance in Acetobacter aceti by several observations, among them the oxidation of acetate to CO2 by highly resistant acetic acid bacteria and the previously unexplained role of A. aceti citrate synthase (AarA) in acetic acid resistance at a low pH. Here we assign specific biochemical roles to the other components of the A. aceti strain 1023 aarABC region. AarC is succinyl-coenzyme A (CoA):acetate CoA-transferase, which replaces succinyl-CoA synthetase in a variant CAC. This new bypass appears to reduce metabolic demand for free CoA, reliance upon nucleotide pools, and the likely effect of variable cytoplasmic pH upon CAC flux. The putative aarB gene is reassigned to SixA, a known activator of CAC flux. Carbon overflow pathways are triggered in many bacteria during metabolic limitation, which typically leads to the production and diffusive loss of acetate. Since acetate overflow is not feasible for A. aceti, a CO(2) loss strategy that allows acetic acid removal without substrate-level (de)phosphorylation may instead be employed. All three aar genes, therefore, support flux through a complete but unorthodox CAC that is needed to lower cytoplasmic acetate levels.

  4. Quantitative assessment of alkali-reactive aggregate mineral content through XRD using polished sections as a supplementary tool to RILEM AAR-1 (petrographic method)

    SciTech Connect

    Castro, Nelia; Sorensen, Bjorn E.; Broekmans, Maarten A.T.M.

    2012-11-15

    The mineral content of 5 aggregate samples from 4 different countries, including reactive and non-reactive aggregate types, was assessed quantitatively by X-ray diffraction (XRD) using polished sections. Additionally, electron probe microanalyzer (EPMA) mapping and cathodoluminescence (CL) were used to characterize the opal-CT identified in one of the aggregate samples. Critical review of results from polished sections against traditionally powdered specimen has demonstrated that for fine-grained rocks without preferred orientation the assessment of mineral content by XRD using polished sections may represent an advantage over traditional powder specimens. Comparison of data on mineral content and silica speciation with expansion data from PARTNER project confirmed that the presence of opal-CT plays an important role in the reactivity of one of the studied aggregates. Used as a complementary tool to RILEM AAR-1, the methodology suggested in this paper has the potential to improve the strength of the petrographic method.

  5. SU-E-T-644: QuAArC: A 3D VMAT QA System Based On Radiochromic Film and Monte Carlo Simulation of Log Files

    SciTech Connect

    Barbeiro, A.R.; Ureba, A.; Baeza, J.A.; Jimenez-Ortega, E.; Plaza, A. Leal; Linares, R.; Mateos, J.C.; Velazquez, S.

    2015-06-15

    Purpose: VMAT involves two main sources of uncertainty: one related to the dose calculation accuracy, and the other linked to the continuous delivery of a discrete calculation. The purpose of this work is to present QuAArC, an alternative VMAT QA system to control and potentially reduce these uncertainties. Methods: An automated MC simulation of log files, recorded during VMAT treatment plans delivery, was implemented in order to simulate the actual treatment parameters. The linac head models and the phase-space data of each Control Point (CP) were simulated using the EGSnrc/BEAMnrc MC code, and the corresponding dose calculation was carried out by means of BEAMDOSE, a DOSXYZnrc code modification. A cylindrical phantom was specifically designed to host films rolled up at different radial distances from the isocenter, for a 3D and continuous dosimetric verification. It also allows axial and/or coronal films and point measurements with several types of ion chambers at different locations. Specific software was developed in MATLAB in order to process and evaluate the dosimetric measurements, which incorporates the analysis of dose distributions, profiles, dose difference maps, and 2D/3D gamma index. It is also possible to obtain the experimental DVH reconstructed on the patient CT, by an optimization method to find the individual contribution corresponding to each CP on the film, taking into account the total measured dose, and the corresponding CP dose calculated by MC. Results: The QuAArC system showed high reproducibility of measurements, and consistency with the results obtained with the commercial system implemented in the verification of the evaluated treatment plans. Conclusion: A VMAT QA system based on MC simulation and high resolution dosimetry with film has been developed for treatment verification. It shows to be useful for the study of the real VMAT capabilities, and also for linac commissioning and evaluation of other verification devices.

  6. Diagnostic Accuracy of APRI, AAR, FIB-4, FI, and King Scores for Diagnosis of Esophageal Varices in Liver Cirrhosis: A Retrospective Study.

    PubMed

    Deng, Han; Qi, Xingshun; Peng, Ying; Li, Jing; Li, Hongyu; Zhang, Yongguo; Liu, Xu; Sun, Xiaolin; Guo, Xiaozhong

    2015-12-20

    BACKGROUND Aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, fibrosis index (FI), and King scores might be alternatives to the use of upper gastrointestinal endoscopy for the diagnosis of esophageal varices (EVs) in liver cirrhosis. This study aimed to evaluate their diagnostic accuracy in predicting the presence and severity of EVs in liver cirrhosis. MATERIAL AND METHODS All patients who were consecutively admitted to our hospital and underwent upper gastrointestinal endoscopy between January 2012 and June 2014 were eligible for this retrospective study. Areas under curve (AUCs) were calculated. Subgroup analyses were performed according to the history of upper gastrointestinal bleeding (UGIB) and splenectomy. RESULTS A total of 650 patients with liver cirrhosis were included, and 81.4% of them had moderate-severe EVs. In the overall analysis, the AUCs of these non-invasive scores for predicting moderate-severe EVs and presence of any EVs were 0.506-0.6 and 0.539-0.612, respectively. In the subgroup analysis of patients without UGIB, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.601-0.664 and 0.596-0.662, respectively. In the subgroup analysis of patients without UGIB or splenectomy, their AUCs for predicting moderate-severe varices and presence of any EVs were 0.627-0.69 and 0.607-0.692, respectively. CONCLUSIONS APRI, AAR, FIB-4, FI, and King scores had modest diagnostic accuracy of EVs in liver cirrhosis. They might not be able to replace the utility of upper gastrointestinal endoscopy for the diagnosis of EVs in liver cirrhosis.

  7. Diagnostic Accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex Scores in Predicting the Presence of Esophageal Varices in Liver Cirrhosis: A Systematic Review and Meta-Analysis.

    PubMed

    Deng, Han; Qi, Xingshun; Guo, Xiaozhong

    2015-10-01

    Aspartate aminotransferase-to-platelet ratio (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), FIB-4, FI, King, Lok, Forns, and FibroIndex scores may be simple and convenient noninvasive diagnostic tests, because they are based on the regular laboratory tests and demographic data. This study aimed to systematically evaluate their diagnostic accuracy for the prediction of varices in liver cirrhosis.All relevant papers were searched via PubMed, EMBASE, CNKI, and Wanfang databases. The area under the summary receiver operating characteristic curve (AUSROC), sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), and diagnostic odds ratio (DOR) were calculated.Overall, 12, 4, 5, 0, 0, 4, 3, and 1 paper was identified to explore the diagnostic accuracy of APRI, AAR, FIB-4, FI, King, Lok, Forns, and FibroIndex scores, respectively. The AUSROCs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of varices were 0.6774, 0.7275, 0.7755, 0.7885, and 0.7517, respectively; and those for the prediction of large varices were 0.7278, 0.7448, 0.7095, 0.7264, and 0.6530, respectively. The diagnostic threshold effects of FIB-4 and Forns scores for the prediction of varices were statistically significant. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, and Lok scores for the prediction of varices were 0.60/0.67/1.77/0.58/3.13, 0.64/0.63/1.97/0.54/4.18, and 0.74/0.68/2.34/0.40/5.76, respectively. The sensitivities/specificities/PLRs/NLRs/DORs of APRI, AAR, FIB-4, Lok, and Forns scores for the prediction of large varices were 0.65/0.66/2.15/0.47/4.97, 0.68/0.58/2.07/0.54/3.93, 0.62/0.64/2.02/0.56/3.57, 0.78/0.63/2.09/0.37/5.55, and 0.65/0.61/1.62/0.59/2.75, respectively.APRI, AAR, FIB-4, Lok, and Forns scores had low to moderate diagnostic accuracy in predicting the presence of varices in liver cirrhosis.

  8. Distribution and inferred age of exfoliation joints in the Aar Granite of the central Swiss Alps and relationship to Quaternary landscape evolution

    NASA Astrophysics Data System (ADS)

    Ziegler, Martin; Loew, Simon; Moore, Jeffrey R.

    2013-11-01

    deepest exfoliation joint generation is associated with erosion of the inner glacial troughs of the upper Aar valley, which likely occurred during the mid-Pleistocene Revolution. Our study shows how exfoliation joint episodes can be dated, and, conversely, that better knowledge of the distribution of exfoliation joint sets can reveal unique information about the morphological evolution of an Alpine valley.

  9. The influence of snow cover on alpine floods reconstructed from the analysis of satellite images. The case of the Hasli-Aare river basin, Berner Oberland (1987-2012)

    NASA Astrophysics Data System (ADS)

    Cabrera-Medina, Paula; Schulte, Lothar; Carvalho, Filipe; Peña, Juan Carlos; García, Carles

    2016-04-01

    Regarding the hydrological hazards in the Hasli-Aare river over the last century, instrumental and documentary data show that flood frequency and magnitude increased since 1977. One of the main water inputs contributing to peak discharges is given by the thaw of the stored snow. Therefore, the knowledge of the evolution of snow cover is considered essential for the assessment of alpine floods. Snow cover studies can be made by different approaches such as the analysis of data provided by field work or by nivometeorological stations. However, these methods are usually expensive and do not present adequate spatial or temporal coverage data. For this reason, satellite images with different spatial and temporal resolution are an interesting complementary source for the understanding of the snow cover dynamics. The aim of the paper is to study the influence of snow cover variations during years of severe floods that occurred in the upper Aare basin from 1987 to 2012. Three satellite images have been selected for each of the 9 studied events: 1) maximum snow cover during winter, 2) the last image before the event and 3) the first image after the flood. Each image has been processed with the ArcGIS software applying a statistical method of supervised classification. This image processing allows the spatial quantification of the variation of the snow cover in the Aare headwater catchment. Because the melting of snow cover is related to the changes of weather situations before and during the flood episode, it is important to analyse also the nivometeorological data of stations located in the catchment (snow depth, temperature and precipitation). From these data we determined 4 types of flood, which can be classified according to their nivometeorological variables and synoptic situation (500 hPa geopotential and Sea Level Pressure) into two patterns. The first group of events can be associated to an Atlantic pattern recording decreasing temperatures, moderate to high

  10. Calibration of amino acid racemization (AAR) kinetics in United States mid-Atlantic Coastal Plain Quaternary mollusks using 87Sr/ 86Sr analyses: Evaluation of kinetic models and estimation of regional Late Pleistocene temperature history

    USGS Publications Warehouse

    Wehmiller, J. F.; Harris, W.B.; Boutin, B.S.; Farrell, K.M.

    2012-01-01

    The use of amino acid racemization (AAR) for estimating ages of Quaternary fossils usually requires a combination of kinetic and effective temperature modeling or independent age calibration of analyzed samples. Because of limited availability of calibration samples, age estimates are often based on model extrapolations from single calibration points over wide ranges of D/L values. Here we present paired AAR and 87Sr/ 86Sr results for Pleistocene mollusks from the North Carolina Coastal Plain, USA. 87Sr/ 86Sr age estimates, derived from the lookup table of McArthur et al. [McArthur, J.M., Howarth, R.J., Bailey, T.R., 2001. Strontium isotopic stratigraphy: LOWESS version 3: best fit to the marine Sr-isotopic curve for 0-509 Ma and accompanying Look-up table for deriving numerical age. Journal of Geology 109, 155-169], provide independent age calibration over the full range of amino acid D/L values, thereby allowing comparisons of alternative kinetic models for seven amino acids. The often-used parabolic kinetic model is found to be insufficient to explain the pattern of racemization, although the kinetic pathways for valine racemization and isoleucine epimerization can be closely approximated with this function. Logarithmic and power law regressions more accurately represent the racemization pathways for all amino acids. The reliability of a non-linear model for leucine racemization, developed and refined over the past 20 years, is confirmed by the 87Sr/ 86Sr age results. This age model indicates that the subsurface record (up to 80m thick) of the North Carolina Coastal Plain spans the entire Quaternary, back to ???2.5Ma. The calibrated kinetics derived from this age model yield an estimate of the effective temperature for the study region of 11??2??C., from which we estimate full glacial (Last Glacial Maximum - LGM) temperatures for the region on the order of 7-10??C cooler than present. These temperatures compare favorably with independent paleoclimate information

  11. Stable isotope and Ar/Ar evidence of prolonged multi-scale fluid flow during exhumation of orogenic crust: example from the Mont Blanc and Aar massifs (NW Alps)

    NASA Astrophysics Data System (ADS)

    Rolland, Yann; Rossi, Magali

    2015-04-01

    The spatial and temporal scales and the geometry of fluid pathways in a collisional orogen are investigated using stable isotope analysis (O, C, H) and 40Ar/39Ar dating of vein minerals formed at c. 11-16 Ma in the Mont Blanc and the Aar External Crystalline Massifs. In both massifs 40Ar/39Ar dating of veins adularia provides evidence for progressive crystallization from 16 to 9 Ma, and mainly at 11-12 Ma following veins opening during shear zone activity. The fluid flow duration thus ranges from 4 to 5 Ma in the two massifs. The δ18O values of vein quartz and calcite are similar to those of undeformed crystalline and sedimentary host-rocks, suggesting rock buffering, while carbon isotope ratios of vein calcites fall into three compositional groups. A-type veins have δ13C values that are buffered by the Helvetic metasediments, which suggests that these veins formed in a closed-system from a locally-derived CO2-rich fluid. The fluid in equilibrium with C-type veins has depleted δ13C values similar to mantle-CO2, while the intermediate δ13C values of B-type veins suggest mixing between the A-type and C-type fluids. These results are in agreement with crustal- to lithosphere-scale upward vertical fluid flow along vertical shear zones related to the strike-slip system bounding the Adriatic block since 16-20 Ma, connecting a deep-seated fluid to some downward flow in the sedimentary cover of External Crystalline Massifs.

  12. Reconstruction of peak water levels, peak discharges and long-term occurrence of extreme- as well as smaller pre-instrumental flood events of river Aare, Limmat, Reuss, Rhine and Saane in Switzerland. Part I

    NASA Astrophysics Data System (ADS)

    Wetter, Oliver; Tuttenuj, Daniel

    2016-04-01

    systematically analysed the period from 1446-1542 and could prove a large number of pre-instrumental flood events of river Rhine, Birs, Birsig and Wiese in Basel. All in all the weekly led account books contained 54 Rhine flood events, whereas chroniclers and annalists only recorded seven floods during the same period. This is a ratio of almost eight to one. This large difference points to the significantly sharper "observation skills" of the account books towards smaller floods, which may be explained by the fact that bridges can be endangered by relatively small floods because of driftwood, whereas it is known that chroniclers or annalists were predominantly focussing on spectacular (extreme) flood events. We [Oliver Wetter and Daniel Tuttenuj] are now able to present first preliminary results of reconstructed peak water levels and peak discharges of pre instrumental river Aare-, Emme-, Limmat-, Reuss-, Rhine- and Saane floods. These first results clearly show the strengths as well as the limits of the data and method used, depending mainly on the river types. Of the above mentioned rivers only the floods of river Emme could not be reconstructed whereas the long-term development of peak water levels and peak discharges of the other rivers clearly correlate with major local and supra-regional Swiss flood corrections over time. PhD student Daniel Tuttenuj is going to present the results for river Emme and Saane (see Abstract Daniel Tuttenuj), whereas Dr Oliver Wetter is going to present the results for the other rivers and gives a first insight on long-term recurring periods of smaller river Birs-, Birsig-, Rhine- and Wiese flood events based on the analysis of the weekly led account books "Wochenausgabenbücher der Stadt Basel" (see also Abstract of Daniel Tuttenuj).

  13. Reconstruction of peak water levels, peak discharges and long-term occurrence of extreme- as well as smaller pre-instrumental flood events of river Aare, Limmat, Reuss, Rhine and Saane in Switzerland. Part II.

    NASA Astrophysics Data System (ADS)

    Tuttenuj, Daniel; Wetter, Oliver

    2016-04-01

    contained 54 Rhine flood events, whereas chroniclers and annalists only recorded seven floods during the same period. This is a ratio of almost eight to one. This large difference points to the significantly sharper "observation skills" of the account books towards smaller floods, which may be explained by the fact that bridges can be endangered by relatively small floods because of driftwood, whereas it is known that chroniclers or annalists were predominantly focussing on spectacular (extreme) flood events. We [Oliver Wetter and Daniel Tuttenuj] are now able to present first preliminary results of reconstructed peak water levels and peak discharges of pre instrumental river Aare-, Emme-, Limmat-, Reuss-, Rhine- and Saane floods. These first results clearly show the strengths as well as the limits of the data and method used, depending mainly on the river types. Of the above mentioned rivers only the floods of river Emme could not be reconstructed whereas the long-term development of peak water levels and peak discharges of the other rivers clearly correlate with major local and supra-regional Swiss flood corrections over time. PhD student Daniel Tuttenuj is going to present the results of river Emme and Saane, whereas Dr Oliver Wetter is going to present the results for the other rivers and gives a first insight on long-term recurring periods of smaller river Birs, Birsig, Rhine and Wiese flood events based on the analysis of the weekly led account books "Wochenausgabenbücher der Stadt Basel" (see Abstract Oliver Wetter).

  14. F/A-18 Automated Aerial Refueling (AAR) Phase 1

    NASA Video Gallery

    Engineers at NASA's Dryden Flight Research Center are evaluating the capability of an F/A-18A aircraft as an in-flight refueling tanker to develop analytical models for an automated aerial refuelin...

  15. AAR in concrete of Asejire spillway (OYO state - Nigeria)

    SciTech Connect

    Lamaudiere, J.P.; Spaeti, F.

    1995-12-31

    The Asejire dam at Ibadan, Nigeria was constructed in the late sixties for the purpose of providing water for the city of Ibadan (presently about 4,5 million inhabitants). It is located on the Oshun river approximately fifteen miles from the city. In 1982 cracks were observed on the wing walls and although these continued to develop, no attempt was made at that time to investigate their causes and no repair was carried out. In 1989 the SGI ENGINEERING Group of Geneva, Switzerland was appointed as the consultant for the complete refurbishment of the Asejire water scheme. The consortium Degremont-Poat-Clemessy was awarded the contract for the project. The African Development Bank and the Nigerian Government have provided the loan to finance the project.

  16. Automated Support for After Action Review (AAR) Presentation

    DTIC Science & Technology

    2009-09-01

    will be per SOP. Casualty collection point will be in the ORP. EPW collection point will be at the ORP area. 5. Command and Signal...from women. Moves occupants to central location, separates, and prevents communication. Need an EPW collection point. Anyone carrying a...weapon will go to an EPW collection point which is often outside the building. After room is cleared and upon encountering non- combative occupants

  17. The NASA Dryden AAR Project: A Flight Test Approach to an Aerial Refueling System

    NASA Technical Reports Server (NTRS)

    Hansen, Jennifer L.; Murray, James E.; Campos, Norma V.

    2004-01-01

    The integration of uninhabited aerial vehicles (UAVs) into controlled airspace has generated a new era of autonomous technologies and challenges. Autonomous aerial refueling would enable UAVs to travel further distances and loiter for extended periods over time-critical targets. The NASA Dryden Flight Research Center recently has completed a flight research project directed at developing a dynamic hose and drogue system model to support the development of an automated aerial refueling system. A systematic dynamic model of the hose and drogue system would include the effects of various influences on the system, such as flight condition, hose and drogue type, tanker type and weight, receiver type, and tanker and receiver maneuvering. Using two NASA F/A-18 aircraft and a conventional hose and drogue aerial refueling store from the Navy, NASA has obtained flight research data that document the response of the hose and drogue system to these effects. Preliminary results, salient trends, and important lessons are presented.

  18. 76 FR 47612 - AAR Manufacturing, Inc.; Completion of Radiological Survey Activities at CSX Transportation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-05

    ... potential doses to the public from the residual radioactivity at the site, it was determined that..., ``Radiological Criteria for License Termination,'' are not being met and residual radioactivity at the site...

  19. The contribution of quartz and the role of aluminum for understanding the AAR with greywacke

    SciTech Connect

    Huenger, Klaus-Juergen E-mail: huenger@tu-cottbus.de

    2007-08-15

    Precambrian Greywacke from Lower Lusatia (Germany) has been well known as an alkali sensitive aggregate for several years. It can cause considerable damages in concrete buildings due to an Alkali-Aggregate-Reaction. The investigations are focused on quartz as the main releaser of silica, its characterization and its behavior in an alkaline solution. But there are no relations between quartz properties and the alkali sensitivities of greywacke samples. To understand this fact the role of aluminum which greywacke releases in different amounts into the alkaline solution too must be considered. Aluminum affects the silica concentration by three different mechanisms. The result is always a decrease of the silica concentration in the solution caused by an alumino silicate formation. The silica bound by alumino silicate structures can be quantified by {sup 27}Al-NMR-spectroscopy. The expansions of concrete samples can now be described much well as a function of a so called 'free' silica. Based on this results a direct test method for the assessment of the alkali sensitivity of greywackes could be created and suggestions for an inhibition can be given.

  20. Current Issues in the Use of Virtual Simulations for Dismounted Soldier Training

    DTIC Science & Technology

    2006-06-01

    Team A Fire Team B SAF AAR Battle Master Bravo Fire Team Leader Squad Leader 40 ft 10 ft10 ft10 ft10 ft AAR Facility Internet Connection Figure 1...Squad Leader 40 ft 10 ft10 ft10 ft10 ft AAR Facility Internet Connection 2004 V-IMTS Network Configuration AAR Leader AAR Operator DIVAARS SL

  1. AarF Domain Containing Kinase 3 (ADCK3) Mutant Cells Display Signs of Oxidative Stress, Defects in Mitochondrial Homeostasis and Lysosomal Accumulation

    PubMed Central

    Cullen, Jason K.; Abdul Murad, Norazian; Yeo, Abrey; McKenzie, Matthew; Ward, Micheal; Chong, Kok Leong; Schieber, Nicole L.; Parton, Robert G.; Lim, Yi Chieh; Wolvetang, Ernst; Maghzal, Ghassan J.; Stocker, Roland; Lavin, Martin F.

    2016-01-01

    Autosomal recessive ataxias are a clinically diverse group of syndromes that in some cases are caused by mutations in genes with roles in the DNA damage response, transcriptional regulation or mitochondrial function. One of these ataxias, known as Autosomal Recessive Cerebellar Ataxia Type-2 (ARCA-2, also known as SCAR9/COQ10D4; OMIM: #612016), arises due to mutations in the ADCK3 gene. The product of this gene (ADCK3) is an atypical kinase that is thought to play a regulatory role in coenzyme Q10 (CoQ10) biosynthesis. Although much work has been performed on the S. cerevisiae orthologue of ADCK3, the cellular and biochemical role of its mammalian counterpart, and why mutations in this gene lead to human disease is poorly understood. Here, we demonstrate that ADCK3 localises to mitochondrial cristae and is targeted to this organelle via the presence of an N-terminal localisation signal. Consistent with a role in CoQ10 biosynthesis, ADCK3 deficiency decreased cellular CoQ10 content. In addition, endogenous ADCK3 was found to associate in vitro with recombinant Coq3, Coq5, Coq7 and Coq9, components of the CoQ10 biosynthetic machinery. Furthermore, cell lines derived from ARCA-2 patients display signs of oxidative stress, defects in mitochondrial homeostasis and increases in lysosomal content. Together, these data shed light on the possible molecular role of ADCK3 and provide insight into the cellular pathways affected in ARCA-2 patients. PMID:26866375

  2. Large scale 3D geometry of deformation structures in the Aar massif and overlying Helvetic nappes (Central Alps, Switzerland) - A combined remote sensing and field work approach

    NASA Astrophysics Data System (ADS)

    Baumberger, R.; Wehrens, Ph.; Herwegh, M.

    2012-04-01

    Allowing deep insight into the formation history of a rock complex, shear zones, faults and joint systems represent important sources of geological information. The granitic rocks of the Haslital valley (Switzerland) show very good outcrop conditions to study these mechanical anisotropies. Furthermore, they permit a quantitative characterisation of the above-mentioned deformation structures on the large-scale, in terms of their 3D orientation, 3D spatial distribution, kinematics and evolution in 3D. A key problem while developing valid geological 3D models is the three-dimensional spatial distribution of geological structures, particularly with increasing distance from the surface. That is especially true in regions, where only little or even no "hard" underground data (e.g. bore holes, tunnel mappings and seismics) is available. In the study area, many subsurface data are available (e.g. cross sections, tunnel and pipeline mappings, bore holes etc.). Therefore, two methods dealing with the problems mentioned are developed: (1) A data acquisition, processing and visualisation method, (2) A methodology to improve the reliability of 3D models regarding the spatial trend of geological structures with increasing depth: 1) Using aerial photographs and a high-resolution digital elevation model, a GIS-based remote-sensing structural map of large-scale structural elements (shear zones, faults) of the study area was elaborated. Based on that lineament map, (i) a shear zone map was derived and (ii) a geostatistical analysis was applied to identify sub regions applicable for serving as field areas to test the methodology presented above. During fieldwork, the shear zone map was evaluated by verifying the occurrence and spatial distribution of the structures designated by remote sensing. Additionally, the geometry of the structures (e.g. 3D orientation, width, kinematics) was characterised and parameterised accordingly. These tasks were partially done using a GPS based Slate PC and the FieldMoveTM software, in order to ease the subsequent data processing. 2) Findings from the field work were visualised in 3D using the MoveTM software suite. Applying its specific tools and incorporating own field data, the structure's near-surface 3D settings was modelled. In a second step, the combined use of surface and subsurface data helped to predict their trend with increasing distance from the surface, bypassing a height difference of partially more than 2000m. Field work shows that the remote-sensing structural map fits very well with the field observations. Nevertheless, the shear zone map underwent an iterative refinement process, based on own observations in the field as well as on already existing maps. It now clearly describes the lithological subdivision of the study area. The incorporation of the data into the 3D modelling software points towards the fact, that own large-scale data fits very well with small-scale structures provided by recent studies in the same area. Yet, their exact interplay in terms of orientation, kinematics and evolution is not clear. Additional analysis is needed in order to gain more detailed insight into the deformation history of the rocks in the study area.

  3. Identification and biochemical characterization of plant acylamino acid-releasing enzyme.

    PubMed

    Yamauchi, Yasuo; Ejiri, Yukinori; Toyoda, Yasuyuki; Tanaka, Kiyoshi

    2003-08-01

    Plant acylamino acid-releasing enzyme (AARE) catalyzing the N-terminal hydrolysis of N(alpha)-acylpeptides to release N(alpha)-acylated amino acids, was biochemically characterized using recombinant and native AAREs. A cDNA encoding a deduced Arabidopsis thaliana AARE (AtAARE) was cloned and sequenced. The deduced amino acid sequence encoded a 764 amino acid protein of 83.9 kDa, which was 31.8% identical with that of rat AARE. In particular, the proposed catalytic residues (Ser, Asp, and His) of AARE, called the "catalytic triad residues, " were completely conserved. Recombinant AtAARE was expressed in Escherichia coli and confirmed to be a functional AARE. Native AAREs were prepared from A. thaliana and cucumber (Cucumis sativus, L.) plants. Both native AAREs were tetrameric proteins of 350 kDa comprising four subunits of 82 kDa, and showed typical enzymological properties of other AAREs, i.e. sensitivity to diisopropyl fluorophosphate, an optimum pH of around 7.0, and an optimum temperature of 37 degrees C. Both the native and recombinant AAREs were immunochemically homologous. Intracelluar fractionation analysis showed that the AARE was mainly present in the stroma of chloroplasts. Native AARE degraded the glycated ribulose-1,5-bisphoshate carboxylase/oxygenase protein but not the native protein. Thus, plant AARE might be involved in not only catalysis of the N-terminal hydrolysis of N(alpha)-acylpeptides but also the elimination of glycated proteins.

  4. After Action Reviews With the Ground Soldier System

    DTIC Science & Technology

    2005-09-01

    The After Action Review (AAR) is critical to the Army’s training process . Much work conducted by the U.S. Army Research Institute (ARI) has been...them to apply their expertise and wisdom to the AAR process . Consequently, the aids suggested here should be viewed as providing a large collection...25 OC use of the LW System in the AAR Process

  5. High salt diet exacerbates vascular contraction in the absence of adenosine A2A receptor

    PubMed Central

    Pradhan, Isha; Zeldin, Darryl C.; Ledent, Catherine; Mustafa, S. Jamal; Falck, John R.; Nayeem, Mohammed A

    2014-01-01

    High salt (4%NaCl, HS) diet modulates adenosine-induced vascular response through adenosine A2A-receptor (A2AAR). Evidence suggests A2AAR stimulates cyp450-epoxygenases, leading to epoxyeicosatrienoic acids (EETs) generation. The aim of this study was to understand the vascular reactivity to HS and underlying signaling mechanism in the presence or absence of A2AAR. Therefore, we hypothesized that HS enhances adenosine-induced relaxation through EETs in A2AAR+/+, but exaggerates contraction in A2AAR−/−. Organ-bath and Western-blot experiments were conducted in HS and normal salt (NS, 0.18% NaCl)-fed A2AAR+/+ and A2AAR−/− mice aortae. HS produced concentration-dependent relaxation to non-selective adenosine analog, NECA in A2AAR+/+, whereas contraction was observed in A2AAR−/− mice and this was attenuated by A1AR antagonist (DPCPX). CGS-21680 (selective A2AAR-agonist) enhanced relaxation in HS-A2AAR+/+ vs. NS-A2AAR+/+, that was blocked by EETs antagonist (14,15-EEZE). Compared to NS, HS significantly upregulated expression of vasodilators A2AAR and cyp2c29, while vasoconstrictors A1AR and cyp4a in A2AAR+/+ were downregulated. In A2AAR−/− mice, however, HS significantly downregulated the expression of cyp2c29, while A1AR and cyp4a were upregulated compared to A2AAR+/+ mice. Hence, our data suggest that in A2AAR+/+, HS enhances A2AAR-induced relaxation through increased cyp-expoxygenases-derived EETs and decreased A1AR levels, whereas in A2AAR−/−, HS exaggerates contraction through decreased cyp-epoxygenases and increased A1AR levels. PMID:24390173

  6. The Incidence, Classification, and Management of Acute Adverse Reactions to the Low-Osmolar Iodinated Contrast Media Isovue and Ultravist in Contrast-Enhanced Computed Tomography Scanning

    PubMed Central

    Zhang, Bin; Dong, Yuhao; Liang, Long; Lian, Zhouyang; Liu, Jing; Luo, Xiaoning; Chen, Wenbo; Li, Xinyu; Liang, Changhong; Zhang, Shuixing

    2016-01-01

    Abstract Some epidemiologic surveillance studies have recorded adverse drug reactions to radiocontrast agents. We aimed to investigate the incidence and management of acute adverse reactions (AARs) to Ultravist-370 and Isovue-370 in patients who underwent contrast-enhanced computed tomography (CT) scanning. Data from 137,473 patients were analyzed. They had undergone enhanced CT scanning with intravenous injection of Ultravist-370 or Isovue-370 during the period of January 1, 2006 to December 31, 2012 in our hospital. We investigated and classified AARs according to the American College of Radiology and the Chinese Society of Radiology (CSR) guidelines for iodinated contrast media. We analyzed risk factors for AARs and compared the AARs induced by Ultravist-370 and Isovue-370. Four hundred and twenty-eight (0.31%) patients experienced AARs, which included 330 (0.24%) patients with mild AARs, 82 (0.06%) patients with moderate AARs, and 16 (0.01%) patients with severe AARs (including 3 cases of cardiac arrest and one case of death). The incidence of AARs was higher with Ultravist-370 than with Isovue-370 (0.38% vs 0.24%, P < 0.001), but only for mild AARs (0.32% vs 0.16%, P < 0.001). Analyses on risk factors indicated that female patients (n = 221, 0.43%, P < 0.001), emergency patients (n = 11, 0.51%, P < 0.001), elderly patients aged 50 to 60 years (n = 135, 0.43%, P < 0.001), and patients who underwent coronary computed tomography angiography (CTA) (n = 55, 0.51%, P < 0.001) had a higher risk of AARs. Cutaneous manifestations (50.52%)—especially rash (59.74%)—were the most frequent mild AARs. Cardiovascular manifestations accounted for most moderate and severe AARs (62.91% and 48.28%, respectively). After proper management, the symptoms and signs of 96.5% of the AARs resolved within 24 hours without sequelae. Ultravist-370 and Isovue-370 are safe for patients undergoing enhanced CT scanning. The incidence of AARs is

  7. A2A Adenosine Receptors Are Differentially Modulated by Pharmacological Treatments in Rheumatoid Arthritis Patients and Their Stimulation Ameliorates Adjuvant-Induced Arthritis in Rats

    PubMed Central

    Vincenzi, Fabrizio; Padovan, Melissa; Targa, Martina; Corciulo, Carmen; Giacuzzo, Sarah; Merighi, Stefania; Gessi, Stefania; Govoni, Marcello; Borea, Pier Andrea; Varani, Katia

    2013-01-01

    A2A adenosine receptors (ARs) play a key role in the inhibition of the inflammatory process. The purpose of this study was to evaluate the modulation of A2AARs in rheumatoid arthritis (RA) patients after different pharmacological treatments and to investigate the effect of A2AAR stimulation in a rat model of arthritis. We investigated A2AAR density and functionality in RA progression by using a longitudinal study in RA patients before and after methotrexate (MTX), anti-TNFα agents or rituximab treatments. A2AARs were analyzed by saturation binding assays in lymphocytes from RA patients throughout the 24-month study timeframe. In an adjuvant-induced arthritis model in rats we showed the efficacy of the A2AAR agonist, CGS 21680 in comparison with standard therapies by means of paw volume assessment, radiographic and ultrasonographic imaging. Arthritic-associated pain was investigated in mechanical allodynia and thermal hyperalgesia tests. IL-10 release following A2AAR stimulation in lymphocytes from RA patients and in serum from arthritic rats was measured. In lymphocytes obtained from RA patients, the A2AAR up-regulation was gradually reduced in function of the treatment time and the stimulation of these receptors mediated a significant increase of IL-10 production. In the same cells, CGS 21680 did not affected cell viability and did not produced cytotoxic effects. The A2AAR agonist CGS 21680 was highly effective, as suggested by the marked reduction of clinical signs, in rat adjuvant-induced arthritis and associated pain. This study highlighted that A2AAR agonists represent a physiological-like therapeutic alternative for RA treatment as suggested by the anti-inflammatory role of A2AARs in lymphocytes from RA patients. The effectiveness of A2AAR stimulation in a rat model of arthritis supported the role of A2AAR agonists as potential pharmacological treatment for RA. PMID:23326596

  8. Cross-talk from β-adrenergic receptors modulates α2A-adrenergic receptor endocytosis in sympathetic neurons via protein kinase A and spinophilin.

    PubMed

    Cottingham, Christopher; Lu, Roujian; Jiao, Kai; Wang, Qin

    2013-10-04

    Inter-regulation of adrenergic receptors (ARs) via cross-talk is a long appreciated but mechanistically unclear physiological phenomenon. Evidence from the AR literature and our own extensive studies on regulation of α2AARs by the scaffolding protein spinophilin have illuminated a potential novel mechanism for cross-talk from β to α2ARs. In the present study, we have characterized a mode of endogenous AR cross-talk in native adrenergic neurons whereby canonical βAR-mediated signaling modulates spinophilin-regulated α2AAR endocytosis through PKA. Our findings demonstrate that co-activation of β and α2AARs, either by application of endogenous agonist or by simultaneous stimulation with distinct selective agonists, results in acceleration of endogenous α2AAR endocytosis in native neurons. We show that receptor-independent PKA activation by forskolin is sufficient to accelerate α2AAR endocytosis and that α2AAR stimulation alone drives accelerated endocytosis in spinophilin-null neurons. Endocytic response acceleration by β/α2AAR co-activation is blocked by PKA inhibition and lost in spinophilin-null neurons, consistent with our previous finding that spinophilin is a substrate for phosphorylation by PKA that disrupts its interaction with α2AARs. Importantly, we show that α2AR agonist-mediated α2AAR/spinophilin interaction is blocked by βAR co-activation in a PKA-dependent fashion. We therefore propose a novel mechanism for cross-talk from β to α2ARs, whereby canonical βAR-mediated signaling coupled to PKA activation results in phosphorylation of spinophilin, disrupting its interaction with α2AARs and accelerating α2AAR endocytic responses. This mechanism of cross-talk has significant implications for endogenous adrenergic physiology and for therapeutic targeting of β and α2AARs.

  9. Differential Occurrence of Interactions and Interaction Domains in Proteins Containing Homopolymeric Amino Acid Repeats

    PubMed Central

    Pelassa, Ilaria; Fiumara, Ferdinando

    2015-01-01

    Homopolymeric amino acids repeats (AARs), which are widespread in proteomes, have often been viewed simply as spacers between protein domains, or even as “junk” sequences with no obvious function but with a potential to cause harm upon expansion as in genetic diseases associated with polyglutamine or polyalanine expansions, including Huntington disease and cleidocranial dysplasia. A growing body of evidence indicates however that at least some AARs can form organized, functional protein structures, and can regulate protein function. In particular, certain AARs can mediate protein-protein interactions, either through homotypic AAR-AAR contacts or through heterotypic contacts with other protein domains. It is still unclear however, whether AARs may have a generalized, proteome-wide role in shaping protein-protein interaction networks. Therefore, we have undertaken here a bioinformatics screening of the human proteome and interactome in search of quantitative evidence of such a role. We first identified the sets of proteins that contain repeats of any one of the 20 amino acids, as well as control sets of proteins chosen at random in the proteome. We then analyzed the connectivity between the proteins of the AAR-containing protein sets and we compared it with that observed in the corresponding control networks. We find evidence for different degrees of connectivity in the different AAR-containing protein networks. Indeed, networks of proteins containing polyglutamine, polyglutamate, polyproline, and other AARs show significantly increased levels of connectivity, whereas networks containing polyleucine and other hydrophobic repeats show lower degrees of connectivity. Furthermore, we observed that numerous protein-protein, -nucleic acid, and -lipid interaction domains are significantly enriched in specific AAR protein groups. These findings support the notion of a generalized, combinatorial role of AARs, together with conventional protein interaction domains, in

  10. Angiographic validation of magnetic resonance assessment of myocardium at risk in non-ST-elevation myocardial infarction.

    PubMed

    Buckert, Dominik; Mariyadas, Manuela; Walcher, Thomas; Rasche, Volker; Wöhrle, Jochen; Rottbauer, Wolfgang; Bernhardt, Peter

    2013-08-01

    In the setting of acute myocardial ischemia, the hypoperfused portion of the myocardium is in danger of becoming irreversibly injured. This portion is called the area at risk (AAR). It is of clinical interest to be able to estimate the AAR for further evaluation and improvement of different revascularization strategies. The Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease Score (APPROACH-score) has been shown to be a jeopardy score with a good performance for angiographic assessment of the myocardium supplied by a coronary vessel, representing the AAR. Recently, cardiac magnetic resonance imaging (CMR) has been demonstrated to also provide good results in determining the AAR, especially in the setting of acute ST-elevation infarction patients. Therefore, the aim of our trial was to compare T2-weighted CMR imaging for assessment of AAR in patients with non-ST-elevation myocardial infarction (NSTEMI) and to validate this approach against the angiographic APPROACH-score. We enrolled sixty-four patients presenting with acute NSTEMI that underwent coronary X-ray angiography within 72 h of symptom onset. Two blinded readers performed offline angiographic AAR assessment using the modified APPROACH-score, as being described elsewhere. Furthermore, with the use of a semi-automatic T2w-CMR approach, the AAR was quantified by two fully blinded readers. The resulting mean AAR determined by the modified APPROACH-score was 28.6 ± 10.0 %. The mean CMR derived AAR was 27.6 ± 12.7 %. CMR assessment tended to slightly underestimate the AAR in comparison to angiographic scoring (difference -0.09 ± 7.6 %). There is a good correlation between the AAR assessed by CMR and by angiography (r = 0.65, p < 0.001). T2-weigthed CMR is able to quantify the AAR with very good correlation to the angiographic APPROACH-score in NSTEMI patients.

  11. 49 CFR 179.2 - Definitions and abbreviations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS SPECIFICATIONS FOR TANK CARS...: (1) AAR means Association of American Railroads. (2) Approved means approval by the AAR Tank Car... 173 of this chapter also apply. (6) F means degrees Fahrenheit. (7) NGT means National Gas...

  12. 49 CFR 179.400-8 - Thickness of plates.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... tensile strength of the plate material, as prescribed in AAR Specifications for Tank Cars, appendix M... inches; S = minimum tensile strength of the plate material, as prescribed in AAR Specifications for Tank..., in inches; r = inside knuckle radius, in inches; S = minimum tensile strength of plate material,...

  13. Defining Educational Research: A Perspective of/on Presidential Addresses and the Australian Association for Research in Education

    ERIC Educational Resources Information Center

    Lingard, Bob; Gale, Trevor

    2010-01-01

    This paper is concerned with the definition of the field of educational research and the changing and developing role of the Australian Association for Research in Education (AARE) in representing and constituting this field. The evidence for the argument is derived from AARE Presidential Addresses across its 40-year history. The paper documents…

  14. Current Practice and Theoretical Foundations of the After Action Review

    DTIC Science & Technology

    2011-06-01

    to understanding and improving the AAR process . Among these are Larry Meliza, David Bessemer , and John Morrison. An early report concerning the...training process . 15. SUBJECT TERMS After Action Review, training, feedback SECURITY CLASSIFICATION OF 19. LIMITATION...Such training should familiarize students with the underlying theoretical and learning principles which inform the process of AAR, provide them

  15. After Action Reviews: Current Observations and Recommendations

    DTIC Science & Technology

    2007-01-01

    starting point for a training aid or self-assessment tool to facilitate this process . Based on the September briefing, the Operations Group immediately...1 Purpose of the Current Research ............................................................................ 1 The Arm y’s AAR Process ...Current Research The purpose of this research was to examine the AAR process as practiced at the Joint Readiness Training Center (JRTC). The Global War

  16. 77 FR 69437 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-19

    .... 9. Missile Approach Warning System (AN/AAR-47): The AN/AAR-47 is an aircraft passive MWS designed... Link-16 Multifunctional Information Distribution Systems, support equipment, spare and repair parts... Multifunctional Information Distribution Systems, support equipment, spare and repair parts, personnel...

  17. 49 CFR 1244.9 - Procedures for the release of waybill data.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... the waybill information or data that each class of users may obtain, and set forth the applicable...). (ii)Accounting Period (Month, Year). (iii)Number of Carloads. (iv)Car Ownership (Rail or Private). (v)AAR Car Type. (vi)AAR Mechanical Designation. (vii)STB Car Type. (viii)TOFC/COFC Plan. (ix)Number...

  18. 49 CFR 1244.9 - Procedures for the release of waybill data.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... the waybill information or data that each class of users may obtain, and set forth the applicable...). (ii)Accounting Period (Month, Year). (iii)Number of Carloads. (iv)Car Ownership (Rail or Private). (v)AAR Car Type. (vi)AAR Mechanical Designation. (vii)STB Car Type. (viii)TOFC/COFC Plan. (ix)Number...

  19. Utilization of Participatory Electronic Technology in Group Communication and Decision-Making Processes. AIR 1983 Annual Forum Paper.

    ERIC Educational Resources Information Center

    Roberts, Adrian R.; Garg, Devendra P.

    The use of an electronic feedback system, the Anonymous Audience Response System (AARS), in educational decision making is described, and the results of use studies in North Carolina are discussed. The AARS insures anonymity of an individual participant's responses, and at the same time, provides immediate feedback of the group's collective…

  20. 2014 Australian Association for Research in Education Presidential Address: Educational Research and the Tree of Knowledge in a Post Human Digital Age

    ERIC Educational Resources Information Center

    Moss, Julianne

    2016-01-01

    The 2014, 41st Australian Association for Research in Education (AARE) presidential address is both inspired and guided by the discursive genres of presidential addresses and the role of the president in a member association such as AARE. In the address, typically the president speaks to the members on an issue or issues that are to shape or…

  1. Trends in organised sport membership: impact on sustainability.

    PubMed

    Eime, Rochelle; Payne, Warren; Harvey, Jack

    2009-01-01

    Sporting clubs play a key role in community-level physical activity. This study investigated participation trends in sport club membership. A survey of 50 State sports governing bodies in Victoria, Australia collected information on factors affecting membership trends. The records for four of these sports were analysed for the 6 years, 1998-2003. Three sports reported increases in total membership (average annual rates (AARs): 0.3, 1.9 and 12.4%), and one reported a decrease (AAR: -1.0%). There was a decrease in both the absolute number (AARs: -1.1%, -2.3%, and -3.5%) and the proportion (AARs: -0.5%, -0.7%, -1.7% and -2.3%) of adult members. The number of junior club members increased slightly over the 6-year period in two sports (AARs: 0.5% and 0.7%), increased substantially in one (AAR: 12.2%) and decreased in one (AAR: -6.7%). The number of members playing modified sports increased in two sports (AARs: 2.8% and 3.3%), increased substantially in one (AARs: 53.1%) and decreased in one (AAR: -16.3%). The introduction of modified sport for younger participants is relatively new, resulting in sports accessing a new market to maintain or increase their total membership. However, the influx of younger members was not matched by associated increases in adult members. This places increased pressure upon adult members to maintain the infrastructure to support younger members. The issues of decreased adult membership and increased junior membership need to be addressed in order to ensure that community sporting clubs can be sustained and fulfil their potential to act as a vehicle for public health initiatives.

  2. A2A adenosine receptors are up-regulated in lymphocytes from amyotrophic lateral sclerosis patients.

    PubMed

    Vincenzi, Fabrizio; Corciulo, Carmen; Targa, Martina; Casetta, Ilaria; Gentile, Mauro; Granieri, Enrico; Borea, Pier Andrea; Popoli, Patrizia; Varani, Katia

    2013-09-01

    Adenosine, a purine nucleoside interacting with A1, A2A, A2B and A3 adenosine receptors (ARs), is a potent endogenous modulator of inflammatory and neuronal processes involved in the pathophysiology of several neurodegenerative diseases. In the present study, ARs were investigated in lymphocytes from patients with amyotrophic lateral sclerosis (ALS) and compared with age-matched healthy subjects. In ALS patients A2AARs were analysed by using RT-PCR, Western blotting and saturation binding experiments. The effect of A2AAR stimulation on cyclic AMP levels was evaluated in lymphocytes from ALS patients and healthy subjects. An up-regulation of A2AARs was observed in ALS patients with respect to healthy subjects while A1, A2B and A3AR affinity and density did not change. In ALS patients, the A2AAR density values correlated with the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores. Furthermore, the stimulation of A2AARs mediated a significant increase in cyclic AMP levels in lymphocytes from ALS patients, with a higher potency than in lymphocytes from healthy subjects. In conclusion, the positive correlation between A2AAR density and ALSFRS-R scores could indicate a possible protective effect of this receptor subtype, representing an interesting starting point for the study of alternative therapeutic approaches for ALS based on A2AAR modulation.

  3. Reduced lipolysis response to adipose afferent reflex involved in impaired activation of adrenoceptor-cAMP-PKA-hormone sensitive lipase pathway in obesity

    PubMed Central

    Ding, Lei; Zhang, Feng; Zhao, Ming-Xia; Ren, Xing-Sheng; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

    2016-01-01

    Chemical stimulation of white adipose tissue (WAT) causes adipose afferent reflex (AAR) and sympathetic activation. This study is to investigate the effects of AAR on lipolysis and the mechanisms of attenuated lipolysis response to enhanced AAR in obesity. Obesity was caused by high-fat diet for 12 weeks in rats. AAR was induced by injection of capsaicin into inguinal WAT or electrical stimulation of epididymal WAT afferent nerve. AAR caused sympathetic activation, which was enhanced in obesity rats. AAR increased cAMP levels and PKA activity, promoted hormone sensitive lipase (HSL) and perilipin phosphorylation, and increased lipolysis in WAT, which were attenuated in obesity rats. PKA activity, cAMP, perilipin and β-adrenoceptor levels were reduced, while HSL was upregulated in adipocytes from obesity rats. In primary adipocytes, isoproterenol increased cAMP levels and PKA activity, promoted HSL and perilipin phosphorylation, and increased lipolysis, which were attenuated in obesity rats. The attenuated effects of isoproterenol in adipocytes from obesity rats were prevented by a cAMP analogue dbcAMP. The results indicate that reduced lipolysis response to enhanced AAR in obesity is attributed to the impaired activation of β-adrenoceptor-cAMP-PKA-HSL pathway. Increased cAMP level in adipocytes rectifies the attenuated lipolysis in obesity. PMID:27694818

  4. Dual allosteric modulation of opioid antinociceptive potency by α2A-adrenoceptors.

    PubMed

    Chabot-Doré, Anne-Julie; Millecamps, Magali; Naso, Lina; Devost, Dominic; Trieu, Phan; Piltonen, Marjo; Diatchenko, Luda; Fairbanks, Carolyn A; Wilcox, George L; Hébert, Terence E; Stone, Laura S

    2015-12-01

    Opioid and α2-adrenoceptor (AR) agonists are analgesic when administered in the spinal cord and show a clinically beneficial synergistic interaction when co-administered. However, α2-AR antagonists can also inhibit opioid antinociception, suggesting a complex interaction between the two systems. The α2A-AR subtype is necessary for spinal adrenergic analgesia and synergy with opioids for most agonist combinations. Therefore, we investigated whether spinal opioid antinociception and opioid-adrenergic synergy were under allosteric control of the α2A-AR. Drugs were administered intrathecally in wild type (WT) and α2A-knock-out (KO) mice and antinociception was measured using the hot water tail immersion or substance P behavioral assays. The α2A-AR agonist clonidine was less effective in α2A-KO mice in both assays. The absence of the α2A-AR resulted in 10-70-fold increases in the antinociceptive potency of the opioid agonists morphine and DeltII. In contrast, neither morphine nor DeltII synergized with clonidine in α2A-KO mice, indicating that the α2AAR has both positive and negative modulatory effects on opioid antinociception. Depletion of descending adrenergic terminals with 6-OHDA resulted in a significant decrease in morphine efficacy in WT but not in α2A-KO mice, suggesting that endogenous norepinephrine acts through the α2A-AR to facilitate morphine antinociception. Based on these findings, we propose a model whereby ligand-occupied versus ligand-free α2A-AR produce distinct patterns of modulation of opioid receptor activation. In this model, agonist-occupied α2A-ARs potentiate opioid analgesia, while non-occupied α2A-ARs inhibit opioid analgesia. Exploiting such interactions between the two receptors could lead to the development of better pharmacological treatments for pain management.

  5. Dual allosteric modulation of opioid antinociceptive potency by a2A-adrenoceptors

    PubMed Central

    Chabot-Doré, Anne-Julie; Millecamps, Magali; Naso, Lina; Devost, Dominic; Trieu, Phan; Piltonen, Marjo; Diatchenko, Luda; Fairbanks, Carolyn A.; Wilcox, George L.; Hébert, Terence E.; Stone, Laura S.

    2015-01-01

    Opioid and α2-adrenoceptor (AR) agonists are analgesic when administered in the spinal cord and show a clinically beneficial synergistic interaction when co-administered. However, α2-AR antagonists can also inhibit opioid antinociception, suggesting a complex interaction between the two systems. The α2A-AR subtype is necessary for spinal adrenergic analgesia and synergy with opioids for most agonist combinations. Therefore, we investigated whether spinal opioid antinociception and opioid-adrenergic synergy were under allosteric control of the α2A-AR. Drugs were administered intrathecally in wild type (WT) and α2A-knock-out (KO) mice and antinociception was measured using hot water tail immersion or substance P behavioral assays. The α2A-AR agonist clonidine was less effective in α2A-KO mice in both assays. The absence of the α2A-AR resulted in 10–70-fold increases in the antinociceptive potency of the opioid agonists morphine and DeltII. In contrast, neither morphine nor DeltII synergized with clonidine in α2AKO mice, indicating that the α2AAR has both positive and negative modulatory effects on opioid antinociception. Depletion of descending adrenergic terminals with 6-OHDA resulted in a significant decrease in morphine efficacy in WT but not in α2A-KO mice, suggesting that endogenous norepinephrine acts through the α2A-AR to facilitate morphine antinociception. Based on these findings, we propose a model whereby ligand-occupied versus ligand-free α2A-AR produce distinct patterns of modulation of opioid receptor activation. In this model, agonist-occupied α2A-ARs potentiate opioid analgesia, while non-occupied α2A-ARs inhibit opioid analgesia. Exploiting such interactions between the two receptors could lead to the development of better pharmacological treatments for pain management. PMID:26254859

  6. Genetic evidence for involvement of multiple effector systems in alpha 2A-adrenergic receptor inhibition of stimulus-secretion coupling.

    PubMed

    Lakhlani, P P; Lovinger, D M; Limbird, L E

    1996-07-01

    The alpha 2A-adrenergic receptor (alpha 2AAR), via its interaction with the pertussis toxin-sensitive Gi/G(o) class of G proteins, modulates multiple effector systems, including inhibition of adenylyl cyclase and Ca2+ channels and activation of K+ channels. Mutation of a membrane-embedded aspartate residue, highly conserved among G protein-coupled receptors, in the alpha 2AAR to asparagine (D79N alpha 2AAR) results in selective uncoupling of the receptor to K+ currents but retention of inhibition of cAMP production and of voltage-sensitive Ca2+ currents when expressed in AtT20 anterior pituitary cells in culture. It is known that attenuation of cAMP synthesis alone cannot account for alpha 2AAR suppression of stimulus-secretion coupling; thus, the D79N alpha 2AAR provides a unique tool with which to assess the relative contribution of K+ current activation and Ca2+ current suppression in mediating the cellular responses of alpha 2AAR. The wild-type alpha 2AAR suppresses basal and secretagogue-evoked adrenocorticotropic hormone (ACTH) release in a manner indistinguishable from response to the endogenous somatostatin receptor. In contrast, the D79N alpha 2AAR does not attenuate basal ACTH release and is only partially effective in suppressing ACTH secretion evoked by the secretagogue isoproterenol. Regulation of ACTH release evoked by 8-bromo-cAMP, which bypasses receptor regulation of cAMP synthesis, suggests that attenuation of cAMP production, although not sufficient for inhibition of ACTH secretion, nevertheless participates in a functionally relevant manner. Taken together, the present findings indicate that alpha 2AAR-mediated suppression of neuropeptide secretion requires concomitant regulation of K+ and Ca2+ currents in parallel with attenuation of cAMP production.

  7. A(2A) adenosine receptors are differentially modulated by pharmacological treatments in rheumatoid arthritis patients and their stimulation ameliorates adjuvant-induced arthritis in rats.

    PubMed

    Vincenzi, Fabrizio; Padovan, Melissa; Targa, Martina; Corciulo, Carmen; Giacuzzo, Sarah; Merighi, Stefania; Gessi, Stefania; Govoni, Marcello; Borea, Pier Andrea; Varani, Katia

    2013-01-01

    A(2A) adenosine receptors (ARs) play a key role in the inhibition of the inflammatory process. The purpose of this study was to evaluate the modulation of A(2A)ARs in rheumatoid arthritis (RA) patients after different pharmacological treatments and to investigate the effect of A(2A)AR stimulation in a rat model of arthritis. We investigated A(2A)AR density and functionality in RA progression by using a longitudinal study in RA patients before and after methotrexate (MTX), anti-TNFα agents or rituximab treatments. A(2A)ARs were analyzed by saturation binding assays in lymphocytes from RA patients throughout the 24-month study timeframe. In an adjuvant-induced arthritis model in rats we showed the efficacy of the A(2A)AR agonist, CGS 21680 in comparison with standard therapies by means of paw volume assessment, radiographic and ultrasonographic imaging. Arthritic-associated pain was investigated in mechanical allodynia and thermal hyperalgesia tests. IL-10 release following A(2A)AR stimulation in lymphocytes from RA patients and in serum from arthritic rats was measured. In lymphocytes obtained from RA patients, the A(2A)AR up-regulation was gradually reduced in function of the treatment time and the stimulation of these receptors mediated a significant increase of IL-10 production. In the same cells, CGS 21680 did not affected cell viability and did not produced cytotoxic effects. The A(2A)AR agonist CGS 21680 was highly effective, as suggested by the marked reduction of clinical signs, in rat adjuvant-induced arthritis and associated pain. This study highlighted that A(2A)AR agonists represent a physiological-like therapeutic alternative for RA treatment as suggested by the anti-inflammatory role of A(2A)ARs in lymphocytes from RA patients. The effectiveness of A(2A)AR stimulation in a rat model of arthritis supported the role of A(2A)AR agonists as potential pharmacological treatment for RA.

  8. 75 FR 13775 - Agency Information Collection Activities: Proposed Collection; Comment Request, 1660-NEW...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-23

    ... SECURITY Federal Emergency Management Agency Agency Information Collection Activities: Proposed Collection; Comment Request, 1660-NEW; Homeland Security Exercise and Evaluation Program (HSEEP) After Action Report... Security Exercise and Evaluation Program (HSEEP) After Action Report (AAR) Improvement Plan (IP)....

  9. 77 FR 31588 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-29

    ... electronic support measures system (ESM), and AN/APS- 153 Multi-Mode Radar (MMR). The electronic warfare systems include the AN/AAR-47 missile warning system, AN/ALQ-144 infrared jammer, Identify Friend or...

  10. 49 CFR 1135.1 - Quarterly adjustment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... railroad productivity as prescribed in Railroad Cost Recovery Procedures, 1 I.C.C.2d 207 (1984), and any subsequent amendments thereto. In addition, the AAR shall calculate the productivity-adjusted RCAF...

  11. 49 CFR 1135.1 - Quarterly adjustment.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... railroad productivity as prescribed in Railroad Cost Recovery Procedures, 1 I.C.C.2d 207 (1984), and any subsequent amendments thereto. In addition, the AAR shall calculate the productivity-adjusted RCAF...

  12. 49 CFR 179.300-9 - Welding.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... fusion welded. Head-to-shell joints must be forge welded on class DOT-106A tanks and fusion welded on... AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7 of this subchapter). (b)...

  13. 49 CFR 179.300-9 - Welding.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... fusion welded. Head-to-shell joints must be forge welded on class DOT-106A tanks and fusion welded on... AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7 of this subchapter). (b)...

  14. 49 CFR 179.300-9 - Welding.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... fusion welded. Head-to-shell joints must be forge welded on class DOT-106A tanks and fusion welded on... AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7 of this subchapter). (b)...

  15. 49 CFR 179.300-9 - Welding.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... fusion welded. Head-to-shell joints must be forge welded on class DOT-106A tanks and fusion welded on... AAR Specifications for Tank Cars, appendix W (IBR, see § 171.7 of this subchapter). (b)...

  16. Concrete modelling for expertise of structures affected by alkali aggregate reaction

    SciTech Connect

    Grimal, E.; Sellier, A.; Multon, S.; Le Pape, Y.; Bourdarot, E.

    2010-04-15

    Alkali aggregate reaction (AAR) affects numerous civil engineering structures and causes irreversible expansion and cracking. In order to control the safety level and the maintenance cost of its hydraulic dams, Electricite de France (EDF) must reach better comprehension and better prediction of the expansion phenomena. For this purpose, EDF has developed a numerical model based on the finite element method in order to assess the mechanical behaviour of damaged structures. The model takes the following phenomena into account: concrete creep, the stress induced by the formation of AAR gel and the mechanical damage. A rheological model was developed to assess the coupling between the different phenomena (creep, AAR and anisotropic damage). Experimental results were used to test the model. The results show the capability of the model to predict the experimental behaviour of beams subjected to AAR. In order to obtain such prediction, it is necessary to take all the phenomena occurring in the concrete into consideration.

  17. The Role of the After Action Review Leader in REALTRAIN: Research and Training Needs

    DTIC Science & Technology

    1979-01-01

    upon. This peer feedback , when integrated with a learner’s own recollections of what led up to the moment he became a casualty, allows him to see...troops (who know what casualties they inflicted/suffered) are inclined either to argue with the leader or to "clam up." Thus, the learning benefit...27 Table C-I. Percentages of Participant Responses to AAR-Related Questions .. .. ... . ...... 28 Figure C-I. Amount Learned from AAR Not

  18. The aspartate aminotransferase-to-alanine aminotransferase ratio predicts all-cause and cardiovascular mortality in patients with type 2 diabetes

    PubMed Central

    Zoppini, Giacomo; Cacciatori, Vittorio; Negri, Carlo; Stoico, Vincenzo; Lippi, Giuseppe; Targher, Giovanni; Bonora, Enzo

    2016-01-01

    Abstract An increased aspartate aminotransferase-to-alanine aminotransferase ratio (AAR) has been widely used as a marker of advanced hepatic fibrosis. Increased AAR was also shown to be significantly associated with the risk of developing cardiovascular (CV) disease. The aim of this study was to assess the relationship between the AAR and mortality risk in a well-characterized cohort of patients with type 2 diabetes. A cohort of 2529 type 2 diabetic outpatients was followed-up for 6 years to collect cause-specific mortality. Cox regression analyses were modeled to estimate the independent association between AAR and the risk of all-cause and CV mortality. Over the 6-year follow-up period, 12.1% of patients died, 47.5% of whom from CV causes. An increased AAR, but not its individual components, was significantly associated with an increased risk of all-cause (adjusted-hazard risk 1.83, confidence interval [CI] 95% 1.14–2.93, P = 0.012) and CV (adjusted-hazard risk 2.60, CI 95% 1.38–4.90, P < 0.003) mortality after adjustment for multiple clinical risk factors and potential confounding variables. The AAR was independently associated with an increased risk of both all-cause and CV mortality in patients with type 2 diabetes. These findings suggest that an increased AAR may reflect more systemic derangements that are not simply limited to liver damage. Further studies are needed to elucidate the pathophysiological implications of an increased AAR. PMID:27787357

  19. Army Leadership. Competent, Confident, and Agile

    DTIC Science & Technology

    2006-10-01

    stowed away, our motor sergeant conducts an after-action review (AAR). An AAR is a professional discussion of an event, focused on performance...War and Captivity: Ronald H. Spector, Eagle Against the Sun (New York: Random House, 1985). A. J. P. Taylor and S. L. Mayer , History of World War II...KS: U.S. Army Command and General Staff College Press, 1997. Taylor, A. J. P. and S. L. Mayer . History of World War II. London: Octopus Books, 1974

  20. UGV Control Interoperability Profile (IOP), Version 0

    DTIC Science & Technology

    2011-12-21

    save mission information Msn Plan - AAR C SW2 CTRL-Msn Plan-28 retrieve of mission information Msn Plan - AAR C SW2 3.9 Mobility...for public release. Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is estimated to...and completing and reviewing the collection of information . Send comments regarding this burden estimate or any other aspect of this collection of

  1. Revising the National Exercise Program

    DTIC Science & Technology

    2008-03-01

    After-Action Report, (Washington D.C.: 2001), 1, http://biotech.law.lsu.edu/ blaw /dhs/TOPOFF-2000-AAR.PDF (accessed October 6, 2007). 19 not...After-Action Report. Washington DC: 2001, http://biotech.law.lsu.edu/ blaw /dhs/TOPOFF- 2000-AAR.PDF(accessed October 6, 2007). North American...Information Center Ft. Belvoir, VA 2. Dudley Knox Library Naval Postgraduate School Monterey, VA 3. Director of Logistics and Engineering

  2. Protein kinase Cε is required for spinal analgesic synergy between delta opioid and alpha-2A adrenergic receptor agonist pairs.

    PubMed

    Schuster, Daniel J; Kitto, Kelley F; Overland, Aaron C; Messing, Robert O; Stone, Laura S; Fairbanks, Carolyn A; Wilcox, George L

    2013-08-14

    We recently showed that spinal synergistic interactions between δ opioid receptors (δORs) and α2A adrenergic receptors (α2AARs) require protein kinase C (PKC). To identify which PKC isoforms contribute to analgesic synergy, we evaluated the effects of various PKC-isoform-specific peptide inhibitors on synergy between δORs and α2AARs using the tail flick assay of thermal nociception in mice. Only a PKCε inhibitor abolished synergy between a δOR agonist and an α2AAR agonist. We tested a panel of combinations of opioid and adrenergic agonists in PKCε knock-out mice and found that all four combinations of a δOR agonist and an α2AAR agonist required PKCε for antinociceptive synergy. None of the combinations of a μOR agonist with an α2AR agonist required PKCε. Immunohistochemistry confirmed that PKCε could be found in the population of peptidergic primary afferent nociceptors where δORs and α2AARs have been found to extensively colocalize. Immunoreactivity for PKCε was found in the majority of dorsal root ganglion neurons and intensely labeled laminae I and II of the spinal cord dorsal horn. PKCε is widespread in the spinal nociceptive system and in peptidergic primary afferents it appears to be specifically involved in mediating the synergistic interaction between δORs and α2AARs.

  3. Enhanced production of n-alkanes in Escherichia coli by spatial organization of biosynthetic pathway enzymes.

    PubMed

    Rahmana, Ziaur; Sung, Bong Hyun; Yi, Ji-Yeun; Bui, Le Minh; Lee, Jun Hyoung; Kim, Sun Chang

    2014-12-20

    Alkanes chemically mimic hydrocarbons found in petroleum, and their demand as biofuels is steadily increasing. Biologically, n-alkanes are produced from fatty acyl-ACPs by acyl-ACP reductases (AARs) and aldehyde deformylating oxygenases (ADOs). One of the major impediments in n-alkane biosynthesis is the low catalytic turnover rates of ADOs. Here, we studied n-alkane biosynthesis in Escherichia coli using a chimeric ADO-AAR fusion protein or zinc finger protein-guided ADO/AAR assembly on DNA scaffolds to control their stoichiometric ratios and spatial arrangements. Bacterial production of n-alkanes with the ADO-AAR fusion protein was increased 4.8-fold (24 mg/L) over a control strain expressing ADO and AAR separately. Optimal n-alkane biosynthesis was achieved when the ADO:AAR binding site ratio on a DNA scaffold was 3:1, yielding an 8.8-fold increase (44 mg/L) over the control strain. Our findings indicate that the spatial organization of alkane-producing enzymes is critical for efficient n-alkane biosynthesis in E. coli.

  4. Effects of hippocampal stimulation on retention and extinction of one way active avoidance response in cats.

    PubMed

    Gralewicz, K; Gralewicz, S

    1984-01-01

    We found previously that hippocampal stimulation (HiSt) at 20 cps, 100 mikroA, applied jointly with a tone (500 Hz) CS in the course of retention test, improved the performance and retarded the extinction of one way active avoidance response (AAR) in cats. During this test failures to perform the AAR were not punished in all but two trials it the beginning of each session. The first experiment of the present studies demonstrated that - (i) the AAR facilitating the effect of HiSt might be prevented by m all electrolytic lesions made around the tips of the stimulating electrodes, (ii) large lesions of the hippocampus exerted little effect on the AAR acquisition, but the response was extinguished faster during the retention test. In the second experiment two response prevention trials (non-reinforced presentations of the CS with no possibility to make the AAR) were run at the beginning of each session after the end of training. In these conditions the HiSt resulted in a faster extinction of the AAR as compared with implanted unstimulated animals. Large lesions of the hippocampus had no effect on the extinction rate. We conclude that the facilitation of retrieval from memory may be responsible for the effects of HiSt on conditioned behavior.

  5. Cluster in the Auroral Acceleration Region

    NASA Technical Reports Server (NTRS)

    Pickett, Jolene S.; Fazakerley, Andrew N.; Marklund, Gorun; Dandouras, Iannis; Christopher, Ivar W.; Kistler, Lynn; Lucek, Elizabeth; Masson, Arnaud; Taylor, Matthew G.; Mutel, Robert L.; Santolik, Ondrej; Bell, Timothy F.; Fung, Shing; Pottelette, Raymond; Hanasz, Jan; Schreiber, Roman; Hull, Arthur J.

    2010-01-01

    Due to a fortuitous evolution of the Cluster orbit, the Cluster spacecraft penetrated for the first time in its mission the heart of Earth's auroral acceleration region (AAR) in December 2009 and January 2010. During this time a special AAR campaign was carried out by the various Cluster instrument teams with special support from ESA and NASA facilities. We present some of the first multi-spacecraft observations of the waves, particles and fields made during that campaign. The Cluster spacecraft configuration during these AAR passages was such that it allowed us to explore the differences in the signatures of waves, particles, and fields on the various spacecraft in ways not possible with single spacecraft. For example, one spacecraft was more poleward than the other three (C2), one was at higher altitude (C1), and one of them (0) followed another (C4) through the AAR on approximately the same track but delayed by three minutes. Their separations were generally on the order of a few thousand km or less and occasionally two of them were lying along the same magnetic field line. We will show some of the first analyses of the data obtained during the AAR campaign, where upward and downward current regions, and the waves specifically associated with those regions, as well as the auroral cavities, were observed similarly and differently on the various spacecraft, helping us to explore the spatial, as well as the temporal, aspects of processes occurring in the AAR.

  6. Protein Kinase Cϵ Is Required for Spinal Analgesic Synergy between Delta Opioid and Alpha-2A Adrenergic Receptor Agonist Pairs

    PubMed Central

    Schuster, Daniel J.; Kitto, Kelley F.; Overland, Aaron C.; Messing, Robert O.; Stone, Laura S.; Fairbanks, Carolyn A.

    2013-01-01

    We recently showed that spinal synergistic interactions between δ opioid receptors (δORs) and α2A adrenergic receptors (α2AARs) require protein kinase C (PKC). To identify which PKC isoforms contribute to analgesic synergy, we evaluated the effects of various PKC-isoform-specific peptide inhibitors on synergy between δORs and α2AARs using the tail flick assay of thermal nociception in mice. Only a PKCϵ inhibitor abolished synergy between a δOR agonist and an α2AAR agonist. We tested a panel of combinations of opioid and adrenergic agonists in PKCϵ knock-out mice and found that all four combinations of a δOR agonist and an α2AAR agonist required PKCϵ for antinociceptive synergy. None of the combinations of a μOR agonist with an α2AR agonist required PKCϵ. Immunohistochemistry confirmed that PKCϵ could be found in the population of peptidergic primary afferent nociceptors where δORs and α2AARs have been found to extensively colocalize. Immunoreactivity for PKCϵ was found in the majority of dorsal root ganglion neurons and intensely labeled laminae I and II of the spinal cord dorsal horn. PKCϵ is widespread in the spinal nociceptive system and in peptidergic primary afferents it appears to be specifically involved in mediating the synergistic interaction between δORs and α2AARs. PMID:23946412

  7. Lithological influence of aggregate in the alkali-carbonate reaction

    SciTech Connect

    Lopez-Buendia, A.M. . E-mail: angel.lopez@aidico.es; Climent, V. . E-mail: vcliment@grupogla.com; Verdu, P.

    2006-08-15

    The reactivity of carbonate rock with the alkali content of cement, commonly called alkali-carbonate reaction (ACR), has been investigated. Alkali-silica reaction (ASR) can also contribute in the alkali-aggregate reaction (AAR) in carbonate rock, mainly due to micro- and crypto-crystalline quartz or clay content in carbonate aggregate. Both ACR and ASR can occur in the same system, as has been also evidenced on this paper. Carbonate aggregate samples were selected using lithological reactivity criteria, taking into account the presence of dedolomitization, partial dolomitization, micro- and crypto-crystalline quartz. Selected rocks include calcitic dolostone with chert (CDX), calcitic dolostone with dedolomitization (CDD), limestone with chert (LX), marly calcitic dolostone with partial dolomitization (CD), high-porosity ferric dolostone with clays (FD). To evaluate the reactivity, aggregates were studied using expansion tests following RILEM AAR-2, AAR-5, a modification using LiOH AAR-5Li was also tested. A complementary study was done using petrographic monitoring with polarised light microscopy on aggregates immersed in NaOH and LiOH solutions after different ages. SEM-EDAX has been used to identify the presence of brucite as a product of dedolomitization. An ACR reaction showed shrinkage of the mortar bars in alkaline solutions explained by induced dedolomitization, while an ASR process typically displayed expansion. Neither shrinkage nor expansion was observed when mortar bars were immersed in solutions of lithium hydroxide. Carbonate aggregate classification with AAR pathology risk has been elaborated based on mechanical behaviours by expansion and shrinkage. It is proposed to be used as a petrographic method for AAR diagnosis to complement the RILEM AAR1 specifically for carbonate aggregate. Aggregate materials can be classified as I (non-reactive), II (potentially reactive), and III (probably reactive), considering induced dedolomitization ACR

  8. Alkali-aggregate reactivity of typical siliceious glass and carbonate rocks in alkali-activated fly ash based geopolymers

    NASA Astrophysics Data System (ADS)

    Lu, Duyou; Liu, Yongdao; Zheng, Yanzeng; Xu, Zhongzi; Shen, Xiaodong

    2013-08-01

    For exploring the behaviour of alkali-aggregate reactivity (AAR) in alkali-activated geopolymeric materials and assessing the procedures for testing AAR in geopolymers, the expansion behaviour of fly ash based geopolymer mortars with pure silica glass and typical carbonate rocks were studied respectively by curing at various conditions, i.e. 23°C and 38°C with relative humidity over 95%, immersed in 1M NaOH solution at 80°C. Results show that, at various curing conditions, neither harmful ASR nor harmful ACR was observed in geopolymers with the criteria specified for OPC system. However, with the change of curing conditions, the geopolymer binder and reactive aggregates may experience different reaction processes leading to quite different dimensional changes, especially with additional alkalis and elevated temperatures. It suggests that high temperature with additional alkali for accelerating AAR in traditional OPC system may not appropriate for assessing the alkali-aggregate reactivity behaviour in geopolymers designed for normal conditions. On the other hand, it is hopeful to control the dimensional change of geopolymer mortar or concrete by selecting the type of aggregates and the appropriate curing conditions, thus changing the harmful AAR in OPC into beneficial AAR in geopolymers and other alkali-activated cementitious systems.

  9. Assignment of two human autoantigen genes-isoleucyl-tRNA synthetase locates to 9q21 and lysyl-tRNA synthetase locates to 16q23-q24

    SciTech Connect

    Nichols, R.C.; Blinder, J.; Pai, S.I.

    1996-08-15

    Protein synthesis is initiated by the attachment of amino acids to cognate tRNAs by aminoacyl-tRNA synthetases (aaRS). Five of twenty human aaRS (histidyl-RS, threonyl-RS, alanyl-RS, glycyl-RS, and isoleucyl-RS) have been identified as targets of autoantibodies in the autoimmune disease polymyositis/dermatomyositis. Autoantibodies to human lysyl-RS, a sixth autoantigenic aminoacyl-RS, were recently identified. The genes for histidyl-RS and threonyl-RS have been localized to chromosome 5, and we recently reported that the genes for alanyl-RS and glycyl-RS localize to chromosomes 16 and 7, respectively. To understand the genesis of autoimmune responses to aaRS better, we have used PCR-based screening of somatic cell hybrid panels and fluorescence in situ hybridization (FISH) to assign the genes for isoleucyl-RS and lysyl-RS. 19 refs., 1 fig.

  10. The growing pipeline of natural aminoacyl-tRNA synthetase inhibitors for malaria treatment.

    PubMed

    Saint-Léger, Adélaïde; Sinadinos, Christopher; Ribas de Pouplana, Lluís

    2016-04-02

    Malaria remains a major global health problem. Parasite resistance to existing drugs makes development of new antimalarials an urgency. The protein synthesis machinery is an excellent target for the development of new anti-infectives, and aminoacyl-tRNA synthetases (aaRS) have been validated as antimalarial drug targets. However, avoiding the emergence of drug resistance and improving selectivity to target aaRS in apicomplexan parasites, such as Plasmodium falciparum, remain crucial challenges. Here we discuss such issues using examples of known inhibitors of P. falciparum aaRS, namely halofuginone, cladosporin and borrelidin (inhibitors of ProRS, LysRS and ThrRS, respectively). Encouraging recent results provide useful guidelines to facilitate the development of novel drug candidates which are more potent and selective against these essential enzymes.

  11. α2 Adrenergic Receptor Trafficking as a Therapeutic Target in Antidepressant Drug Action.

    PubMed

    Cottingham, Christopher; Ferryman, Craig J; Wang, Qin

    2015-01-01

    Antidepressant drugs remain poorly understood, especially with respect to pharmacological mechanisms of action. This lack of knowledge results from the extreme complexity inherent to psychopharmacology, as well as to a corresponding lack of knowledge regarding depressive disorder pathophysiology. While the final analysis is likely to be multifactorial and heterogeneous, compelling evidence exists for upregulation of brain α2 adrenergic receptors (ARs) in depressed patients. This evidence has sparked a line of research into actions of a particular antidepressant drug class, the tricyclic antidepressants (TCAs), as direct ligands at α(2A)ARs. Our findings, as outlined herein, demonstrate that TCAs function as arrestin-biased ligands at α(2A)ARs. Importantly, TCA-induced α(2A)AR/arrestin recruitment leads to receptor endocytosis and downregulation of α(2A)AR expression with prolonged exposure. These findings represent a novel mechanism linking α(2)AR trafficking with antidepressant pharmacology.

  12. Geophysical Investigation of Australian-Antarctic Ridge Using High-Resolution Gravity and Bathymetry

    NASA Astrophysics Data System (ADS)

    Kim, S. S.; Lin, J.; Park, S. H.; Choi, H.

    2015-12-01

    Much of the Australian-Antarctic Ridge (AAR) has been remained uncharted until 2011 because of its remoteness and harsh weather conditions. From 2011, the multidisciplinary ridge program initiated by the Korea Polar Research Institute (KOPRI) surveyed the little-explored eastern ends of the AAR to characterize the tectonics, geochemistry, and hydrothermal activity of this intermediate spreading system. In this study, we present a detailed analysis of a 300-km-long supersegment of the AAR to quantify the spatial variations in ridge morphology and axial and off-axis volcanisms as constrained by high-resolution shipboard bathymetry and gravity. The ridge axis morphology alternates between rift valleys and axial highs within relatively short ridge segments. To obtain a geological proxy for regional variations in magma supply, we calculated residual mantle Bouguer gravity anomalies (RMBA), gravity-derived crustal thickness, and residual topography for neighboring seven sub-segments. The results of the analyses revealed that the southern flank of the AAR is associated with shallower seafloor, more negative RMBA, thicker crust, and/or less dense mantle in comparison to the conjugate northern flank. Furthermore, this north-south asymmetry becomes more prominent toward the KR1 supersegment of the AAR. The axial topography of the KR1 supersegment exhibits a sharp transition from axial highs at the western end to rift valleys at the eastern end, with regions of axial highs being associated with more robust magma supply as indicated by more negative RMBA. We also compare and contrast the characteristics of the AAR supersegment with that of other ridges of intermediate spreading rates, including the Juan de Fuca Ridge, Galápagos Spreading Center, and Southeast Indian Ridge west of the Australian-Antarctic Discordance, to investigate the influence of ridge-hotspot interaction on ridge magma supply and tectonics.

  13. Excellent amino acid racemization results from Holocene sand dollars

    NASA Astrophysics Data System (ADS)

    Kosnik, M.; Kaufman, D. S.; Kowalewski, M.; Whitacre, K.

    2015-12-01

    Amino acid racemization (AAR) is widely used as a cost-effective method to date molluscs in time-averaging and taphonomic studies, but it has not been attempted for echinoderms despite their paleobiological importance. Here we demonstrate the feasibility of AAR geochronology in Holocene aged Peronella peronii (Echinodermata: Echinoidea) collected from Sydney Harbour (Australia). Using standard HPLC methods we determined the extent of AAR in 74 Peronella tests and performed replicate analyses on 18 tests. We sampled multiple areas of two individuals and identified the outer edge as a good sampling location. Multiple replicate analyses from the outer edge of 18 tests spanning the observed range of D/Ls yielded median coefficients of variation < 4% for Asp, Phe, Ala, and Glu D/L values, which overlaps with the analytical precision. Correlations between D/L values across 155 HPLC injections sampled from 74 individuals are also very high (pearson r2 > 0.95) for these four amino acids. The ages of 11 individuals spanning the observed range of D/L values were determined using 14C analyses, and Bayesian model averaging was used to determine the best AAR age model. The averaged age model was mainly composed of time-dependent reaction kinetics models (TDK, 71%) based on phenylalanine (Phe, 94%). Modelled ages ranged from 14 to 5539 yrs, and the median 95% confidence interval for the 74 analysed individuals is ±28% of the modelled age. In comparison, the median 95% confidence interval for the 11 calibrated 14C ages was ±9% of the median age estimate. Overall Peronella yields exceptionally high-quality AAR D/L values and appears to be an excellent substrate for AAR geochronology. This work opens the way for time-averaging and taphonomic studies of echinoderms similar to those in molluscs.

  14. Automatic anatomy recognition in post-tonsillectomy MR images of obese children with OSAS

    NASA Astrophysics Data System (ADS)

    Tong, Yubing; Udupa, Jayaram K.; Odhner, Dewey; Sin, Sanghun; Arens, Raanan

    2015-03-01

    Automatic Anatomy Recognition (AAR) is a recently developed approach for the automatic whole body wide organ segmentation. We previously tested that methodology on image cases with some pathology where the organs were not distorted significantly. In this paper, we present an advancement of AAR to handle organs which may have been modified or resected by surgical intervention. We focus on MRI of the neck in pediatric Obstructive Sleep Apnea Syndrome (OSAS). The proposed method consists of an AAR step followed by support vector machine techniques to detect the presence/absence of organs. The AAR step employs a hierarchical organization of the organs for model building. For each organ, a fuzzy model over a population is built. The model of the body region is then described in terms of the fuzzy models and a host of other descriptors which include parent to offspring relationship estimated over the population. Organs are recognized following the organ hierarchy by using an optimal threshold based search. The SVM step subsequently checks for evidence of the presence of organs. Experimental results show that AAR techniques can be combined with machine learning strategies within the AAR recognition framework for good performance in recognizing missing organs, in our case missing tonsils in post-tonsillectomy images as well as in simulating tonsillectomy images. The previous recognition performance is maintained achieving an organ localization accuracy of within 1 voxel when the organ is actually not removed. To our knowledge, no methods have been reported to date for handling significantly deformed or missing organs, especially in neck MRI.

  15. Message Network Simulation

    DTIC Science & Technology

    1990-03-01

    i.96*SR10 Si UR10 = AR10+1. 96*SR10 LBF = ABF-1.96*SBF UBF = ABF+1.96*SBF LPMR = APMR-1. 96*SPMR UPHR = APMR+1. 96*SPMR LAR = AAR-1. 96*SAR...WRITEC13,141) LN,AR1,AR2,AR3,AR6A,AR4,AR5,AR7,AR10 WRITE(13,141) LN,UR1,UR2,UR3,UR6A,UR4,UR5,UR7, UR10 WRITEC15,137) LN,LRS,LPMR,LBF,LAR,LAC,LR9

  16. Amino acid racemization on planktic foraminifera from the central Arctic Ocean

    NASA Astrophysics Data System (ADS)

    Hanslik, D.; Kaufman, D. S.; Jakobsson, M.

    2009-12-01

    Amino acid racemization (AAR) is the interconversion of amino acids from one chiral form (L - levo) to a mixture of L- and D- (dextro) forms as a function of time and temperature. The extent of AAR in foraminifera shells can be determined by measuring the ratio of D/L amino acids, and can be used as a relative dating method. The technique can also be used to determine numerical ages once the rate of racemization is calibrated for a study area using samples of known ages. In this study sediment cores from the Lomonosov Ridge (88°N) and Morris Jesup Rise (85°N), in the central Arctic Ocean, were analyzed for AAR on monospecific samples of the polar planktic foraminifera Neogloboquadrina pachyderma sinistral. Numerical ages were derived using an equation developed for aspartic and glutamic acids in a previous study on other cores from the Northwind, Mendeleev and Lomonosov ridges, which applies to samples younger than about 150 ka (Kaufman et al., 2008, Paleoceanography 23:PA3224). The calculated AAR ages are in relatively good agreement with 14C ages throughout the range of 14C dating for both of our cores. The core from Morris Jesup Rise includes older sediment beyond the range of 14C dating where ages were inferred from benthic foraminifera events and correlation with other cores with previously published age models. The AAR age for the level of unique occurrence of the benthic foramifera Bulimina aculeata from this core is about 85 ka, which agrees with previous work that assigned this level to MIS 5.1. Beyond about 85 ka, there is a progressively increasing age discrepancy between calculated AAR ages and estimated ages based on benthic foraminifera events. For MIS 5.5, the D/L values for the Epistominella exigua marker are lower in our core than in the cores analyzed by Kaufman et al. (2008). Assuming that this event is a chronostratigraphic marker, then the AAR results suggest that deepwater temperature at our site during MIS 5 was lower than at the other

  17. Consensus recommendations from the American Acne & Rosacea Society on the management of rosacea, part 5: a guide on the management of rosacea.

    PubMed

    Del Rosso, James Q; Thiboutot, Diane; Gallo, Richard; Webster, Guy; Tanghetti, Emil; Eichenfield, Lawrence F; Stein-Gold, Linda; Berson, Diane; Zaenglein, Andrea

    2014-03-01

    The last article in this 5-part series provides a final overview of consensus recommendations from the American Acne & Rosacea Society (AARS) on the management of the common presentations of cutaneous rosacea. Optimal management of rosacea requires careful assessment of the patient's clinical features with integration of therapies that adequately treat the presenting signs and symptoms. The treatment consensus recommendations from the AARS are based on 2 major common clinical presentations of rosacea: (1) centrofacial erythema with papulopustular lesions, and (2) centrofacial erythema without papulopustular lesions. The recommendations provided here serve to guide clinicians in their clinical practice.

  18. Analytical Support Across the Range of Military Operations

    DTIC Science & Technology

    2011-04-06

    Michael Mayne , USMC, interview by MCCLL Mr. Robert Clark. Company Commander, B Co 1/3 (April15, 2009). 13 Mayne , AAR 2009. 14 2Bn 24th Mar "AAR OIF...Michael Mayne , USMC, interview by MCCLL Mr."Robert Clark. Company Commander, B Co 1/3 (April15, 2009). 17 Major General Michael T. Flynn, Captain...USMC, interview by MCCLL LNO Mr. Chris Wilk.Battalion S2 Intelligence Officer 112 (April 15, 2009). Captain Michael Mayne , USMC, interview by M’CCLL

  19. Chapter K: Progress in the Evaluation of Alkali-Aggregate Reaction in Concrete Construction in the Pacific Northwest, United States and Canada

    USGS Publications Warehouse

    Shrimer, Fred H.

    2005-01-01

    The supply of aggregates suitable for use in construction and maintenance of infrastructure in western North America is a continuing concern to the engineering and resources-management community. Steady population growth throughout the region has fueled demand for high-quality aggregates, in the face of rapid depletion of existing aggregate resources and slow and difficult permitting of new sources of traditional aggregate types. In addition to these challenges, the requirement for aggregates to meet various engineering standards continues to increase. In addition to their physical-mechanical properties, other performance characteristics of construction aggregates specifically depend on their mineralogy and texture. These properties can result in deleterious chemical reactions when aggregate is used in concrete mixes. When this chemical reaction-termed 'alkali-aggregate reaction' (AAR)-occurs, it can pose a major problem for concrete structures, reducing their service life and requiring expensive repair or even replacement of the concrete. AAR is thus to be avoided in order to promote the longevity of concrete structures and to ensure that public moneys invested in infrastructure are well spent. Because the AAR phenomenon is directly related to the mineral composition, texture, and petrogenesis of the rock particles that make up aggregates, an understanding of the relation between the geology and the performance of aggregates in concrete is important. In the Pacific Northwest, some aggregates have a moderate to high AAR potential, but many others have no or only a low AAR potential. Overall, AAR is not as widespread or serious a problem in the Pacific Northwest as in other regions of North America. The identification of reactive aggregates in the Pacific Northwest and the accurate prediction of their behavior in concrete continue to present challenges for the assessment and management of geologic resources to the owners and operators of pits and quarries and to the

  20. 49 CFR 176.76 - Transport vehicles, freight containers, and portable tanks containing hazardous materials.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS CARRIAGE BY VESSEL General Handling and Stowage § 176.76 Transport... in which any flammable liquid or gas is stowed. Any heating or air conditioning equipment having a... Class DOT-113 or AAR-204W tank cars. (h) A fumigated cargo transport unit may only be transported...

  1. 77 FR 76169 - Quarterly Rail Cost Adjustment Factor

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-26

    ... Surface Transportation Board Quarterly Rail Cost Adjustment Factor AGENCY: Surface Transportation Board, DOT. ACTION: Approval of rail cost adjustment factor. SUMMARY: The Board has approved the AAR's proposed rebasing calculations and the rebased first quarter 2013 rail cost adjustment factor (RCAF)...

  2. 75 FR 75448 - Revised Proposal for Revisions to the Schedules of Civil Penalties for a Violation of a Federal...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-03

    ... time to review all the penalties listed in the proposal to determine if they match the severity-scale... period in order to allow AAR more time to review the penalties in the severity scale and to identify and comment more fully on which individual penalties do not in its opinion satisfy the severity-scale...

  3. 49 CFR 179.2 - Definitions and abbreviations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Introduction, Approvals and... Association of American Railroads. (2) Approved means approval by the AAR Tank Car Committee. (3) ASTM means...) F means degrees Fahrenheit. (7) NGT means National Gas Taper Threads. (8) NPT means an...

  4. 49 CFR 179.2 - Definitions and abbreviations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Introduction, Approvals and... Association of American Railroads. (2) Approved means approval by the AAR Tank Car Committee. (3) ASTM means...) F means degrees Fahrenheit. (7) NGT means National Gas Taper Threads. (8) NPT means an...

  5. 49 CFR 179.2 - Definitions and abbreviations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Introduction, Approvals and... Association of American Railroads. (2) Approved means approval by the AAR Tank Car Committee. (3) ASTM means...) F means degrees Fahrenheit. (7) NGT means National Gas Taper Threads. (8) NPT means an...

  6. 49 CFR 179.2 - Definitions and abbreviations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS Introduction, Approvals and... Association of American Railroads. (2) Approved means approval by the AAR Tank Car Committee. (3) ASTM means...) F means degrees Fahrenheit. (7) NGT means National Gas Taper Threads. (8) NPT means an...

  7. 77 FR 41473 - Proposed Technical Standard Order (TSO)-C126b, 406 MHz Emergency Locator Transmitters (ELT) and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... mounting tray has caused the antenna connection to sever, rendering the ELT ineffective and severely... Aircraft Accident Report AAR-11-03: The antenna cable was severed from the ELT when the ELT slipped out of... NTSB ID WPR10FA273: The antenna cable was severed from the ELT when the ELT slipped out of the hook...

  8. Measuring Stability and Security in Iraq

    DTIC Science & Technology

    2008-12-01

    remains unfunded at this time. These centers include a range complex, combat assault course, live fire shoot house, and outdoor classrooms . They...combined capacity is limited to 14,600 students. Additional facilities planned in 2009 include dedicated AAR and medical training classrooms and... meditated murder, manslaughter, kidnapping, stealing, aggravating circumstances, embezzlement, rape, sodomy, incest, counterfeiting, drug crimes

  9. Effects of Synephrine and B-Phenethylamine on Human a-Adrenoceptor Subtypes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Synephrine and B-phenethylamine are structurally related to ephedrine. In this study, the effects of synephrine and B-phenethylamine are investigated on a-adrenoceptor (a-AR) subtypes expressed in human embroyonic kidney (HEK293) or Chinese hamster ovary (CHO) cells, and compared to that of 1R,2S-no...

  10. 75 FR 8817 - Annual Submission of Tax Information for Use in the Revenue Shortfall Allocation Method

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-26

    ...The Surface Transportation Board (Board) is amending 49 CFR part 1135 to add a rule that requires the Association of American Railroads (AAR) to annually update each Class I railroad's weighted average State tax rate for use in the Revenue Shortfall Allocation Method (RSAM). RSAM is one of three benchmarks that together are used to determine the reasonableness of a challenged rate under the......

  11. LACK OF EFFECT OF AGE AND ANTIOXIDANT DEPLETION ON RESPIRATORY RESPONSES TO CONCENTRATED AMBIENT PARTICULATES (CAPS) IN RATS

    EPA Science Inventory

    2003 AAR PM Meeting
    Particulate Matter: Atmospheric Sciences,
    Exposure and the Fourth Colloquium on PM and Human Health

    LACK OF EFFECT OF AGE AND ANTIOXIDANT DEPLETION ON RESPIRATORY RESPONSES TO CONCENTRATED AMBIENT PARTICULATES (CAPs) IN RATS. JA Dye, LC Walsh, C...

  12. Preparing Specialized Undergraduate Pilot Training Graduates for F-35A Training

    DTIC Science & Technology

    2010-06-11

    visual systems like Night Vision Goggles or Distributed Aperture System. Using these three tasks as a starting point, the FNA accomplished a...are necessary to accomplish the assigned task or mission. Examples include use of Night Vision Goggles or night -aided visual systems such as the...

  13. 78 FR 48765 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-09

    ... Federal Railroad Administration Petition for Waiver of Compliance In accordance with Part 211 of Title 49... July 19, 2013, the Association of American Railroads (AAR) has petitioned the Federal Railroad Administration (FRA) for a waiver of compliance from certain provisions of the Federal railroad...

  14. 49 CFR 179.220-18 - Bottom outlets.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION HAZARDOUS MATERIALS REGULATIONS SPECIFICATIONS FOR TANK CARS Specifications for Non-Pressure Tank Car Tanks (Classes DOT-111AW and 115AW) § 179.220-18 Bottom outlets. (a) The... of the AAR Specifications for Tank Cars (IBR, see § 171.7 of this subchapter). All bottom...

  15. 49 CFR 179.22 - Marking.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK CARS General Design Requirements... requirements apply: (a) Each tank car must be marked according to the requirements in appendix C of the AAR Specifications for Tank Cars (IBR, see § 171.7 of this subchapter). (b) Each tank car that requires a...

  16. 49 CFR 179.200-13 - Manway ring or flange, pressure relief device flange, bottom outlet nozzle flange, bottom washout...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SPECIFICATIONS FOR TANK CARS Specifications for Non-Pressure Tank Car Tanks (Classes DOT-111AW and 115AW) § 179..., figure 10, of the AAR Specifications for Tank Cars (IBR, see § 171.7 of this subchapter). (b) The opening... cast, forged or fabricated metal. The metal of the dome, tank, or nozzle must be compatible with...

  17. Obstacle Avoidance Control for the REMUS Autonomous Underwater Vehicle

    DTIC Science & Technology

    2002-12-01

    the advent of improved mines, submarine quieting, and other littoral threats. It has often been said that the best way to combat threats in a...are often linearized using Tayor series expansion terms in individual motion components. These expansion terms are termed ‘hydrodynamic

  18. 76 FR 51324 - Hazardous Materials: Incorporating Rail Special Permits Into the Hazardous Materials Regulations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-18

    ... 105J300W tank cars containing certain flammable liquids; (f) permit certain DOT and AAR specification tank... level of Minor edits. reliability and safety. Interior heating system. No change. Lining/Coating owner...)........ Added last sentence for clarity. Paragraph (d)(3)........ Added ``Corrosion'' as specific element...

  19. Investigation of Diesel Fuel Fire Vulnerability Parameters in Armored Personnel Carriers due to Ballistic Penetration

    DTIC Science & Technology

    1985-03-22

    BRADELY FIGHTING CDR VEHICLE SYS US ARMY FOREIGN SCIENCE & TECH ATTN: AMCPM-FVS-M I CENTER WARREN MI 48090 ATTN: AMXST-MT-1 AMXST-BA PROG MGR, M113...ATZL-CAT-A 6 ATTN: CODE 05M4 (MR R LAYNE) FORT. LEAVENWORTH KA 66027 WASHINGTON DC 20362 CDR CDR US ARMY LOGISTICS CIRCDATTN: ARYLOGS (R AARS ) I DAVID

  20. 78 FR 44189 - Petition for Modification of Single Car Air Brake Test Procedures

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ... Federal Railroad Administration Petition for Modification of Single Car Air Brake Test Procedures In... the Federal Railroad Administration (FRA) per 49 CFR 232.307 to modify the single car air brake test procedures located in AAR Standard S-486, Code of Air Brake System Tests for Freight Equipment-- Single...

  1. 49 CFR 179.200-7 - Materials.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... metal (longitudinal) AAR TC 128, Gr. B 81,000 19 ASTM A 516 2 70,000 20 1 Minimum stresses to be used in....i.) welded condition 3,4 Minimum elongation in 2 inches (percent) 0 temper weld metal (longitudinal... only. 3 Weld filler metal 5556 must not be used. 4 Maximum stresses to be used in calculations....

  2. 49 CFR Appendix B to Part 232 - Part 232 Prior to May 31, 2001 as Clarified Effective April 10, 2002

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...; or (2) Rapid transit operations in an urban area that are not connected with the general railroad... include rapid transit operations within an urban area that are not connected to the general railroad... accordance with the applicable AAR Code of Tests or the American Public Transportation Association...

  3. 49 CFR Appendix B to Part 232 - Part 232 Prior to May 31, 2001 as Clarified Effective April 10, 2002

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...; or (2) Rapid transit operations in an urban area that are not connected with the general railroad... include rapid transit operations within an urban area that are not connected to the general railroad... accordance with the applicable AAR Code of Tests or the American Public Transportation Association...

  4. 49 CFR Appendix B to Part 232 - Part 232 Prior to May 31, 2001 as Clarified Effective April 10, 2002

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...; or (2) Rapid transit operations in an urban area that are not connected with the general railroad... include rapid transit operations within an urban area that are not connected to the general railroad... accordance with the applicable AAR Code of Tests or the American Public Transportation Association...

  5. 77 FR 75045 - Locomotive Safety Standards

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-19

    ... Justice (AAJ), the Association of American Railroads (AAR), the Central Railway MFG (CRM), D. P. Honold... ZTR Equipment Management (ZTR). The petitions filed by these parties principally relate to the... of the scope of subpart E. A vendor's railroad customer therefore would determine the level of...

  6. Evolutionary Limitation and Opportunities for Developing tRNA Synthetase Inhibitors with 5-Binding-Mode Classification

    PubMed Central

    Fang, Pengfei; Guo, Min

    2015-01-01

    Aminoacyl-tRNA synthetases (aaRSs) are enzymes that catalyze the transfer of amino acids to their cognate tRNAs as building blocks for translation. Each of the aaRS families plays a pivotal role in protein biosynthesis and is indispensable for cell growth and survival. In addition, aaRSs in higher species have evolved important non-translational functions. These translational and non-translational functions of aaRS are attractive for developing antibacterial, antifungal, and antiparasitic agents and for treating other human diseases. The interplay between amino acids, tRNA, ATP, EF-Tu and non-canonical binding partners, had shaped each family with distinct pattern of key sites for regulation, with characters varying among species across the path of evolution. These sporadic variations in the aaRSs offer great opportunity to target these essential enzymes for therapy. Up to this day, growing numbers of aaRS inhibitors have been discovered and developed. Here, we summarize the latest developments and structural studies of aaRS inhibitors, and classify them with distinct binding modes into five categories. PMID:26670257

  7. 75 FR 4703 - Track Safety Standards; Continuous Welded Rail (CWR)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-29

    ... received one petition questioning the definitions of ``adjusting/de-stressing'' and ``buckling-prone... the petitioner. ``Buckling-Prone Condition'' Definition In the petition, AAR stated that the definition of ``buckling prone condition'' included in the final rule at Sec. 213.119(l) was not proposed...

  8. 78 FR 60301 - Agency Information Collection Activities: Proposed Collection; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-01

    ... the method used for submitting comments or material, all submissions will be posted, without change... identifying, correcting and sharing as appropriate strengths and areas for improvement. Thus, the HSEEP AAR/IP... and provides assessments of the respondent's capabilities so that strengths and areas for...

  9. JPRS Report, Soviet Union, Military Affairs.

    DTIC Science & Technology

    2007-11-02

    General I. Pavlov . Ivan Andreyevich later explained that the call was from the party gorkom, that they had asked for a deferment from the draft for a...Are Prepared for Military Service in Leningrad, and by Whom"] [Text] I went to see Major General I. Pavlov , military commissar for Leningrad

  10. An Evaluation of New After-Action Review Tools in Exercise Black Skies 10 & Exercise Black Skies 12

    DTIC Science & Technology

    2013-10-01

    and Projects), to address client requirements set forth by Air Force Headquarters. These requirements relate to the development of tools and processes ...between AARs using AWAR or more standard tools; and (2) identify how AWAR tools and processes may be improved for future synthetic mission training...2.4.3 Cognitive and Social Process Changes ................................................. 7 2.5 Method

  11. Usability Evaluation of Air Warfare Assessment & Review Toolset in Exercise Black Skies 2012

    DTIC Science & Technology

    2013-12-01

    AWAR tool on the AAR learning process is reported separately. User Testing and Activity Theory approaches were applied in parallel to test the...comment process .................................. 41 B.2. Save Session process ...Activity Theory ADGE Air Defence Ground Environment AOD Air Operations Division AWAR Air Warfare Assessment & Review CSUQ Computer System

  12. 49 CFR 179.102-4 - Vinyl fluoride, stabilized.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... performed as follows: (i) ASTM A 516/A 516M and A 537/A 537M material must meet the Charpy V-Notch test...). (ii) AAR Specification TC 128 material must meet the Charpy V-Notch test requirements, in longitudinal... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) SPECIFICATIONS FOR TANK...

  13. 49 CFR 232.307 - Modification of the single car air brake test procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Modification of the single car air brake test... Requirements § 232.307 Modification of the single car air brake test procedures. (a) Request. The AAR or other authorized representative of the railroad industry may seek modification of the single car air brake...

  14. 77 FR 58615 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-21

    ... at Class 5 speeds over ``heavy-point'' frog designs conforming to the standards for Class 4 track frogs guard check and face gage dimensions. The heavy-point frog is a unique design, which has a thicker frog point. As proposed in the original waiver petition, AAR states that it offers safety benefits...

  15. Automatic anatomy recognition on CT images with pathology

    NASA Astrophysics Data System (ADS)

    Huang, Lidong; Udupa, Jayaram K.; Tong, Yubing; Odhner, Dewey; Torigian, Drew A.

    2016-03-01

    Body-wide anatomy recognition on CT images with pathology becomes crucial for quantifying body-wide disease burden. This, however, is a challenging problem because various diseases result in various abnormalities of objects such as shape and intensity patterns. We previously developed an automatic anatomy recognition (AAR) system [1] whose applicability was demonstrated on near normal diagnostic CT images in different body regions on 35 organs. The aim of this paper is to investigate strategies for adapting the previous AAR system to diagnostic CT images of patients with various pathologies as a first step toward automated body-wide disease quantification. The AAR approach consists of three main steps - model building, object recognition, and object delineation. In this paper, within the broader AAR framework, we describe a new strategy for object recognition to handle abnormal images. In the model building stage an optimal threshold interval is learned from near-normal training images for each object. This threshold is optimally tuned to the pathological manifestation of the object in the test image. Recognition is performed following a hierarchical representation of the objects. Experimental results for the abdominal body region based on 50 near-normal images used for model building and 20 abnormal images used for object recognition show that object localization accuracy within 2 voxels for liver and spleen and 3 voxels for kidney can be achieved with the new strategy.

  16. 49 CFR 1180.4 - Procedures.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Waybill Sample. (7) Federal Reserve Board Production Statistics. (8) AAR compilations of bad order ratios... order. At any time, the Board may require the submission of additional copies of any document previously...) Prefiling notification. When filing the notice of intent required by paragraph (b)(1) of this...

  17. 49 CFR 180.517 - Reporting and record retention requirements.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., see § 171.7 of this subchapter) apply. The builder of the car or a facility performing work on the car... QUALIFICATION AND MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Tank Cars § 180.517 Reporting and... car must retain the certificate of construction (AAR Form 4-2) and related papers certifying that...

  18. 49 CFR 180.517 - Reporting and record retention requirements.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., see § 171.7 of this subchapter) apply. The builder of the car or a facility performing work on the car... QUALIFICATION AND MAINTENANCE OF PACKAGINGS Qualification and Maintenance of Tank Cars § 180.517 Reporting and... car must retain the certificate of construction (AAR Form 4-2) and related papers certifying that...

  19. 49 CFR 179.4 - Changes in specifications for tank cars.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Changes in specifications for tank cars. 179.4... TANK CARS Introduction, Approvals and Reports § 179.4 Changes in specifications for tank cars. (a...—Tank Car Safety, AAR, for consideration by its Tank Car Committee. An application for construction...

  20. 49 CFR 232.307 - Modification of the single car air brake test procedures.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Modification of the single car air brake test... Requirements § 232.307 Modification of the single car air brake test procedures. (a) Request. The AAR or other authorized representative of the railroad industry may seek modification of the single car air brake...

  1. 49 CFR 232.307 - Modification of the single car air brake test procedures.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Modification of the single car air brake test... Requirements § 232.307 Modification of the single car air brake test procedures. (a) Request. The AAR or other authorized representative of the railroad industry may seek modification of the single car air brake...

  2. 76 FR 40701 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-11

    ... Systems, 6 AAR-57(V)3 Common Missile Warning Systems, 6 AN/AVR-2B Laser Warning Sets, C406 Electronic... AN/AVR-2B Laser Warning Set is a passive laser warning system that receives, processes and displays... a passive laser warning system that receives, processes, and displays threat information......

  3. 77 FR 40023 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-06

    ... Looking Infrared system. Self Protection systems include the AN/AAR-47 Missile Warning Set, AN/ALQ-144A... mm and .50-calibre (12.7 mm)), Electronic Warfare Self-Defense Suite (including Missile/Laser Warning.... The navigation suite includes the LN-100G inertial navigation system with an embedded...

  4. 78 FR 47824 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-06

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION... continue in service a car if an end of car cushioning unit is leaking clearly formed droplets. In its... droplets. AAR requests a 3-year test period during which it may be shown that end of car cushioning...

  5. 76 FR 76217 - Petition for Waiver of Compliance

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-06

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF TRANSPORTATION...)(3), which requires that end platforms on boxcars be ``centered on each end of car between inner ends... inches. AAR and ASLRRA stated that more than 18,000 cars and 20 different car owners are affected....

  6. Developing Learning Organizations at the Small Unit Level

    DTIC Science & Technology

    2010-01-01

    the After Action Review (AAR) is another highlighted success in its holistic attempts to become a learning organization. In his Harvard Business Review article...reexamined/index.html. Garvin, David A., Edmondson, Amy C. & Gino Francesca (2008). Is Yours a Learning Organization? Harvard Business Review . www.hbr.org

  7. Crossing the River: A Conceptual Framework for Response to Chaos

    DTIC Science & Technology

    2012-03-01

    coordination difficult (Moynihan, 2006). The vastly different mission of police officers, firefighters, paramedics , and emergency managers is enough...Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget...ABBREVIATIONS AAR After Action Report CAD Computer Aided Dispatch CRM Crew Resource Management FEMA Federal Emergency Management GPS Global

  8. Rocket-Based Combined Cycle Engine Concept Development

    NASA Technical Reports Server (NTRS)

    Ratekin, G.; Goldman, Allen; Ortwerth, P.; Weisberg, S.; McArthur, J. Craig (Technical Monitor)

    2001-01-01

    The development of rocket-based combined cycle (RBCC) propulsion systems is part of a 12 year effort under both company funding and contract work. The concept is a fixed geometry integrated rocket, ramjet, scramjet, which is hydrogen fueled and uses hydrogen regenerative cooling. The baseline engine structural configuration uses an integral structure that eliminates panel seals, seal purge gas, and closeout side attachments. Engine A5 is the current configuration for NASA Marshall Space Flight Center (MSFC) for the ART program. Engine A5 models the complete flight engine flowpath of inlet, isolator, airbreathing combustor, and nozzle. High-performance rocket thrusters are integrated into the engine enabling both low speed air-augmented rocket (AAR) and high speed pure rocket operation. Engine A5 was tested in GASL's new Flight Acceleration Simulation Test (FAST) facility in all four operating modes, AAR, RAM, SCRAM, and Rocket. Additionally, transition from AAR to RAM and RAM to SCRAM was also demonstrated. Measured performance demonstrated vision vehicle performance levels for Mach 3 AAR operation and ramjet operation from Mach 3 to 4. SCRAM and rocket mode performance was above predictions. For the first time, testing also demonstrated transition between operating modes.

  9. The infarct-sparing effect of IB-MECA against myocardial ischemia/reperfusion injury in mice is mediated by sequential activation of adenosine A3 and A 2A receptors.

    PubMed

    Tian, Yikui; Marshall, Melissa; French, Brent A; Linden, Joel; Yang, Zequan

    2015-03-01

    Conflicting results exist regarding the role of A3 adenosine receptors (A3ARs) in mediating cardioprotection during reperfusion following myocardial infarction. We hypothesized that the effects of the A3AR agonist IB-MECA to produce cardioprotection might involve activation of other adenosine receptor subtypes. C57Bl/6 (B6), A3AR KO, A2AAR KO, and A2AAR KO/WT bone marrow chimeric mice were assigned to 12 groups undergoing either hemodynamic studies or 45 min of LAD occlusion and 60 min of reperfusion. IB-MECA (100 μg/kg) or vehicle was administered by iv bolus 5 min before reperfusion. Radioligand binding assays showed that IB-MECA has high affinity for the mouse A3AR (K i = 0.17 ± 0.05 nM), but also can bind with lower affinity to the A1AR (9.0 ± 2.4 nM) or the A2AAR (56.5 ± 10.2 nM). IB-MECA caused bi-phasic hemodynamic changes, which were completely absent in A3AR KO mice and were modified by A2AAR blockade or deletion. IB-MECA stimulated histamine release, increased heart rate, and significantly reduced IF size in B6 mice from 61.5 ± 1.4 to 48.6 ± 2.4% of risk region (RR; 21% reduction, p < 0.05) but not in A3AR KO mice. Compared to B6, A3AR KO mice had significantly reduced IF size (p < 0.05). In B6/B6 bone marrow chimeras, IB-MECA caused a 47% reduction of IF size (from 47.3 ± 3.9 to 24.7 ± 4.5, p < 0.05). However, no significant cardioprotective effect of IB-MECA was observed in A2AARKO/B6 mice, which lacked A2AARs only on their bone marrow-derived cells. Activation of A3ARs induces a bi-phasic hemodynamic response, which is partially mediated by activation of A2AARs. The cardioprotective effect of IB-MECA is due to the initial activation of A3AR followed by activation of A2AARs in bone marrow-derived cells.

  10. Reproducibility of area at risk assessment in acute myocardial infarction by T1- and T2-mapping sequences in cardiac magnetic resonance imaging in comparison to Tc99m-sestamibi SPECT.

    PubMed

    Langhans, Birgit; Nadjiri, Jonathan; Jähnichen, Christin; Kastrati, Adnan; Martinoff, Stefan; Hadamitzky, Martin

    2014-10-01

    Area at risk (AAR) is an important parameter for the assessment of the salvage area after revascularization in acute myocardial infarction (AMI). By combining AAR assessment by T2-weighted imaging and scar quantification by late gadolinium enhancement imaging cardiovascular magnetic resonance (CMR) offers a promising alternative to the "classical" modality of Tc99m-sestamibi single photon emission tomography (SPECT). Current T2 weighted sequences for edema imaging in CMR are limited by low contrast to noise ratios and motion artifacts. During the last years novel CMR imaging techniques for quantification of acute myocardial injury, particularly the T1-mapping and T2-mapping, have attracted rising attention. But no direct comparison between the different sequences in the setting of AMI or a validation against SPECT has been reported so far. We analyzed 14 patients undergoing primary coronary revascularization in AMI in whom both a pre-intervention Tc99m-sestamibi-SPECT and CMR imaging at a median of 3.4 (interquartile range 3.3-3.6) days after the acute event were performed. Size of AAR was measured by three different non-contrast CMR techniques on corresponding short axis slices: T2-weighted, fat-suppressed turbospin echo sequence (TSE), T2-mapping from T2-prepared balanced steady state free precession sequences (T2-MAP) and T1-mapping from modified look locker inversion recovery (MOLLI) sequences. For each CMR sequence, the AAR was quantified by appropriate methods (absolute values for mapping sequences, comparison with remote myocardium for other sequences) and correlated with Tc99m-sestamibi-SPECT. All measurements were performed on a 1.5 Tesla scanner. The size of the AAR assessed by CMR was 28.7 ± 20.9 % of left ventricular myocardial volume (%LV) for TSE, 45.8 ± 16.6 %LV for T2-MAP, and 40.1 ± 14.4 %LV for MOLLI. AAR assessed by SPECT measured 41.6 ± 20.7 %LV. Correlation analysis revealed best correlation with SPECT for T2-MAP at a T2-threshold of 60 ms

  11. Functional Dissection of the Bipartite Active Site of the Class I Coenzyme A (CoA)-Transferase Succinyl-CoA:Acetate CoA-Transferase

    PubMed Central

    Murphy, Jesse R.; Mullins, Elwood A.; Kappock, T. Joseph

    2016-01-01

    Coenzyme A (CoA)-transferases catalyze the reversible transfer of CoA from acyl-CoA thioesters to free carboxylates. Class I CoA-transferases produce acylglutamyl anhydride intermediates that undergo attack by CoA thiolate on either the internal or external carbonyl carbon atoms, forming distinct tetrahedral intermediates <3 Å apart. In this study, crystal structures of succinyl-CoA:acetate CoA-transferase (AarC) from Acetobacter aceti are used to examine how the Asn347 carboxamide stabilizes the internal oxyanion intermediate. A structure of the active mutant AarC-N347A bound to CoA revealed both solvent replacement of the missing contact and displacement of the adjacent Glu294, indicating that Asn347 both polarizes and orients the essential glutamate. AarC was crystallized with the nonhydrolyzable acetyl-CoA (AcCoA) analog dethiaacetyl-CoA (1a) in an attempt to trap a closed enzyme complex containing a stable analog of the external oxyanion intermediate. One active site contained an acetylglutamyl anhydride adduct and truncated 1a, an unexpected result hinting at an unprecedented cleavage of the ketone moiety in 1a. Solution studies confirmed that 1a decomposition is accompanied by production of near-stoichiometric acetate, in a process that seems to depend on microbial contamination but not AarC. A crystal structure of AarC bound to the postulated 1a truncation product (2a) showed complete closure of one active site per dimer but no acetylglutamyl anhydride, even with acetate added. These findings suggest that an activated acetyl donor forms during 1a decomposition; a working hypothesis involving ketone oxidation is offered. The ability of 2a to induce full active site closure furthermore suggests that it subverts a system used to impede inappropriate active site closure on unacylated CoA. PMID:27242998

  12. Functional dissection of the bipartite active site of the class I coenzyme A (CoA)-transferase succinyl-CoA:acetate CoA-transferase

    NASA Astrophysics Data System (ADS)

    Murphy, Jesse; Mullins, Elwood; Kappock, T.

    2016-05-01

    Coenzyme A (CoA)-transferases catalyze the reversible transfer of CoA from acyl-CoA thioesters to free carboxylates. Class I CoA-transferases produce acylglutamyl anhydride intermediates that undergo attack by CoA thiolate on either the internal or external carbonyl carbon atoms, forming distinct tetrahedral intermediates less than 3 Å apart. In this study, crystal structures of succinyl-CoA:acetate CoA-transferase (AarC) from Acetobacter aceti are used to examine how the Asn347 carboxamide stabilizes the internal oxyanion intermediate. A structure of the active mutant AarC-N347A bound to CoA revealed both solvent replacement of the missing contact and displacement of the adjacent Glu294, indicating that Asn347 both polarizes and orients the essential glutamate. AarC was crystallized with the nonhydrolyzable acetyl-CoA (AcCoA) analogue dethiaacetyl-CoA (1a) in an attempt to trap a closed enzyme complex containing a stable analogue of the external oxyanion intermediate. One active site contained an acetylglutamyl anhydride adduct and truncated 1a, an unexpected result hinting at an unprecedented cleavage of the ketone moiety in 1a. Solution studies confirmed that 1a decomposition is accompanied by production of near-stoichiometric acetate, in a process that seems to depend on microbial contamination but not AarC. A crystal structure of AarC bound to the postulated 1a truncation product (2a) showed complete closure of one active site per dimer but no acetylglutamyl anhydride, even with acetate added. These findings suggest that an activated acetyl donor forms during 1a decomposition; a working hypothesis involving ketone oxidation is offered. The ability of 2a to induce full active site closure furthermore suggests that it subverts a system used to impede inappropriate active site closure on unacylated CoA.

  13. Geophysical Characteristics of the Australian-Antarctic Ridge

    NASA Astrophysics Data System (ADS)

    Kim, S. S.; Lin, J.; Park, S. H.; Choi, H.; Lee, S. M.

    2014-12-01

    Between 2011 and 2013, the Korea Polar Research Institute (KOPRI) conducted three consecutive geologic surveys at the little explored eastern ends of the Australian-Antarctic Ridge (AAR) to characterize the tectonics, geochemistry, and hydrothermal activity of this intermediate spreading system. Using the Korean icebreaker R/V Araon, the multi-disciplinary research team collected bathymetry, gravity, magnetics, and rock and water column samples. In addition, Miniature Autonomous Plume Recorders (MAPRs) were deployed at wax-core rock sampling sites to detect the presence of active hydrothermal vents. Here we present a detailed analysis of a 300-km-long supersegment of the AAR to quantify the spatial variations in ridge morphology and robust axial and off-axis volcanisms. The ridge axis morphology alternates between rift valleys and axial highs within relatively short ridge segments. To obtain a geological proxy for regional variations in magma supply, we calculated residual mantle Bouguer gravity anomalies (RMBA), gravity-derived crustal thickness, and residual topography for seven sub-segments. The results of the analyses revealed that the southern flank of the AAR is associated with shallower seafloor, more negative RMBA, thicker crust, and/or less dense mantle than the conjugate northern flank. Furthermore, this north-south asymmetry becomes more prominent toward the KR1 supersegment of the AAR. The axial topography of the KR1 supersegment exhibits a sharp transition from axial highs at the western end to rift valleys at the eastern end, with regions of axial highs being associated with more magma supply as indicated by more negative RMBA. We also compare and contrast the characteristics of the AAR supersegment with that of other ridges of intermediate spreading rates, including the Juan de Fuca Ridge, Galápagos Spreading Center, and Southeast Indian Ridge west of the Australian-Antarctic Discordance, to investigate the influence of ridge-hotspot interaction on

  14. Cell membrane chromatography competitive binding analysis for characterization of α1A adrenoreceptor binding interactions.

    PubMed

    Du, Hui; Ren, Jing; Wang, Sicen; He, Langchong

    2011-07-01

    A new high α(1A) adrenoreceptor (α(1A)AR) expression cell membrane chromatography (CMC) method was developed for characterization of α(1A)AR binding interactions. HEK293 α(1A) cell line, which expresses stably high levels of α(1A)AR, was used to prepare the stationary phase in the CMC model. The HEK293 α(1A)/CMC-offline-HPLC system was applied to specifically recognize the ligands which interact with the α(1A)AR, and the dissociation equilibrium constants (K (D)) obtained from the model were (1.87 ± 0.13) × 10(-6) M for tamsulosin, (2.86 ± 0.20) × 10(-6) M for 5-methylurapidil, (3.01 ± 0.19) × 10(-6) M for doxazosin, (3.44 ± 0.19) × 10(-6) M for terazosin, (3.50 ± 0.21) × 10(-6) M for alfuzosin, and (7.57 ± 0.31) × 10(-6) M for phentolamine, respectively. The competitive binding study between tamsulosin and terazosin indicated that the two drugs interacted at the common binding site of α(1A)AR. However, that was not the case between tamsulosin and oxymetazoline. The results had a positive correlation with those from radioligand binding assay and indicated that the CMC method combined modified competitive binding could be a quick and efficient way for characterizing the drug-receptor interactions.

  15. Cannabinoid modulation of alpha2 adrenergic receptor function in rodent medial prefrontal cortex

    PubMed Central

    Cathel, Alessandra M.; Reyes, Beverly A. S.; Wang, Qin; Palma, Jonathan; Mackie, Kenneth; Bockstaele, Elisabeth J. Van; Kirby, Lynn G.

    2014-01-01

    Endocannabinoids acting at the cannabinoid type 1 receptor (CB1R) are known to regulate attention, cognition and mood. Previous studies have shown that, in the rat medial prefrontal cortex (mPFC), CB1R agonists increase norepinephrine release, an effect that may be attributed, in part, to CB1Rs localized to noradrenergic axon terminals. The present study was aimed at further characterizing functional interactions between CB1R and adrenergic receptor (AR) systems in the mPFC using in-vitro intracellular electrophysiology and high-resolution neuroanatomical techniques. Whole-cell patch-clamp recordings of layer V/VI cortical pyramidal neurons in rats revealed that both acute and chronic treatment with the synthetic CB1R agonist WIN 55,212-2 blocked elevations in cortical pyramidal cell excitability and increases in input resistance evoked by the α2-adrenergic receptor (α2-AR) agonist clonidine, suggesting a desensitization of α2-ARs. These CB1R–α2-AR interactions were further shown to be both action potential- and gamma-aminobutyric acid-independent. To better define sites of cannabinoid–AR interactions, we localized α2A-ARs in a genetically modified mouse that expressed a hemoagglutinin (HA) tag downstream of the α2A-AR promoter. Light and electron microscopy indicated that HA-α2A-AR was distributed in axon terminals and somatodendritic processes especially in layer V of the mPFC. Triple-labeling immunocytochemistry revealed that α2A-AR and CB1R were localized to processes that contained dopamine-β-hydroxylase, a marker of norepinephrine. Furthermore, HA-α2A-AR was localized to processes that were directly apposed to CB1R. These findings suggest multiple sites of interaction between cortical cannabinoid–adrenergic systems that may contribute to understanding the effect of cannabinoids on executive functions and mood. PMID:25131562

  16. Different APC genotypes in proximal and distal sporadic colorectal cancers suggest distinct WNT/β-catenin signalling thresholds for tumourigenesis.

    PubMed

    Christie, M; Jorissen, R N; Mouradov, D; Sakthianandeswaren, A; Li, S; Day, F; Tsui, C; Lipton, L; Desai, J; Jones, I T; McLaughlin, S; Ward, R L; Hawkins, N J; Ruszkiewicz, A R; Moore, J; Burgess, A W; Busam, D; Zhao, Q; Strausberg, R L; Simpson, A J; Tomlinson, I P M; Gibbs, P; Sieber, O M

    2013-09-26

    Biallelic protein-truncating mutations in the adenomatous polyposis coli (APC) gene are prevalent in sporadic colorectal cancer (CRC). Mutations may not be fully inactivating, instead producing WNT/β-catenin signalling levels 'just-right' for tumourigenesis. However, the spectrum of optimal APC genotypes accounting for both hits, and the influence of clinicopathological features on genotype selection remain undefined. We analysed 630 sporadic CRCs for APC mutations and loss of heterozygosity (LOH) using sequencing and single-nucleotide polymorphism microarrays, respectively. Truncating APC mutations and/or LOH were detected in 75% of CRCs. Most truncating mutations occurred within a mutation cluster region (MCR; codons 1282-1581) leaving 1-3 intact 20 amino-acid repeats (20AARs) and abolishing all Ser-Ala-Met-Pro (SAMP) repeats. Cancers commonly had one MCR mutation plus either LOH or another mutation 5' to the MCR. LOH was associated with mutations leaving 1 intact 20AAR. MCR mutations leaving 1 vs 2-3 intact 20AARs were associated with 5' mutations disrupting or leaving intact the armadillo-repeat domain, respectively. Cancers with three hits had an over-representation of mutations upstream of codon 184, in the alternatively spliced region of exon 9, and 3' to the MCR. Microsatellite unstable cancers showed hyper-mutation at MCR mono- and di-nucleotide repeats, leaving 2-3 intact 20AARs. Proximal and distal cancers exhibited different preferred APC genotypes, leaving a total of 2 or 3 and 0 to 2 intact 20AARs, respectively. In conclusion, APC genotypes in sporadic CRCs demonstrate 'fine-tuned' interdependence of hits by type and location, consistent with selection for particular residual levels of WNT/β-catenin signalling, with different 'optimal' thresholds for proximal and distal cancers.

  17. Cluster Multi-Point Studies of the Auroral Acceleration Region

    NASA Astrophysics Data System (ADS)

    Marklund, G. T.

    2014-12-01

    Multi-point studies of the auroral acceleration region (AAR) by the Cluster spacecraft has enabled a number of open issues on the auroral acceleration to be addressed and revealed. Data from AAR crossings of Inverted-V aurora, by the C1 and C3 spacecraft at different altitudes, enabled a detailed reconstruction of the acceleration potential and a verification of its stability on a five min time scale. The relative role of quasi-static and Alfvénic acceleration behind aurora are addressed in two event studies. In one of these, the two processes are shown to operate jointly on the plasma population within the polar cap boundary. In the other, the electron energy flux producing multiple arcs within a surge is found to be generally dominated by the quasi-static contribution. Acceleration features and the FAC closure associated with surge-horn aurora crossed by the Cluster fleet were derived in another event study. A study of the density distribution within the auroral cavity, showed for all included events, exponential density decreases, relative to the ambient densities, from the mid to top of the AAR. In another study, cavities were found to extend well beyond the top of the AAR. Finally, statistical high-latitude electric field and plasma density distributions are presented based on 10 years of Cluster data collected between 2 and 4 RE altitudes. Intense electric fields appear in two altitude regimes on the nightside, separated by a gap at 2.8 RE. The upper altitude fields were interpreted to be Alfvénic and the lower altitude fields quasi-static, related to the AAR. The gap in the electric field intensity indicates a partial closure of the potentials in the lower region, with similarities to model results of reflected Alfvén waves and earlier reported observations

  18. Distribution of adrenergic receptors in the enteric nervous system of the guinea pig, mouse, and rat.

    PubMed

    Nasser, Yasmin; Ho, Winnie; Sharkey, Keith A

    2006-04-10

    Adrenergic receptors in the enteric nervous system (ENS) are important in control of the gastrointestinal tract. Here we describe the distribution of adrenergic receptors in the ENS of the ileum and colon of the guinea pig, rat, and mouse by using single- and double-labelling immunohistochemistry. In the myenteric plexus (MP) of the rat and mouse, alpha2a-adrenergic receptors (alpha2a-AR) were widely distributed on neurons and enteric glial cells. alpha2a-AR mainly colocalized with calretinin in the MP, whereas submucosal alpha2a-AR neurons colocalized with vasoactive intestinal polypeptide (VIP), neuropeptide Y, and calretinin in both species. In the guinea pig ileum, we observed widespread alpha2a-AR immunoreactivity on nerve fibers in the MP and on VIP neurons in the submucosal plexus (SMP). We observed extensive beta1-adrenergic receptor (beta1-AR) expression on neurons and nerve fibers in both the MP and the SMP of all species. Similarly, the beta2-adrenergic receptor (beta2-AR) was expressed on neurons and nerve fibers in the SMP of all species, as well as in the MP of the mouse. In the MP, beta1- and beta2-AR immunoreactivity was localized to several neuronal populations, including calretinin and nitrergic neurons. In the SMP of the guinea pig, beta1- and beta2-AR mainly colocalized with VIP, whereas, in the rat and mouse, beta1- and beta2-AR were distributed among the VIP and calretinin populations. Adrenergic receptors were widely localized on specific neuronal populations in all species studied. The role of glial alpha2a-AR is unknown. These results suggest that sympathetic innervation of the ENS is directed toward both enteric neurons and enteric glia.

  19. 5-HT1A receptor pharmacophores to screen for off-target activity of α1-adrenoceptor antagonists

    NASA Astrophysics Data System (ADS)

    Ngo, Tony; Nicholas, Timothy J.; Chen, Junli; Finch, Angela M.; Griffith, Renate

    2013-04-01

    The α1-adrenoceptors (α1-ARs), in particular the α1A-AR subtype, are current therapeutic targets of choice for the treatment of urogenital conditions, such as benign prostatic hyperplasia (BPH). Due to the similarity between the transmembrane domains of the α1-AR subtypes, and the serotonin receptor subtype 1A (5-HT1A-R), currently used α1-AR subtype-selective drugs to treat BPH display considerable off-target affinity for the 5-HT1A-R, leading to side effects. We describe the construction and validation of pharmacophores for 5-HT1A-R agonists and antagonists. Through the structural diversity of the training sets used in their development, these pharmacophores define the properties of a compound needed to bind to 5-HT1A receptors. Using these and previously published pharmacophores in virtual screening and profiling, we have identified unique chemical compounds (hits) that fit the requirements to bind to our target, the α1A-AR, selectively over the off-target, the 5-HT1A-R. Selected hits have been obtained and their affinities for α1A-AR, α1B-AR and 5-HT1A-R determined in radioligand binding assays, using membrane preparations which contain human receptors expressed individually. Three of the tested hits demonstrate statistically significant selectivity for α1A-AR over 5-HT1A-R. All seven tested hits bind to α1A-AR, with two compounds displaying K i values below 1 μM, and a further two K i values of around 10 μM. The insights and knowledge gained through the development of the new 5-HT1A-R pharmacophores will greatly aid in the design and synthesis of derivatives of our lead compound, and allow the generation of more efficacious and selective ligands.

  20. Functional dissection of the bipartite active site of the class I coenzyme A (CoA)-transferase succinyl-CoA:acetate CoA-transferase

    DOE PAGES

    Murphy, Jesse R.; Mullins, Elwood A.; Kappock, T. Joseph

    2016-05-23

    Coenzyme A (CoA)-transferases catalyze the reversible transfer of CoA from acyl-CoA thioesters to free carboxylates. Class I CoA-transferases produce acylglutamyl anhydride intermediates that undergo attack by CoA thiolate on either the internal or external carbonyl carbon atoms, forming distinct tetrahedral intermediates <3 Å apart. Here in this study, crystal structures of succinyl-CoA:acetate CoA-transferase (AarC) from Acetobacter aceti are used to examine how the Asn347 carboxamide stabilizes the internal oxyanion intermediate. A structure of the active mutant AarC-N347A bound to CoA revealed both solvent replacement of the missing contact and displacement of the adjacent Glu294, indicating that Asn347 both polarizes andmore » orients the essential glutamate. AarC was crystallized with the nonhydrolyzable acetyl-CoA (AcCoA) analog dethiaacetyl-CoA (1a) in an attempt to trap a closed enzyme complex containing a stable analog of the external oxyanion intermediate. One active site contained an acetylglutamyl anhydride adduct and truncated 1a, an unexpected result hinting at an unprecedented cleavage of the ketone moiety in 1a. Solution studies confirmed that 1a decomposition is accompanied by production of near-stoichiometric acetate, in a process that seems to depend on microbial contamination but not AarC. A crystal structure of AarC bound to the postulated 1a truncation product (2a) showed complete closure of one active site per dimer but no acetylglutamyl anhydride, even with acetate added. These findings suggest that an activated acetyl donor forms during 1a decomposition; a working hypothesis involving ketone oxidation is offered. Finally, the ability of 2a to induce full active site closure furthermore suggests that it subverts a system used to impede inappropriate active site closure on unacylated CoA.« less

  1. Functional dissection of the bipartite active site of the class I coenzyme A (CoA)-transferase succinyl-CoA:acetate CoA-transferase

    SciTech Connect

    Murphy, Jesse R.; Mullins, Elwood A.; Kappock, T. Joseph

    2016-05-23

    Coenzyme A (CoA)-transferases catalyze the reversible transfer of CoA from acyl-CoA thioesters to free carboxylates. Class I CoA-transferases produce acylglutamyl anhydride intermediates that undergo attack by CoA thiolate on either the internal or external carbonyl carbon atoms, forming distinct tetrahedral intermediates <3 Å apart. Here in this study, crystal structures of succinyl-CoA:acetate CoA-transferase (AarC) from Acetobacter aceti are used to examine how the Asn347 carboxamide stabilizes the internal oxyanion intermediate. A structure of the active mutant AarC-N347A bound to CoA revealed both solvent replacement of the missing contact and displacement of the adjacent Glu294, indicating that Asn347 both polarizes and orients the essential glutamate. AarC was crystallized with the nonhydrolyzable acetyl-CoA (AcCoA) analog dethiaacetyl-CoA (1a) in an attempt to trap a closed enzyme complex containing a stable analog of the external oxyanion intermediate. One active site contained an acetylglutamyl anhydride adduct and truncated 1a, an unexpected result hinting at an unprecedented cleavage of the ketone moiety in 1a. Solution studies confirmed that 1a decomposition is accompanied by production of near-stoichiometric acetate, in a process that seems to depend on microbial contamination but not AarC. A crystal structure of AarC bound to the postulated 1a truncation product (2a) showed complete closure of one active site per dimer but no acetylglutamyl anhydride, even with acetate added. These findings suggest that an activated acetyl donor forms during 1a decomposition; a working hypothesis involving ketone oxidation is offered. Finally, the ability of 2a to induce full active site closure furthermore suggests that it subverts a system used to impede inappropriate active site closure on unacylated CoA.

  2. Automatic localization of IASLC-defined mediastinal lymph node stations on CT images using fuzzy models

    NASA Astrophysics Data System (ADS)

    Matsumoto, Monica M. S.; Beig, Niha G.; Udupa, Jayaram K.; Archer, Steven; Torigian, Drew A.

    2014-03-01

    Lung cancer is associated with the highest cancer mortality rates among men and women in the United States. The accurate and precise identification of the lymph node stations on computed tomography (CT) images is important for staging disease and potentially for prognosticating outcome in patients with lung cancer, as well as for pretreatment planning and response assessment purposes. To facilitate a standard means of referring to lymph nodes, the International Association for the Study of Lung Cancer (IASLC) has recently proposed a definition of the different lymph node stations and zones in the thorax. However, nodal station identification is typically performed manually by visual assessment in clinical radiology. This approach leaves room for error due to the subjective and potentially ambiguous nature of visual interpretation, and is labor intensive. We present a method of automatically recognizing the mediastinal IASLC-defined lymph node stations by modifying a hierarchical fuzzy modeling approach previously developed for body-wide automatic anatomy recognition (AAR) in medical imagery. Our AAR-lymph node (AAR-LN) system follows the AAR methodology and consists of two steps. In the first step, the various lymph node stations are manually delineated on a set of CT images following the IASLC definitions. These delineations are then used to build a fuzzy hierarchical model of the nodal stations which are considered as 3D objects. In the second step, the stations are automatically located on any given CT image of the thorax by using the hierarchical fuzzy model and object recognition algorithms. Based on 23 data sets used for model building, 22 independent data sets for testing, and 10 lymph node stations, a mean localization accuracy of within 1-6 voxels has been achieved by the AAR-LN system.

  3. A lack of α1A-adrenergic receptor-mediated antidepressant-like effects of S-(+)-niguldipine and B8805-033 in the forced swim test.

    PubMed

    Kreiner, Grzegorz; Roman, Adam; Zelek-Molik, Agnieszka; Kowalska, Marta; Nalepa, Irena

    2016-06-01

    The α1-adrenergic receptors (α1-ARs), which belong to a G protein-coupled receptor family, consist of three highly homologous subtypes known as α1A-ARs, α1B-ARs, and α1D-ARs. Our previous findings suggested that α1A-ARs are an important target for imipramine and electroconvulsive therapy. The current study sought to evaluate whether S-(+)-niguldipine and B8805-033, two selective antagonists of α1A-ARs, can evoke antidepressant-like effects in the forced swim test in rats. Both compounds were administered at three time points (24, 5, and 1 h before testing), and the effects of three doses (2, 5, and 10 mg/kg) of each compound were investigated. S-(+)-Niguldipine produced no antidepressant-like effects other than a 14% reduction in immobility time at the highest dose. Although B8805-033 at a dose of 2 mg/kg did not influence the rats' behavior, higher B8805-033 doses (5 and 10 mg/kg) produced significant reductions in immobility time (approximately 42 and 44% vs. controls, respectively; P<0.01). However, this effect was abolished by the concomitant administration of WAY100135, a serotonin receptor antagonist, suggesting that the observed antidepressant-like effects of B8805-033 are unrelated to α1A-ARs. Nevertheless, given the current dearth of selective α1A-AR agonists, the question of whether this particular subtype could be involved in antidepressant therapy mechanisms remains unresolved.

  4. Expression of striatal adenosine and dopamine receptors in mice deficient in the p50 subunit of NF-κB

    PubMed Central

    Xie, Xiaobin; Jhaveri, Krishna A.; Ding, Ming; Hughes, Larry F.; Toth, Linda A.; Ramkumar, Vickram

    2007-01-01

    The striatal dopamine D2 receptor (D2R) and adenosine A2A receptor (A2AAR) exhibit mutually antagonistic effects through physical interactions and by differential modulation of post-receptor signaling pathways. The expression of the A2AAR and the D2R are differentially regulated by nuclear factor-κB (NFkB). In this report, we determined the role of NFkB in regulation of these receptors by comparing mice deficient in the NFκB p50 subunit (p50 KO) with genetically intact B6129PF2/J (F2) mice. Quantification of adenosine receptor (AR) subtypes in mouse striatum by real time PCR, immunocytochemistry and radioligand binding assays showed more A2AAR but less A1AR in p50 KO mice as compared with F2 mice. Striata from p50 KO mice also had less D2R mRNA and [3H]-methylspiperone binding than did striata from F2 mice. Gαolf and Gαs proteins, which are transducers of A2AAR signals, were also present at a higher level in striata from the p50 KO versus F2 mice. In contrast, the Gαi1 protein, which transduces signals from the A1AR and D2R, was significantly reduced in striata from p50-/ mice. Behaviorally, p50 KO mice exhibited increased locomotor activity relative to that of F2 mice after caffeine ingestion. These data are consistent with a role for the NFkB in the regulation of A1AR, A2AAR, D2R and possibly their coupling G proteins in the striatum. Dysregulation of these receptors in the striata of p50 KO mice might sensitize these animals to locomotor stimulatory action of caffeine. PMID:17869311

  5. Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group

    PubMed Central

    Pleyer, Lisa; Döhner, Hartmut; Dombret, Hervé; Seymour, John F.; Schuh, Andre C.; Beach, CL; Swern, Arlene S.; Burgstaller, Sonja; Stauder, Reinhard; Girschikofsky, Michael; Sill, Heinz; Schlick, Konstantin; Thaler, Josef; Halter, Britta; Machherndl Spandl, Sigrid; Zebisch, Armin; Pichler, Angelika; Pfeilstöcker, Michael; Autzinger, Eva M.; Lang, Alois; Geissler, Klaus; Voskova, Daniela; Sperr, Wolfgang R.; Hojas, Sabine; Rogulj, Inga M.; Andel, Johannes; Greil, Richard

    2017-01-01

    We recently published a clinically-meaningful improvement in median overall survival (OS) for patients with acute myeloid leukaemia (AML), >30% bone marrow (BM) blasts and white blood cell (WBC) count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010). As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012) and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML. Firstly, we compared data from AML patients with WBC ≤ 15 G/L and >30% BM blasts included within the AZA-AML-001 trial treated with azacitidine (“AML-001” cohort; n = 214) with AAR patients meeting the same inclusion criteria (“AAR (001-like)” cohort; n = 95). The current analysis thus represents a new sub-analysis of the AML-001 trial, which is directly compared with a new sub-analysis of the AAR. Baseline characteristics, azacitidine application, response rates and OS were comparable between all patient cohorts within the trial or registry setting. Median OS was 9.9 versus 10.8 months (p = 0.616) for “AML-001” versus “AAR (001-like)” cohorts, respectively. Secondly, we pooled data from both cohorts (n = 309) and assessed the outcome. Median OS of the pooled cohorts was 10.3 (95% confidence interval: 8.7, 12.6) months, and the one-year survival rate was 45.8%. Thirdly, we compared data from AAR patients meeting AZA-AML-001 trial inclusion criteria (n = 95) versus all AAR patients with World Health Organization (WHO)-defined AML (“AAR (WHO

  6. Azacitidine for Front-Line Therapy of Patients with AML: Reproducible Efficacy Established by Direct Comparison of International Phase 3 Trial Data with Registry Data from the Austrian Azacitidine Registry of the AGMT Study Group.

    PubMed

    Pleyer, Lisa; Döhner, Hartmut; Dombret, Hervé; Seymour, John F; Schuh, Andre C; Beach, C L; Swern, Arlene S; Burgstaller, Sonja; Stauder, Reinhard; Girschikofsky, Michael; Sill, Heinz; Schlick, Konstantin; Thaler, Josef; Halter, Britta; Machherndl Spandl, Sigrid; Zebisch, Armin; Pichler, Angelika; Pfeilstöcker, Michael; Autzinger, Eva M; Lang, Alois; Geissler, Klaus; Voskova, Daniela; Sperr, Wolfgang R; Hojas, Sabine; Rogulj, Inga M; Andel, Johannes; Greil, Richard

    2017-02-15

    We recently published a clinically-meaningful improvement in median overall survival (OS) for patients with acute myeloid leukaemia (AML), >30% bone marrow (BM) blasts and white blood cell (WBC) count ≤15 G/L, treated with front-line azacitidine versus conventional care regimens within a phase 3 clinical trial (AZA-AML-001; NCT01074047; registered: February 2010). As results obtained in clinical trials are facing increased pressure to be confirmed by real-world data, we aimed to test whether data obtained in the AZA-AML-001 trial accurately represent observations made in routine clinical practice by analysing additional AML patients treated with azacitidine front-line within the Austrian Azacitidine Registry (AAR; NCT01595295; registered: May 2012) and directly comparing patient-level data of both cohorts. We assessed the efficacy of front-line azacitidine in a total of 407 patients with newly-diagnosed AML. Firstly, we compared data from AML patients with WBC ≤ 15 G/L and >30% BM blasts included within the AZA-AML-001 trial treated with azacitidine ("AML-001" cohort; n = 214) with AAR patients meeting the same inclusion criteria ("AAR (001-like)" cohort; n = 95). The current analysis thus represents a new sub-analysis of the AML-001 trial, which is directly compared with a new sub-analysis of the AAR. Baseline characteristics, azacitidine application, response rates and OS were comparable between all patient cohorts within the trial or registry setting. Median OS was 9.9 versus 10.8 months (p = 0.616) for "AML-001" versus "AAR (001-like)" cohorts, respectively. Secondly, we pooled data from both cohorts (n = 309) and assessed the outcome. Median OS of the pooled cohorts was 10.3 (95% confidence interval: 8.7, 12.6) months, and the one-year survival rate was 45.8%. Thirdly, we compared data from AAR patients meeting AZA-AML-001 trial inclusion criteria (n = 95) versus all AAR patients with World Health Organization (WHO)-defined AML ("AAR (WHO-AML)" cohort; n

  7. The presence of β2-adrenoceptors sensitizes α2A-adrenoceptors to desensitization after chronic epinephrine treatment

    PubMed Central

    Bawa-Khalfe, Tasneem; Altememi, Ghazi F; Mandyam, Chitra D; Schwarz, Lindsay A; Eikenburg, Douglas C; Standifer, Kelly M

    2007-01-01

    Background In addition to the regulation of blood pressure, α2- and β-adrenoceptor (AR) subtypes play an important role in the modulation of noradrenergic neurotransmission in the human CNS and PNS. Several studies suggest that the α2-AR responsiveness in cells and tissues after chronic epinephrine (EPI) or norepinephrine (NE) exposure may vary, depending on the β-AR activity present there. Recently, we reported that in BE(2)-C human neuroblastoma cells (endogenously expressing α2A- and β2-AR), chronic EPI treatment (300 nM) produced a dramatic β-adrenoceptor-dependent desensitization of the α2A-AR response. The aim of this study is to determine if stable addition of a β2-AR to a second neuroblastoma cell line (SH-SY5Y), that normally expresses only α2A-ARs that are not sensitive to 300 nM EPI exposure, would suddenly render α2A-ARs in that cell line sensitive to treatment with the same EPI concentration. Methods These studies employed RT-PCR, receptor binding and inhibition of cAMP accumulation to confirm α2-AR subtype expression. Stable clones of SH-SY5Y cells transfected to stably express functional β2-ARs (SHβ2AR4) were selected to compare sensitivity of α2-AR to EPI in the presence or absence of β2-ARs. Results A series of molecular, biochemical and pharmacological studies indicated that the difference between the cell lines could not be attributed to α2-AR heterogeneity. We now report that after transfection of functional β2-AR into SH-SY5Y cells (SHβ2AR4), chronic treatment with modest levels of EPI desensitizes the α2A-AR. This effect results from a β2-AR dependent down-regulation of native α2A-ARs by EPI accompanied by enhanced translocation of GRK2 and GRK3 to the membrane (required for GRK-mediated phosphorylation of agonist-occupied receptors). Conclusion This study further supports the hypothesis that the presence of the β-AR renders the α2A-AR more susceptible to desensitization with physiological levels of EPI. PMID:18096057

  8. Improvements of a Brain-Computer Interface Applied to a Robotic Wheelchair

    NASA Astrophysics Data System (ADS)

    Ferreira, André; Bastos-Filho, Teodiano Freire; Sarcinelli-Filho, Mário; Sánchez, José Luis Martín; García, Juan Carlos García; Quintas, Manuel Mazo

    Two distinct signal features suitable to be used as input to a Support-Vector Machine (SVM) classifier in an application involving hands motor imagery and the correspondent EEG signal are evaluated in this paper. Such features are the Power Spectral Density (PSD) components and the Adaptive Autoregressive (AAR) parameters. The best result (an accuracy of 97.1%) is obtained when using PSD components, while the AAR parameters generated an accuracy of 91.4%. The results also demonstrate that it is possible to use only two EEG channels (bipolar configuration around C 3 and C 4), discarding the bipolar configuration around C z . The algorithms were tested with a proprietary EEG data set involving 4 individuals and with a data set provided by the University of Graz (Austria) as well. The resulting classification system is now being implemented in a Brain-Computer Interface (BCI) used to guide a robotic wheelchair.

  9. Modern and Little Ice Age equilibrium-line altitudes on Outlet Valley glaciers from Jostedalsbreen, western Norway: An evaluation of different approaches to their calculation

    SciTech Connect

    Torsnes, I.; Rye, N. ); Nesje, A. )

    1993-05-01

    The modern and Little Ice Age (LIA) equilibrium-line altitude (ELA) of 20 outlet valley glacier from Jostedalsbreen, western Norway, has been calculated using different approaches. Using an accumulation area ratio (AAR) of 0.6 [+-] 0.05 gave a mean little Ice Age ELA depression of 70 m. A method developed by M. Kuhle, taking the influence by topography into account gave a mean ELA depression of 35-255 m, the median elevation of glaciers 115 m, and the toe-to-headwall altitude ration 140 m. Differences in the ELA estimates can be attributed to the differences in topography and morphology of the glaciers. The AAR method appears to provide the most reliable results. This will aid in determining mean global temperatures during the LIA. 34 refs., 9 figs., 5 tabs.

  10. Assessing amino acid racemization variability in coral intra-crystalline protein for geochronological applications.

    PubMed

    Hendy, Erica J; Tomiak, Peter J; Collins, Matthew J; Hellstrom, John; Tudhope, Alexander W; Lough, Janice M; Penkman, Kirsty E H

    2012-06-01

    Over 500 Free Amino Acid (FAA) and corresponding Total Hydrolysed Amino Acid (THAA) analyses were completed from eight independently-dated, multi-century coral cores of massive Porites sp. colonies. This dataset allows us to re-evaluate the application of amino acid racemization (AAR) for dating late Holocene coral material, 20 years after Goodfriend et al. (GCA56 (1992), 3847) first showed AAR had promise for developing chronologies in coral cores. This re-assessment incorporates recent method improvements, including measurement by RP-HPLC, new quality control approaches (e.g. sampling and sub-sampling protocols, statistically-based data screening criteria), and cleaning steps to isolate the intra-crystalline skeletal protein. We show that the removal of the extra-crystalline contaminants and matrix protein is the most critical step for reproducible results and recommend a protocol of bleaching samples in NaOCl for 48 h to maximise removal of open system proteins while minimising the induced racemization. We demonstrate that AAR follows closed system behaviour in the intra-crystalline fraction of the coral skeletal proteins. Our study is the first to assess the natural variability in intra-crystalline AAR between colonies, and we use coral cores taken from the Great Barrier Reef, Australia, and Jarvis Island in the equatorial Pacific to explore variability associated with different environmental conditions and thermal histories. Chronologies were developed from THAA Asx D/L, Ala D/L, Glx D/L and FAA Asx D/L for each core and least squares Monte Carlo modelling applied in order to quantify uncertainty of AAR age determinations and assess the level of dating resolution possible over the last 5 centuries. AAR within colonies follow consistent stratigraphic aging. However, there are systematic differences in rates between the colonies, which would preclude direct comparison from one colony to another for accurate age estimation. When AAR age models are developed

  11. Assessing amino acid racemization variability in coral intra-crystalline protein for geochronological applications

    NASA Astrophysics Data System (ADS)

    Hendy, Erica J.; Tomiak, Peter J.; Collins, Matthew J.; Hellstrom, John; Tudhope, Alexander W.; Lough, Janice M.; Penkman, Kirsty E. H.

    2012-06-01

    Over 500 Free Amino Acid (FAA) and corresponding Total Hydrolysed Amino Acid (THAA) analyses were completed from eight independently-dated, multi-century coral cores of massive Porites sp. colonies. This dataset allows us to re-evaluate the application of amino acid racemization (AAR) for dating late Holocene coral material, 20 years after Goodfriend et al. (GCA56 (1992), 3847) first showed AAR had promise for developing chronologies in coral cores. This re-assessment incorporates recent method improvements, including measurement by RP-HPLC, new quality control approaches (e.g. sampling and sub-sampling protocols, statistically-based data screening criteria), and cleaning steps to isolate the intra-crystalline skeletal protein. We show that the removal of the extra-crystalline contaminants and matrix protein is the most critical step for reproducible results and recommend a protocol of bleaching samples in NaOCl for 48 h to maximise removal of open system proteins while minimising the induced racemization. We demonstrate that AAR follows closed system behaviour in the intra-crystalline fraction of the coral skeletal proteins. Our study is the first to assess the natural variability in intra-crystalline AAR between colonies, and we use coral cores taken from the Great Barrier Reef, Australia, and Jarvis Island in the equatorial Pacific to explore variability associated with different environmental conditions and thermal histories. Chronologies were developed from THAA Asx D/L, Ala D/L, Glx D/L and FAA Asx D/L for each core and least squares Monte Carlo modelling applied in order to quantify uncertainty of AAR age determinations and assess the level of dating resolution possible over the last 5 centuries. AAR within colonies follow consistent stratigraphic aging. However, there are systematic differences in rates between the colonies, which would preclude direct comparison from one colony to another for accurate age estimation. When AAR age models are developed from

  12. Body-wide hierarchical fuzzy modeling, recognition, and delineation of anatomy in medical images.

    PubMed

    Udupa, Jayaram K; Odhner, Dewey; Zhao, Liming; Tong, Yubing; Matsumoto, Monica M S; Ciesielski, Krzysztof C; Falcao, Alexandre X; Vaideeswaran, Pavithra; Ciesielski, Victoria; Saboury, Babak; Mohammadianrasanani, Syedmehrdad; Sin, Sanghun; Arens, Raanan; Torigian, Drew A

    2014-07-01

    To make Quantitative Radiology (QR) a reality in radiological practice, computerized body-wide Automatic Anatomy Recognition (AAR) becomes essential. With the goal of building a general AAR system that is not tied to any specific organ system, body region, or image modality, this paper presents an AAR methodology for localizing and delineating all major organs in different body regions based on fuzzy modeling ideas and a tight integration of fuzzy models with an Iterative Relative Fuzzy Connectedness (IRFC) delineation algorithm. The methodology consists of five main steps: (a) gathering image data for both building models and testing the AAR algorithms from patient image sets existing in our health system; (b) formulating precise definitions of each body region and organ and delineating them following these definitions; (c) building hierarchical fuzzy anatomy models of organs for each body region; (d) recognizing and locating organs in given images by employing the hierarchical models; and (e) delineating the organs following the hierarchy. In Step (c), we explicitly encode object size and positional relationships into the hierarchy and subsequently exploit this information in object recognition in Step (d) and delineation in Step (e). Modality-independent and dependent aspects are carefully separated in model encoding. At the model building stage, a learning process is carried out for rehearsing an optimal threshold-based object recognition method. The recognition process in Step (d) starts from large, well-defined objects and proceeds down the hierarchy in a global to local manner. A fuzzy model-based version of the IRFC algorithm is created by naturally integrating the fuzzy model constraints into the delineation algorithm. The AAR system is tested on three body regions - thorax (on CT), abdomen (on CT and MRI), and neck (on MRI and CT) - involving a total of over 35 organs and 130 data sets (the total used for model building and testing). The training and

  13. A 9,000-year-old caribou hunting structure beneath Lake Huron.

    PubMed

    O'Shea, John M; Lemke, Ashley K; Sonnenburg, Elizabeth P; Reynolds, Robert G; Abbott, Brian D

    2014-05-13

    Some of the most pivotal questions in human history necessitate the investigation of archaeological sites that are now under water. Nine thousand years ago, the Alpena-Amberley Ridge (AAR) beneath modern Lake Huron was a dry land corridor that connected northeast Michigan to southern Ontario. The newly discovered Drop 45 Drive Lane is the most complex hunting structure found to date beneath the Great Lakes. The site and its associated artifacts provide unprecedented insight into the social and seasonal organization of prehistoric caribou hunting. When combined with environmental and simulation studies, it is suggested that distinctly different seasonal strategies were used by early hunters on the AAR, with autumn hunting being carried out by small groups, and spring hunts being conducted by larger groups of cooperating hunters.

  14. A 9,000-year-old caribou hunting structure beneath Lake Huron

    PubMed Central

    O’Shea, John M.; Lemke, Ashley K.; Sonnenburg, Elizabeth P.; Reynolds, Robert G.; Abbott, Brian D.

    2014-01-01

    Some of the most pivotal questions in human history necessitate the investigation of archaeological sites that are now under water. Nine thousand years ago, the Alpena-Amberley Ridge (AAR) beneath modern Lake Huron was a dry land corridor that connected northeast Michigan to southern Ontario. The newly discovered Drop 45 Drive Lane is the most complex hunting structure found to date beneath the Great Lakes. The site and its associated artifacts provide unprecedented insight into the social and seasonal organization of prehistoric caribou hunting. When combined with environmental and simulation studies, it is suggested that distinctly different seasonal strategies were used by early hunters on the AAR, with autumn hunting being carried out by small groups, and spring hunts being conducted by larger groups of cooperating hunters. PMID:24778246

  15. On primordial sense-antisense coding.

    PubMed

    Rodin, Andrei S; Rodin, Sergei N; Carter, Charles W

    2009-11-01

    The genetic code is implemented by aminoacyl-tRNA synthetases (aaRS). These 20 enzymes are divided into two classes that, despite performing same functions, have nothing common in structure. The mystery of this striking partition of aaRSs might have been concealed in their sterically complementary modes of tRNA recognition that, as we have found recently, protect the tRNAs with complementary anticodons from confusion in translation. This finding implies that, in the beginning, life increased its coding repertoire by the pairs of complementary codons (rather than one-by-one) and used both complementary strands of genes as templates for translation. The class I and class II aaRSs may represent one of the most important examples of such primordial sense-antisense (SAS) coding (Rodin and Ohno, Orig Life Evol Biosph 25:565-589, 1995). In this report, we address the issue of SAS coding in a wider scope. We suggest a variety of advantages that such coding would have had in exploring a wider sequence space before translation became highly specific. In particular, we confirm that in Achlya klebsiana a single gene might have originally coded for an HSP70 chaperonin (class II aaRS homolog) and an NAD-specific GDH-like enzyme (class I aaRS homolog) via its sense and antisense strands. Thus, in contrast to the conclusions in Williams et al. (Mol Biol Evol 26:445-450, 2009), this could indeed be a "Rosetta stone" gene (Carter and Duax, Mol Cell 10:705-708, 2002) (eroded somewhat, though) for the SAS origin of the two aaRS classes.

  16. Large Space Structure Figure Estimation and Control

    DTIC Science & Technology

    1989-01-01

    adjusted via manipulation of the LQG design parameters so that the control system acts primarily upon the first two bands of the boom-dish modes, for a...are applied. Each focuses on adjusting parameters in the estimator to achieve a more robust design. One approach which will be demonstrated is to... adjust parameters in the Kalman filter design in a way that asymptotically recovers the loop gain of the full state feedback. This method is called loop

  17. Recent Research in Behind-Armor Blunt Trauma and Traumatic Brain Injury

    DTIC Science & Technology

    2014-02-01

    are crucial in gaining an accurate assessment of injuries to the head caused ballistic impact. This knowledge is important in the development of...future ballistic helmet design. Aare and Kleiven (36) investigated the effects of helmet shell stiffness and different impact angles on load levels in...spread the ballistic loads over a larger area and longer time. Despite the technological advancements of modern combat helmets in preventing bullets of

  18. Sustainment of Army Forces in Operation Iraqi Freedom. Battlefield Logistics and Effects on Operations

    DTIC Science & Technology

    2005-01-01

    prepare and format the document. Rick Eden and John Dumond provided excellent comments to help with the organization of the report. LTG (retired...the problems or symptoms should be determined. Thus, this ____________ 8 Eric Peltz, Marc L. Robbins, Kenneth J. Girardini, Rick Eden , John M...Memorandum for Record, Subject: Operation Iraqi Freedom AAR, 19 May 2003. Interviews at 3rd ID Division Support Com- mand with LTC Bobby Towery (3rd FSB

  19. Future Generation Tactical Engagement Simulation, U.S. Army Prioritized Needs and Recommended Supporting Technology Development. Volume 2

    DTIC Science & Technology

    1988-08-19

    be all that important. A-1O TO: Distribution - 3 - June 16, 1986 Area weapons might be handled by instrumenting only one man in a squad since, by...doctrine, the squad always stays together. Data gathering would be very desirable from an AAR standpoint; position location would be necessary. Mentioned...ten combat mi ssi ons. Readiness: The cost of training is pennies compared to the investment in tactical equipment. Squad -level training is probably the

  20. α1A-Adrenergic Receptor Induces Activation of Extracellular Signal-Regulated Kinase 1/2 through Endocytic Pathway

    PubMed Central

    Liu, Fei; He, Kangmin; Yang, Xinxing; Xu, Ning; Liang, Zhangyi; Xu, Ming; Zhao, Xinsheng; Han, Qide; Zhang, Youyi

    2011-01-01

    G protein-coupled receptors (GPCRs) activate mitogen-activated protein kinases through a number of distinct pathways in cells. Increasing evidence has suggested that endosomal signaling has an important role in receptor signal transduction. Here we investigated the involvement of endocytosis in α1A-adrenergic receptor (α1A-AR)-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2). Agonist-mediated endocytic traffic of α1A-AR was assessed by real-time imaging of living, stably transfected human embryonic kidney 293A cells (HEK-293A). α1A-AR was internalized dynamically in cells with agonist stimulation, and actin filaments regulated the initial trafficking of α1A-AR. α1A-AR-induced activation of ERK1/2 but not p38 MAPK was sensitive to disruption of endocytosis, as demonstrated by 4°C chilling, dynamin mutation and treatment with cytochalasin D (actin depolymerizing agent). Activation of protein kinase C (PKC) and C-Raf by α1A-AR was not affected by 4°C chilling or cytochalasin D treatment. U73122 (a phospholipase C [PLC] inhibitor) and Ro 31–8220 (a PKC inhibitor) inhibited α1B-AR- but not α1A-AR-induced ERK1/2 activation. These data suggest that the endocytic pathway is involved in α1A-AR-induced ERK1/2 activation, which is independent of Gq/PLC/PKC signaling. PMID:21738688

  1. Body-wide anatomy recognition in PET/CT images

    NASA Astrophysics Data System (ADS)

    Wang, Huiqian; Udupa, Jayaram K.; Odhner, Dewey; Tong, Yubing; Zhao, Liming; Torigian, Drew A.

    2015-03-01

    With the rapid growth of positron emission tomography/computed tomography (PET/CT)-based medical applications, body-wide anatomy recognition on whole-body PET/CT images becomes crucial for quantifying body-wide disease burden. This, however, is a challenging problem and seldom studied due to unclear anatomy reference frame and low spatial resolution of PET images as well as low contrast and spatial resolution of the associated low-dose CT images. We previously developed an automatic anatomy recognition (AAR) system [15] whose applicability was demonstrated on diagnostic computed tomography (CT) and magnetic resonance (MR) images in different body regions on 35 objects. The aim of the present work is to investigate strategies for adapting the previous AAR system to low-dose CT and PET images toward automated body-wide disease quantification. Our adaptation of the previous AAR methodology to PET/CT images in this paper focuses on 16 objects in three body regions - thorax, abdomen, and pelvis - and consists of the following steps: collecting whole-body PET/CT images from existing patient image databases, delineating all objects in these images, modifying the previous hierarchical models built from diagnostic CT images to account for differences in appearance in low-dose CT and PET images, automatically locating objects in these images following object hierarchy, and evaluating performance. Our preliminary evaluations indicate that the performance of the AAR approach on low-dose CT images achieves object localization accuracy within about 2 voxels, which is comparable to the accuracies achieved on diagnostic contrast-enhanced CT images. Object recognition on low-dose CT images from PET/CT examinations without requiring diagnostic contrast-enhanced CT seems feasible.

  2. Leader Development in Army Units: Views From the Field

    DTIC Science & Technology

    2008-01-01

    Classroom lectures or seminars on leadership topics Developing and following a self-development plan Professional reading AARs for a deployment or field...PlatoonLeader.army.mil Staff rides to sites off base Classroom lectures or seminars on leadership topics Developing and following a self-development...Staff rides to sites off base Classroom lectures or seminars on leadership topics Developing and following a self-development plan Professional reading

  3. Novel Alexa Fluor-488 labeled antagonist of the A(2A) adenosine receptor: Application to a fluorescence polarization-based receptor binding assay.

    PubMed

    Kecskés, Miklós; Kumar, T Santhosh; Yoo, Lena; Gao, Zhan-Guo; Jacobson, Kenneth A

    2010-08-15

    Fluorescence polarization (FP) assay has many advantages over the traditional radioreceptor binding studies. We developed an A(2A) adenosine receptor (AR) FP assay using a newly synthesized fluorescent antagonist of the A(2A)AR (MRS5346), a pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine derivative conjugated to the fluorescent dye Alexa Fluor-488. MRS5346 displayed a K(i) value of 111+/-16nM in radioligand binding using [(3)H]CGS21680 and membranes prepared from HEK293 cells stably expressing the human A(2A)AR. In a cyclic AMP functional assay, MRS5346 was shown to be an A(2A)AR antagonist. MRS5346 did not show any effect on A(1) and A(3) ARs in binding or the A(2B)AR in a cyclic AMP assay at 10microM. Its suitability as a fluorescent tracer was indicated in an initial observation of an FP signal following A(2A)AR binding. The FP signal was optimal with 20nM MRS5346 and 150microg protein/mL HEK293 membranes. The association and dissociation kinetic parameters were readily determined using this FP assay. The K(d) value of MRS5346 calculated from kinetic parameters was 16.5+/-4.7nM. In FP competition binding experiments using MRS5346 as a tracer, K(i) values of known AR agonists and antagonists consistently agreed with K(i) values from radioligand binding. Thus, this FP assay, which eliminates using radioisotopes, appears to be appropriate for both routine receptor binding and high-throughput screening with respect to speed of analysis, displaceable signal and precision. The approach used in the present study could be generally applicable to other GPCRs.

  4. After Action Review Tools for Dismounted Soldier Systems

    DTIC Science & Technology

    2008-06-01

    trainer to elicit feedback from unit personnel concerning what transpired during an event with a focus on determining how future events could benefit...team building. It is the involvement of participants , the discussions and exchanges during the course of the AAR that permit Soldiers and leaders to ...up replay of events and allow the participants to view the action from varied views and perspectives. * Still images that can be viewed from the varied

  5. Orientation-dependent potential of mean force for protein folding.

    PubMed

    Mukherjee, Arnab; Bhimalapuram, Prabhakar; Bagchi, Biman

    2005-07-01

    We present a solvent-implicit minimalistic model potential among the amino acid residues of proteins, obtained by using the known native structures [deposited in the Protein Data Bank (PDB)]. In this model, the amino acid side chains are represented by a single ellipsoidal site, defined by the group of atoms about the center of mass of the side chain. These ellipsoidal sites interact with other sites through an orientation-dependent interaction potential which we construct in the following fashion. First, the site-site potential of mean force (PMF) between heavy atoms is calculated [following F. Melo and E. Feytsman, J. Mol. Biol. 267, 207 (1997)] from statistics of their distance separation obtained from crystal structures. These site-site potentials are then used to calculate the distance and the orientation-dependent potential between side chains of all the amino acid residues (AAR). The distance and orientation dependencies show several interesting results. For example, we find that the PMF between two hydrophobic AARs, such as phenylalanine, is strongly attractive at short distances (after the obvious repulsive region at very short separation) and is characterized by a deep minimum, for specific orientations. For the interaction between two hydrophilic AARs, such a deep minimum is absent and in addition, the potential interestingly reveals the combined effect of polar (charge) and hydrophobic interactions among some of these AARs. The effectiveness of our potential has been tested by calculating the Z-scores for a large set of proteins. The calculated Z-scores show high negative values for most of them, signifying the success of the potential to identify the native structure from among a large number of its decoy states.

  6. Low-Torque Seal Development

    NASA Technical Reports Server (NTRS)

    Lattime, Scott B.; Borowski, Richard

    2009-01-01

    The EcoTurn Class K production prototypes have passed all AAR qualification tests and received conditional approval. The accelerated life test on the second set of seals is in progress. Due to the performance of the first set, no problems are expected.The seal has demonstrated superior performance over the HDL seal in the test lab with virtually zero torque and excellent contamination exclusion and grease retention.

  7. Impact of white blood cell count on myocardial salvage, infarct size, and clinical outcomes in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a magnetic resonance imaging study.

    PubMed

    Chung, Seungmin; Song, Young Bin; Hahn, Joo-Yong; Chang, Sung-A; Lee, Sang-Chol; Choe, Yeon Hyeon; Choi, Seung-Hyuk; Choi, Jin-Ho; Lee, Sang Hoon; Oh, Jae K; Gwon, Hyeon-Cheol

    2014-01-01

    We sought to determine the relationship between white blood cell count (WBCc) and infarct size assessed by cardiovascular magnetic resonance imaging (CMR) in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). In 198 patients undergoing primary PCI for STEMI, WBCc was measured upon arrival and CMR was performed a median of 7 days after the index event. Infarct size was measured on delayed enhancement imaging and the area at risk (AAR) was quantified on T2-weighted images. Baseline characteristics were not significantly different between the high WBCc group (>11,000/mm(3), n = 91) and low WBCc group (≤11,000/mm(3), n = 107). The median infarct size was larger in the high WBCc group than in the low WBCc group [22.0% (16.7-33.9) vs. 14.7% (8.5-24.7), p < 0.01]. Compared with the low WBCc group, the high WBCc group had a greater extent of AAR and a smaller myocardial salvage index [MSI = (AAR-infarct size)/AAR × 100]. The major adverse cardiovascular events (MACE) including cardiac death, nonfatal reinfarction, and rehospitalization for congestive heart failure at 12-month occurred more frequently in the high WBCc group (12.1 vs. 0.9%, p < 0.01). In multivariate analysis, high WBCc significantly increased the risk of a large infarct (OR 3.04 95% CI 1.65-5.61, p < 0.01), a low MSI (OR 2.08, 95% CI 1.13-3.86, p = 0.02), and 1-year MACE (OR 16.0, 95% CI 1.89-134.5, p = 0.01). In patients undergoing primary PCI for STEMI, an elevated baseline WBCc is associated with less salvaged myocardium, larger infarct size and poorer clinical outcomes.

  8. Strategies for Civilian-Military Communication

    DTIC Science & Technology

    2013-04-01

    studiesabroad.com/about/press (accessed February 25, 2013). 30 Julius Caesar , Gaius Julius Caesar Commentaries on the Gallic War, trans. W.A. McDevitte and W.S...concerns, and capture lessons learned; from a small project to a major military mission. One of the first known examples of an AAR is Julius Caesar’s...Bohn (New York: Harper & Brothers, 1869), http://www.forumromanum.org/literature/ caesar /gallic_e1.html (accessed February 21, 2013). 31 Gerard

  9. Comparisons of noninvasive indices based on daily practice parameters for predicting liver cirrhosis in chronic hepatitis B and hepatitis C patients in hospital and community populations.

    PubMed

    Tseng, Po-Lin; Wang, Jing-Houng; Hung, Chao-Hung; Tung, Hung-Da; Chen, Tsung-Ming; Huang, Wu-Shiung; Liu, Shiann-Long; Hu, Tsung-Hui; Lee, Chuan-Mo; Lu, Sheng-Nan

    2013-07-01

    Several noninvasive indices have been proposed for predicting liver cirrhosis (LC), particularly in chronic hepatitis C (CHC). In this study, noninvasive indices for predicting LC and hepatocellular carcinoma (HCC) were compared. A total of 119 chronic hepatitis B (CHB) patients and 240 CHC patients were evaluated in a hospital-based setting using various predictors for pathologic LC such as aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio (AAR), AAR-to-platelet ratio index (AARPRI), AST-to-platelet ratio index (APRI), age-platelet (AP) index, and platelet counts. In addition, these indices were used to predict LC [based on ultrasound (US)] in a community-based population of 201 patients with endemic hepatitis C virus (HCV). These indices were evaluated for their ability to predict HCC in CHB and CHC patients (n = 200). In CHB patients, the diagnostic performance of all indices was inadequate for predicting LC (areas under receiver operating characteristic curves < 0.7). Thrombocytopenia consistently demonstrated comparable accuracy to AARPRI ≥ 0.7 in CHB and AP index ≥ 7.0 in CHC patients. The best cut-off values for APRI, AARPRI, and AP index in predicting LC in CHC were 1.3, 0.8, and 7.0, respectively. The best cut-off values for APRI, AARPRI, and AP index in predicting LC (based on US) were 1.0, 1.2, and 8.0, respectively, in a HCV endemic community. An AAR > 1.4 might be a useful tool to identify candidates at high risk for HCC. In conclusion, platelet count was both consistent and accurate in predicting LC. An AAR > 1.4 is proposed as a possible surrogate marker for identifying patients at high risk for developing HCC.

  10. Strategy Differences in Map Information Use for Route Following in Unfamiliar Cities; Implications for In-Car Navigation Systems (Strategieverschillen in Kaart-Informatiegebruik bij het Volgen van Routes in Onbekends Steden; Implicaties voor Navigatie-Systemen in Auto’s)

    DTIC Science & Technology

    1990-04-03

    Technology, INRETS-LEN, Philips Research Laboratories, Saab/Scania, TNO Institute for Perception, YARD Ltd., NRC-Applied Psychology Unit, Tregie...Renault Regie, Swedish Road and Traffic Researh Institute VTI, Universitat der Bundeswehr HMnchen, and University College Dublin are represented as...Siegel, A.W., and Rosin’ki, R.R. (1978). The role of perceptual context in structuring spatial knowledge. Journal of Experimental Psychology : H-Aar

  11. Galvanic Corrosion Study on Stainless Steel Cartridge Design

    DTIC Science & Technology

    2008-11-01

    Department of Defense, Washington Headquarters Services Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway...NJ 07806- 5000 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) U.S. Army ARDEC, ESIC Technical...Research Center (AMSRD-AAR-EIK) Picatinny Arsenal, NJ 07806- 5000 10. SPONSOR/MONITOR’S ACRONYM(S) 11. SPONSOR/MONITOR’S REPORT NUMBER(S) Technical

  12. When Will We Ever Learn? The After Action Review, Lessons Learned and the Next Steps in Training and Educating the Homeland Security Enterprise for the 21st Century

    DTIC Science & Technology

    2013-06-01

    Moynihan, “Learning under Uncertainty: Networks in Crisis Management,” Public Administration Review 68, no. 2 (2008): 352. 6 professionals to make...essentially valid. Another related , yet unexplored area within the literature is whether or not the AAR practice is based upon pedagogy or andragogy...NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA THESIS Approved for public release; distribution is unlimited WHEN WILL WE EVER

  13. Adenosine receptors and the central nervous system.

    PubMed

    Sebastião, Ana M; Ribeiro, Joaquim A

    2009-01-01

    The adenosine receptors (ARs) in the nervous system act as a kind of "go-between" to regulate the release of neurotransmitters (this includes all known neurotransmitters) and the action of neuromodulators (e.g., neuropeptides, neurotrophic factors). Receptor-receptor interactions and AR-transporter interplay occur as part of the adenosine's attempt to control synaptic transmission. A(2A)ARs are more abundant in the striatum and A(1)ARs in the hippocampus, but both receptors interfere with the efficiency and plasticity-regulated synaptic transmission in most brain areas. The omnipresence of adenosine and A(2A) and A(1) ARs in all nervous system cells (neurons and glia), together with the intensive release of adenosine following insults, makes adenosine a kind of "maestro" of the tripartite synapse in the homeostatic coordination of the brain function. Under physiological conditions, both A(2A) and A(1) ARs play an important role in sleep and arousal, cognition, memory and learning, whereas under pathological conditions (e.g., Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, stroke, epilepsy, drug addiction, pain, schizophrenia, depression), ARs operate a time/circumstance window where in some circumstances A(1)AR agonists may predominate as early neuroprotectors, and in other circumstances A(2A)AR antagonists may alter the outcomes of some of the pathological deficiencies. In some circumstances, and depending on the therapeutic window, the use of A(2A)AR agonists may be initially beneficial; however, at later time points, the use of A(2A)AR antagonists proved beneficial in several pathologies. Since selective ligands for A(1) and A(2A) ARs are now entering clinical trials, the time has come to determine the role of these receptors in neurological and psychiatric diseases and identify therapies that will alter the outcomes of these diseases, therefore providing a hopeful future for the patients who suffer from these diseases.

  14. An experimental study on use of 7T MRI for evaluation of myocardial infarction in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid

    PubMed Central

    Zhang, Yan; Tian, Ruiqing; Shen, Xiangchun; Chen, Yushu; Chen, Wei; Gan, Lu; Shen, Guiquan; Ju, Haiyue; Yang, Li; Gao, Fabao

    2016-01-01

    This study aims to build the myocardial infarction model in SD rats transfected with pcDNA 3.1(+)/VEGF121 plasmid and study the effect of the transfection using 7T MRI. Twenty-four male SD rats were randomly divided into 2 groups, pcDNA 3.1(+)/VEGF121 plasmid transfection group (with improved coronary perfusion delivery) and myocardial infarction model group. Cardiac cine magnetic resonance imaging (Cine-MRI), T2-mapping and late gadolinium enhancement (LGE) cardiac imaging were performed at 24 h, 48 h, 72 h and 7 d after myocardial infarction, respectively. The signal intensity, area at risk (AAR), myocardium infarction core (MIC) and salvageable myocardial zone (SMZ) were compared. The hearts were harvested for anatomic characterization, which was related to pathological examination (TTC staining, HE staining, Masson staining and immunohistochemical staining). The Cine-MRI results showed that pcDNA 3.1(+)/VEGF121 plasmid transfection group had higher end-diastolic volume (EDV) with a reduction in MIC and SMZ, as compared with the myocardial infarction model group. MIC, SMZ and AAR of the plasmid transfection declined over time. At 7 d, the two groups did not differ significantly in AAR and T2 value. According to Western Blotting, VEGF was up-regulated, while CaSR and caspase-3 were downregulated in the plasmid transfection group, as compared with the model group. In conclusion, a good treatment effect was achieved by coronary perfusion of pcDNA 3.1(+)/VEGF121 plasmid. 7T CMR sequences provide a non-invasive quantification of the treatment efficacy. However, the assessment of myocardial injury using T2 value and AAR in the presence of edema is less accurate. The myocardial protection of the plasmid transfection group may be related to the inhibition of myocardial apoptosis, vascular endothelial cell (VEC) proliferation and collagen proliferation. The CaSR signaling pathway may contribute to reversing the apoptosis. PMID:27648128

  15. The Command Operations Dashboard: A Common Operating Picture of the Operators

    DTIC Science & Technology

    2014-06-01

    realistic week-long exercises. Observer/ coach /trainers (OCTs) shape the exercise scenario to the unit commander?s training objectives, provide training...the Operators Abstract The Army trains battalion and higher units in Mission Command during realistic week-long exercises. Observer/ coach ...execution phase. Observer/ coach /trainers, or OCTs, conduct these exercises, supporting the commander’s training goals, and running mid and final AARs

  16. On the Design and Optimization of Distributed Signal Detection and Parameter Estimation Systems.

    DTIC Science & Technology

    1987-09-01

    Assume that the costs C,, i, - Ol ,... ,M-l and the a priori probabilities are known. For the Bayesian DDF system of Figure 3.1, the optimum fusion rule...nLnormation Theory, IT-I4, pp. 349-353, March 1968. £362 J. F. Walker, "Performance Data for a Double-Threshold Detection Radar," EEE TranmaAar- espa " and

  17. Prediction of the Impact Sensitivity of Energetic Molecules Using Symmetry Adapted Perturbation Theory

    DTIC Science & Technology

    2011-05-01

    Bukowski , R.; Szalewicz, K. J. Chem. Theory Comput. 2006, 2, 400. 20. Bukowski , R.; Cencek, W.; Jankowski, P.; Jeziorski, B.; Jeziorska, M.; Kucharski, S...udel.edu/~szalewic/SAPT/license.html (accessed 10 January 2009). 21. Podeszwa, R.; Bukowski , R.; Rice, B. M.; Szalewicz, K. Phys. Chem. Chem. Phys...106B GOLDEN CO 80401 7 DIRECTOR US ARMY ARDEC AMSRD AAR AEE W W DAVIS L COSTAS A DAWSON W BUKOWSKI R SURAPANENI R

  18. The structure of the Alpine distal margin: insights from the proximal margin shortening kinematics during collision, Western Alps

    NASA Astrophysics Data System (ADS)

    Bellahsen, N.; Mouthereau, F.; Lacombe, O.; Jolivet, L.

    2011-12-01

    In mountain belts, along strike variations of inherited passive margin structure can affect the collision dynamics. Particularly, the structure the distal part can potentially drive the collision evolution and thus the proximal part inversion. In most orogens however (as in the Alps for example), the initial structure of the subducted distal margin is largely hidden by subduction- and exhumation-related deformations and metamorphism. In this contribution, the structure of the European distal margin in Western Alps is discussed in the light of the collision kinematics. More precisely, we aim at constraining the structure of the "distal" Dauphinois/Helvetic that might be the western lateral termination of the Valais ocean in Switzerland separating Europe and the Brianconnais block. The Dauphinois/Helvetic zone deformation is characterized and described using several balanced cross-sections. The timing, amount of shortening and exhumation of various External Crystalline Massifs from France to Switzerland (Oisans, Mont Blanc, Aar) are compared. In the Aar and Mont Blanc massifs, the averaged amount of shortening and exhumation during Oligo-Miocene times is around three times higher than in the Oisans massif. The P,T conditions are of higher grade in the Aar and Mont Blanc and the foreland basin (the Oligo-miocene molasse) is more developed. Finally, deformation mechanisms and geometries are significantly different, from brittle-ductile to ductile, from south to north, respectively. We tentatively propose that these differences can be due to an evolution from hyper-extended crust with mantle exhumation in the Northeast (Aar) to an "aborted rift" configuration in the Southwest (Oisans). The presence of a (light) continental crust in the Southwest may have prevented a strong tectonic burying of the proximal margin and promoted its early shortening.

  19. Strategic Partners: South Korea and the United States

    DTIC Science & Technology

    1989-01-01

    South Korea’s economic growth, has fallen off, forcing South Korea into new mar- kets. In 1984, the construction industry received a...are in - cluded in the calculation. Since the 1970s, South Korea and the United States have begun a new stage of extensive economic contact, although...The Japanese Outlook 78 The Korean Peninsula’s Future 80 6. US INTERESTS AND OPTIONS IN SOUTH KOREA 83 Carter Administration Korean Policy 83

  20. Measurements on Two-Dimensional Arrays of Mesoscopic Josephson Junctions

    DTIC Science & Technology

    1993-02-01

    effect, the magnetic analog of the Aharonov - Bohm effect (with the AC effect, it is theoretically predicted that one can measure the interference... Aharonov and Bohm (1959), and Aharonov and Casher (1984). 148 REFERENCES Aharonov , Y., and D. Bohm , Phys. Rev. B 3, 485 (1959). Aharonoy, Y., and A...are reasonably well- understood, with the possible exceptions of ballistic motion of vortices [van der Zant, et al. (1992b)] and the Aharonov -Casher (AC

  1. After Action Review in Simulation-Based Training

    DTIC Science & Technology

    2007-07-01

    feedback to organizations on their performance of collective tasks. It is an active process that requires unit members to participate in order to... processes . A second more recent form of constructive simulation is more entity and rule-based. These simulations provide semi-automated forces to...feedback. Extrinsic feedback can be used to correct misperceptions and clarify events and effects. The AAR process may provide unit members with a view

  2. Establishing an Intellectual and Theoretical Foundation for the After Action Review Process - A Literature Review

    DTIC Science & Technology

    2011-04-01

    Research Note 2011-07 Establishing an Intellectual and Theoretical Foundation for the After Action Review Process – A Literature Review...Dec 2009 4. TITLE AND SUBTITLE Establishing an Intellectual and Theoretical Foundation for the After Action Review Process – A Literature Review...of the cognitive and learning science research that is relevant to defining an effective after action review (AAR) process . The goal of this review

  3. Simulating Remediation of Trichloroethylene in Fractured Bedrock by Thermal Conductive Heating Using the Numerical Model TMVOC

    DTIC Science & Technology

    2013-01-01

    heat transfer rate positive (Thomas, 1980). 18 Equation 2.4 can be applied to a three-dimensional system where the thermal conductivity, K...consideration when heat is being applied to the system , as the compressibility properties will be changed due to changes in pressure (Fatt, 1958). A...are extracted by a vacuum system . Wells are typically placed 6 to 12 ft apart to ensure complete heating of the source zone when dealing with semi

  4. GCN2 is required to increase fibroblast growth factor 21 and maintain hepatic triglyceride homeostasis during asparaginase treatment.

    PubMed

    Wilson, Gabriel J; Lennox, Brittany A; She, Pengxiang; Mirek, Emily T; Al Baghdadi, Rana J T; Fusakio, Michael E; Dixon, Joseph L; Henderson, Gregory C; Wek, Ronald C; Anthony, Tracy G

    2015-02-15

    The antileukemic agent asparaginase triggers the amino acid response (AAR) in the liver by activating the eukaryotic initiation factor 2 (eIF2) kinase general control nonderepressible 2 (GCN2). To explore the mechanism by which AAR induction is necessary to mitigate hepatic lipid accumulation and prevent liver dysfunction during continued asparaginase treatment, wild-type and Gcn2 null mice were injected once daily with asparaginase or phosphate buffered saline for up to 14 days. Asparaginase induced mRNA expression of multiple AAR genes and greatly increased circulating concentrations of the metabolic hormone fibroblast growth factor 21 (FGF21) independent of food intake. Loss of Gcn2 precluded mRNA expression and circulating levels of FGF21 and blocked mRNA expression of multiple genes regulating lipid synthesis and metabolism including Fas, Ppara, Pparg, Acadm, and Scd1 in both liver and white adipose tissue. Furthermore, rates of triglyceride export and protein expression of apolipoproteinB-100 were significantly reduced in the livers of Gcn2 null mice treated with asparaginase, providing a mechanistic basis for the increase in hepatic lipid content. Loss of AAR-regulated antioxidant defenses in Gcn2 null livers was signified by reduced Gpx1 gene expression alongside increased lipid peroxidation. Substantial reductions in antithrombin III hepatic expression and activity in the blood of asparaginase-treated Gcn2 null mice indicated liver dysfunction. These results suggest that the ability of the liver to adapt to prolonged asparaginase treatment is influenced by GCN2-directed regulation of FGF21 and oxidative defenses, which, when lost, corresponds with maladaptive effects on lipid metabolism and hemostasis.

  5. Geotechnical Factors in the Dredgeability of Sediments. Report 2. Geotechnical Site Investigation Strategy for Dredging Projects

    DTIC Science & Technology

    1993-10-01

    site investigations must be commu- tifed and discussed. Guidance on sequencing nicated to and understood by all persons in- an investigation includes a...are mechanically compacted in the containment area. 34. DiGeorge and Herbich (1978) reported a laboratory study of bulking factors in fine-grained...occupied by the same amount of soil in-situ. Laboratory tests used for this purpose were described in DiGeorge and Herbich (1978), based on work by Lacasse

  6. DOD Ammunition and Explosives Safety Standards

    DTIC Science & Technology

    2008-02-29

    DoD 6055.09-STD, February 29, 2008 ACRONYMS AND ABBREVIATIONS AAE arms, ammunition, and explosives AAR after action report AC hydrogen cyanide ...Materials ASU ammunition storage unit B barricaded BATF Bureau of Alcohol, Tobacco and Firearms BEM buried explosion module BIP blow-in-place BLAHA...activities must also comply with Bureau of Alcohol, Tobacco , and Firearms (BATF), Federal Aviation Administration (FAA), and other Federal, State, and

  7. 49 CFR 179.102-4 - Vinyl fluoride, stabilized.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... impact tests must be performed as follows: (i) ASTM A 516/A 516M and A 537/A 537M material must meet the... subchapter), Type 304, 304L, 316 or 316L, in which case impact tests are not required; or (2) Steel complying... § 171.7 of this subchapter). (ii) AAR Specification TC 128 material must meet the Charpy V-Notch...

  8. U.S. Army Research Institute for the Behavioral and Social Sciences 1940-2015: 75 years of Science and Innovation

    DTIC Science & Technology

    2015-09-01

    millions of high school students each year. By 1940, mental ability testing was an accepted practice , if not com- mon place. Establishing a Research...fully engaged in human systems integration research as well, although that research mission was separated from ARI in the early 1990s and shifted...future engage - ments. The AAR has been so completely absorbed into Ar- my culture that it is no longer taught. It has morphed into multiple formats, is

  9. Effects of Electromagnetic Pulses on a Multilayered System

    DTIC Science & Technology

    2014-07-01

    University at Buffalo, 230 Davis Hall, Buffalo, NY 14260 H. L. Moore, P. Haney US Army ARDEC, AMSRD-AAR-MEM, Building 65 S, Picatinny Arsenal, NJ...types of EMPs that are of concern regarding electronics and system infrastructures; they are high-altitude EMP ( HEMP ) generated from nuclear...is for 3-D full-wave electromagnetic field simulation and high frequency and high speed components [2]. The model used was designed and imported

  10. Projectile Roll Dynamics and Control With a Low-Cost Skid-to-Turn Maneuver System

    DTIC Science & Technology

    2013-03-01

    11 viii INTENTIONALLY LEFT BLANK. 1 1. Introduction The overarching motivation for this...attack at 10-Hz initial roll rate – deflections. 8. Conclusions The motivation for this effort is a new capability of affordable interception of...TACOM ARDEC RDAR MEM M C MOEHRINGER J TRAVAILLE BLDG 94 PICATINNY ARSENAL NJ 07806-5000 1 US ARMY TACOM ARDEC AMSRD AAR AEPS J

  11. Failure Mechanisms and Interphase Chemistry of Gold Films on Ti6Al4V. Part II. Etching of Ti6Al4V and its Effect on Evaporated Gold and Commercial Adhesive Adhesion.

    DTIC Science & Technology

    1980-01-01

    varying periods of time in aqueous solution of hydrofluoric acid and ammonium phosphate . Following etching, one-half of the specimens were covered with...Observed in Gold Peel Tests Using 19 Commercial Transparent Tape 4 Single Overlap Shear Test Results for Etched Specimens 20 Held in Condensing Steam A...are results from specimens held for 16 hours in condens - ing steam. It can be seen that the trend here is the same as in the gold coated specimens; that

  12. In search of novel ligands using a structure-based approach: a case study on the adenosine A2A receptor

    NASA Astrophysics Data System (ADS)

    Lenselink, Eelke B.; Beuming, Thijs; van Veen, Corine; Massink, Arnault; Sherman, Woody; van Vlijmen, Herman W. T.; IJzerman, Adriaan P.

    2016-10-01

    In this work, we present a case study to explore the challenges associated with finding novel molecules for a receptor that has been studied in depth and has a wealth of chemical information available. Specifically, we apply a previously described protocol that incorporates explicit water molecules in the ligand binding site to prospectively screen over 2.5 million drug-like and lead-like compounds from the commercially available eMolecules database in search of novel binders to the adenosine A2A receptor (A2AAR). A total of seventy-one compounds were selected for purchase and biochemical assaying based on high ligand efficiency and high novelty (Tanimoto coefficient ≤0.25 to any A2AAR tested compound). These molecules were then tested for their affinity to the adenosine A2A receptor in a radioligand binding assay. We identified two hits that fulfilled the criterion of 50 % radioligand displacement at a concentration of 10 μM. Next we selected an additional eight novel molecules that were predicted to make a bidentate interaction with Asn2536.55, a key interacting residue in the binding pocket of the A2AAR. None of these eight molecules were found to be active. Based on these results we discuss the advantages of structure-based methods and the challenges associated with finding chemically novel molecules for well-explored targets.

  13. Molecular evolution of aminoacyl tRNA synthetase proteins in the early history of life.

    PubMed

    Fournier, Gregory P; Andam, Cheryl P; Alm, Eric J; Gogarten, J Peter

    2011-12-01

    Aminoacyl-tRNA synthetases (aaRS) consist of several families of functionally conserved proteins essential for translation and protein synthesis. Like nearly all components of the translation machinery, most aaRS families are universally distributed across cellular life, being inherited from the time of the Last Universal Common Ancestor (LUCA). However, unlike the rest of the translation machinery, aaRS have undergone numerous ancient horizontal gene transfers, with several independent events detected between domains, and some possibly involving lineages diverging before the time of LUCA. These transfers reveal the complexity of molecular evolution at this early time, and the chimeric nature of genomes within cells that gave rise to the major domains. Additionally, given the role of these protein families in defining the amino acids used for protein synthesis, sequence reconstruction of their pre-LUCA ancestors can reveal the evolutionary processes at work in the origin of the genetic code. In particular, sequence reconstructions of the paralog ancestors of isoleucyl- and valyl- RS provide strong empirical evidence that at least for this divergence, the genetic code did not co-evolve with the aaRSs; rather, both amino acids were already part of the genetic code before their cognate aaRSs diverged from their common ancestor. The implications of this observation for the early evolution of RNA-directed protein biosynthesis are discussed.

  14. Molecular Evolution of Aminoacyl tRNA Synthetase Proteins in the Early History of Life

    NASA Astrophysics Data System (ADS)

    Fournier, Gregory P.; Andam, Cheryl P.; Alm, Eric J.; Gogarten, J. Peter

    2011-12-01

    Aminoacyl-tRNA synthetases (aaRS) consist of several families of functionally conserved proteins essential for translation and protein synthesis. Like nearly all components of the translation machinery, most aaRS families are universally distributed across cellular life, being inherited from the time of the Last Universal Common Ancestor (LUCA). However, unlike the rest of the translation machinery, aaRS have undergone numerous ancient horizontal gene transfers, with several independent events detected between domains, and some possibly involving lineages diverging before the time of LUCA. These transfers reveal the complexity of molecular evolution at this early time, and the chimeric nature of genomes within cells that gave rise to the major domains. Additionally, given the role of these protein families in defining the amino acids used for protein synthesis, sequence reconstruction of their pre-LUCA ancestors can reveal the evolutionary processes at work in the origin of the genetic code. In particular, sequence reconstructions of the paralog ancestors of isoleucyl- and valyl- RS provide strong empirical evidence that at least for this divergence, the genetic code did not co-evolve with the aaRSs; rather, both amino acids were already part of the genetic code before their cognate aaRSs diverged from their common ancestor. The implications of this observation for the early evolution of RNA-directed protein biosynthesis are discussed.

  15. Parallel loss of nuclear-encoded mitochondrial aminoacyl-tRNA synthetases and mtDNA-encoded tRNAs in Cnidaria.

    PubMed

    Haen, Karri M; Pett, Walker; Lavrov, Dennis V

    2010-10-01

    Unlike most animal mitochondrial (mt) genomes, which encode a set of 22 transfer RNAs (tRNAs) sufficient for mt protein synthesis, those of cnidarians have only retained one or two tRNA genes. Whether the missing cnidarian mt-tRNA genes relocated outside the main mt chromosome or were lost remains unclear. It is also unknown what impact the loss of tRNA genes had on other components of the mt translational machinery. Here, we explored the nuclear genome of the cnidarian Nematostella vectensis for the presence of mt-tRNA genes and their corresponding mt aminoacyl-tRNA synthetases (mt-aaRS). We detected no candidates for mt-tRNA genes and only two mt-aaRS orthologs. At the same time, we found that all but one cytosolic aaRS appear to be targeted to mitochondria. These results indicate that the loss of mt-tRNAs in Cnidaria is genuine and occurred in parallel with the loss of nuclear-encoded mt-aaRS. Our phylogenetic analyses of individual aaRS revealed that although the nearly total loss of mt-aaRS is rare, aaRS gene deletion and replacement have occurred throughout the evolution of Metazoa.

  16. Hematopoietic activity of Smilax aristolochiaefolia (zarzaparrilla) in mice with aplastic anemia.

    PubMed

    Velasco-Lezama, Rodolfo; Muñoz Torres, Antonio; Tapia Aguilar, Rafaela; Flores Saenz, José Luis; Fregoso Padilla, Martha; Vega Avila, Elisa; Barrera Escorcia, Eduardo

    2009-01-01

    Smilax aristolochiaefolia (Liliaceae) has been used in Mexican traditional medicine for the treatment of tumors, leprosy, anemia and as a tonic for skin infections and anemia. Aplastic anemia (AA) was induced in CD1 mice 8-12 weeks old distributed 10 animals each in Groups VSC, AA, AASa and AAr. Groups AA, AASa and AAr received benzene (2 ml/kg diluted v/v with corn oil) subcutaneously every three days until 20 dosages had been administered. The vehicular solution control group (VSC) received corn oil and the HC group (healthy control) received saline solution. Two days after the last benzene inoculation, groups AA and HC were bled and sacrificed to count blood and bone marrow cells. Group AASa received an aqueous S. aristolochiaefolia (0.4 g/kg) solution orally on days 3, 5 and 7 after the last dosage of benzene, meanwhile group AAr received no treatment after induction of AA (self recovery). On day 9 these groups were bled and sacrificed to count blood and bone marrow cells. Mice with aplastic anemia treated with S. aristolochiaefolia extract, recovered normal platelet levels and nucleated bone marrow cells as compared with the control, but the counts of erythrocytes and leukocyte were lower than controls (p<0.005). The aqueous extract of S. aristolochiaefolia (zarzaparrilla) restores hematopoeisis in the bone marrow of mice with aplastic anemia.

  17. Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) Studies on α1A-Adrenergic Receptor Antagonists Based on Pharmacophore Molecular Alignment

    PubMed Central

    Zhao, Xin; Chen, Minsheng; Huang, Biyun; Ji, Hong; Yuan, Mu

    2011-01-01

    The α1A-adrenergic receptor (α1A-AR) antagonist is useful in treating benign prostatic hyperplasia, lower urinary tract symptoms, and cardiac arrhythmia. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on a set of α1A-AR antagonists of N-aryl and N-nitrogen class. Statistically significant models constructed from comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were established based on a training set of 32 ligands using pharmacophore-based molecular alignment. The leave-oneout cross-validation correlation coefficients were q2 CoMFA = 0.840 and q2 CoMSIA = 0.840. The high correlation between the cross-validated/predicted and experimental activities of a test set of 12 ligands revealed that the CoMFA and CoMSIA models were robust (r2 pred/CoMFA = 0.694; r2 pred/CoMSIA = 0.671). The generated models suggested that electrostatic, hydrophobic, and hydrogen bonding interactions play important roles between ligands and receptors in the active site. Our study serves as a guide for further experimental investigations on the synthesis of new compounds. Structural modifications based on the present 3D-QSAR results may lead to the discovery of other α1A-AR antagonists. PMID:22072933

  18. Alkane production by the marine cyanobacterium Synechococcus sp. NKBG15041c possessing the α-olefin biosynthesis pathway.

    PubMed

    Yoshino, Tomoko; Liang, Yue; Arai, Daichi; Maeda, Yoshiaki; Honda, Toru; Muto, Masaki; Kakunaka, Natsumi; Tanaka, Tsuyoshi

    2015-02-01

    The production of alkanes in a marine cyanobacterium possessing the α-olefin biosynthesis pathway was achieved by introducing an exogenous alkane biosynthesis pathway. Cyanobacterial hydrocarbons are synthesized via two separate pathways: the acyl-acyl carrier protein (ACP) reductase/aldehyde-deformylating oxygenase (AAR/ADO) pathway for the alkane biosynthesis and the α-olefin synthase (OLS) pathway for the α-olefin biosynthesis. Coexistence of these pathways has not yet been reported. In this study, the marine cyanobacterium Synechococcus sp. NKBG15041c was shown to produce α-olefins similar to those of Synechococcus sp. PCC7002 via the α-olefin biosynthesis pathway. The production of heptadecane in Synechococcus sp. NKBG15041c was achieved by expressing the AAR/ADO pathway genes from Synechococcus elongatus PCC 7942. The production yields of heptadecane in Synechococcus sp. NKBG15041c varied with the expression level of the aar and ado genes. The maximal yield of heptadecane was 4.2 ± 1.2 μg/g of dried cell weight in the transformant carrying a homologous promoter. Our results also suggested that the effective activation of ADO may be more important for the enhancement of alkane production by cyanobacteria.

  19. A Modified Johnson-Cook Constitutive Equation to Predict Hot Deformation Behavior of Ti-6Al-4V Alloy

    NASA Astrophysics Data System (ADS)

    Cai, Jun; Wang, Kuaishe; Zhai, Peng; Li, Fuguo; Yang, Jie

    2015-01-01

    A modified Johnson-Cook constitutive equation of Ti-6Al-4V alloy is proposed based on hot compression tests performed in the temperature range of 1073-1323 K and strain rate 0.001-1 s-1. The experimental stress-strain data were employed to develop the modified Johnson-Cook constitutive equation of different phase regimes (α + β and β phase). The predicted flow stresses using the developed equation were compared with experimental data. Correlation coefficient ( R) and average absolute relative error (AARE) were introduced to verify the validity of the constitutive equation. The values of R and AARE for α + β phase were 0.990 and 7.81%, respectively. And in β phase region, the values of R and AARE were 0.985 and 10.36%, respectively. Meanwhile, the accuracy, the number of material constants involved, and the computational time required of the constitutive equation were evaluated by comparing with a strain-compensated Arrhenius-type constitutive equation. The results indicate that accuracy of modified Johnson-Cook constitutive equation is higher than that of compensated Arrhenius-type model at α + β phase, while lower at single β phase region. Meanwhile, the time required for evaluating the material constants of modified Johnson-Cook constitutive equation is much shorter than that of the strain-compensated Arrhenius type ones.

  20. A Modified Johnson-Cook Constitutive Equation to Predict Hot Deformation Behavior of Ti-6Al-4V Alloy

    NASA Astrophysics Data System (ADS)

    Cai, Jun; Wang, Kuaishe; Zhai, Peng; Li, Fuguo; Yang, Jie

    2014-09-01

    A modified Johnson-Cook constitutive equation of Ti-6Al-4V alloy is proposed based on hot compression tests performed in the temperature range of 1073-1323 K and strain rate 0.001-1 s-1. The experimental stress-strain data were employed to develop the modified Johnson-Cook constitutive equation of different phase regimes (α + β and β phase). The predicted flow stresses using the developed equation were compared with experimental data. Correlation coefficient (R) and average absolute relative error (AARE) were introduced to verify the validity of the constitutive equation. The values of R and AARE for α + β phase were 0.990 and 7.81%, respectively. And in β phase region, the values of R and AARE were 0.985 and 10.36%, respectively. Meanwhile, the accuracy, the number of material constants involved, and the computational time required of the constitutive equation were evaluated by comparing with a strain-compensated Arrhenius-type constitutive equation. The results indicate that accuracy of modified Johnson-Cook constitutive equation is higher than that of compensated Arrhenius-type model at α + β phase, while lower at single β phase region. Meanwhile, the time required for evaluating the material constants of modified Johnson-Cook constitutive equation is much shorter than that of the strain-compensated Arrhenius type ones.

  1. The DarkSide physics program and its recent results

    DOE PAGES

    D'Angelo, D.

    2017-01-12

    Here, DarkSide (DS) at Gran Sasso underground laboratory is a direct Dark Matter search program based on Time Projection Chambers (TPC) with liquid Argon from underground sources. The DarkSide-50 (DS-50) TPC, with 150 kg of Argon is installed inside active neutron and muon detectors. DS-50 has been taking data since November 2013 with Atmospheric Argon (AAr) and since April 2015 with Underground Argon (UAr), depleted in radioactive 39Ar by a factor ~1400. The exposure of 1422 kg d of AAr has demonstrated that the operation of DS-50 for three years in a background free condition is a solid reality, thanksmore » to the superb performance of the Pulse Shape Analysis. The first release of results from an exposure of 2616 kg d of UAr has shown no candidate Dark Matter events. We have set the best limit for Spin-Independent elastic nuclear scattering of WIMPs obtained by Argon-based detectors, corresponding to a cross-section of 2 10–44 cm2 at a WIMP mass of 100 GeV. We present the detector design and performance, the results from the AAr run and the first results from the UAr run and we briefly introduce the future of the DarkSide program.« less

  2. Galvanising the NHS to Adopt Innovation

    PubMed Central

    Parris, Stuart; Cochrane, Gavin; Marjanovic, Sonja; Ling, Tom; Chataway, Joanna

    2016-01-01

    Abstract The Department of Health and the Wellcome Trust, in co-operation with NHS England, asked RAND Europe to conduct a limited consultation with key stakeholders about the practicality of measures and incentives proposed as part of the NHS Accelerated Access Review (AAR), which aims to assess the pathways for the development, assessment, and adoption of innovative medicines and medical technology. Through a focused engagement exercise with key healthcare stakeholders this project explored the implications of selected interim AAR propositions and feasibility of implementation for key actors, in primary and secondary care as well as commissioners and academia. Specifically, the project investigated the feasibility of implementation of three specific propositions including: a new earmarked fund to encourage AHSNs and other key innovation actors to re-design systems to embrace innovation; mobilising the influence of clinical system leaders to champion change; and encouraging secondary care organisations to take on “innovation champion” roles linked to financial incentives and a new emphasis on accountable care organisations. Data was collected on the feasibility of the three AAR propositions from a workshop with AHSN CEOs and Commercial Directors and interviews with senior NHS staff in three AHSN regions (South West, University College London Partners, and North East, North Cumbria). The study concludes with reflections on the feasibility of each recommendation and identifies factors expected to facilitate or challenge their implementation, as well as considering the wider cross cutting issues that may influence the adoption and diffusion of innovation in the NHS. PMID:28083436

  3. Rocketdyne RBCC Engine Concept Development

    NASA Technical Reports Server (NTRS)

    Ratckin, G.; Goldman, A.; Ortwerth, P.; Weisberg, S.

    1999-01-01

    Boeing Rocketdyne is pursuing the development of Rocket Based Combined Cycle (RBCC), propulsion systems as demonstrated by significant contract work in the hypersonic arena (ART, NASP, SCT, system studies) and over 12 years of steady company discretionary investment. The Rocketdyne concept is a fixed geometry integrated rocket, ramjet, scramjet which is hydrogen fueled and uses hydrogen regenerative cooling. The baseline engine structural configuration uses an integral structure that eliminates panel seals. seal purge gas, and closeout side attachments. Rocketdyne's experimental RBCC engine (Engine A5) was constructed under contract with the NASA Marshall Space Flight Center. Engine A5 models the complete flight engine flowpath consisting of an inlet, isolator, airbreathing combustor and nozzle. High performance rocket thrusters are integrated into the engine to enable both air-augmented rocket (AAR) and pure rocket operation. Engine A5 was tested in CASL's new FAST facility as an air-augmented rocket, a ramjet and a pure rocket. Measured performance demonstrated vision vehicle performance levels for Mach 3 AAR operation and ramjet operation from Mach 3 to 4. Rocket mode performance was above predictions. For the first time. testing also demonstrated transition from AAR operation to ramjet operation. This baseline configuration has also been shown, in previous testing, to perform well in the scramjet mode.

  4. In silico detection of tRNA sequence features characteristic to aminoacyl-tRNA synthetase class membership

    PubMed Central

    Jakó, Éena; Ittzés, Péter; Szenes, Áron; Kun, Ádám; Szathmáry, Eörs; Pál, Gábor

    2007-01-01

    Aminoacyl tRNA synthetases (aaRS) are grouped into Class I and II based on primary and tertiary structure and enzyme properties suggesting two independent phylogenetic lineages. Analogously, tRNA molecules can also form two respective classes, based on the class membership of their corresponding aaRS. Although some aaRS–tRNA interactions are not extremely specific and require editing mechanisms to avoid misaminoacylation, most aaRS–tRNA interactions are rather stereospecific. Thus, class-specific aaRS features could be mirrored by class-specific tRNA features. However, previous investigations failed to detect conserved class-specific nucleotides. Here we introduce a discrete mathematical approach that evaluates not only class-specific ‘strictly present’, but also ‘strictly absent’ nucleotides. The disjoint subsets of these elements compose a unique partition, named extended consensus partition (ECP). By analyzing the ECP for both Class I and II tDNA sets from 50 (13 archaeal, 30 bacterial and 7 eukaryotic) species, we could demonstrate that class-specific tRNA sequence features do exist, although not in terms of strictly conserved nucleotides as it had previously been anticipated. This finding demonstrates that important information was hidden in tRNA sequences inaccessible for traditional statistical methods. The ECP analysis might contribute to the understanding of tRNA evolution and could enrich the sequence analysis tool repertoire. PMID:17704131

  5. Pharmacologic Effects of Cannabidiol on Acute Reperfused Myocardial Infarction in Rabbits: Evaluated With 3.0T Cardiac Magnetic Resonance Imaging and Histopathology.

    PubMed

    Feng, Yuanbo; Chen, Feng; Yin, Ting; Xia, Qian; Liu, Yewei; Huang, Gang; Zhang, Jian; Oyen, Raymond; Ni, Yicheng

    2015-10-01

    Cannabidiol (CBD) has anti-inflammatory effects. We explored its therapeutic effects on cardiac ischemia-reperfusion injury with an experimental imaging platform. Reperfused acute myocardial infarction (AMI) was induced in rabbits with a 90-minute coronary artery occlusion followed by 24-hour reperfusion. Before reperfusion, rabbits received 2 intravenous doses of 100 μg/kg CBD (n = 10) or vehicle (control, n = 10). Evans blue was intravenously injected for later detection of the AMI core. Cardiac magnetic resonance imaging was performed to evaluate cardiac morphology and function. After euthanasia, blood troponin I (cTnI) was assessed, and the heart was excised and infused with multifunctional red iodized oil dye. The heart was sliced for digital radiography to quantify the perfusion density rate, area at risk (AAR), and myocardial salvage index, followed by histomorphologic staining. Compared with controls, CBD treatment improved systolic wall thickening (P < 0.05), significantly increased blood flow in the AAR (P < 0.05), significantly decreased microvascular obstruction (P < 0.05), increased the perfusion density rate by 1.7-fold, lowered the AMI core/AAR ratio (P < 0.05), and increased the myocardial salvage index (P < 0.05). These improvements were associated with reductions in serum cTnI, cardiac leukocyte infiltration, and myocellular apoptosis (P < 0.05). Thus, CBD therapy reduced AMI size and facilitated restoration of left ventricular function. We demonstrated that this experimental platform has potential theragnostic utility.

  6. Influence of steel fibers on the development of alkali-aggregate reaction

    SciTech Connect

    Pires de Carvalho, Maria Rita; Pagan Hasparyk, Nicole

    2010-04-15

    This work presents the results of an experimental research concerning the use of fibers in mortar specimens subjected to alkali-aggregate reaction (AAR). Two types of steel fibers (0.16 mm diameter and 6.0 mm length, and 0.20 mm diameter and 13.0 mm length) were used with fiber volume contents of 1% and 2%. Besides the expansion accelerated tests, compressive tests and flexural tests have also been carried out to display the main mechanical characteristics of the fiber-reinforced mortars after being subjected to AAR. Moreover, the microstructure of the specimens was analyzed by scanning electron microscopy and energy dispersive X-ray. The results shown that the addition of steel fibers reduced the expansion due to AAR for the experimental conditions studied in this paper. The most expressive benefit corresponded to the addition of 13.0 mm fibers in the mixture containing 2% fiber content. This fiber volume content also corresponded to the maximum increment in the mechanical properties compared to the reference mortar, mainly for the post-cracking strength and for the toughness in bending. It was observed that the fibers have a beneficial effect on the material, without compromising its main mechanical properties.

  7. Amino Acid Availability Controls TRB3 Transcription in Liver through the GCN2/eIF2α/ATF4 Pathway

    PubMed Central

    Carraro, Valérie; Maurin, Anne-Catherine; Lambert-Langlais, Sarah; Averous, Julien; Chaveroux, Cédric; Parry, Laurent; Jousse, Céline; Örd, Daima; Örd, Tõnis; Fafournoux, Pierre; Bruhat, Alain

    2010-01-01

    In mammals, plasma amino acid concentrations are markedly affected by dietary or pathological conditions. It has been well established that amino acids are involved in the control of gene expression. Up to now, all the information concerning the molecular mechanisms involved in the regulation of gene transcription by amino acid availability has been obtained in cultured cell lines. The present study aims to investigate the mechanisms involved in transcriptional activation of the TRB3 gene following amino acid limitation in mice liver. The results show that TRB3 is up-regulated in the liver of mice fed a leucine-deficient diet and that this induction is quickly reversible. Using transient transfection and chromatin immunoprecipitation approaches in hepatoma cells, we report the characterization of a functional Amino Acid Response Element (AARE) in the TRB3 promoter and the binding of ATF4, ATF2 and C/EBPβ to this AARE sequence. We also provide evidence that only the binding of ATF4 to the AARE plays a crucial role in the amino acid-regulated transcription of TRB3. In mouse liver, we demonstrate that the GCN2/eIF2α/ATF4 pathway is essential for the induction of the TRB3 gene transcription in response to a leucine-deficient diet. Therefore, this work establishes for the first time that the molecular mechanisms involved in the regulation of gene transcription by amino acid availability are functional in mouse liver. PMID:21203563

  8. Structural diversity and protein engineering of the aminoacyl-tRNA synthetases.

    PubMed

    Perona, John J; Hadd, Andrew

    2012-11-06

    Aminoacyl-tRNA synthetases (aaRS) are the enzymes that ensure faithful transmission of genetic information in all living cells, and are central to the developing technologies for expanding the capacity of the translation apparatus to incorporate nonstandard amino acids into proteins in vivo. The 24 known aaRS families are divided into two classes that exhibit functional evolutionary convergence. Each class features an active site domain with a common fold that binds ATP, the amino acid, and the 3'-terminus of tRNA, embellished by idiosyncratic further domains that bind distal portions of the tRNA and enhance specificity. Fidelity in the expression of the genetic code requires that the aaRS be selective for both amino acids and tRNAs, a substantial challenge given the presence of structurally very similar noncognate substrates of both types. Here we comprehensively review central themes concerning the architectures of the protein structures and the remarkable dual-substrate selectivities, with a view toward discerning the most important issues that still substantially limit our capacity for rational protein engineering. A suggested general approach to rational design is presented, which should yield insight into the identities of the protein-RNA motifs at the heart of the genetic code, while also offering a basis for improving the catalytic properties of engineered tRNA synthetases emerging from genetic selections.

  9. The aminoacyl-tRNA synthetases of Drosophila melanogaster

    PubMed Central

    Lu, Jiongming; Marygold, Steven J; Gharib, Walid H; Suter, Beat

    2015-01-01

    Aminoacyl-tRNA synthetases (aaRSs) ligate amino acids to their cognate tRNAs, allowing them to decode the triplet code during translation. Through different mechanisms aaRSs also perform several non-canonical functions in transcription, translation, apoptosis, angiogenesis and inflammation. Drosophila has become a preferred system to model human diseases caused by mutations in aaRS genes, to dissect effects of reduced translation or non-canonical activities, and to study aminoacylation and translational fidelity. However, the lack of a systematic annotation of this gene family has hampered such studies. Here, we report the identification of the entire set of aaRS genes in the fly genome and we predict their roles based on experimental evidence and/or orthology. Further, we propose a new, systematic and logical nomenclature for aaRSs. We also review the research conducted on Drosophila aaRSs to date. Together, our work provides the foundation for further research in the fly aaRS field. PMID:26761199

  10. Hazmat on the rails: A closer look

    SciTech Connect

    Larson, K.M.

    1996-10-01

    Despite what appears to be a rash of railroad incidents involving hazardous materials, the Association of American Railroads (AAR; Washington, DC) maintains that 1995 was the safest year in railroad history, even though rail freight traffic was at an all-time high. AAR says railroads have an especially good record when it comes to moving hazardous waste. Railroads in 1994 moved more than 1.6 million carloads of hazardous materials, yet only 43 cars released hazardous contents--fewer than one for every 37,000 cars moved, AAR notes. Preliminary figures indicate another 43 cars released hazardous materials in 1995. Not all rail car releases occur as a result of an accident or derailment. Nonaccident releases (NARs) can result from such problems as tank car overfilling, chemical reactions during temperature changes, or loose tank closures. The top 10 hazardous commodities are: sulfuric acid, hydrochloric acid solution, anhydrous ammonia, liquefied petroleum gases, sodium hydroxide solution, flammable liquids not otherwise specified, corrosive liquids not otherwise specified, phosphoric acid, methyl tertiary butyl ether, and methanol.

  11. Segmentation of cytoplasm and nuclei of abnormal cells in cervical cytology using global and local graph cuts.

    PubMed

    Zhang, Ling; Kong, Hui; Chin, Chien Ting; Liu, Shaoxiong; Chen, Zhi; Wang, Tianfu; Chen, Siping

    2014-07-01

    Automation-assisted reading (AAR) techniques have the potential to reduce errors and increase productivity in cervical cancer screening. The sensitivity of AAR relies heavily on automated segmentation of abnormal cervical cells, which is handled poorly by current segmentation algorithms. In this paper, a global and local scheme based on graph cut approach is proposed to segment cervical cells in images with a mix of healthy and abnormal cells. For cytoplasm segmentation, the multi-way graph cut is performed globally on the a* channel enhanced image, which can be effective when the image histogram presents a non-bimodal distribution. For segmentation of nuclei, especially when they are abnormal, we propose to use graph cut adaptively and locally, which allows the combination of intensity, texture, boundary and region information. Two concave points-based approaches are integrated to split the touching-nuclei. As part of an ongoing clinical trial, preliminary validation results obtained from 21 cervical cell images with non-ideal imaging condition and pathology show that our segmentation method achieved 93% accuracy for cytoplasm, and 88.4% F-measure for abnormal nuclei, outperforming state of the art methods in terms of accuracy. Our method has the potential to improve the sensitivity of AAR in screening for cervical cancer.

  12. Crystal structure of histidyl-tRNA synthetase from Escherichia coli complexed with histidyl-adenylate.

    PubMed Central

    Arnez, J G; Harris, D C; Mitschler, A; Rees, B; Francklyn, C S; Moras, D

    1995-01-01

    The crystal structure at 2.6 A of the histidyl-tRNA synthetase from Escherichia coli complexed with histidyl-adenylate has been determined. The enzyme is a homodimer with a molecular weight of 94 kDa and belongs to the class II of aminoacyl-tRNA synthetases (aaRS). The asymmetric unit is composed of two homodimers. Each monomer consists of two domains. The N-terminal catalytic core domain contains a six-stranded antiparallel beta-sheet sitting on two alpha-helices, which can be superposed with the catalytic domains of yeast AspRS, and GlyRS and SerRS from Thermus thermophilus with a root-mean-square difference on the C alpha atoms of 1.7-1.9 A. The active sites of all four monomers are occupied by histidyl-adenylate, which apparently forms during crystallization. The 100 residue C-terminal alpha/beta domain resembles half of a beta-barrel, and provides an independent domain oriented to contact the anticodon stem and part of the anticodon loop of tRNA(His). The modular domain organization of histidyl-tRNA synthetase reiterates a repeated theme in aaRS, and its structure should provide insight into the ability of certain aaRS to aminoacylate minihelices and other non-tRNA molecules. Images PMID:7556055

  13. Automated Aerial Refueling Hitches a Ride on AFF

    NASA Technical Reports Server (NTRS)

    Hansen, Jennifer L.; Murray, James E.; Bever, Glenn; Campos, Norma V.; Schkolnik, Gerard

    2007-01-01

    The recent introduction of uninhabited aerial vehicles [UAVs (basically, remotely piloted or autonomous aircraft)] has spawned new developments in autonomous operation and posed new challenges. Automated aerial refueling (AAR) is a capability that will enable UAVs to travel greater distances and loiter longer over targets. NASA Dryden Flight Research Center, in cooperation with the Defense Advanced Research Projects Agency (DARPA), the Naval Air Systems Command (NAVAIR), the Naval Air Force Pacific Fleet, and the Air Force Research Laboratory, rapidly conceived and accomplished an AAR flight research project focused on collecting a unique, high-quality database on the dynamics of the hose and drogue of an aerial refueling system. This flight-derived database would be used to validate mathematical models of the dynamics in support of design and analysis of AAR systems for future UAVs. The project involved the use of two Dryden F/A-18 airplanes and an S-3 hose-drogue refueling store on loan from the Navy. In this year-long project, which was started on October 1, 2002, 583 research maneuvers were completed during 23 flights.

  14. Age estimation based on aspartic acid racemization in human sclera.

    PubMed

    Klumb, Karolin; Matzenauer, Christian; Reckert, Alexandra; Lehmann, Klaus; Ritz-Timme, Stefanie

    2016-01-01

    Age estimation based on racemization of aspartic acid residues (AAR) in permanent proteins has been established in forensic medicine for years. While dentine is the tissue of choice for this molecular method of age estimation, teeth are not always available which leads to the need to identify other suitable tissues. We examined the suitability of total tissue samples of human sclera for the estimation of age at death. Sixty-five samples of scleral tissue were analyzed. The samples were hydrolyzed and after derivatization, the extent of aspartic acid racemization was determined by gas chromatography. The degree of AAR increased with age. In samples from younger individuals, the correlation of age and D-aspartic acid content was closer than in samples from older individuals. The age-dependent racemization in total tissue samples proves that permanent or at least long-living proteins are present in scleral tissue. The correlation of AAR in human sclera and age at death is close enough to serve as basis for age estimation. However, the precision of age estimation by this method is lower than that of age estimation based on the analysis of dentine which is due to molecular inhomogeneities of total tissue samples of sclera. Nevertheless, the approach may serve as a valuable alternative or addition in exceptional cases.

  15. Plasma Levels of Dimethylarginines in Preterm Very Low Birth Weight Neonates: Its Relation with Perinatal Factors and Short-Term Outcome

    PubMed Central

    Moonen, Rob M.; Huizing, Maurice J.; Cavallaro, Giacomo; González-Luis, Gema E.; Bas-Suárez, Pilar; Bakker, Jaap A.; Villamor, Eduardo

    2014-01-01

    Endogenously produced inhibitors of nitric oxide (NO) synthase, in particular asymmetric dimethylarginine (ADMA), are currently considered of importance in various disease states characterized by reduced NO availability. We investigated the association between plasma levels of ADMA, symmetric dimethylarginine (SDMA), l-arginine, and citrulline and perinatal factors and outcome in 130 preterm (gestational age ≤30 weeks) very low birth weight (VLBW, <1500 g) infants. Plasma samples were collected 6–12 h after birth. We did not find significant correlations between ADMA, SDMA, l-arginine, and citrulline levels and gestational age or birth weight. However, the arginine:ADMA ratio (AAR, a better indicator of NO availability than either arginine or ADMA separately) was positively correlated with gestational age. ADMA and arginine levels were not significantly different between males and females but males showed a negative correlation between ADMA levels and gestational age. Perinatal factors such as preeclampsia, chrorioamnionitis, prolonged rupture of membranes, or form of delivery did not significantly alter dimethylarginine levels or AAR. In contrast, the AAR was significantly reduced in the infants with respiratory distress, mechanical ventilation, and systemic hypotension Therefore, our data suggest that altered NO availability may play a role in the respiratory and cardiovascular adaptation in preterm VLBW infants. PMID:25546385

  16. High salt diet exacerbates vascular contraction in the absence of adenosine A₂A receptor.

    PubMed

    Pradhan, Isha; Zeldin, Darryl C; Ledent, Catherine; Mustafa, Jamal S; Falck, John R; Nayeem, Mohammed A

    2014-05-01

    High salt (4% NaCl, HS) diet modulates adenosine-induced vascular response through adenosine A(2A) receptor (A(2A)AR). Evidence suggests that A(2A)AR stimulates cyp450-epoxygenases, leading to epoxyeicosatrienoic acids (EETs) generation. The aim of this study was to understand the vascular reactivity to HS and underlying signaling mechanism in the presence or absence of A(2A)AR. Therefore, we hypothesized that HS enhances adenosine-induced relaxation through EETs in A(2A)AR⁺/⁺, but exaggerates contraction in A(2A)AR⁻/⁻. Organ bath and Western blot experiments were conducted in HS and normal salt (NS, 0.18% NaCl)-fed A(2A)AR⁺/⁺ and A(2A)AR⁻/⁻ mice aorta. HS produced concentration-dependent relaxation to non-selective adenosine analog, NECA in A(2A)AR⁺/⁺, whereas contraction was observed in A(2A)AR⁻/⁻ mice and this was attenuated by A₁AR antagonist (DPCPX). CGS 21680 (selective A(2A)AR agonist) enhanced relaxation in HS-A(2A)AR⁺/⁺ versus NS-A(2A)AR⁺/⁺, which was blocked by EETs antagonist (14,15-EEZE). Compared with NS, HS significantly upregulated the expression of vasodilators A(2A)AR and cyp2c29, whereas vasoconstrictors A₁AR and cyp4a in A(2A)AR⁺/⁺ were downregulated. In A(2A)AR⁻/⁻ mice, however, HS significantly downregulated the expression of cyp2c29, whereas A₁AR and cyp4a were upregulated compared with A(2A)AR⁺/⁺ mice. Hence, our data suggest that in A(2A)AR⁺/⁺, HS enhances A(2A)AR-induced relaxation through increased cyp-expoxygenases-derived EETs and decreased A₁AR levels, whereas in A(2A)AR⁻/⁻, HS exaggerates contraction through decreased cyp-epoxygenases and increased A₁AR levels.

  17. Does a Superswell Exist Between Antarctica and Australia?

    NASA Astrophysics Data System (ADS)

    Park, S. H.; Langmuir, C. H.; Scott, S. R.; Sims, K. W. W.; Lin, J.; Kim, S.; Michael, P. J.; Hahm, D.

    2015-12-01

    The Australian-Antarctic Ridge (AAR) is located between the Australian-Antarctic Discordance (AAD) of the Southeast Indian ridge (SEIR) in the west and Pacific-Antarctic Ridge (PAR) in the east. The AAR has intermediate spreading rate (~70 mm/yr) and consists of a series of 1st order segments bounded by parallel transform faults. KR1, a southernmost segment (63°S) of the AAR, is a 300-km-long super-segment with shallow axial depth (~2000 m). KR1 is bounded by the Macquarie transform fault in the east and the Balleney transform fault in the west, which connects KR1 with KR2 at ~ 200 km north. KR2 is 180 km long with axial depth (~2300 m) deeper than KR1. Both KR1 and KR2 are shallow relative to global mid-ocean ridges. Most of the basaltic rocks from the two segments show enriched geochemical characteristics that differ from both the AAD (Southeast Indian Ridge) and the PAR. La/Sm ratios vary from N-MORB to T-MORB; however, K2O/Nb ratios of all samples are consistently low like OIB. Their Pb isotopes are mostly more radiogenic than the N-MORB samples from PAR (and EPR) and SEIR, with 206Pb/204Pb mostly >18.6. At a given 206Pb/204Pb, their 87Sr/86Sr are higher than the PAR, but lower than the SEIR. The basalts from the two segments are geochemically similar to Cenozoic volcanoes erupted on southeast Australia, Zealandia and northwest Antarctica, suggesting a genetic relationship. According to tectonic reconstruction models, these three continents were originally joined, but separated from each other after ~80 Ma. Notably, the KR1 and KR2 segments are located at the boundary of this continental separation. The ages of Cenozoic volcanoes span from ~ 60 Ma to the recent, and the volcanoes might be related to a plume head that caused the breakup of the continents. Seismic tomography studies show that there is a low velocity zone (LVZ) in the shallow mantle (> 250 km) between Antarctica and Australia where the AAR is located. The AAR would be sampling this LVZ, and this

  18. Aminoacylating Urzymes Challenge the RNA World Hypothesis*♦

    PubMed Central

    Li, Li; Francklyn, Christopher; Carter, Charles W.

    2013-01-01

    We describe experimental evidence that ancestral peptide catalysts substantially accelerated development of genetic coding. Structurally invariant 120–130-residue Urzymes (Ur = primitive plus enzyme) derived from Class I and Class II aminoacyl-tRNA synthetases (aaRSs) acylate tRNA far faster than the uncatalyzed rate of nonribosomal peptide bond formation from activated amino acids. These new data allow us to demonstrate statistically indistinguishable catalytic profiles for Class I and II aaRSs in both amino acid activation and tRNA acylation, over a time period extending to well before the assembly of full-length enzymes and even further before the Last Universal Common Ancestor. Both Urzymes also exhibit ∼60% of the contemporary catalytic proficiencies. Moreover, they are linked by ancestral sense/antisense genetic coding, and their evident modularities suggest descent from even simpler ancestral pairs also coded by opposite strands of the same gene. Thus, aaRS Urzymes substantially pre-date modern aaRS but are, nevertheless, highly evolved. Their unexpectedly advanced catalytic repertoires, sense/antisense coding, and ancestral modularities imply considerable prior protein-tRNA co-evolution. Further, unlike ribozymes that motivated the RNA World hypothesis, Class I and II Urzyme·tRNA pairs represent consensus ancestral forms sufficient for codon-directed synthesis of nonrandom peptides. By tracing aaRS catalytic activities back to simpler ancestral peptides, we demonstrate key steps for a simpler and hence more probable peptide·RNA development of rapid coding systems matching amino acids with anticodon trinucleotides. PMID:23867455

  19. A large family of anti-activators accompanying XylS/AraC family regulatory proteins.

    PubMed

    Santiago, Araceli E; Yan, Michael B; Tran, Minh; Wright, Nathan; Luzader, Deborah H; Kendall, Melissa M; Ruiz-Perez, Fernando; Nataro, James P

    2016-07-01

    AraC Negative Regulators (ANR) suppress virulence genes by directly down-regulating AraC/XylS members in Gram-negative bacteria. In this study, we sought to investigate the distribution and molecular mechanisms of regulatory function for ANRs among different bacterial pathogens. We identified more than 200 ANRs distributed in diverse clinically important gram negative pathogens, including Vibrio spp., Salmonella spp., Shigella spp., Yersinia spp., Citrobacter spp., enterotoxigenic (ETEC) and enteroaggregative E. coli (EAEC), and members of the Pasteurellaceae. By employing a bacterial two hybrid system, pull down assays and surface plasmon resonance (SPR) analysis, we demonstrate that Aar (AggR-activated regulator), a prototype member of the ANR family in EAEC, binds with high affinity to the central linker domain of AraC-like member AggR. ANR-AggR binding disrupted AggR dimerization and prevented AggR-DNA binding. ANR homologs of Vibrio cholerae, Citrobacter rodentium, Salmonella enterica and ETEC were capable of complementing Aar activity by repressing aggR expression in EAEC strain 042. ANR homologs of ETEC and Vibrio cholerae bound to AggR as well as to other members of the AraC family, including Rns and ToxT. The predicted proteins of all ANR members exhibit three highly conserved predicted α-helices. Site-directed mutagenesis studies suggest that at least predicted α-helices 2 and 3 are required for Aar activity. In sum, our data strongly suggest that members of the novel ANR family act by directly binding to their cognate AraC partners.

  20. Reversible Unfolding of Rhomboid Intramembrane Proteases

    PubMed Central

    Panigrahi, Rashmi; Arutyunova, Elena; Panwar, Pankaj; Gimpl, Katharina; Keller, Sandro; Lemieux, M. Joanne

    2016-01-01

    Denaturant-induced unfolding of helical membrane proteins provides insights into their mechanism of folding and domain organization, which take place in the chemically heterogeneous, anisotropic environment of a lipid membrane. Rhomboid proteases are intramembrane proteases that play key roles in various diseases. Crystal structures have revealed a compact helical bundle with a buried active site, which requires conformational changes for the cleavage of transmembrane substrates. A dimeric form of the rhomboid protease has been shown to be important for activity. In this study, we examine the mechanism of refolding for two distinct rhomboids to gain insight into their secondary structure-activity relationships. Although helicity is largely abolished in the unfolded states of both proteins, unfolding is completely reversible for HiGlpG but only partially reversible for PsAarA. Refolding of both proteins results in reassociation of the dimer, with a 90% regain of catalytic activity for HiGlpG but only a 70% regain for PsAarA. For both proteins, a broad, gradual transition from the native, folded state to the denatured, partly unfolded state was revealed with the aid of circular dichroism spectroscopy as a function of denaturant concentration, thus arguing against a classical two-state model as found for many globular soluble proteins. Thermal denaturation has irreversible destabilizing effects on both proteins, yet reveals important functional details regarding substrate accessibility to the buried active site. This concerted biophysical and functional analysis demonstrates that HiGlpG, with a simple six-transmembrane-segment organization, is more robust than PsAarA, which has seven predicted transmembrane segments, thus rendering HiGlpG amenable to in vitro studies of membrane-protein folding. PMID:27028647

  1. Proteomic-coupled-network analysis of T877A-androgen receptor interactomes can predict clinical prostate cancer outcomes between White (non-Hispanic) and African-American groups.

    PubMed

    Zaman, Naif; Giannopoulos, Paresa N; Chowdhury, Shafinaz; Bonneil, Eric; Thibault, Pierre; Wang, Edwin; Trifiro, Mark; Paliouras, Miltiadis

    2014-01-01

    The androgen receptor (AR) remains an important contributor to the neoplastic evolution of prostate cancer (CaP). CaP progression is linked to several somatic AR mutational changes that endow upon the AR dramatic gain-of-function properties. One of the most common somatic mutations identified is Thr877-to-Ala (T877A), located in the ligand-binding domain, that results in a receptor capable of promiscuous binding and activation by a variety of steroid hormones and ligands including estrogens, progestins, glucocorticoids, and several anti-androgens. In an attempt to further define somatic mutated AR gain-of-function properties, as a consequence of its promiscuous ligand binding, we undertook a proteomic/network analysis approach to characterize the protein interactome of the mutant T877A-AR in LNCaP cells under eight different ligand-specific treatments (dihydrotestosterone, mibolerone, R1881, testosterone, estradiol, progesterone, dexamethasone, and cyproterone acetate). In extending the analysis of our multi-ligand complexes of the mutant T877A-AR we observed significant enrichment of specific complexes between normal and primary prostatic tumors, which were furthermore correlated with known clinical outcomes. Further analysis of certain mutant T877A-AR complexes showed specific population preferences distinguishing primary prostatic disease between white (non-Hispanic) vs. African-American males. Moreover, these cancer-related AR-protein complexes demonstrated predictive survival outcomes specific to CaP, and not for breast, lung, lymphoma or medulloblastoma cancers. Our study, by coupling data generated by our proteomics to network analysis of clinical samples, has helped to define real and novel biological pathways in complicated gain-of-function AR complex systems.

  2. Alkane Biosynthesis Genes in Cyanobacteria and Their Transcriptional Organization

    PubMed Central

    Klähn, Stephan; Baumgartner, Desirée; Pfreundt, Ulrike; Voigt, Karsten; Schön, Verena; Steglich, Claudia; Hess, Wolfgang R.

    2014-01-01

    In cyanobacteria, alkanes are synthesized from a fatty acyl-ACP by two enzymes, acyl–acyl carrier protein reductase and aldehyde deformylating oxygenase. Despite the great interest in the exploitation for biofuel production, nothing is known about the transcriptional organization of their genes or the physiological function of alkane synthesis. The comparison of 115 microarray datasets indicates the relatively constitutive expression of aar and ado genes. The analysis of 181 available genomes showed that in 90% of the genomes both genes are present, likely indicating their physiological relevance. In 61% of them they cluster together with genes encoding acetyl-CoA carboxyl transferase and a short-chain dehydrogenase, strengthening the link to fatty acid metabolism and in 76% of the genomes they are located in tandem, suggesting constraints on the gene arrangement. However, contrary to the expectations for an operon, we found in Synechocystis sp. PCC 6803 specific promoters for the two genes, sll0208 (ado) and sll0209 (aar), which give rise to monocistronic transcripts. Moreover, the upstream located ado gene is driven by a proximal as well as a second, distal, promoter, from which a third transcript, the ~160 nt sRNA SyR9 is transcribed. Thus, the transcriptional organization of the alkane biosynthesis genes in Synechocystis sp. PCC 6803 is of substantial complexity. We verified all three promoters to function independently from each other and show a similar promoter arrangement also in the more distant Nodularia spumigena, Trichodesmium erythraeum, Anabaena sp. PCC 7120, Prochlorococcus MIT9313, and MED4. The presence of separate regulatory elements and the dominance of monocistronic mRNAs suggest the possible autonomous regulation of ado and aar. The complex transcriptional organization of the alkane synthesis gene cluster has possible metabolic implications and should be considered when manipulating the expression of these genes in cyanobacteria. PMID

  3. A large family of anti‐activators accompanying XylS/AraC family regulatory proteins

    PubMed Central

    Yan, Michael B.; Tran, Minh; Wright, Nathan; Luzader, Deborah H.; Kendall, Melissa M.; Ruiz‐Perez, Fernando; Nataro, James P.

    2016-01-01

    Summary AraC Negative Regulators (ANR) suppress virulence genes by directly down‐regulating AraC/XylS members in Gram‐negative bacteria. In this study, we sought to investigate the distribution and molecular mechanisms of regulatory function for ANRs among different bacterial pathogens. We identified more than 200 ANRs distributed in diverse clinically important gram negative pathogens, including Vibrio spp., Salmonella spp., Shigella spp., Yersinia spp., Citrobacter spp., enterotoxigenic (ETEC) and enteroaggregative E. coli (EAEC), and members of the Pasteurellaceae. By employing a bacterial two hybrid system, pull down assays and surface plasmon resonance (SPR) analysis, we demonstrate that Aar (AggR‐activated regulator), a prototype member of the ANR family in EAEC, binds with high affinity to the central linker domain of AraC‐like member AggR. ANR‐AggR binding disrupted AggR dimerization and prevented AggR‐DNA binding. ANR homologs of Vibrio cholerae, Citrobacter rodentium, Salmonella enterica and ETEC were capable of complementing Aar activity by repressing aggR expression in EAEC strain 042. ANR homologs of ETEC and Vibrio cholerae bound to AggR as well as to other members of the AraC family, including Rns and ToxT. The predicted proteins of all ANR members exhibit three highly conserved predicted α‐helices. Site‐directed mutagenesis studies suggest that at least predicted α‐helices 2 and 3 are required for Aar activity. In sum, our data strongly suggest that members of the novel ANR family act by directly binding to their cognate AraC partners. PMID:27038276

  4. Estimation of glacier mass balance: An approach based on satellite-derived transient snowlines and a temperature index driven by meteorological observations

    NASA Astrophysics Data System (ADS)

    Tawde, S. A.; Kulkarni, A. V.; Bala, G.

    2015-12-01

    In the Himalaya, large area is comprised of glaciers and seasonal snow, mainly due to its high elevated mountain ranges. Long term and continuous assessment of glaciers in this region is important for climatological and hydrological applications. However, rugged terrains and severe weather conditions in the Himalaya lead to paucity in field observations. Therefore, in recent decades, glacier dynamics are extensively monitored using remote sensing in inaccessible terrain like Himalaya. Estimation of glacier mass balance using empirical relationship between mass balance and area accumulation ratio (AAR) requires an accurate estimate of equilibrium-line altitude (ELA). ELA is defined as the snowline at the end of the hydrological year. However, identification of ELA, using remote sensing is difficult because of temporal gaps, cloud cover and intermediate snowfall on glaciers. This leads to large uncertainty in glacier mass-balance estimates by the conventional AAR method that uses satellite-derived highest snowline in ablation season as an ELA. The present study suggests a new approach to improve estimates of ELA location. First, positions of modelled snowlines are optimized using satellite-derived snowlines in the early melt season. Secondly, ELA at the end of the glaciological year is estimated by the melt and accumulation models driven using in situ temperature and precipitation records. From the modelled ELA, mass balance is estimated using the empirical relationship between AAR and mass balance. The modelled mass balance is validated using field measurements on Chhota Shigri and Hamtah glaciers, Himachal Pradesh, India. The new approach shows a substantial improvement in glacier mass-balance estimation, reducing bias by 46% and 108% for Chhota Shigiri and Hamtah glaciers respectively. The cumulative mass loss reconstructed from our approach is 0.85 Gt for nine glaciers in the Chandra basin from 2001 to 2009. The result of the present study is in agreement with

  5. Automatic anatomy recognition via fuzzy object models

    NASA Astrophysics Data System (ADS)

    Udupa, Jayaram K.; Odhner, Dewey; Falcão, Alexandre X.; Ciesielski, Krzysztof C.; Miranda, Paulo A. V.; Matsumoto, Monica; Grevera, George J.; Saboury, Babak; Torigian, Drew A.

    2012-02-01

    To make Quantitative Radiology a reality in routine radiological practice, computerized automatic anatomy recognition (AAR) during radiological image reading becomes essential. As part of this larger goal, last year at this conference we presented a fuzzy strategy for building body-wide group-wise anatomic models. In the present paper, we describe the further advances made in fuzzy modeling and the algorithms and results achieved for AAR by using the fuzzy models. The proposed AAR approach consists of three distinct steps: (a) Building fuzzy object models (FOMs) for each population group G. (b) By using the FOMs to recognize the individual objects in any given patient image I under group G. (c) To delineate the recognized objects in I. This paper will focus mostly on (b). FOMs are built hierarchically, the smaller sub-objects forming the offspring of larger parent objects. The hierarchical pose relationships from the parent to offspring are codified in the FOMs. Several approaches are being explored currently, grouped under two strategies, both being hierarchical: (ra1) those using search strategies; (ra2) those strategizing a one-shot approach by which the model pose is directly estimated without searching. Based on 32 patient CT data sets each from the thorax and abdomen and 25 objects modeled, our analysis indicates that objects do not all scale uniformly with patient size. Even the simplest among the (ra2) strategies of recognizing the root object and then placing all other descendants as per the learned parent-to-offspring pose relationship bring the models on an average within about 18 mm of the true locations.

  6. APC mutations as a potential biomarker for sensitivity to tankyrase inhibitors in colorectal cancer.

    PubMed

    Tanaka, Noritaka; Mashima, Tetsuo; Mizutani, Anna; Sato, Ayana; Aoyama, Aki; Gong, Bo; Yoshida, Haruka; Muramatsu, Yukiko; Nakata, Kento; Matsuura, Masaaki; Katayama, Ryohei; Nagayama, Satoshi; Fujita, Naoya; Sugimoto, Yoshikazu; Seimiya, Hiroyuki

    2017-02-08

    In most colorectal cancers (CRCs), Wnt/β-catenin signaling is activated by loss-of-function mutations in the adenomatous polyposis coli (APC) gene and plays a critical role in tumorigenesis. Tankyrases poly(ADP-ribosyl)ate and destabilize Axins, a negative regulator of β-catenin, and upregulate β-catenin signaling. Tankyrase inhibitors downregulate β-catenin and are expected to be promising therapeutics for CRC. However, CRC cells are not always sensitive to tankyrase inhibitors, and predictive biomarkers for the drug sensitivity remain elusive. Here we demonstrate that the short-form APC mutations predict the sensitivity of CRC cells to tankyrase inhibitors. By using well-established CRC cell lines, we found that tankyrase inhibitors downregulated β-catenin in the drug-sensitive but not resistant CRC cells. The drug-sensitive cells showed higher Tcf/LEF transcriptional activity than the resistant cells and possessed 'short' truncated APCs lacking all seven β-catenin-binding 20-amino-acid repeats (20-AARs). By contrast, the drug-resistant cells possessed 'long' APC retaining two or more 20-AARs. Knockdown of the long APCs with two 20-AARs increased β-catenin, Tcf/LEF transcriptional activity and its target gene AXIN2 expression. Under these conditions, tankyrase inhibitors were able to downregulate β-catenin in the resistant cells. These results indicate that the long APCs are hypomorphic mutants whereas they exert a dominant-negative effect on Axin-dependent β-catenin degradation caused by tankyrase inhibitors. Finally, we established 16 patient-derived CRC cells and confirmed that the tankyrase inhibitor-responsive cells harbor the short-form APC mutations. These observations exemplify the predictive importance of APC mutations, the most common genetic alteration in CRCs, for molecular targeted therapeutics.

  7. Comprehensive Profiling of Amino Acid Response Uncovers Unique Methionine-Deprived Response Dependent on Intact Creatine Biosynthesis

    PubMed Central

    Tang, Xiaohu; Keenan, Melissa M.; Wu, Jianli; Lin, Chih-An; Dubois, Laura; Thompson, J. Will; Freedland, Stephen J.; Murphy, Susan K.; Chi, Jen-Tsan

    2015-01-01

    Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized transcriptional amino acid response (AAR). However, it is not clear whether the deprivation of different individual amino acids triggers identical or distinct AARs. Here, we characterized the global transcriptional response upon deprivation of one amino acid at a time. With the exception of glycine, which was not required for the proliferation of MCF7 cells, we found that the deprivation of most amino acids triggered a shared transcriptional response that included the activation of ATF4, p53 and TXNIP. However, there was also significant heterogeneity among different individual AARs. The most dramatic transcriptional response was triggered by methionine deprivation, which activated an extensive and unique response in different cell types. We uncovered that the specific methionine-deprived transcriptional response required creatine biosynthesis. This dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L-methionine (SAM) during creatine biosynthesis that helps to deplete SAM under methionine deprivation and reduces histone methylations. As such, the simultaneous deprivation of methionine and sources of creatine biosynthesis (either arginine or glycine) abolished the reduction of histone methylation and the methionine-specific transcriptional response. Arginine-derived ornithine was also required for the complete induction of the methionine-deprived specific gene response. Collectively, our data identify a previously unknown set of heterogeneous amino acid responses and reveal a distinct methionine-deprived transcriptional response that results from the crosstalk of arginine, glycine and methionine metabolism via arginine

  8. Comprehensive profiling of amino acid response uncovers unique methionine-deprived response dependent on intact creatine biosynthesis.

    PubMed

    Tang, Xiaohu; Keenan, Melissa M; Wu, Jianli; Lin, Chih-An; Dubois, Laura; Thompson, J Will; Freedland, Stephen J; Murphy, Susan K; Chi, Jen-Tsan

    2015-04-01

    Besides being building blocks for protein synthesis, amino acids serve a wide variety of cellular functions, including acting as metabolic intermediates for ATP generation and for redox homeostasis. Upon amino acid deprivation, free uncharged tRNAs trigger GCN2-ATF4 to mediate the well-characterized transcriptional amino acid response (AAR). However, it is not clear whether the deprivation of different individual amino acids triggers identical or distinct AARs. Here, we characterized the global transcriptional response upon deprivation of one amino acid at a time. With the exception of glycine, which was not required for the proliferation of MCF7 cells, we found that the deprivation of most amino acids triggered a shared transcriptional response that included the activation of ATF4, p53 and TXNIP. However, there was also significant heterogeneity among different individual AARs. The most dramatic transcriptional response was triggered by methionine deprivation, which activated an extensive and unique response in different cell types. We uncovered that the specific methionine-deprived transcriptional response required creatine biosynthesis. This dependency on creatine biosynthesis was caused by the consumption of S-Adenosyl-L-methionine (SAM) during creatine biosynthesis that helps to deplete SAM under methionine deprivation and reduces histone methylations. As such, the simultaneous deprivation of methionine and sources of creatine biosynthesis (either arginine or glycine) abolished the reduction of histone methylation and the methionine-specific transcriptional response. Arginine-derived ornithine was also required for the complete induction of the methionine-deprived specific gene response. Collectively, our data identify a previously unknown set of heterogeneous amino acid responses and reveal a distinct methionine-deprived transcriptional response that results from the crosstalk of arginine, glycine and methionine metabolism via arginine

  9. Ash recycling - the coming of age!

    SciTech Connect

    Barnes, J.M.; Roffman, H.K.; Roethel, F.J.

    1997-12-01

    A major concern of the Waste-To-Energy (WTE) industry is ash disposal and the uncertainty of controlled long term ash management. Ash management costs have risen steadily over the last ten years making it the fastest rising cost segment of the WTE industry. The challenge of how to curb the rising cost while maintaining the protection of human health and the environment has been accomplished by responsibly recycling the ash on a commercial basis. American Ash Recycling Corp. (AAR), utilizing the Duos Engineering (USA), Inc. patent pending ash recycling technology, has promoted ash recycling on a commercial basis in the United States. An important product of the processing and recycling of non-hazardous municipal waste combustor (MWC) ash is Treated Ash Aggregate (TAA). Additionally, ferrous and non-ferrous metals are recovered and unburned materials removed and returned to the WTE facility for re-combustion. The TAA is sized and then treated by the WES-PHix{reg_sign} immobilization process in order to reduce the potential solubility and environmental availability of the metal constituents of the MWC ash. The TAA is available for commercial use in such applications as an aggregate substitute in roadway materials, asphalt and concrete applications, as structural fill, and as landfill cover. Commercial and technical considerations that must be addressed before ash can be beneficially recycled are: permitting requirements, physical and chemical characteristics, potential end uses, environmental concerns (product safety), product market development, and economic viability. True recycling only occurs if all of these considerations can be addressed. This paper presents the details of AAR`s most recent experience in the development of an ash recycling facility in the State of Maine and the associated beneficial use of the TAA product. Each of the considerations listed above are discussed with a special focus on the permitting process.

  10. Aminoacyl-tRNA Synthetases, the Genetic Code, and the Evolutionary Process

    PubMed Central

    Woese, Carl R.; Olsen, Gary J.; Ibba, Michael; Söll, Dieter

    2000-01-01

    The aminoacyl-tRNA synthetases (AARSs) and their relationship to the genetic code are examined from the evolutionary perspective. Despite a loose correlation between codon assignments and AARS evolutionary relationships, the code is far too highly structured to have been ordered merely through the evolutionary wanderings of these enzymes. Nevertheless, the AARSs are very informative about the evolutionary process. Examination of the phylogenetic trees for each of the AARSs reveals the following. (i) Their evolutionary relationships mostly conform to established organismal phylogeny: a strong distinction exists between bacterial- and archaeal-type AARSs. (ii) Although the evolutionary profiles of the individual AARSs might be expected to be similar in general respects, they are not. It is argued that these differences in profiles reflect the stages in the evolutionary process when the taxonomic distributions of the individual AARSs became fixed, not the nature of the individual enzymes. (iii) Horizontal transfer of AARS genes between Bacteria and Archaea is asymmetric: transfer of archaeal AARSs to the Bacteria is more prevalent than the reverse, which is seen only for the “gemini group.” (iv) The most far-ranging transfers of AARS genes have tended to occur in the distant evolutionary past, before or during formation of the primary organismal domains. These findings are also used to refine the theory that at the evolutionary stage represented by the root of the universal phylogenetic tree, cells were far more primitive than their modern counterparts and thus exchanged genetic material in far less restricted ways, in effect evolving in a communal sense. PMID:10704480

  11. Treatment with the C5a receptor antagonist ADC-1004 reduces myocardial infarction in a porcine ischemia-reperfusion model

    PubMed Central

    2010-01-01

    Background Polymorphonuclear neutrophils, stimulated by the activated complement factor C5a, have been implicated in cardiac ischemia/reperfusion injury. ADC-1004 is a competitive C5a receptor antagonist that has been shown to inhibit complement related neutrophil activation. ADC-1004 shields the neutrophils from C5a activation before they enter the reperfused area, which could be a mechanistic advantage compared to previous C5a directed reperfusion therapies. We investigated if treatment with ADC-1004, according to a clinically applicable protocol, would reduce infarct size and microvascular obstruction in a large animal myocardial infarct model. Methods In anesthetized pigs (42-53 kg), a percutaneous coronary intervention balloon was inflated in the left anterior descending artery for 40 minutes, followed by 4 hours of reperfusion. Twenty minutes after balloon inflation the pigs were randomized to an intravenous bolus administration of ADC-1004 (175 mg, n = 8) or saline (9 mg/ml, n = 8). Area at risk (AAR) was evaluated by ex vivo SPECT. Infarct size and microvascular obstruction were evaluated by ex vivo MRI. The observers were blinded to the treatment at randomization and analysis. Results ADC-1004 treatment reduced infarct size by 21% (ADC-1004: 58.3 ± 3.4 vs control: 74.1 ± 2.9%AAR, p = 0.007). Microvascular obstruction was similar between the groups (ADC-1004: 2.2 ± 1.2 vs control: 5.3 ± 2.5%AAR, p = 0.23). The mean plasma concentration of ADC-1004 was 83 ± 8 nM at sacrifice. There were no significant differences between the groups with respect to heart rate, mean arterial pressure, cardiac output and blood-gas data. Conclusions ADC-1004 treatment reduces myocardial ischemia-reperfusion injury and represents a novel treatment strategy of myocardial infarct with potential clinical applicability. PMID:20875134

  12. Command Center Training Tool (C2T2)

    NASA Technical Reports Server (NTRS)

    Jones, Phillip; Drucker, Nich; Mathews, Reejo; Stanton, Laura; Merkle, Ed

    2012-01-01

    This abstract presents the training approach taken to create a management-centered, experiential learning solution for the Virginia Port Authority's Port Command Center. The resultant tool, called the Command Center Training Tool (C2T2), follows a holistic approach integrated across the training management cycle and within a single environment. The approach allows a single training manager to progress from training design through execution and AAR. The approach starts with modeling the training organization, identifying the organizational elements and their individual and collective performance requirements, including organizational-specific performance scoring ontologies. Next, the developer specifies conditions, the problems, and constructs that compose exercises and drive experiential learning. These conditions are defined by incidents, which denote a single, multi-media datum, and scenarios, which are stories told by incidents. To these layered, modular components, previously developed meta-data is attached, including associated performance requirements. The components are then stored in a searchable library An event developer can create a training event by searching the library based on metadata and then selecting and loading the resultant modular pieces. This loading process brings into the training event all the previously associated task and teamwork material as well as AAR preparation materials. The approach includes tools within an integrated management environment that places these materials at the fingertips of the event facilitator such that, in real time, the facilitator can track training audience performance and resultantly modify the training event. The approach also supports the concentrated knowledge management requirements for rapid preparation of an extensive AAR. This approach supports the integrated training cycle and allows a management-based perspective and advanced tools, through which a complex, thorough training event can be developed.

  13. A Human Disease-causing Point Mutation in Mitochondrial Threonyl-tRNA Synthetase Induces Both Structural and Functional Defects*

    PubMed Central

    Wang, Yong; Zhou, Xiao-Long; Ruan, Zhi-Rong; Liu, Ru-Juan; Eriani, Gilbert; Wang, En-Duo

    2016-01-01

    Mitochondria require all translational components, including aminoacyl-tRNA synthetases (aaRSs), to complete organelle protein synthesis. Some aaRS mutations cause mitochondrial disorders, including human mitochondrial threonyl-tRNA synthetase (hmtThrRS) (encoded by TARS2), the P282L mutation of which causes mitochondrial encephalomyopathies. However, its catalytic and structural consequences remain unclear. Herein, we cloned TARS2 and purified the wild-type and P282L mutant hmtThrRS. hmtThrRS misactivates non-cognate Ser and uses post-transfer editing to clear erroneously synthesized products. In vitro and in vivo analyses revealed that the mutation induces a decrease in Thr activation, aminoacylation, and proofreading activities and a change in the protein structure and/or stability, which might cause reduced catalytic efficiency. We also identified a splicing variant of TARS2 mRNA lacking exons 8 and 9, the protein product of which is targeted into mitochondria. In HEK293T cells, the variant does not dimerize and cannot complement the ThrRS knock-out strain in yeast, suggesting that the truncated protein is inactive and might have a non-canonical function, as observed for other aaRS fragments. The present study describes the aminoacylation and editing properties of hmtThrRS, clarifies the molecular consequences of the P282L mutation, and shows that the yeast ThrRS-deletion model is suitable to test pathology-associated point mutations or alternative splicing variants of mammalian aaRS mRNAs. PMID:26811336

  14. New Insights into Mechanisms and Functions of Chemokine (C-X-C Motif) Receptor 4 Heteromerization in Vascular Smooth Muscle

    PubMed Central

    Evans, Ann E.; Tripathi, Abhishek; LaPorte, Heather M.; Brueggemann, Lioubov I.; Singh, Abhay Kumar; Albee, Lauren J.; Byron, Kenneth L.; Tarasova, Nadya I.; Volkman, Brian F.; Cho, Thomas Yoonsang; Gaponenko, Vadim; Majetschak, Matthias

    2016-01-01

    Recent evidence suggests that C-X-C chemokine receptor type 4 (CXCR4) heteromerizes with α1A/B-adrenoceptors (AR) and atypical chemokine receptor 3 (ACKR3) and that CXCR4:α1A/B-AR heteromers are important for α1-AR function in vascular smooth muscle cells (VSMC). Structural determinants for CXCR4 heteromerization and functional consequences of CXCR4:α1A/B-AR heteromerization in intact arteries, however, remain unknown. Utilizing proximity ligation assays (PLA) to visualize receptor interactions in VSMC, we show that peptide analogs of transmembrane-domain (TM) 2 and TM4 of CXCR4 selectively reduce PLA signals for CXCR4:α1A-AR and CXCR4:ACKR3 interactions, respectively. While both peptides inhibit CXCL12-induced chemotaxis, only the TM2 peptide inhibits phenylephrine-induced Ca2+-fluxes, contraction of VSMC and reduces efficacy of phenylephrine to constrict isolated arteries. In a Cre-loxP mouse model to delete CXCR4 in VSMC, we observed 60% knockdown of CXCR4. PLA signals for CXCR4:α1A/B-AR and CXCR4:ACKR3 interactions in VSMC, however, remained constant. Our observations point towards TM2/4 of CXCR4 as possible contact sites for heteromerization and suggest that TM-derived peptide analogs permit selective targeting of CXCR4 heteromers. A molecular dynamics simulation of a receptor complex in which the CXCR4 homodimer interacts with α1A-AR via TM2 and with ACKR3 via TM4 is presented. Our findings further imply that CXCR4:α1A-AR heteromers are important for intrinsic α1-AR function in intact arteries and provide initial and unexpected insights into the regulation of CXCR4 heteromerization in VSMC. PMID:27331810

  15. Amelie: A Recombinant Computing Framework for Ambient Awareness

    NASA Astrophysics Data System (ADS)

    Metaxas, Georgios; Markopoulos, Panos; Aarts, Emile

    This paper presents Amelie, a service oriented framework that supports the implementation of awareness systems. Amelie adopts the tenets of Recombinant computing to address an important non-functional requirement for Ambient Intelligence software, namely the heterogeneous combination of services and components. Amelie is founded upon FN-AAR an abstract model of Awareness Systems which enables the immediate expression and implementation of socially salient requirements, such as symmetry and social translucence. We discuss the framework and show how system behaviours can be specified using the Awareness Mark-up Language AML.

  16. A luminol chemiluminescence method for sensing histidine and lysine using enzyme reactions.

    PubMed

    Kugimiya, Akimitsu; Fukada, Rie; Funamoto, Daiki

    2013-12-01

    The analysis of free amino acids in urine and plasma is useful for estimating disease status in clinical diagnoses. Changes in the concentration of free amino acids in foods are also useful markers of freshness, nutrition, and taste. In this study, the specific interaction between aminoacyl-tRNA synthetase (aaRS) and its corresponding amino acid was used to measure amino acid concentrations. Pyrophosphate released by the amino acid-aaRS binding reaction was detected by luminol chemiluminescence; the method provided selective quantitation of 1.0-30 μM histidine and 1.0-60 μM lysine.

  17. Exercise Black Skies 2008: Enhancing Live Training Through Virtual Preparation -- Part Two: An Evaluation of Tools and Techniques

    DTIC Science & Technology

    2009-06-01

    software testing, an improvised ‘air warfare game ’ was conducted in place of the AAR session on Day 2. This game required each ABM to pair with a SIMOP...and control two fighter pairs. The aim of the game was to be the first formation to fly through the centre of an arbitrary hexagonal airspace and...the latest simulation tools. The software proved to be stable throughout the game and the remaining vignettes. 2.1.5 Procedure DSTO human

  18. Overdeepened glacigenic landforms in Lake Thun (Switzerland) revealed by a multichannel reflection seismic survey

    NASA Astrophysics Data System (ADS)

    Fabbri, Stefano; Herwegh, Marco; Schlunegger, Fritz; Hübscher, Christian; Weiss, Benedikt J.; Schmelzbach, Cédric; Horstmeyer, Heinrich; Buechi, Marius W.; Anselmetti, Flavio S.

    2016-04-01

    Recently acquired high-resolution multibeam bathymetry, in combination with a 2D multichannel reflection seismic campaign on perialpine Lake Thun (Switzerland) reveals new insights into the diverse geometry of the lake basin and a so far unknown subaquatic moraine crest with unprecedented clarity. These new data will improve our comprehension concerning the retreat phases of the Aare glacier, the morphology of its proximal deposits and the facies architecture of the subglacial units. The overdeepened basin of Lake Thun was formed by a combination of tectonically predefined weak zones and glacial erosion during the last glacial periods. The new data indicate that below the outermost edge of a morphologically distinct platform in the south eastern part of the lake basin, a ridge structure marked by strong reflection amplitudes occurs. This structure is interpreted as a subaquatic terminal moraine crest, most likely created by a slightly advancing or stagnant grounded Aare glacier during its major retreating phase. The terminal moraine smoothly transforms downstream into well distinguishable foresets with internally recognisable layering, which dip steeply towards the deepest part of the basin, eventually transforming into bottomsets. This depositional sequence formed by the fore- and bottomsets represents ˜50% of the overall sediment volume that fills the basin and was deposited while the glacier was stagnant, interpreted to represent a rather short period of time of a few hundreds of years. This sequence is overlain by lacustrine deposits formed by late-glacial and Holocene laminated muds comprising intercalated turbidites (Wirth et al. 2011). Little is known about the exact timing and behaviour of retreating glaciers between their recessional phase from the Alpine foreland to the deglaciation of the inner-Alpine ice cap, mostly due to the lack of well-developed moraines that indicate glacial stabilization or slight readvance. Findings from pollen analyses by

  19. Forward Air Controller: Task Analysis and Development of Team Training Measures for Close Air Support

    DTIC Science & Technology

    2007-12-01

    d’AAR, ainsi que de déterminer les mesures adéquates pour évaluer le rendement de l’équipe. À cette fin, on a effectué une analyse hiérarchique des...certain nombre de recommandations visant à améliorer l’instrument avant son application aux exercices futurs de simulation répartie. Les...assessing the team’s performance as a whole. To that end, the contractor constructed hierarchical task analyses for the principal members of this team, the

  20. An Irreversible Thermodynamics Model for Graphite Sublimation in Intense Radiation Environments.

    DTIC Science & Technology

    1980-09-15

    27 8. Relationship of T w to 4rad at Several Pressures, Irreversible Thermodynamics Model ... ............. .... 29 TABLES 1. Q ...rela- tionships [see Eqs. (lla,b)]. -11- -~~RGO -11 --- ___RGO I RESERVOIRR I1 Fig 1 Rprsetaio o Pas C ang Trb[em as a T Dicniu Syte REGONII REIO& where...AT AAR (17a) q qqI qv T ~AT Jv A - (17b) 17 1Schrage, R. W., A Theoretical Study of Interphase Mass Transfer, Columbia University Press, New York

  1. Elmendorf AFB, Anchorage, Alaska. Revised Uniform Summary of Surface Weather Observations (RUSSWO). Parts A-F

    DTIC Science & Technology

    1979-09-17

    These is no objection to unlimited distribution of this report to the public at large, or by DDC to the National Technical V Information Service (NTIS...11 93 . ?. o’~ *r7~ L DATA PROCESSING BRANCH 2 USAF TAC PSYCHROMETRIC SUMMARY!, AIR WEATER SERVICE /MAC 6401 ELt4ENDORF AFB ALASKA/ANCHORAGE M- AAR...Air Weather Service ( MAC ) E-EM0RF AFB ALASKA/AllCHORAGE WI3AI Y 26401 N 61 15 W149 48 ELD ELEV 212 FT EDF V81O # 70272 POR: FROM- BOUBLY 035 JUN, 66

  2. Heat Stress Illness in a Mechanized Infantry Brigade During Simulated Combat at Fort Irwin

    DTIC Science & Technology

    1994-05-01

    exercise. There were fixed latrine, shower, and laundry facilities in the main post bivouac area (appropriately referred to as the " Dust Bowl " because of the...u•t Sick call Heat illness B &g Db W Cag Level 3 43 7 74 139 114 91 5 1 Dust bowl bivouac 4 58 10 69 108 94 79.3 1 1 5 52 2 69 132 98 84.5 2 1 6 54 4...82.1 2 Movement to contact 22 - - - Brigade force on force 23 - - - End of exercise move back to Dust Bowl *AAR: After Action Report ATLS Tent

  3. Reduction of Residual Stresses and Distortion in Girth Welded Pipes.

    DTIC Science & Technology

    1987-06-01

    M7 26 REP-WTION-OF-RESIDUA-L -STRESSES N D 113 II i m IA WELDED PIPES (U) MASSACHUSETTS INST OF TECH CURIDol DEPT OF WOOE ENGINERING P K DAMS JUN 67... WELDED PIPES bv PANIEL KAY BARNES Ocean Engineering - Course XIIIA NAVAL ENG. & SM(M!E) -- 7fSTUl-O,,CON STT"ne 1987 Aar P b’-i ’w REDUCTION OF RESIDUAL...STRESSES AND DISTORTION IN GIRTH WELDED PIPES by PAMELA KAY BARNES B.S., South Dakota School of Mines and Technology (1977) Submitted to the Department

  4. Overview of overseas humanitarian, disaster, and civic aid programs.

    PubMed

    Drifmeyer, Jeff; Llewellyn, Craig

    2003-12-01

    The U.S. Department of Defense (DoD) conducts humanitarian assistance missions under the Overseas Humanitarian Disaster and Civic Aid program for the statutory purposes of training military personnel, serving the political interests of the host nation and United States, and providing humanitarian relief to foreign civilians. These purposes are undertaken via the humanitarian assistance (HA), humanitarian and civic assistance, and excess property donation programs. DoD conducts over 200 such projects annually at a direct cost of approximately 27 million dollars in fiscal year 2001. Although varying by year and command, as many as one-half of these projects involve aspects of health care. These range from short-term patient care to donation of medical supplies and equipment excess to the needs of the DoD. Despite the considerable resources invested and importance of international actions, there is presently no formal evaluation system for these HA projects. Current administrative staffing of these programs by military personnel is often by individuals with many other duties and responsibilities. As a result, humanitarian projects are often inadequately coordinated with nongovernmental organizations, private volunteer organizations, or host-nation officials. Nonmedical military personnel sometimes plan health-related projects with little or no coordination with medical experts, military or civilian. After action reports (AARs) on these humanitarian projects are often subjective, lack quantitative details, and are devoid of measures of effectiveness. AARs are sometimes inconsistently completed, and there is no central repository of information for analysis of lessons learned. (The approximate 100 AARs used in the conduct of these studies are available for official use in the Learning Resources Center, Uniformed Services University of Health Sciences.) Feedback from past humanitarian projects is rare and with few exceptions; DoD-centric projects of a similar design are

  5. Mechanics in Material Space

    DTIC Science & Technology

    1992-12-01

    Applied Mechanics Division 0 TEN E L Mechanical Engineering Departet AAR 11 S3 O;76a Stanford, CA 94305-4040 oR I�’ (2DJ6409) L 9. SPONSOR I0:NG...Division of Applied Mechanics Department of Mechanical Engineering Stanford University Stanford CA 94305-4040 3oession F’or OTIS.’ GWAI DTIC TAB 0 Unanno...numerical anaiysis of the sysstem , as well as in providing irnsights into the behavior of the fluid, both mathematically and physically. Restolt obtained

  6. The Lucky Seventh in the Bulge: A Case Study for the Airland Battle

    DTIC Science & Technology

    1985-05-15

    Why then did VIII Corps not advise Jones of the truth? 9 7th AD Combat Interview3, Major Fred Sweat, S-3 CCR, 28 December 1944. * l0 lt is difficult...1SG Hoyle H. Ladd. Ladd brought out thirty-five soldiers of the original six 81 % officers and 136 enlisted men. See, AARs of 23rd AIB, 38th AIB, 87th...Vith) was probably in the worst shaoe. First Sergeant Hoyle Ladd, senior surviving man in the troop brought out only thirty-- .five soldiers when the

  7. Doing Business with the Naval Air Systems Command

    DTIC Science & Technology

    2014-08-13

    PRECISION APPROACH & LANDING SYSTEM (JPALS) • E -2D ADVANCED HAWKEYE (AHE) • EA-6B ICAP-III • EA-18G AIRBORNE ELECTRONIC ATTACK • F/A-18E/F...ARRESTING GEAR • ALR-67(V)3 ADVANCED SPECIAL RECEIVER (ASR) • E -6B MERCURY BLOCK 1 MOD • F/A-18 IRST ACAT III • EA-6B ALQ-99 LOW BAND...CONTROL AND COMMUNICATIONS E -6B MERCURY PMA272 ADVANCED TACTICAL AIRCRAFT PROTECTION SYSTEMS ALR67(V)2 ADV SPECIAL RECEIVER AAR-47

  8. Operation Strong Wind (Fort Lee’s Response to a Local Tornado Disaster, 6 August 1993)

    DTIC Science & Technology

    1993-11-01

    A. Maps of area and mall B. AAR of HQ 49th QM Group(Petroleum) by MAJ Victoria Spinelli C. 49th Gp, EOC Log D. Fort Lee’s Duty Officer’s Log E. Kenner...for cellular phone services. Reaction and Organization On Fort Lee, MAJ Victoria Spinelli , acting commander of the 49th Quartermaster Group (Petroleum...the tornado had touched down. After the phone conversation with COL Ferguson, MAJ Spinelli drove to his office in Mifflin Hall about 1355, and met with

  9. Sex-specific modulation of spinal nociception by alpha2-adrenoceptors: differential regulation by estrogen and testosterone.

    PubMed

    Thompson, A D; Angelotti, T; Nag, S; Mokha, S S

    2008-06-02

    Sex-related differences in antinociception produced by the activation of alpha(2)-adrenoceptors (alpha(2)-ARs) have been reported, however, the precise role of gonadal steroids is still unknown. Hence, we hypothesized that estrogen and testosterone modulate antinociceptive effects of clonidine (an alpha(2)-AR agonist) on N-methyl-D-aspartate- (NMDA) and heat-induced spinal nociception. We also investigated whether estrogen or testosterone alters the expression of alpha(2A)-adrenoceptors in the spinal cord. Sprague-Dawley (SD) rats were implanted with PE10 cannulae in the intrathecal space of the lumbosacral spinal cord and divided into male, proestrous and diestrous female, ovariectomized (OVX), estradiol-treated OVX (OVX+E), castrated male (GDX), testosterone (GDX+T) and estradiol-treated castrated male (GDX+E) groups. Clonidine dose-dependently inhibited NMDA-induced scratching behavior in the male and OVX groups but to a significantly lesser extent in the OVX+E group. It also increased the tail withdrawal latency in the male, OVX, diestrous and GDX+T groups but not in the OVX+E, proestrous, GDX and GDX+E groups. Levels of alpha(2A)-AR mRNA were significantly higher in the OVX, estradiol-treated OVX, GDX and GDX+E animals. In contrast, alpha(2A)-AR protein levels were higher in estradiol-treated OVX, GDX, GDX+T and GDX+E animals as compared with the male. Indeed, no correlations were observed between changes in the mRNA or protein levels of alpha(2A)-AR and behavioral observations. These results support our hypothesis that sex-related differences in alpha(2)-AR-mediated modulation of spinal nociception are gonadal hormone-dependent: estrogen attenuates antinociceptive effects in females whereas testosterone is required for the expression of antinociception in males. In addition, results also revealed that the mechanism of action of gonadal hormones may not involve a global alternation in expression of alpha(2A)-AR in the spinal cord. Estrogen-induced attenuation

  10. Physics-Based Constitutive Model to Predict Dynamic Recovery Behavior of BFe10-1-2 Cupronickel Alloy during Hot Working

    NASA Astrophysics Data System (ADS)

    Cai, Jun; Zhang, Xiaolu; Wang, Kuaishe; Miao, Chengpeng

    2016-11-01

    The hot deformation behavior of BFe10-1-2 cupronickel alloy was investigated over wide ranges of deformation temperature and strain rate. The physics-based constitutive model was developed to predict the dynamic recovery (DRV) behavior of BFe10-1-2 cupronickel alloy at elevated temperatures. In order to verify the validity of the developed constitutive equation, the correlation coefficient (R) and average absolute relative error (AARE) were introduced to make statistics. The results indicated that the developed constitutive equation lead a good agreement between the calculated and experimental data and can accurately characterize the hot DRV behaviors for the BFe10-1-2 cupronickel alloy.

  11. Role of Adenosine Receptor A2A in Traumatic Optic Neuropathies (Addendum)

    DTIC Science & Technology

    2016-03-01

    diabetic retinopathy. Life Sci. 2013 Jul 30;93(2-3):78-88. doi: 10.1016/j.lfs.2013.05.024. Epub 2013 Jun 12.PMID:23770229 7 AIMS: This study was...undertaken to determine the effect of an adenosine kinase inhibitor (AKI) in diabetic retinopathy (DR). We have shown previously that adenosine signaling...via A2A receptors (A2AAR) is involved in retinal protection from diabetes -induced inflammation. Here we demonstrate that AKI-enhanced adenosine

  12. Testing of the Strutjet RBCC Engine

    NASA Technical Reports Server (NTRS)

    Bulman, Mel; Neill, Todd; Yam, Clement

    1999-01-01

    The testing of the Strutjet Rocket-Based Combined Cycle (RBCC) engine is described in this presentation. Since 1996 Aerojet has conducted thousands of tests on its Strutjet RBCC Engine. The Strutjet is specifically designed as an RBCC engine. The tests included: (1) Inlet, (2) Rocket Checkouts, (3) Direct Connect Mach 6 and 8, and (4) Freejet M = 0, 2.4, 4.1. The modes tested include: (1) Air Augmented Rocket (AAR), (2) Ramjet (3) Scramjet (4) Scram/Rocket (5) Ascent/Rocket. The Strutjet RBCC engine has been tested across the complete airbreathing trajectory. The presentation shows the results of the tests, through diagrams, charts and pictures.

  13. Spatial and temporal modelling of fluvial aggradation in the Hasli Valley (Swiss Alps) during the last 1300 years

    NASA Astrophysics Data System (ADS)

    Llorca, Jaime; Schulte, Lothar; Carvalho, Filipe

    2016-04-01

    The Haslital delta (upper Aare River catchment, Bernese Alps) progradated into the Lake Brienz after the retreat of the Aare Glacier (post-LGM). Present delta plain geomorphology and spatial distribution of sedimentary facies result from historical fluvial dynamics and aggradation. Over centuries, local communities have struggled to control the Aare floods and to mitigate their effects on the floodplain (by means of raising artificial levees, channelizing the course, creating an underground drainage network, constructing dams at the basin headwaters). This study focuses on the spatial and temporal evolution of sediment dynamics of the floodplain by analyzing fluvial sedimentary records . The internal variability of lithostratigraphic sequences is a key issue to understand hydrological processes in the basin under the effect of environmental and anthropogenic changes of the past. The floodplain lithostratigraphy was reconstructed by coring alongside four cross-sections; each one is composed of more than 25 shallow boreholes (2 m deep) and two long drillings (variable depth, up to 9 m). The chronostratigraphical models were obtained by AMS 14C dating, and information of paleofloods and channel migration were reconstructed from historical sources (Schulte et al., 2015). The identification of different sedimentary facies, associated with the fluvial architecture structures, provides information on variations of vertical and lateral accretion processes (Houben, 2007). The location and geometry of buried channel-levee facies (gravel and coarse sand layers) indicate a significant mobility of the riverbed of the Hasli-Aare river, following an oscillatory pattern during the last millennia. Furthermore, fine sedimentary deposits and peat layers represent the existence of stable areas where floods have a low incidence. Once the different types of deposits were identified, aggradation rates were estimated in order to determine the spatial variability of the accumulation

  14. Equilibrium Line Altitude fluctuations at HualcaHualca volcano (southern Peru).

    NASA Astrophysics Data System (ADS)

    Alcalá, Jesus; Palacios, David; Juan Zamorano, Jose

    2015-04-01

    Interest in Andean glaciers has substantially increased during the last decades, due to its high sensitivity to climate fluctuations. In this sense, Equilibrium Line Altitude (ELA) is a reliable indicator of climate variability that has been frequently used to reconstruct palaeoenvironmental conditions at different temporal and spatial scales. However, the number of sites with ELA reconstructions is still insufficient to determine patterns in tropical climate or estimations of atmospheric cooling since the Last Glacial Maximum. The main purpose of this study is to contribute in resolving tropical climate evolution through ELA calculations on HualcaHualca (15° 43' S; 71° 52' W; 6,025 masl), a large andesitic stratovolcano located in the south-western Peruvian Andes approximately 70 km north-west of Arequipa. We applied Terminus Headwall Altitude Ratio (THAR) with 0.2; 0.4; 0.5; 0.57 ratios, Accumulation Area Ratio (AAR) and Accumulation Area Balance Ratio (AABR) methods in four valleys of HualcaHualca volcano: Huayuray (north side), Pujro Huayjo (southwest side), Mollebaya (east side) and Mucurca (west side). To estimate ELA depression, we calculated the difference between the ELA on 1955 with its position in the Maximum Glacier Extent (MGE), Tardiglacial phases, little Ice Age (LIA) and 2000. Paleotemperature reconstructions derived from vertical temperature gradient 6.5° C / 1 km, based on GODDARD global observation system considered the most appropriate model for arid Andes. During MGE, the ELA was located between 5,005 (AABR) and 5,215 (AAR 0.67) masl. But in 1955, ELA rose to 5,685 (AABR) - 5,775 (AAR 0.67) masl. The ELA depression between those two phases is 560 - 680 m that implies a temperature decrease of 3.5° - 4.4° C. The experimental process based in the use and contrast of different ELA reconstruction techniques applied in this study suggests that THAR (0.57), AAR (0.67) or AABR are the most consistent procedures for HualcaHualca glaciers, while

  15. Advanced Aircrew Display Symposium Proceedings (5th) Held at the Naval Air Test Center, Patuxent, Maryland on 15-16 September 1981

    DTIC Science & Technology

    1981-01-01

    2 M s test and Avgr ley$, sle t ts vu ~ ~ ~ ~ n go Warfn u~lr 1.2 Power ’on, 31 79J~f~7 Vig 1 ADANED OCPI 4 32 \\ \\4 hm 33 7$ • i!i*𔃻 -, Jr• Si -- i...8217 trillT9M 13 ANA kAtAM AVA THE NAVALAIR Ir TWA., PATUXeNt. MVIERI’A-AR LAND t 4; U COMPONENT PART NOTICE THiS PAPER IS A COMPONENT PART OF THE FOLLOWING...Aircraft - MR. R. CHORLEY ..................... 198 Helmet Mounted Display for Helicopter Landing on Small Ships’- DR. T . DUKES

  16. Fluxes, Dynamics, and Chemistry of Particulates in the Ocean

    DTIC Science & Technology

    1978-08-01

    nepheloid layer and how long might particles be expected to be in the layer? Before this. work ..could,be .-carried.*«ufe*4A *w»a n«o«»aar>y to study the...Ryther, 1963). Likewise, there have been numerous studies of the rates of accumulation of these components from deep sea cores. The present work ...8217-.-*J.y-1-,--■.-....■ —r-w~ -317- PREVIOUS WORK ON CALIBRATION OF TRAPPING EFFICIENCY Still Water For quantitative studies to be made with sediment

  17. Proteomic analysis of human norepinephrine transporter complexes reveals associations with protein phosphatase 2A anchoring subunit and 14-3-3 proteins

    SciTech Connect

    Sung, Uhna; Jennings, Jennifer L.; Link, Andrew J.; Blakely, Randy D.; E-mail: andy.blakely@vanderbilt.edu

    2005-08-05

    The norepinephrine transporter (NET) terminates noradrenergic signals by clearing released NE at synapses. NET regulation by receptors and intracellular signaling pathways is supported by a growing list of associated proteins including syntaxin1A, protein phosphatase 2A (PP2A) catalytic subunit (PP2A-C), PICK1, and Hic-5. In the present study, we sought evidence for additional partnerships by mass spectrometry-based analysis of proteins co-immunoprecipitated with human NET (hNET) stably expressed in a mouse noradrenergic neuroblastoma cell line. Our initial proteomic analyses reveal multiple peptides derived from hNET, peptides arising from the mouse PP2A anchoring subunit (PP2A-Ar) and peptides derived from 14-3-3 proteins. We verified physical association of NET with PP2A-Ar via co-immunoprecipitation studies using mouse vas deferens extracts and with 14-3-3 via a fusion pull-down approach, implicating specifically the hNET NH{sub 2}-terminus for interactions. The transporter complexes described likely support mechanisms regulating transporter activity, localization, and trafficking.

  18. Alteration of Multiple Leukocyte Gene Expression Networks is Linked with Magnetic Resonance Markers of Prognosis After Acute ST-Elevation Myocardial Infarction

    PubMed Central

    Teren, A.; Kirsten, H.; Beutner, F.; Scholz, M.; Holdt, L. M.; Teupser, D.; Gutberlet, M.; Thiery, J.; Schuler, G.; Eitel, I.

    2017-01-01

    Prognostic relevant pathways of leukocyte involvement in human myocardial ischemic-reperfusion injury are largely unknown. We enrolled 136 patients with ST-elevation myocardial infarction (STEMI) after primary angioplasty within 12 h after onset of symptoms. Following reperfusion, whole blood was collected within a median time interval of 20 h (interquartile range: 15–25 h) for genome-wide gene expression analysis. Subsequent CMR scans were performed using a standard protocol to determine infarct size (IS), area at risk (AAR), myocardial salvage index (MSI) and the extent of late microvascular obstruction (lateMO). We found 398 genes associated with lateMO and two genes with IS. Neither AAR, nor MSI showed significant correlations with gene expression. Genes correlating with lateMO were strongly related to several canonical pathways, including positive regulation of T-cell activation (p = 3.44 × 10−5), and regulation of inflammatory response (p = 1.86 × 10−3). Network analysis of multiple gene expression alterations associated with larger lateMO identified the following functional consequences: facilitated utilisation and decreased concentration of free fatty acid, repressed cell differentiation, enhanced phagocyte movement, increased cell death, vascular disease and compensatory vasculogenesis. In conclusion, the extent of lateMO after acute, reperfused STEMI correlated with altered activation of multiple genes related to fatty acid utilisation, lymphocyte differentiation, phagocyte mobilisation, cell survival, and vascular dysfunction. PMID:28155873

  19. Anabolic and androgenic activities of 19-nor-testosterone steroids: QSAR study using quantum and physicochemical molecular descriptors.

    PubMed

    Alvarez-Ginarte, Yoanna María; Montero-Cabrera, Luis Alberto; de la Vega, José Manuel García; Noheda-Marín, Pedro; Marrero-Ponce, Yovani; Ruíz-García, José Alberto

    2011-08-01

    Quantitative structure-activity relationship (QSAR) study of 19-nor-testosterone steroids family was performed using quantum and physicochemical molecular descriptors. The quantum-chemical descriptors were calculated using semiempirical calculations. The descriptor values were statistically correlated using multi-linear regression analysis. The QSAR study indicated that the electronic properties of these derivatives have significant relationship with observed biological activities. The found QSAR equations explain that the energy difference between the LUMO and HOMO, the total dipole moment, the chemical potential and the value of the net charge of different carbon atoms in the steroid nucleus showed key interaction of these steroids with their anabolic-androgenic receptor binding site. The calculated values predict that the 17α-cyclopropyl-17β, 3β-hydroxy-4-estrene compound presents the highest anabolic-androgenic ratio (AAR) and the 7α-methyl-17β-acetoxy-estr-4-en-3-one compound the lowest AAR. This study might be helpful in the future successful identification of "real" or "virtual" anabolic-androgenic steroids.

  20. Hot compression deformation behavior and a modified physically-based constitutive model of Cu-6 %Ag alloy

    NASA Astrophysics Data System (ADS)

    Meng, Lie; Wang, Menghan; Liu, Xiao; Wang, Fenglin

    2016-04-01

    In order to reveal the flow characteristics of Cu-6 %Ag alloy on the condition of hot deformation, the isothermal compression experiments are carried out at the temperatures of 973-1123 K under strain rates of 0.01-10 s-1. The effects of deformation condition on the hot compression deformation behavior are investigated. The low instability strain (ɛ i) behavior at high strain rate (10 s-1) is discussed in this paper. According to the experiment results and analyses, the deformation twinning and inhomogeneous grains are thought to be the possible reasons for low strain cracking. Then, a modified physically based constitutive model is established. The strain for maximum softening rate (\\varepsilon_{ *} ) is quoted in the constitutive equation which is proved that there is a nearly linear relationship between { ln }\\varepsilon_{ *} and { ln }Z . What's more, the correlation coefficient (R) and the average absolute relative error (AARE) are used to evaluate the accuracy of the established constitutive model. The values of R and AARE are 0.99612 and 3.47 %, respectively, which show that the modified constitutive model can exactly reveal the flow stress of Cu-6 %Ag alloy.

  1. Ultraviolet a induces endoplasmic reticulum stress response in human dermal fibroblasts.

    PubMed

    Komori, Ryota; Taniguchi, Mai; Ichikawa, Yoshiaki; Uemura, Aya; Oku, Masaya; Wakabayashi, Sadao; Higuchi, Kazuhiko; Yoshida, Hiderou

    2012-01-01

    The endoplasmic reticulum (ER) stress response is a cytoprotective mechanism against the accumulation of unfolded proteins in the ER (ER stress) that consists of three response pathways (the ATF6, IRE1 and PERK pathways) in mammals. These pathways regulate the transcription of ER-related genes through specific cis-acting elements, ERSE, UPRE and AARE, respectively. Because the mammalian ER stress response is markedly activated in professional secretory cells, its main function was thought to be to upregulate the capacity of protein folding in the ER in accordance with the increased synthesis of secretory proteins. Here, we found that ultraviolet A (UVA) irradiation induced the conversion of an ER-localized sensor pATF6α(P) to an active transcription factor pATF6α(N) in normal human dermal fibroblasts (NHDFs). UVA also induced IRE1-mediated splicing of XBP1 mRNA as well as PERK-mediated phosphorylation of an α subunit of eukaryotic initiation factor 2. Consistent with these observations, we found that UVA increased transcription from ERSE, UPRE and AARE elements. From these results, we concluded that UVA irradiation activates all branches of the mammalian ER stress response in NHDFs. This suggests that the mammalian ER stress response is activated by not only intrinsic stress but also environmental stress.

  2. Providencia stuartii genes activated by cell-to-cell signaling and identification of a gene required for production or activity of an extracellular factor.

    PubMed

    Rather, P N; Ding, X; Baca-DeLancey, R R; Siddiqui, S

    1999-12-01

    By utilizing reporter transposons, five Providencia stuartii genes that are activated by the accumulation of self-produced extracellular signals have been identified. These genes have been designated cma for conditioned medium activated. The presence of conditioned medium from stationary-phase cultures grown in rich media resulted in the premature activation of each gene in cells at early log phase, with activation values ranging from 6- to 26-fold. Preparation of conditioned medium from an M9 salts medium and fractionation by gel filtration chromatography resulted in fractions within the included volume which activated three of the cma fusions. In addition, depending on the reporter fusion, peak activity was found in different fractions. The partially purified factors activated in a dose-dependent manner. Characterization of the factors activating the cma fusions indicated that they were stable to heat, alkali, and acid. Furthermore, for each cma fusion, factor activity was not reproduced by the addition of homoserine lactone, homocysteine thiolactone, pyruvate, Casamino Acids, or alpha-ketoglutarate. The identities of three cma genes have been determined and revealed physiological roles in amino acid biosynthesis and nutrient import. To begin to address the pathways for production of or response to the extracellular factors, we have identified a locus, aarA, that is required for the activation of four cma fusions. The AarA product was required for factor activity in extracellular supernatants, indicating a possible role in biosynthesis or export.

  3. Validation of Arabic and English versions of the ARSMA-II Acculturation Rating Scale.

    PubMed

    Jadalla, Ahlam; Lee, Jerry

    2015-02-01

    To translate and adapt the Acculturation Rating Scale of Mexican-Americans II (ARSMA-II) for Arab Americans. A multistage translation process followed by a pilot and a large study. The translated and adapted versions, Acculturation Rating Scale for Arabic Americans-II Arabic and English (ARSAA-IIA, ARSAA-IIE), were validated in a sample of 297 Arab Americans. Factor analyses with principal axis factoring extractions and direct oblimin rotations were used to identify the underlying structure of ARSAA-II. Factor analysis confirmed the underlying structure of ARSAA-II and produced two interpretable factors labeled as 'Attraction to American Culture' (AAmC) and 'Attraction to Arabic Culture' (AArC). The Cronbach's alphas of AAmC and AArC were .89 and .85 respectively. Findings support ARSAA-II A & E to assess acculturation among Arab Americans. The emergent factors of ARSAA-II support the theoretical structure of the original ARSMA-II tool and show high internal consistency.

  4. [Looking back but facing ahead: implementing lessons learned from the 2nd Lebanon War].

    PubMed

    Adini, Bruria; Laor, Danny; Lev, Boaz; Israeli, Avi

    2010-07-01

    The medical system utilizes a structured culture for learning lessons in order to improve the supply of services. Various tools are utilized to evaluate performance. The aim of the article is to describe the processes for learning lessons which were carried out following the Second Lebanon War and the major lessons that were identified and implemented. Three processes were performed: a process of learning Lessons of the heaLthcare system, initiated and led by the Supreme HeaLth Authority (SHA); After action review (AAR), initiated and led by the military Medical Corps and; at a later stage, a critique, initiated and led by the State Comptroller, that examined the performance of the medical system, as part of a critique on the preparedness of the home front. The following elements were defined as highly prioritized for improvement to elevate the preparedness for a future war: (1) deployment of unified clinics in conflict areas; (2) supply of medical services to the population in shelters; (3) deploying emergency medicine services, including the relationship between the Ministry of Health (MOH) and the Home Front Command (HFC); (4) defining the relationships between the MOH and HFC in deploying the community health services in emergencies; (5) protecting medical facilities and personal protection equipment for medical teams and; (6) treating acute stress reactions. The AAR, critique and learning lessons signify three different processes that can sometimes be contradictory. Nevertheless, it is possible to achieve organizational improvement white integrating between these three processes, as was displayed by the SHA.

  5. Descriptive Epidemiology of Musculoskeletal Injuries and Concussions in the National Football League, 2012-2014

    PubMed Central

    Lawrence, David W.; Hutchison, Michael G.; Comper, Paul

    2015-01-01

    Background: The risk of all-cause injury and concussion associated with football is significant. The National Football League (NFL) has implemented changes to increase player safety warranting investigation into the incidence and patterns of injury. Purpose: To document the incidence and patterns of all-cause injury and concussions in the NFL. Study Design: Descriptive epidemiology study. Methods: Injury data were collected prospectively from official NFL injury reports over 2 regular seasons from 2012 to 2014, with identification of injury incidence rates and patterns. Concussion rate ratios were calculated using previously reported NFL rates. Results: A total of 4284 injuries were identified, including 301 concussions. The all-cause injury rate was 395.8 per 1000 athletes at risk (AAR) and concussion incidence was 27.8 per 1000 AAR. Only 2.3% of team games were injury free. Wide receivers, tight ends, and defensive backs had the highest incidence of injury and concussion. Concussion incidence was 1.61-fold higher in 2012 to 2014 compared with 2002 to 2007. The knee was injured most frequently, followed by the ankle, hamstring, shoulder, and head. Conclusion: The incidence of all-cause injury and concussion in the NFL is significant. Concussion injury rates are higher than previous reports, potentially reflecting an improvement in recognition and awareness. Injury prevention efforts should continue to reduce the prevalence of injury associated with football. PMID:26675321

  6. Multilevel populations and the evolution of antibiotic resistance through horizontal gene transfer.

    PubMed

    Andam, Cheryl P; Fournier, Gregory P; Gogarten, Johann Peter

    2011-09-01

    Horizontal gene transfer (HGT) can create diversity in the genetic repertoire of a lineage. Successful gene transfer likely occurs more frequently between more closely related organisms, leading to the formation of higher-level exchange groups that in some respects are comparable to single-species populations. Genes that appear fixed in a single species can be replaced through distant homologs or iso-functional analogs acquired through HGT. These genes may originate from other species or they may be acquired by an individual strain from the species pan-genome. Because of their similarity to alleles in a population, we label these gene variants that are exchanged between related species as homeoalleles. In a case study, we show that biased gene transfer plays an important role in the evolution of aminoacyl-tRNA synthetases (aaRS). Many microorganisms make use of these genes against naturally occurring antibiotics. We suggest that the resistance against naturally occurring antibiotics is the likely driving force behind the frequent switching between divergent aaRS types and the reason for the maintenance of these homeoalleles in higher-level exchange groups. Resistance to naturally occurring antibiotics may lead to the maintenance of different types of aminoacyl-tRNA synthetases in Bacteria through gene transfer.

  7. Niemeyer Virus: A New Mimivirus Group A Isolate Harboring a Set of Duplicated Aminoacyl-tRNA Synthetase Genes

    PubMed Central

    Boratto, Paulo V. M.; Arantes, Thalita S.; Silva, Lorena C. F.; Assis, Felipe L.; Kroon, Erna G.; La Scola, Bernard; Abrahão, Jônatas S.

    2015-01-01

    It is well recognized that gene duplication/acquisition is a key factor for molecular evolution, being directly related to the emergence of new genetic variants. The importance of such phenomena can also be expanded to the viral world, with impacts on viral fitness and environmental adaptations. In this work we describe the isolation and characterization of Niemeyer virus, a new mimivirus isolate obtained from water samples of an urban lake in Brazil. Genomic data showed that Niemeyer harbors duplicated copies of three of its four aminoacyl-tRNA synthetase genes (cysteinyl, methionyl, and tyrosyl RS). Gene expression analysis showed that such duplications allowed significantly increased expression of methionyl and tyrosyl aaRS mRNA by Niemeyer in comparison to APMV. Remarkably, phylogenetic data revealed that Niemeyer duplicated gene pairs are different, each one clustering with a different group of mimivirus strains. Taken together, our results raise new questions about the origins and selective pressures involving events of aaRS gain and loss among mimiviruses. PMID:26635738

  8. Representative rainfall thresholds for flash floods in the Cali river watershed, Colombia

    NASA Astrophysics Data System (ADS)

    Ávila, A. D.; Carvajal, Y. E.; Justino, F.

    2015-06-01

    In the 21st century, societies face a significant increase in the number of extreme hydrometeorological events associated with climate variability (CV) and/or climate change (CC). Research has recently focused on establishing adaptation and mitigation measures to counteract the effects of CV and CC, especially those associated with precipitation, such as flash floods and flooding. In this study, 27 floods, listed in the historical database of natural disasters (DesInventar), occurring between 1980 and 2012, were analyzed. Using the daily hydrometeorological data, representative rainfall thresholds were defined to predict flash floods in the hydrographic basin of the Cali River, Colombia. Antecedent rainfall (AR), or short-term rain (1, 3, 5 and 7 days), and accumulated antecedent rainfall (AAR), or long-term rain (5, 7, 10, 15, 20, 25, 30, 60 and 90 days), levels were defined. The analysis showed that the greatest determinant for the occurrence of floods is AAR, with thresholds greater than 73, 95, 124, 170, 218 and 273 mm, for 5, 7, 10, 15, 20 and 25 days, respectively. Additionally, the data showed that, historically, the greatest number of flash floods (81.7 %) occurred in the Cali River basin in the months of April, May, and June.

  9. Adaptive autoregressive identification with spectral power decomposition for studying movement-related activity in scalp EEG signals and basal ganglia local field potentials

    NASA Astrophysics Data System (ADS)

    Foffani, Guglielmo; Bianchi, Anna M.; Priori, Alberto; Baselli, Giuseppe

    2004-09-01

    We propose a method that combines adaptive autoregressive (AAR) identification and spectral power decomposition for the study of movement-related spectral changes in scalp EEG signals and basal ganglia local field potentials (LFPs). This approach introduces the concept of movement-related poles, allowing one to study not only the classical event-related desynchronizations (ERD) and synchronizations (ERS), which correspond to modulations of power, but also event-related modulations of frequency. We applied the method to analyze movement-related EEG signals and LFPs contemporarily recorded from the sensorimotor cortex, the globus pallidus internus (GPi) and the subthalamic nucleus (STN) in a patient with Parkinson's disease who underwent stereotactic neurosurgery for the implant of deep brain stimulation (DBS) electrodes. In the AAR identification we compared the whale and the exponential forgetting factors, showing that the whale forgetting provides a better disturbance rejection and it is therefore more suitable to investigate movement-related brain activity. Movement-related power modulations were consistent with previous studies. In addition, movement-related frequency modulations were observed from both scalp EEG signals and basal ganglia LFPs. The method therefore represents an effective approach to the study of movement-related brain activity.

  10. A Comparative Study on Improved Arrhenius-Type and Artificial Neural Network Models to Predict High-Temperature Flow Behaviors in 20MnNiMo Alloy

    PubMed Central

    Yu, Chun-tang; Liu, Ying-ying; Xia, Yu-feng

    2014-01-01

    The stress-strain data of 20MnNiMo alloy were collected from a series of hot compressions on Gleeble-1500 thermal-mechanical simulator in the temperature range of 1173∼1473 K and strain rate range of 0.01∼10 s−1. Based on the experimental data, the improved Arrhenius-type constitutive model and the artificial neural network (ANN) model were established to predict the high temperature flow stress of as-cast 20MnNiMo alloy. The accuracy and reliability of the improved Arrhenius-type model and the trained ANN model were further evaluated in terms of the correlation coefficient (R), the average absolute relative error (AARE), and the relative error (η). For the former, R and AARE were found to be 0.9954 and 5.26%, respectively, while, for the latter, 0.9997 and 1.02%, respectively. The relative errors (η) of the improved Arrhenius-type model and the ANN model were, respectively, in the range of −39.99%∼35.05% and −3.77%∼16.74%. As for the former, only 16.3% of the test data set possesses η-values within ±1%, while, as for the latter, more than 79% possesses. The results indicate that the ANN model presents a higher predictable ability than the improved Arrhenius-type constitutive model. PMID:24688358

  11. Constitutive Equations and Flow Behavior of an As-Extruded AZ31 Magnesium Alloy Under Large Strain Condition

    NASA Astrophysics Data System (ADS)

    Dong, Yuanyuan; Zhang, Cunsheng; Lu, Xing; Wang, Cuixue; Zhao, Guoqun

    2016-06-01

    A reasonable constitutive model is the key to achieving the accurate numerical simulation of magnesium alloy extrusion process. Based on the hot compression tests of the as-extruded AZ31 magnesium alloy, the strain-compensated Arrhenius equation, the constitutive equation taking into account dynamic recovery (DRV) and dynamic recrystallization (DRX), and the modified Fields-Backofen equation (FB) are established to describe the deformation behavior of this alloy under large strain condition (strain level greater than 1.0) and wide strain rate range (0.01 to 10 s-1), respectively. Then material parameters in each constitutive model are determined by linear fitting method. The comparison of these three kinds of equations shows that the strain-compensated Arrhenius model provides the best prediction of flow stress, and the calculated value of correlation coefficient ( R) is the highest as 0.9945 and the average absolute relative error (AARE) is the lowest as 3.11%. The constitutive equation with DRV + DRX can also predict flow stress accurately, and its values of R and AARE are 0.9920 and 4.41%, respectively. However, compared to the other two constitutive equations, the modified FB equation does not give good description of hot deformation behavior for this magnesium alloy. Finally, the advantages and drawbacks of these three kinds of constitutive models are discussed and compared. Therefore, this work could provide theoretical guidelines for investigating hot deformation behavior of wrought magnesium alloys and determining the appropriate extrusion process parameters under large strain condition.

  12. LV wall segmentation using the variational level set method (LSM) with additional shape constraint for oedema quantification

    NASA Astrophysics Data System (ADS)

    Kadir, K.; Gao, H.; Payne, A.; Soraghan, J.; Berry, C.

    2012-10-01

    In this paper an automatic algorithm for the left ventricle (LV) wall segmentation and oedema quantification from T2-weighted cardiac magnetic resonance (CMR) images is presented. The extent of myocardial oedema delineates the ischaemic area-at-risk (AAR) after myocardial infarction (MI). Since AAR can be used to estimate the amount of salvageable myocardial post-MI, oedema imaging has potential clinical utility in the management of acute MI patients. This paper presents a new scheme based on the variational level set method (LSM) with additional shape constraint for the segmentation of T2-weighted CMR image. In our approach, shape information of the myocardial wall is utilized to introduce a shape feature of the myocardial wall into the variational level set formulation. The performance of the method is tested using real CMR images (12 patients) and the results of the automatic system are compared to manual segmentation. The mean perpendicular distances between the automatic and manual LV wall boundaries are in the range of 1-2 mm. Bland-Altman analysis on LV wall area indicates there is no consistent bias as a function of LV wall area, with a mean bias of -121 mm2 between individual investigator one (IV1) and LSM, and -122 mm2 between individual investigator two (IV2) and LSM when compared to two investigators. Furthermore, the oedema quantification demonstrates good correlation when compared to an expert with an average error of 9.3% for 69 slices of short axis CMR image from 12 patients.

  13. Numerical dating of a Late Quaternary spit-shoreline complex at the northern end of Silver Lake playa, Mojave Desert, California: A comparison of the applicability of radiocarbon, luminescence, terrestrial cosmogenic nuclide, electron spin resonance, U-series and amino acid racemization methods

    USGS Publications Warehouse

    Owen, L.A.; Bright, Jordon; Finkel, R.C.; Jaiswal, M.K.; Kaufman, D.S.; Mahan, S.; Radtke, U.; Schneider, J.S.; Sharp, W.; Singhvi, A.K.; Warren, C.N.

    2007-01-01

    A Late Quaternary spit-shoreline complex on the northern shore of Pleistocene Lake Mojave of southeastern California, USA was studied with the goal of comparing accelerator mass spectrometry (AMS) radiocarbon, luminescence, electron spin resonance (ESR), terrestrial cosmogenic radionuclide (TCN) surface exposure, amino acid racemization (AAR) and U-series dating methods. The pattern of ages obtained by the different methods illustrates the complexity of processes acting in the lakeshore environment and highlights the utility of a multi-method approach. TCN surface exposure ages (mostly ???20-30 ka) record the initial erosion of shoreline benches, whereas radiocarbon ages on shells (determined in this and previous studies) within the spit, supported by AAR data, record its construction at fluctuating lake levels from ???16 to 10 ka. Luminescence ages on spit sediment (???6-7 ka) and ESR ages on spit shells (???4 ka) are anomalously young relative to radiocarbon ages of shells within the same deposits. The significance of the surprisingly young luminescence ages is not clear. The younger ESR ages could be a consequence of post-mortem enrichment of U in the shells. High concentrations of detrital thorium in tufa coating spit gravels inhibited the use of single-sample U-series dating. Detailed comparisons such as this provide one of the few means of assessing the accuracy of Quaternary dating techniques. More such comparisons are needed. ?? 2007 Elsevier Ltd and INQUA.

  14. A Transform-Based Feature Extraction Approach for Motor Imagery Tasks Classification.

    PubMed

    Baali, Hamza; Khorshidtalab, Aida; Mesbah, Mostefa; Salami, Momoh J E

    2015-01-01

    In this paper, we present a new motor imagery classification method in the context of electroencephalography (EEG)-based brain-computer interface (BCI). This method uses a signal-dependent orthogonal transform, referred to as linear prediction singular value decomposition (LP-SVD), for feature extraction. The transform defines the mapping as the left singular vectors of the LP coefficient filter impulse response matrix. Using a logistic tree-based model classifier; the extracted features are classified into one of four motor imagery movements. The proposed approach was first benchmarked against two related state-of-the-art feature extraction approaches, namely, discrete cosine transform (DCT) and adaptive autoregressive (AAR)-based methods. By achieving an accuracy of 67.35%, the LP-SVD approach outperformed the other approaches by large margins (25% compared with DCT and 6 % compared with AAR-based methods). To further improve the discriminatory capability of the extracted features and reduce the computational complexity, we enlarged the extracted feature subset by incorporating two extra features, namely, Q- and the Hotelling's [Formula: see text] statistics of the transformed EEG and introduced a new EEG channel selection method. The performance of the EEG classification based on the expanded feature set and channel selection method was compared with that of a number of the state-of-the-art classification methods previously reported with the BCI IIIa competition data set. Our method came second with an average accuracy of 81.38%.

  15. SMALL ACIDIC PROTEIN1 acts with RUB modification components, the COP9 signalosome, and AXR1 to regulate growth and development of Arabidopsis.

    PubMed

    Nakasone, Akari; Fujiwara, Masayuki; Fukao, Yoichiro; Biswas, Kamal Kanti; Rahman, Abidur; Kawai-Yamada, Maki; Narumi, Issay; Uchimiya, Hirofumi; Oono, Yutaka

    2012-09-01

    Previously, a dysfunction of the SMALL ACIDIC PROTEIN1 (SMAP1) gene was identified as the cause of the anti-auxin resistant1 (aar1) mutant of Arabidopsis (Arabidopsis thaliana). SMAP1 is involved in the response pathway of synthetic auxin, 2,4-dichlorophenoxyacetic acid, and functions upstream of the auxin/indole-3-acetic acid protein degradation step in auxin signaling. However, the exact mechanism by which SMAP1 functions in auxin signaling remains unknown. Here, we demonstrate that SMAP1 is required for normal plant growth and development and the root response to indole-3-acetic acid or methyl jasmonate in the auxin resistant1 (axr1) mutation background. Deletion analysis and green fluorescent protein/glutathione S-transferase pull-down assays showed that SMAP1 physically interacts with the CONSTITUTIVE PHOTOMORPHOGENIC9 SIGNALOSOME (CSN) via the SMAP1 F/D region. The extremely dwarf phenotype of the aar1-1 csn5a-1 double mutant confirms the functional role of SMAP1 in plant growth and development under limiting CSN functionality. Our findings suggest that SMAP1 is involved in the auxin response and possibly in other cullin-RING ubiquitin ligase-regulated signaling processes via its interaction with components associated with RELATED TO UBIQUITIN modification.

  16. Direct dating of human fossils.

    PubMed

    Grün, Rainer

    2006-01-01

    The methods that can be used for the direct dating of human remains comprise of radiocarbon, U-series, electron spin resonance (ESR), and amino acid racemization (AAR). This review gives an introduction to these methods in the context of dating human bones and teeth. Recent advances in ultrafiltration techniques have expanded the dating range of radiocarbon. It now seems feasible to reliably date bones up to 55,000 years. New developments in laser ablation mass spectrometry permit the in situ analysis of U-series isotopes, thus providing a rapid and virtually non-destructive dating method back to about 300,000 years. This is of particular importance when used in conjunction with non-destructive ESR analysis. New approaches in AAR analysis may lead to a renaissance of this method. The potential and present limitations of these direct dating techniques are discussed for sites relevant to the reconstruction of modern human evolution, including Florisbad, Border Cave, Tabun, Skhul, Qafzeh, Vindija, Banyoles, and Lake Mungo.

  17. No rosetta stone for a sense-antisense origin of aminoacyl tRNA synthetase classes.

    PubMed

    Williams, Tom A; Wolfe, Kenneth H; Fares, Mario A

    2009-02-01

    Aminoacyl tRNA synthetases (aaRS) are crucial enzymes that join amino acids to their cognate tRNAs, thereby implementing the genetic code. These enzymes fall into two unrelated structural classes whose evolution has not been explained. The leading hypothesis, proposed by Rodin and Ohno, is that the two classes originated as a pair of sense-antisense genes encoded on opposite strands of a single DNA molecule. This unusual idea obtained its main support from reports of a "Rosetta stone": a locus where genes for heat shock protein 70 (HSP70) and an Nicotinamide adenine dinulecotide-specific glutamate dehydrogenase (NAD-GDH), which are structurally homologous to the two classes of aaRS, overlap extensively on complementary DNA strands. This remarkable locus was first characterized in the oomycete Achlya klebsiana and has since been reported in many other species. Here we present evidence that the open reading frames on the antisense strand of HSP70 genes are spurious, and we identify a more probable candidate for the gene encoding the oomycete NAD-GDH enzyme. These results cast extensive doubt on the Rosetta Stone argument.

  18. Archaeal aminoacyl-tRNA synthetases interact with the ribosome to recycle tRNAs.

    PubMed

    Godinic-Mikulcic, Vlatka; Jaric, Jelena; Greber, Basil J; Franke, Vedran; Hodnik, Vesna; Anderluh, Gregor; Ban, Nenad; Weygand-Durasevic, Ivana

    2014-04-01

    Aminoacyl-tRNA synthetases (aaRS) are essential enzymes catalyzing the formation of aminoacyl-tRNAs, the immediate precursors for encoded peptides in ribosomal protein synthesis. Previous studies have suggested a link between tRNA aminoacylation and high-molecular-weight cellular complexes such as the cytoskeleton or ribosomes. However, the structural basis of these interactions and potential mechanistic implications are not well understood. To biochemically characterize these interactions we have used a system of two interacting archaeal aaRSs: an atypical methanogenic-type seryl-tRNA synthetase and an archaeal ArgRS. More specifically, we have shown by thermophoresis and surface plasmon resonance that these two aaRSs bind to the large ribosomal subunit with micromolar affinities. We have identified the L7/L12 stalk and the proteins located near the stalk base as the main sites for aaRS binding. Finally, we have performed a bioinformatics analysis of synonymous codons in the Methanothermobacter thermautotrophicus genome that supports a mechanism in which the deacylated tRNAs may be recharged by aaRSs bound to the ribosome and reused at the next occurrence of a codon encoding the same amino acid. These results suggest a mechanism of tRNA recycling in which aaRSs associate with the L7/L12 stalk region to recapture the tRNAs released from the preceding ribosome in polysomes.

  19. The A2B adenosine receptor impairs the maturation and immunogenicity of dendritic cells.

    PubMed

    Wilson, Jeffrey M; Ross, William G; Agbai, Oma N; Frazier, Renea; Figler, Robert A; Rieger, Jayson; Linden, Joel; Ernst, Peter B

    2009-04-15

    The endogenous purine nucleoside adenosine is an important antiinflammatory mediator that contributes to the control of CD4(+) T cell responses. While adenosine clearly has direct effects on CD4(+) T cells, it remains to be determined whether actions on APC such as dendritic cells (DC) are also important. In this report we characterize DC maturation and function in BMDC stimulated with LPS in the presence or absence of the nonselective adenosine receptor agonist NECA (5'-N-ethylcarboxamidoadenosine). We found that NECA inhibited TNF-alpha and IL-12 in a concentration-dependent manner, whereas IL-10 production was increased. NECA-treated BMDC also expressed reduced levels of MHC class II and CD86 and were less effective at stimulating CD4(+) T cell proliferation and IL-2 production compared with BMDC exposed to vehicle control. Based on real-time RT-PCR, the A(2A) adenosine receptor (A(2A)AR) and A(2B)AR were the predominant adenosine receptors expressed in BMDC. Using adenosine receptor subtype selective antagonists and BMDC derived from A(2A)AR(-/-) and A(2B)AR(-/-)mice, it was shown that NECA modulates TNF-alpha, IL-12, IL-10, and CD86 responses predominantly via A(2B)AR. These data indicate that engagement of A(2B)AR modifies murine BMDC maturation and suggest that adenosine regulates CD4(+) T cell responses by selecting for DC with impaired immunogencity.

  20. Amino acid racemization dating of marine shells: A mound of possibilities

    PubMed Central

    Demarchi, Beatrice; Williams, Matt G.; Milner, Nicky; Russell, Nicola; Bailey, Geoff; Penkman, Kirsty

    2011-01-01

    Shell middens are one of the most important and widespread indicators for human exploitation of marine resources and occupation of coastal environments. Establishing an accurate and reliable chronology for these deposits has fundamental implications for understanding the patterns of human evolution and dispersal. This paper explores the potential application of a new methodology of amino acid racemization (AAR) dating of shell middens and describes a simple protocol to test the suitability of different molluscan species. This protocol provides a preliminary test for the presence of an intracrystalline fraction of proteins (by bleaching experiments and subsequent heating at high temperature), checking the closed system behaviour of this fraction during diagenesis. Only species which pass both tests can be considered suitable for further studies to obtain reliable age information. This amino acid geochronological technique is also applied to midden deposits at two latitudinal extremes: Northern Scotland and the Southern Red Sea. Results obtained in this study indicate that the application of this new method of AAR dating of shells has the potential to aid the geochronological investigation of shell mounds in different areas of the world. PMID:21776187

  1. Characterization of Hot Deformation Behavior of a New Near-β Titanium Alloy: Ti555211

    NASA Astrophysics Data System (ADS)

    An, Zhen; Li, Jinshan; Feng, Yong; Liu, Xianghong; Du, Yuxuan

    2016-10-01

    The deformation behavior of an isothermally compressed Ti555211 titanium alloy was examined by an Arrhenius-type constitutive model using experimental data obtained from hot compression tests; these tests were performed at temperatures and strain rates of 750-950°C and 0.001-1 s-1, respectively. Activation energies of hot deformation were calculated in 0.05 intervals for strains ranging from 0.1 to 0.7. The respective values of were obtained for the (α+β) and β region. In addition, the predictive capability of the model was described by the average absolute relative error (AARE) and the correlation coefficient (R). The simulated values were compared with the experimental values, and R and AARE of 0.99084 and 6.914%, respectively, were obtained for the Arrhenius-type constitutive model. These values were indicative of the good predictive capabilities of the developed strain-compensated constitutive equation. Moreover, in this work isothermal compression tests, scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), and transmission electron microscopy (TEM) were used to systematically investigate the high-temperature deformation behavior of Ti555211 alloy under different processing conditions. EBSD and TEM were used to reveal the substructure and grain orientation of samples of the hot-deformed Ti555211 alloy. The phenomenon of discontinuous yielding was also discussed.

  2. Low Doses of Allyphenyline and Cyclomethyline, Effective against Morphine Dependence, Elicit an Antidepressant-like Effect

    PubMed Central

    2012-01-01

    This study demonstrated that cyclomethyline (2) and the corresponding enantiomers (R)-(−)-2 and (S)-(+)-2, displaying α2C-adrenoreceptor (AR) agonism/α2A-AR antagonism, similarly to allyphenyline (1) and its enantiomers, significantly decreased the naloxone-precipitated withdrawal symptoms in mice at very low doses. It also highlighted that such positive effects on morphine dependence can even be improved by additional serotoninergic 5-HT1A receptor (5-HT1A-R) activation. Indeed, 1 or the single (S)-(+)-1, 2, or both its enantiomers, all behaving as α2C-AR agonists/α2A-AR antagonists/5-HT1A-R agonists, alone and at the same low dose, improved morphine withdrawal syndrome and exerted a potent antidepressant-like effect. Therefore, considering the elevated comorbidity between opiate abuse and depressed mood and the benefit of these multifunctional compounds to both disorders, it is possible that they prove more efficacious and less toxic than a cocktail of drugs in managing opioid addiction. PMID:24900506

  3. A unified model of the standard genetic code

    PubMed Central

    Morgado, Eberto R.

    2017-01-01

    The Rodin–Ohno (RO) and the Delarue models divide the table of the genetic code into two classes of aminoacyl-tRNA synthetases (aaRSs I and II) with recognition from the minor or major groove sides of the tRNA acceptor stem, respectively. These models are asymmetric but they are biologically meaningful. On the other hand, the standard genetic code (SGC) can be derived from the primeval RNY code (R stands for purines, Y for pyrimidines and N any of them). In this work, the RO-model is derived by means of group actions, namely, symmetries represented by automorphisms, assuming that the SGC originated from a primeval RNY code. It turns out that the RO-model is symmetric in a six-dimensional (6D) hypercube. Conversely, using the same automorphisms, we show that the RO-model can lead to the SGC. In addition, the asymmetric Delarue model becomes symmetric by means of quotient group operations. We formulate isometric functions that convert the class aaRS I into the class aaRS II and vice versa. We show that the four polar requirement categories display a symmetrical arrangement in our 6D hypercube. Altogether these results cannot be attained, neither in two nor in three dimensions. We discuss the present unified 6D algebraic model, which is compatible with both the SGC (based upon the primeval RNY code) and the RO-model.

  4. A Characterization of Hot Flow Behaviors Involving Different Softening Mechanisms by ANN for As-Forged Ti-10V-2Fe-3Al Alloy

    NASA Astrophysics Data System (ADS)

    Quan, Guo-zheng; Zou, Zhen-yu; Wen, Hai-rong; Pu, Shi-ao; Lv, Wen-quan

    2015-11-01

    The isothermal compressions of as-forged Ti-10V-2Fe-3Al alloy at the deformation temperature range of 948-1,123 K and the strain rates in the range of 0.001-10 s-1 with a height reduction of 60% were conducted on a Gleeble-3500 thermo-mechanical simulator. The flow behaviors show nonlinear sensitivity to strain, strain rate and temperature. Based on the experimental data, an artificial neural network (ANN) with back-propagation algorithm was developed to deal with the complex deformation behavior characteristics. In the present ANN model, strain, strain rate and temperature were taken as inputs, and flow stress as output. A comparative study on the constitutive relationships based on regression and ANN methods was conducted. According to the predicted and experimental results, the predictabilities of the two models have been evaluated in terms of correlation coefficient (R) and average absolute relative error (AARE). The R-value and the AARE-value at strain of 0.5 from the ANN model is 0.9998 and 0.572%, respectively, better than 0.9902 and 6.583% from the regression model. The predicted strain-stress curves outside of experimental conditions indicate similar characteristics with experimental curves. The results have sufficiently articulated that the well-trained ANN model with back-propagation algorithm has excellent capability to deal with the complex flow behaviors of as-forged Ti-10V-2Fe-3Al alloy.

  5. Large-Scale Crustal-Block-Extrusion During Late Alpine Collision.

    PubMed

    Herwegh, Marco; Berger, Alfons; Baumberger, Roland; Wehrens, Philip; Kissling, Edi

    2017-03-24

    The crustal-scale geometry of the European Alps has been explained by a classical subduction-scenario comprising thrust-and-fold-related compressional wedge tectonics and isostatic rebound. However, massive blocks of crystalline basement (External Crystalline Massifs) vertically disrupt the upper-crustal wedge. In the case of the Aar massif, top basement vertically rises for >12 km and peak metamorphic temperatures increase along an orogen-perpendicular direction from 250 °C-450 °C over horizontal distances of only <15 km (Innertkirchen-Grimselpass), suggesting exhumation of midcrustal rocks with increasing uplift component along steep vertical shear zones. Here we demonstrate that delamination of European lower crust during lithosphere mantle rollback migrates northward in time. Simultaneously, the Aar massif as giant upper crustal block extrudes by buoyancy forces, while substantial volumes of lower crust accumulate underneath. Buoyancy-driven deformation generates dense networks of steep reverse faults as major structures interconnected by secondary branches with normal fault component, dissecting the entire crust up to the surface. Owing to rollback fading, the component of vertical motion reduces and is replaced by a late stage of orogenic compression as manifest by north-directed thrusting. Buoyancy-driven vertical tectonics and modest late shortening, combined with surface erosion, result in typical topographic and metamorphic gradients, which might represent general indicators for final stages of continent-continent collisions.

  6. Cardiorespiratory responses and reduced apneic time to cold-water face immersion after high intensity exercise.

    PubMed

    Konstantinidou, Sylvia; Soultanakis, Helen

    2016-01-01

    Apnea after exercise may evoke a neurally mediated conflict that may affect apneic time and create a cardiovascular strain. The physiological responses, induced by apnea with face immersion in cold water (10 °C), after a 3-min exercise bout, at 85% of VO2max,were examined in 10 swimmers. A pre-selected 40-s apnea, completed after rest (AAR), could not be met after exercise (AAE), and was terminated with an agonal gasp reflex, and a reduction of apneic time, by 75%. Bradycardia was evident with immersion after both, 40-s of AAR and after AAE (P<0.05). The dramatic elevation of, systolic pressure and pulse pressure, after AAE, were indicative of cardiovascular stress. Blood pressure after exercise without apnea was not equally elevated. The activation of neurally opposing functions as those elicited by the diving reflex after high intensity exercise may create an autonomic conflict possibly related to oxygen-conserving reflexes stimulated by the trigeminal nerve, and those elicited by exercise.

  7. Sediment accumulation, stratigraphic order, and the extent of time-averaging in lagoonal sediments: a comparison of 210Pb and 14C/amino acid racemization chronologies

    NASA Astrophysics Data System (ADS)

    Kosnik, Matthew A.; Hua, Quan; Kaufman, Darrell S.; Zawadzki, Atun

    2015-03-01

    Carbon-14 calibrated amino acid racemization (14C/AAR) data and lead-210 (210Pb) data are used to examine sediment accumulation rates, stratigraphic order, and the extent of time-averaging in sediments collected from the One Tree Reef lagoon (southern Great Barrier Reef, Australia). The top meter of lagoonal sediment preserves a stratigraphically ordered deposit spanning the last 600 yrs. Despite different assumptions, the 210Pb and 14C/AAR chronologies are remarkably similar indicating consistency in sedimentary processes across sediment grain sizes spanning more than three orders of magnitude (0.1-10 mm). Estimates of long-term sediment accumulation rates range from 2.2 to 1.2 mm yr-1. Molluscan time-averaging in the taphonomically active zone is 19 yrs, whereas below the depth of final burial (~15 cm), it is ~110 yrs/5 cm layer. While not a high-resolution paleontological record, this reef lagoon sediment is suitable for paleoecological studies spanning the period of Western colonization and development. This sedimentary deposit, and others like it, should be useful, albeit not ideal, for quantifying anthropogenic impacts on coral reef systems.

  8. Adding intelligent services to an object oriented system

    NASA Technical Reports Server (NTRS)

    Robideaux, Bret R.; Metzler, Theodore A.

    1994-01-01

    As today's software becomes increasingly complex, the need grows for intelligence of one sort or another to becomes part of the application, often an intelligence that does not readily fit the paradigm of one's software development. There are many methods of developing software, but at this time, the most promising is the object oriented (OO) method. This method involves an analysis to abstract the problem into separate 'objects' that are unique in the data that describe them and the behavior that they exhibit, and eventually to convert this analysis into computer code using a programming language that was designed (or retrofitted) for OO implementation. This paper discusses the creation of three different applications that are analyzed, designed, and programmed using the Shlaer/Mellor method of OO development and C++ as the programming language. All three, however, require the use of an expert system to provide an intelligence that C++ (or any other 'traditional' language) is not directly suited to supply. The flexibility of CLIPS permitted us to make modifications to it that allow seamless integration with any of our applications that require an expert system. We illustrate this integration with the following applications: (1) an after action review (AAR) station that assists a reviewer in watching a simulated tank battle and developing an AAR to critique the performance of the participants in the battle; (2) an embedded training system and over-the-shoulder coach for howitzer crewmen; and (3) a system to identify various chemical compounds from their infrared absorption spectra.

  9. A unified model of the standard genetic code.

    PubMed

    José, Marco V; Zamudio, Gabriel S; Morgado, Eberto R

    2017-03-01

    The Rodin-Ohno (RO) and the Delarue models divide the table of the genetic code into two classes of aminoacyl-tRNA synthetases (aaRSs I and II) with recognition from the minor or major groove sides of the tRNA acceptor stem, respectively. These models are asymmetric but they are biologically meaningful. On the other hand, the standard genetic code (SGC) can be derived from the primeval RNY code (R stands for purines, Y for pyrimidines and N any of them). In this work, the RO-model is derived by means of group actions, namely, symmetries represented by automorphisms, assuming that the SGC originated from a primeval RNY code. It turns out that the RO-model is symmetric in a six-dimensional (6D) hypercube. Conversely, using the same automorphisms, we show that the RO-model can lead to the SGC. In addition, the asymmetric Delarue model becomes symmetric by means of quotient group operations. We formulate isometric functions that convert the class aaRS I into the class aaRS II and vice versa. We show that the four polar requirement categories display a symmetrical arrangement in our 6D hypercube. Altogether these results cannot be attained, neither in two nor in three dimensions. We discuss the present unified 6D algebraic model, which is compatible with both the SGC (based upon the primeval RNY code) and the RO-model.

  10. Magnetic fabrics, rock magnetism, cathodoluminescence and petrography of apparently undeformed Bambui carbonates from São Francisco Basin (Minas Gerais State, SE Brazil): An integrated study

    NASA Astrophysics Data System (ADS)

    Raposo, M. Irene B.; McReath, Ian; D'Agrella-Filho, Manoel S.

    2006-05-01

    Magnetic measurements were performed on apparently undeformed limestones and carbonate shales from 44 sites in nearly horizontal stratigraphic layers mainly from the basal units of the Neoproterozoic Bambui Group in the southern part of the São Francisco Basin. Rock magnetism, cathodoluminescence, transmitted and reflected light microscopy analyses reveal that there is a mix of ferromagnetic minerals, mainly magnetite and pyrrhotite, in most sites. In some sites, however, the ferromagnetic minerals are magnetite and hematite. Fine-grained pyrrhotite and pyrite accompany rare fine-grained graphite and probably amorphous carbon in some of stylolites, while pyrrhotite is also present as larger interstitial masses in coarse-grained domains outside, but close to the stylolites. Magnetic fabrics were determined applying both anisotropy of low-field magnetic susceptibility (AMS) and anisotropy of anhysteretic remanence magnetization (AAR). The AAR tensor was less well defined than the AMS fabric due to the low ferromagnetic mineral content. The analysis at the individual-site scale defines three AMS fabric types. The first type (two sites) shows Kmin perpendicular to the bedding plane, while Kmax and Kint are scattered within bedding plane itself. This fabric is usually interpreted as primary (sedimentary-compactional), typical of totally undeformed sediments. The second type shows the three well-clustered AMS axes with Kmin still perpendicular to the bedding plane. This fabric is the most important since it was found in the majority of the sites. The third type (two sites) is characterized by well-clustered Kmax in the bedding plane, while Kmin and Kint are distributed along a girdle. The second and third fabric types are interpreted as combinations of sedimentary-compactional and tectonic contributions at the earliest, and at a slightly later stage of deformation, respectively. AMS represents the contribution of all the rock-forming minerals, while AAR isolates the

  11. Modified spleen stiffness measurement by transient elastography is associated with presence of large oesophageal varices in patients with compensated hepatitis C virus cirrhosis.

    PubMed

    Calvaruso, V; Bronte, F; Conte, E; Simone, F; Craxì, A; Di Marco, V

    2013-12-01

    To evaluate the accuracy of liver transient elastography (TE), spleen TE and other noninvasive tests (AAR, APRI score, platelet count, platelet/spleen ratio) in predicting the presence and the size of oesophageal varices in compensated hepatitis C virus (HCV) cirrhosis, we studied 112 consecutive patients with compensated HCV cirrhosis who underwent biochemical tests, gastrointestinal endoscopy, liver TE and spleen TE by Fibroscan(®) (Echosens, Paris, France) using a modified software version with a range between 1.5 and 150 kPa. Spleen TE was not reliable in 16 patients (14.3%). Among the 96 patients with a valid measurement (69.8% men, mean age: 63.2 ± 9.5 years), 43.7% had no oesophageal varices, 29.2% had grade 1% and 27.1% had grade 2 or grade 3 oesophageal varices. Patients with values of 75 kPa by standard spleen TE had mean values of modified spleen TE of 117 kPa (range: 81.7-149.5). Linear regression revealed a significant correlation between modified spleen TE and oesophageal varix size (r = 0.501; beta: 0.763, SE: 0.144; P < 0.001). On univariate analysis, the variables associated with grade 2/grade 3 oesophageal varices were AAR score, APRI score, platelet/spleen ratio, liver TE and modified spleen TE. On multivariate analysis, only modified spleen TE (OR: 1.026; 95% CI: 1.007-1.046; P = 0.006) and AAR (OR: 14.725; 95% CI: 1.928-112.459; P = 0.010) remained independently associated with grade 2/grade 3 oesophageal varices. Platelet/spleen ratio was the best predictor of oesophageal varices area under the ROC curve (AUROC: 0.763, cut-off: 800, sensitivity: 74%, specificity: 70%), while modified spleen TE was more accurate in predicting grade 2/grade 3 oesophageal varices (AUROC: 0.82, cut-off: 54.0 kPa, sensitivity: 80%, specificity: 70%). Portal hypertension increases spleen stiffness, and the measurement of modified spleen TE is an accurate, noninvasive tool for predicting the presence of large oesophageal varices in patients with compensated HCV

  12. Sensitivity of annual mass balance gradient and Hypsometry to the changing climate: the case of Dokriani Glacier, central Himalaya, India

    NASA Astrophysics Data System (ADS)

    Pratap, B.

    2015-12-01

    The glacier mass balance is undelayed, unfiltered and direct method to assess the impact of climate change on the glaciers. Many studies suggest that some of the Himalayan glaciers have lost their mass at an increased rate during the past few decades. Furthermore, the mass balance gradient and hypsometric analysis are important to understand the glacier response towards climatic perturbations. Our long term in-situ monitoring on the Dokriani Glacier provides great insights to understand the variability in central Himalayan glaciers. We report the relationship between glacier hypsometry and annual mass balance gradient (12 years) to understand the glacier's response towards climate change. Dokriani Glacier in the Bhagirathi basin is a small (7 km2) NNW exposed glacier in the western part of central Himalaya, India. The study analysed the annual balance, mass balance gradient and length changes observed during first decade of 21st century (2007-2013) and compare with the previous observations of 1990s (1992-2000). A large spatial variability in the mass balance gradients of two different periods has been observed. The equilibrium-line altitude (ELA) was fluctuated between 5000 and 5100 m a.s.l. and the derived time averaged ELA (ELAn) and balance budget ELA (ELA0) were 5075 and 4965 m a.s.l respectively during 1992-2013. The observed time-averaged accumulation-area ratio (AARn) and balance budget AAR (AAR0) were 0.67 and 0.72 respectively during 1992-2013. The higher value of AAR comprises due to flat and broader accumulation area (4.50 km2) of the glacier. Although, having larger accumulation area, the glacier has faced strong mass wasting with average annual ablation of -1.82 m w.e. a-1 in the ablation zone as compare to residual average annual accumulation of 0.41 m w.e. a-1. Based on the annual mass balance series (12 years) Dokriani Glacier has continuous negative annual balances with monotonically negative cumulative mass loss of -3.86 m w.e with the average

  13. High Temperature Calcination - MACT Upgrade Equipment Pilot Plant Test

    SciTech Connect

    Richard D. Boardman; B. H. O'Brien; N. R. Soelberg; S. O. Bates; R. A. Wood; C. St. Michel

    2004-02-01

    About one million gallons of acidic, hazardous, and radioactive sodium-bearing waste are stored in stainless steel tanks at the Idaho Nuclear Technology and Engineering Center (INTEC), which is a major operating facility of the Idaho National Engineering and Environmental Laboratory. Calcination at high-temperature conditions (600 C, with alumina nitrate and calcium nitrate chemical addition to the feed) is one of four options currently being considered by the Department of Energy for treatment of the remaining tank wastes. If calcination is selected for future processing of the sodium-bearing waste, it will be necessary to install new off-gas control equipment in the New Waste Calcining Facility (NWCF) to comply with the Maximum Achievable Control Technology (MACT) standards for hazardous waste combustors and incinerators. This will require, as a minimum, installing a carbon bed to reduce mercury emissions from their current level of up to 7,500 to <45 {micro}g/dscm, and a staged combustor to reduce unburned kerosene fuel in the off-gas discharge to <100 ppm CO and <10 ppm hydrocarbons. The staged combustor will also reduce NOx concentrations of about 35,000 ppm by 90-95%. A pilot-plant calcination test was completed in a newly constructed 15-cm diameter calciner vessel. The pilot-plant facility was equipped with a prototype MACT off-gas control system, including a highly efficient cyclone separator and off-gas quench/venturi scrubber for particulate removal, a staged combustor for unburned hydrocarbon and NOx destruction, and a packed activated carbon bed for mercury removal and residual chloride capture. Pilot-plant testing was performed during a 50-hour system operability test January 14-16, followed by a 100-hour high-temperature calcination pilot-plant calcination run January 19-23. Two flowsheet blends were tested: a 50-hour test with an aluminum-to-alkali metal molar ratio (AAR) of 2.25, and a 50-hour test with an AAR of 1.75. Results of the testing

  14. Fluid circulation systems in the Alpine External Crystalline Massifs

    NASA Astrophysics Data System (ADS)

    Boutoux, Alexandre; Bellahsen, Nicolas; Verlaguet, Anne; Lacombe, Olivier

    2014-05-01

    At mid-crustal levels, rock permeability is believed to be very low except in active fault/shear zones. In sedimentary rocks undergoing tectonic burial during collisional shortening, fluid flow is thus considered to be a small-scale process restricted to the sedimentary unit, until the fluid system locally opens during strain localization in fault/shear zones. During the Alpine collision, the European proximal passive margin (Dauphinois/Helvetic domains, including the External Crystalline Massifs, ECM: Aar, Mont Blanc, Aiguilles Rouges, Oisans massifs) was buried at mid-crustal depth under the internal units and was subsequently shortened and exhumed with contrasting kinematics. Indeed, some of the main tectonic units are sedimentary nappes detached from their basement while other are linked to main basement shear zones. In this context, many studies of fluid system evolution have been published, mainly focused on the largest tectonic units (e.g., Morcles nappe) and/or on thrust/shear zones with large displacement (e.g., Glarus thrust). In this contribution, we focused on tectonic structures located in the Oisans massif where small amount of shortening occurred (smaller than in the northern ECM, Mont Blanc and Aar). We performed geochemical and microthermometric analyses on calcite + quartz vein and host-rock samples to document and discuss the fluid source and pathway, the scale of circulation and the fluid-rock interactions. The fluid system in the Oisans ECM is compared to the fluid systems in other ECM and can be considered as an early and/or less shortened analogue. In the Oisans massif cover, the fluid system is generally closed, except locally above the main basement shear zones where signatures of basement-derived fluids were identified by trace element analysis. In contrast, in the Mont Blanc massif, fluids were channelized in the main basement shear zones, while in the Morcles nappe (i.e., the presumable cover of the Mont Blanc), deep fluids may have been

  15. How logical reasoning ability and empirical knowledge interact in the process of solving problems about light and vision among Taiwanese secondary school students

    NASA Astrophysics Data System (ADS)

    Liao, Shih-Chieh

    Piagetian scholars argue that the effect of problem content, e.g., empirical knowledge, should decrease with age. Indeed, they believe that the empirical knowledge cannot affect human problem-solving after individuals approach the formal operation stage. In arguing this point, this study uses an A-AR model to address how empirical knowledge affects the problem-solving process among Taiwanese secondary students. The A-AR model is borrowed from mathematics and the symbols, A, A, and R, represent Assumption, Answering, and Reasoning, respectively. Similar to solving mathematics problems, the A-AR model problems require participants to use the given assumptions by logical reasoning in order to respond to the problems. In this situation, the effect of empirical knowledge on problem-solving is easy to detect. There are three results about human problem-solving found in this study. First, the empirical knowledge still affects human problem-solving at the formal operation stage. Not like the Piagetian scholars' assumption: the effect of empirical knowledge is decreasing with age, this study finds that the effect of empirical knowledge is S-shape. The S-shape is a result of academic training. Second, the academic training, major, shapes human problem-solving strategies. For instance, the 12th grade science students' problem-solving strategy is based on logical reasoning ability by the given assumptions and the same grade social science students' strategy is according of their empirical knowledge. Third, the interference of logical reasoning ability and empirical knowledge is a predictor of the empirical knowledge effect on human problem-solving. The relation between the empirical knowledge and interference can be characterized as: the more negative interference the participants have, the more of the empirical knowledge effect they will have in the next year. This study does not agree with the Piagetian theory about human problem-solving: the effect of empirical knowledge

  16. Calculation and visualisation of future glacier extent in the Swiss Alps by means of hypsographic modelling

    NASA Astrophysics Data System (ADS)

    Paul, F.; Maisch, M.; Rothenbühler, C.; Hoelzle, M.; Haeberli, W.

    2007-02-01

    The observed rapid glacier wastage in the European Alps during the past 20 years already has strong impacts on the natural environment (rock fall, lake formation) as well as on human activities (tourism, hydro-power production, etc.) and poses several new challenges also for glacier monitoring. With a further increase of global mean temperature in the future, it is likely that Alpine glaciers and the high-mountain environment as an entire system will further develop into a state of imbalance. Hence, the assessment of future glacier geometries is a valuable prerequisite for various impact studies. In order to calculate and visualize in a consistent manner future glacier extent for a large number of individual glaciers (> 100) according to a given climate change scenario, we have developed an automated and simple but robust approach that is based on an empirical relationship between glacier size and the steady-state accumulation area ratio (AAR 0) in the Alps. The model requires digital glacier outlines and a digital elevation model (DEM) only and calculates new glacier geometries from a given shift of the steady-state equilibrium line altitude (ELA 0) by means of hypsographic modelling. We have calculated changes in number, area and volume for 3062 individual glacier units in Switzerland and applied six step changes in ELA 0 (from + 100 to + 600 m) combined with four different values of the AAR 0 (0.5, 0.6, 0.67, 0.75). For an AAR 0 of 0.6 and an ELA 0 rise of 200 m (400 m) we calculate a total area loss of - 54% (- 80%) and a corresponding volume loss of - 50% (- 78%) compared to the 1973 glacier extent. In combination with a geocoded satellite image, the future glacier outlines are also used for automated rendering of perspective visualisations. This is a very attractive tool for communicating research results to the general public. Our study is illustrated for a test site in the Upper Engadine (Switzerland), where landscape changes above timberline play an

  17. Quantification of the cumulative effects of river training works on the basin scale with 2D flood modelling

    NASA Astrophysics Data System (ADS)

    Zischg, Andreas Paul; Felder, Guido; WWeingartner, Rolf

    2015-04-01

    The catchment of the river Aare upstream of Bern, Switzerland, with an area of approx. 3000 km2 is a complex network of sub-catchments with different runoff characteristics; it also includes two larger lakes. Most of the rivers were regulated in the 18th century. An important regulation, however, was realised as early as in the 17th century. For this catchment, the worst case flood event was identified and its consequences were analysed. Beside the hydro-meteorological characteristics, an important basis to model the worst case flood is to understand the non-linear effects of flood retention in the valley bottom and in the lakes. The aim of this study was to compare these effects based on both the current river network and the historic one prior to the main river training works. This allows to quantify the human impacts. Methodologically, we set up a coupled 2D flood model representing the floodplains of the river Aare as well as of the tributaries Lombach, Lütschine, Zulg, Rotache, Chise and Guerbe. The flood simulation was made in 2D with the software BASEMENT-ETH (Vetsch et al. 2014). The model was calibrated by means of reproducing the large floods in August 2005 and the bankfull discharge for all river reaches. The model computes the discharge at the outlet of the Aare catchment at Bern by routing all discharges from the sub-catchments through the river reaches and their floodplains. With this, the modulation of the input hydrographs by widespread floodings in the floodplains can be quantified. The same configuration was applied on the basis of reconstructed digital terrain models representing the landscape and the river network before the first significant river training works had been realised. This terrain model was reconstructed by georeferencing and digitalizing historic maps and cross-sections combined with the mapping of the geomorphologic evidences of former river structures in non-modified areas. The latter mapping procedure was facilitated by the

  18. Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor.

    PubMed

    Mirando, Adam C; Fang, Pengfei; Williams, Tamara F; Baldor, Linda C; Howe, Alan K; Ebert, Alicia M; Wilkinson, Barrie; Lounsbury, Karen M; Guo, Min; Francklyn, Christopher S

    2015-08-14

    Aminoacyl-tRNA synthetases (AARSs) catalyze an early step in protein synthesis, but also regulate diverse physiological processes in animal cells. These include angiogenesis, and human threonyl-tRNA synthetase (TARS) represents a potent pro-angiogenic AARS. Angiogenesis stimulation can be blocked by the macrolide antibiotic borrelidin (BN), which exhibits a broad spectrum toxicity that has discouraged deeper investigation. Recently, a less toxic variant (BC194) was identified that potently inhibits angiogenesis. Employing biochemical, cell biological, and biophysical approaches, we demonstrate that the toxicity of BN and its derivatives is linked to its competition with the threonine substrate at the molecular level, which stimulates amino acid starvation and apoptosis. By separating toxicity from the inhibition of angiogenesis, a direct role for TARS in vascular development in the zebrafish could be demonstrated. Bioengineered natural products are thus useful tools in unmasking the cryptic functions of conventional enzymes in the regulation of complex processes in higher metazoans.

  19. Anal carcinoma and HIV infection: is it time for screening?

    PubMed

    Herranz-Pinto, P; Sendagorta-Cudós, E; Bernardino-de la Serna, J I; Peña-Sánchez de Rivera, J M

    2014-03-01

    A 38-year-old white man had a 10-year history of human immunodeficiency virus (HIV) infection (A3), with no episodes of opportunistic diseases and in good immunologic recovery (CD4 cell count: 450 and indetectable HIV viral load) while on HAART. He presented with a two-month history of mild anal symptoms, including pruritus and episodic bleeding. He referred past episodes of anal warts, self-treated with several topical compounds, all proven unsuccessful. Perianal examination showed erythema and scratching. A 0.5cm sized tumor, with infiltration at the base was detected on digital exam, located at 15mm from the anal margin. Local biopsy driven by high-resolution anuscopy (AAR) yielded a final diagnosis of infiltrative epidermoid carcinoma. Might that neoplasia have been prevented?

  20. The glaciers of Sierra Segundera (Zamora, NW Spain) during their Maximum Ice Extent: area, volume, Glacial Equilibrium Line Altitude and paleo-climatic implications

    NASA Astrophysics Data System (ADS)

    María Fernández, Jose; Ubeda, Jose; Palacios, David

    2015-04-01

    The aim of this paper is to reconstruct the Quaternary glaciers which formed the eastern sector of the Sierra Segundera ice-cap (NW Iberian Peninsula) during its Maximum Ice Extent (MIE) local phase (33 ka) in a surface area of 165 km2, to estimate the ice volumes and Equilibrium Line Altitudes (ELAs). The study area presents a wide altimetric range of approx. 1200 m, from the Tera glacier front to the Peña Trevinca (42°14'33'' N, 6°47'46'' W; 2127 m) and Peña Negra (42°14'58'' N, 6°47'39'' W; 2121 m) horns, covering a wide plateau at an altitude of over 1700 m. The reconstruction of the MIE paleoglaciers used a combination of various tools: a rheological numerical model which describes the ice flow, GIS and geomorphological field work to validate the results. The model used here allowed the reconstruction of the surface topography of the paleoglacial ice, even though there is no existing geomorphologic evidence to reveal the thickness of the ice at that time. The GIS enabled the creation of Digital Elevation Models (DEMs) and the estimation of thicknesses and volumes. The reconstructed topography and the delimitation of the geomorphologic features were used to estimate the ELA using the following methods: Area x Altitude Balance Ratio (AABR), Accumulation Area Ratio (AAR), Terminus Headwall Altitude Ratio (THAR) and Maximum Elevation of Lateral Moraines (MELM). The DEM reconstructed for the surface of the paleoglaciers obtained an estimated maximum ice thickness of over 450 m during the MIE, and a total ice volume of 2.63 x 10(10)m3 for the eastern half of the ice-cap. When estimating the paleo-ELAs, the AABR and AAR methods obtain more logical values. The AABR method obtains BR=1, which questions the BR=2 assumed as representative for medium latitude glaciers with oceanic influence; the paleo-ELA AABR was 1739 m. Applying the AAR method with the ratio 0.65 gives the result 1735 m. The THAR and MELM methods give values of 1637 m and 1651 m respectively for

  1. Peripatetic Highlights in Bern

    NASA Astrophysics Data System (ADS)

    Hentschel, Ann M.

    The capital city of the Swiss Canton of Bern and of the Swiss Confederation is nestled in a narrow loop of the Aare river, at the foot of the Alps. The old town, founded around 1191, is well preserved despite a devastating fire in 1405.** Major industries of the region developed under the constraints of modest domestic markets, high transportation costs, and protectionist legislation across national borders. Switzerland thus found its niche in higher-end markets, such as chocolate making, engine building, instruments, fine textiles, and chemicals or pharmaceuticals. My tour past historically significant scientific sites in Bern will use the local legacy of its most illustrious residents, Albert Einstein (1879-1955), who lived there from 1902-1909, and Fritz Houtermans (1903-1966), who lived there from 1952-1966, as its guiding thread through the old town and the university district. Place names in italics mark stops along the tour.

  2. Alternative Environments for Army Recruiting, 1987-2001. Volume 3

    DTIC Science & Technology

    1988-01-01

    8217Flo.ruI7?-,4 P4Bs/DO-r 45" 0 0 2.I F7103. 0h.7*’,J /4oi -to 0 0 / 3 2 Ewoel. AAR’admoT~L PErb ~-5-CO I I II FrSo. Ag’xco -P c1#4 Ef o$- Pfic &’ v’rA 7...I1TIc FR E C’OP’ ,- * Research Report 1493 00 Alternative Environments for Army Recruiting, IN 1987-2001 NVolume 3 I Wayne I. Boucher Benton...2a. SECURITY CLASSIFICATION AUTHORITY 3 . DISTRIBUTION/AVAILABILITY OF REPORT Approved for public release; distribution Zb. DECLASSIFICATION

  3. Transfer Relations Between Landscape Functions - The Hydrological Point of View

    NASA Astrophysics Data System (ADS)

    Fohrer, N.; Lenhart, T.; Eckhardt, K.; Frede, H.-G.

    EC market policies and regional subsidy programs have an enormous impact on local land use. This has far reaching consequences on various landscape functions. In the joint research project SFB299 at the Giessen University the effect of land use options on economic, ecological and hydrological landscape functions are under investigation. The continuous time step model SWAT-G (Eckhardt et al., 2000; Arnold et al., 1998) is employed to characterize the influence of land use patterns on hydrological processes. The model was calibrated and validated employing a split sample approach. For two mesoscale watersheds (Aar, 60 km2; Dietzhölze, 81 km2) located in the Lahn-Dill- Bergland, Germany, different land use scenarios were analyzed with regard to their hydrological impact. Additionally the effect of land use change was analyzed with an ecological and an agro-economic model. The impact of the stepwise changing land use was expressed as trade off relations between different landscape functions.

  4. Determination of Constitutive Equation for Thermo-mechanical Processing of INCONEL 718 Through Double Multivariate Nonlinear Regression Analysis

    NASA Astrophysics Data System (ADS)

    Hussain, Mirza Zahid; Li, Fuguo; Wang, Jing; Yuan, Zhanwei; Li, Pan; Wu, Tao

    2015-07-01

    The present study comprises the determination of constitutive relationship for thermo-mechanical processing of INCONEL 718 through double multivariate nonlinear regression, a newly developed approach which not only considers the effect of strain, strain rate, and temperature on flow stress but also explains the interaction effect of these thermo-mechanical parameters on flow behavior of the alloy. Hot isothermal compression experiments were performed on Gleeble-3500 thermo-mechanical testing machine in the temperature range of 1153 to 1333 K within the strain rate range of 0.001 to 10 s-1. The deformation behavior of INCONEL 718 is analyzed and summarized by establishing the high temperature deformation constitutive equation. The calculated correlation coefficient ( R) and average absolute relative error ( AARE) underline the precision of proposed constitutive model.

  5. Contest of Web-Based Geospatial Applications for Students and Young Scientists

    NASA Astrophysics Data System (ADS)

    Tsai, F.; Cho, K.

    2016-06-01

    The Asian Association on Remote Sensing (AARS) organizes a web contest (WEBCON) of photogrammetry, remote sensing and spatial information sciences in the annual meeting of Asian Conference on Remote Sensing (ACRS) every year. The purpose of WEBCON is to promote the development of web and other forms of internet services of the internet related to geo-information sciences and to attract more students and young scientists participating in the related fields of study and applications. Since 2011, WEBCON has become one of the major events in ACRS and successfully increased the interest in the research, development and applications of photogrammetry, remote sensing and spatial information sciences among students and young scientist. The success of WEBCON is an excellent example of promoting the profession of spatial information to young people.

  6. Protein kinase Cμ mediates adenosine-stimulated steroidogenesis in primary rat adrenal cells.

    PubMed

    Chen, Yung-Chia; Chen, Ying; Huang, Shih-Horng; Wang, Seu-Mei

    2010-11-05

    Adenosine (Ado), an endogenous nucleoside, can stimulate corticosterone synthesis in adrenal cells via the A(2A)/A(2B) adenosine receptors (ARs). This study evaluated the contribution of protein kinase C (PKC) isoforms in Ado-induced steroidogenesis. The PKC inhibitor calphostin c blocked Ado-induced steroidogenesis, the mitogen-activated protein kinase (MEK)-extracellular signal-related regulated kinase (ERK)-cyclic AMP responsive element-binding protein cascade, and the mRNA expression of steroidogenic acute regulatory protein and CYP11B1. Further analyses revealed that PKCμ was indeed activated by Ado. Moreover, downregulation of PKCμ by small interfering RNA (siRNA) inhibited Ado-stimulated steroidogenesis and ERK phosphorylation. Finally, inhibition of either A(2A)AR or A(2B)AR led to the suppression of PKCμ phosphorylation. Together, these findings suggest that A(2)AR-PKCμ-MEK signaling mediates Ado-stimulated adrenal steroidogenesis.

  7. Trophic conditions govern summer zooplankton production variability along the SE Spanish coast (SW Mediterranean)

    NASA Astrophysics Data System (ADS)

    Yebra, Lidia; Putzeys, Sébastien; Cortés, Dolores; Mercado, Jesús M.; Gómez-Jakobsen, Francisco; León, Pablo; Salles, Soluna; Herrera, Inma

    2017-03-01

    The influence of hydrochemistry and trophic conditions on the coastal zooplankton community metabolic rates was investigated along the southeastern Spanish coast, from Algeciras to Cartagena. Zooplankton metabolism was assessed from measurements of gut fluorescence (GF), electron transport system (ETS) and aminoacyl-tRNA synthetases (AARS) activities. Zooplankton had higher biomass-specific respiration and growth rates in the Mediterranean stations to the East, driven by warmer seawater temperatures. However, zooplankton biomass and abundance were significantly higher in the Alboran Sea and, consequently, the zooplankton community in these coastal waters presented the highest production rates of the study area and among the highest of the Mediterranean Sea. We observed that summer zooplankton production variability was driven by the trophic conditions rather than by the hydrological variability.

  8. A genetically encoded fluorescent probe in mammalian cells.

    PubMed

    Chatterjee, Abhishek; Guo, Jiantao; Lee, Hyun Soo; Schultz, Peter G

    2013-08-28

    Fluorescent reporters are useful in vitro and in vivo probes of protein structure, function, and localization. Here we report that the fluorescent amino acid, 3-(6-acetylnaphthalen-2-ylamino)-2-aminopropanoic acid (Anap), can be site-specifically incorporated into proteins in mammalian cells in response to the TAG codon with high efficiency using an orthogonal amber suppressor tRNA/aminoacyl-tRNA synthetase (aaRS) pair. We further demonstrate that Anap can be used to image the subcellular localization of proteins in live mammalian cells. The small size of Anap, its environment-sensitive fluorescence, and the ability to introduce Anap at specific sites in the proteome by simple mutagenesis make it a unique and valuable tool in eukaryotic cell biology.

  9. On the Theory of Bodily Tides

    DTIC Science & Technology

    2007-01-01

    planetary equation in the Euler-Gauss form were employed:8 = 2a2[SesinV + S(l+ecosv)]G~ 1 = p [Rsinv + 5(cosv + cos£)]G_ 1 = rWcos(© + v)G _ 1...rWsin(© +v) / (G sini) dt -pScosV + (r + p )5sinV-Gecosi JQe 2rR + G ( hcosi dt dt da dt de dt di dt \\ dQ. (27) dt d(0 dt dM dt where (a...are the masses of Mars and Phobos, G = ^/JTp and p = a{\\ — e2) are the ellipse parameters, and F = (R, S, W) is the perturbative force expanded in

  10. Mantle Heterogeneity and Mixing Beneath the Bouvet Triple Junction Region: Hf Isotope Constraints from the Westernmost Southwest Indian Ridge (0-11deg.E)

    NASA Astrophysics Data System (ADS)

    Janney, P. E.; le Roex, A. P.

    2013-12-01

    SWIR (0-26E) appears to be fairly similar to that sampled by the American Antarctic Ridge (AAR) and southernmost Mid-Atlantic Ridge (MAR; 49-54°S) in the BTJ region. The most depleted MORB from these areas have similar maximum ɛHf values of +13 to +14 (Andres et al., G-cubed, 2002; Barry et al., EPSL, 2006). The southern MAR extends to slightly higher ɛNd and lower 206Pb/204Pb values than SWIR or AAR MORB, but it is possible that this reflects the greater density of analyzed samples from the southern MAR. Mixing trends between depleted and variably enriched compositions displayed on 206Pb/204Pb-ɛHf, -ɛNd and -87Sr/86Sr diagrams for southern MAR and AAR MORB are not consistent with significant addition of Bouvet hot spot material to the mantle beneath these ridges. Rather, they are more consistent with mixing between a depleted end-member and enriched material from the Shona anomaly (which lies between the MAR and AAR, ≈300 km northwest of the BTJ), which has similar Sr, Nd and Hf isotopic characteristics to Bouvet, but less radiogenic 206Pb/204Pb ratios (Douglass et al., JGR, 1995; Andres et al, G-cubed, 2002).

  11. A SOLAR SPECTROSCOPIC ABSOLUTE ABUNDANCE OF ARGON FROM RESIK

    SciTech Connect

    Sylwester, J.; Sylwester, B.; Phillips, K. J. H.; Kuznetsov, V. D. E-mail: kjhp@mssl.ucl.ac.u

    2010-09-10

    Observations of He-like and H-like Ar (Ar XVII and Ar XVIII) lines at 3.949 A and 3.733 A, respectively, with the RESIK X-ray spectrometer on the CORONAS-F spacecraft, together with temperatures and emission measures from the two channels of GOES, have been analyzed to obtain the abundance of Ar in flare plasmas in the solar corona. The line fluxes per unit emission measure show a temperature dependence like that predicted from theory and lead to spectroscopically determined values for the absolute Ar abundance, A(Ar) = 6.44 {+-} 0.07 (Ar XVII) and 6.49 {+-} 0.16 (Ar XVIII), which are in agreement to within uncertainties. The weighted mean is 6.45 {+-} 0.06, which is between two recent compilations of the solar Ar abundance and suggests that the photospheric and coronal abundances of Ar are very similar.

  12. Consensus recommendations from the American acne & rosacea society on the management of rosacea, part 4: a status report on physical modalities and devices.

    PubMed

    Tanghetti, Emil; Del Rosso, James Q; Thiboutot, Diane; Gallo, Richard; Webster, Guy; Eichenfield, Lawrence F; Stein-Gold, Linda; Berson, Diane; Zaenglein, Andrea

    2014-02-01

    The fourth article in this 5-part series reviews physical modalities and devices used to treat cutaneous rosacea based on consensus recommendations from the American Acne & Rosacea Society (AARS) on the management of the common presentations of cutaneous rosacea. The major therapeutic uses of physical modalities and devices, especially laser and light-based systems, are for treatment of telangiectases and persistent facial erythema (background erythema). Phymas, especially rhinophyma, also are treated with physical modalities such as ablative lasers or surgical devices (eg, electrosurgical loop). Appropriately selected and properly used lasers and intense pulsed light (IPL) devices can successfully address specific clinical manifestations of rosacea that exhibit limited or no response to available medical therapies, such as telangiectases and background centrofacial erythema. Rosacea-associated symptoms also may improve. In most cases, treatment will need to be repeated intermittently to sustain improvement.

  13. Consensus recommendations from the American Acne & Rosacea Society on the management of rosacea, part 3: a status report on systemic therapies.

    PubMed

    Del Rosso, James Q; Thiboutot, Diane; Gallo, Richard; Webster, Guy; Tanghetti, Emil; Eichenfield, Lawrence F; Stein-Gold, Linda; Berson, Diane; Zaenglein, Andrea

    2014-01-01

    The third article in this 5-part series reviews systemic therapies used to treat cutaneous rosacea based on consensus recommendations from the American Acne & Rosacea Society (AARS) on the management of the common presentations of cutaneous rosacea. The consensus recommendations are based on current understanding of research that describes pathophysiologic mechanisms that appear to be operative in rosacea, correlation of these underlying pathophysiologic mechanisms with specific clinical manifestations of rosacea, and outcomes from clinical trials that evaluate therapies for rosacea both as monotherapy and in combination with other agents. Systemic agents used for treatment of rosacea have been administered as oral formulations (ie, tablets, capsules). The only oral agent for rosacea approved by the US Food and Drug Administration (FDA) is a modified-release doxycycline 40-mg capsule. Other non-FDA-approved oral agents also are discussed including other tetracyclines, macrolides, metronidazole, and isotretinoin.

  14. Strutjet RBCC Engine Performance

    NASA Technical Reports Server (NTRS)

    Bulman, Mel; Neill, Todd; Yam, Clement

    1999-01-01

    In the past two years Strutjet Rocket Based Combined Cycle (RBCC) engine has been tested extensively under the Advanced Reusable Technology (ART) contract from NASA MSFC. RBCC Engines combine the high thrust to weight of the rocket with the high efficiency of the ramjet engine. This propulsion system has the potential to reduce the cost of launching payloads to orbit by up to a factor of 100. In the ART program we have conducted over 100 hot fire tests. The propellants have been hydrogen and oxygen. The Modes tested have included the Air Augmented Rocket (AAR) from M = 0 to 2.4, the Ramjet at M = 2.4 & 6, Scramjet at M = 6 & 8, Scram/Rocket at Mach 8 and Ascent Rocket in Vacuum. This invited paper will present an overview of these test results and plans for future development of this propulsion cycle.

  15. Aminoacyl-tRNA synthetase dependent angiogenesis revealed by a bioengineered macrolide inhibitor

    PubMed Central

    Mirando, Adam C.; Fang, Pengfei; Williams, Tamara F.; Baldor, Linda C.; Howe, Alan K.; Ebert, Alicia M.; Wilkinson, Barrie; Lounsbury, Karen M.; Guo, Min; Francklyn, Christopher S.

    2015-01-01

    Aminoacyl-tRNA synthetases (AARSs) catalyze an early step in protein synthesis, but also regulate diverse physiological processes in animal cells. These include angiogenesis, and human threonyl-tRNA synthetase (TARS) represents a potent pro-angiogenic AARS. Angiogenesis stimulation can be blocked by the macrolide antibiotic borrelidin (BN), which exhibits a broad spectrum toxicity that has discouraged deeper investigation. Recently, a less toxic variant (BC194) was identified that potently inhibits angiogenesis. Employing biochemical, cell biological, and biophysical approaches, we demonstrate that the toxicity of BN and its derivatives is linked to its competition with the threonine substrate at the molecular level, which stimulates amino acid starvation and apoptosis. By separating toxicity from the inhibition of angiogenesis, a direct role for TARS in vascular development in the zebrafish could be demonstrated. Bioengineered natural products are thus useful tools in unmasking the cryptic functions of conventional enzymes in the regulation of complex processes in higher metazoans. PMID:26271225

  16. How to predict Italy L'Aquila M6.3 earthquake

    NASA Astrophysics Data System (ADS)

    Guo, Guangmeng

    2016-04-01

    According to the satellite cloud anomaly appeared over eastern Italy on 21-23 April 2012, we predicted the M6.0 quake occurred in north Italy successfully. Here checked the satellite images in 2011-2013 in Italy, and 21 cloud anomalies were found. Their possible correlation with earthquakes bigger than M4.7 which located in Italy main fault systems was statistically examined by assuming various lead times. The result shows that when the leading time interval is set to 23≤ΔT≤45 days, 8 of the 10 quakes were preceded by cloud anomalies. Poisson random test shows that AAR (anomaly appearance rate) and EOR (EQ occurrence rate) is much higher than the values by chance. This study proved the relation between cloud anomaly and earthquake in Italy. With this method, we found that L'Aquila earthquake can also be predicted according to cloud anomaly.

  17. Aminophylline suppresses stress-induced visceral hypersensitivity and defecation in irritable bowel syndrome

    PubMed Central

    Asano, Teita; Tanaka, Ken-ichiro; Tada, Arisa; Shimamura, Hikaru; Tanaka, Rikako; Maruoka, Hiroki; Takenaga, Mitsuko; Mizushima, Tohru

    2017-01-01

    Pharmacological therapy for irritable bowel syndrome (IBS) has not been established. In order to find candidate drugs for IBS with diarrhea (IBS-D), we screened a compound library of drugs clinically used for their ability to prevent stress-induced defecation and visceral hypersensitivity in rats. We selected the bronchodilator aminophylline from this library. Using a specific inhibitor for each subtype of adenosine receptors (ARs) and phosphodiesterases (PDEs), we found that both A2BARs and PDE4 are probably mediated the inhibitory effect of aminophylline on wrap restraint stress (WRS)-induced defecation. Aminophylline suppressed maternal separation- and acetic acid administration-induced visceral hypersensitivity to colorectal distension (CRD), which was mediated by both A2AARs and A2BARs. We propose that aminophylline is a candidate drug for IBS-D because of its efficacy in both of stress-induced defecation and visceral hypersensitivity, as we observed here, and because it is clinically safe. PMID:28054654

  18. Airland Battle and the Division Artillery Counterfire Dilemma,

    DTIC Science & Technology

    1987-11-30

    ITRRY STUDIESUN A I F J iI36 l NOEhhEE|IIhimI----- i----i---i I’llIIIII 4.’ ....~ - - - -- S -U S.t -. -". ’. . -’.. -’- - -- - ’. _- _ - _ r...celegating part of the counter fire mission to an F .’- a~. . he abilit to mass fires required numerous field artillery D Ar.g’orld A~ar 11, a corps could...envisioned by the -V tle De ense Doctrine. Furthermore, the AirLand Ihattle is not ,itniply a brigade 3 S f ig h t n o r r e a . Cl a i ,i T h r’ t

  19. Prediction of Weather Impacted Airport Capacity using Ensemble Learning

    NASA Technical Reports Server (NTRS)

    Wang, Yao Xun

    2011-01-01

    Ensemble learning with the Bagging Decision Tree (BDT) model was used to assess the impact of weather on airport capacities at selected high-demand airports in the United States. The ensemble bagging decision tree models were developed and validated using the Federal Aviation Administration (FAA) Aviation System Performance Metrics (ASPM) data and weather forecast at these airports. The study examines the performance of BDT, along with traditional single Support Vector Machines (SVM), for airport runway configuration selection and airport arrival rates (AAR) prediction during weather impacts. Testing of these models was accomplished using observed weather, weather forecast, and airport operation information at the chosen airports. The experimental results show that ensemble methods are more accurate than a single SVM classifier. The airport capacity ensemble method presented here can be used as a decision support model that supports air traffic flow management to meet the weather impacted airport capacity in order to reduce costs and increase safety.

  20. Preparation and characterization of human ADCK3, a putative atypical kinase.

    PubMed

    Wheeler, Brody; Jia, Zongchao

    2015-04-01

    AarF domain containing kinase 3 (ADCK3) is a mitochondrial protein known to have a role in the electron transport chain. Despite being required for the biosynthesis of coenzyme Q10, a lipid-soluble electron transporter found to be essential for aerobic cellular respiration, the precise biological function of ADCK3 remains unknown. Patients with mutations in ADCK3 experience an onset of neurological disorders from childhood, including cerebellar ataxia and exercise intolerance. After extensive screening for soluble recombinant protein expression, an N-terminal fusion of maltose-binding protein was found to facilitate the overexpression of the human ADCK3 kinase domain in Escherichia coli as a soluble and biologically active entity. For the first time our work reveals Mg(2+)-dependent ATPase activity of ADCK3, providing strong support for the theoretical prediction of this protein being a functional atypical kinase.

  1. Presence of arylsulfatase A (ARS A) in multiple sulfatase deficiency disorder fibroblasts.

    PubMed

    Fluharty, A L; Stevens, R L; Davis, L L; Shapiro, L J; Kihara, H

    1978-05-01

    Multiple deficiency disorder fibroblasts cultured in MEM-CO2 showed deficiencies of arylsulfatase A(ARS A) comparable to the deficiency in metachromatic leukodystrophy fibroblasts. However, the MSDD fibroblasts cultured in MEM-HEPES contained near normal levels of ARS A. Moreover, the enzyme from the latter fibroblasts was indistinguishable from ARS A of control fibroblasts on DEAE-cellulose chromatography, ratio of activity with several substrates, thermal inactivation, sensitivity to inhibitors, and precipitation by antiserum to human ARS A. These data support the conclusion that the ARS A genome is intact in MSDD fibroblasts and, by extension, in MSDD patients. Other sulfatases were present at levels ranging from mildly deficient to near normal but never as low as seen in the corresponding specific sulfatase deficient disorders.

  2. Clone and functional analysis of Seryl-tRNA synthetase and Tyrosyl-tRNA synthetase from silkworm, Bombyx mori

    PubMed Central

    Hu, Jingsheng; Tian, Jianghai; Li, Fanchi; Xue, Bin; Hu, Jiahuan; Cheng, Xiaoyu; Li, Jinxin; Shen, Weide; Li, Bing

    2017-01-01

    Aminoacyl-tRNA synthetases are the key enzymes for protein synthesis. Glycine, alanine, serine and tyrosine are the major amino acids composing fibroin of silkworm. Among them, the genes of alanyl-tRNA synthetase (AlaRS) and glycyl-tRNA synthetase (GlyRS) have been cloned. In this study, the seryl-tRNA synthetase (SerRS) and tyrosyl-tRNA synthetase (TyrRS) genes from silkworm were cloned. Their full length are 1709 bp and 1868 bp and contain open reading frame (ORF) of 1485 bp and 1575 bp, respectively. RT-PCR examination showed that the transcription levels of SerRS, TyrRS, AlaRS and GlyRS are significantly higher in silk gland than in other tissues. In addition, their transcription levels are much higher in middle and posterior silk gland than in anterior silk gland. Moreover, treatment of silkworms with phoxim, an inhibitor of silk protein synthesis, but not TiO2 NP, an enhancer of silk protein synthesis, significantly reduced the transcription levels of aaRS and content of free amino acids in posterior silk gland, therefore affecting silk protein synthesis, which may be the mechanism of phoxim-silking disorders. Furthermore, low concentration of TiO2 NPs showed no effect on the transcription of aaRS and content of free amino acids, suggesting that TiO2 NPs promotes silk protein synthesis possibly by increasing the activity of fibroin synthase in silkworm. PMID:28134300

  3. Genetic variant rs3750625 in the 3'UTR of ADRA2A affects stress-dependent acute pain severity after trauma and alters a microRNA-34a regulatory site.

    PubMed

    Linnstaedt, Sarah D; Walker, Margaret G; Riker, Kyle D; Nyland, Jennifer E; Hu, JunMei; Rossi, Catherine; Swor, Robert A; Jones, Jeffrey S; Diatchenko, Luda; Bortsov, Andrey V; Peak, David A; McLean, Samuel A

    2017-02-01

    α2A adrenergic receptor (α2A-AR) activation has been shown in animal models to play an important role in regulating the balance of acute pain inhibition vs facilitation after both physical and psychological stress. To our knowledge, the influence of genetic variants in the gene encoding α2A-AR, ADRA2A, on acute pain outcomes in humans experiencing traumatic stress has not been assessed. In this study, we tested whether a genetic variant in the 3'UTR of ADRA2A, rs3750625, is associated with acute musculoskeletal pain (MSP) severity following motor vehicle collision (MVC, n = 948) and sexual assault (n = 84), and whether this influence was affected by stress severity. We evaluated rs3750625 because it is located in the seed binding region of miR-34a, a microRNA (miRNA) known to regulate pain and stress responses. In both cohorts, the minor allele at rs3750625 was associated with increased musculoskeletal pain in distressed individuals (stress*rs3750625 P = 0.043 for MVC cohort and P = 0.007 for sexual assault cohort). We further found that (1) miR-34a binds the 3'UTR of ADRA2A, (2) the amount of repression is greater when the minor (risk) allele is present, (3) miR-34a in the IMR-32 adrenergic neuroblastoma cell line affects ADRA2A expression, (4) miR-34a and ADRA2A are expressed in tissues known to play a role in pain and stress, (5) following forced swim stress exposure, rat peripheral nerve tissue expression changes are consistent with miR-34a regulation of ADRA2A. Together, these results suggest that ADRA2A rs3750625 contributes to poststress musculoskeletal pain severity by modulating miR-34a regulation.

  4. Commercially available antibodies directed against α-adrenergic receptor subtypes and other G protein-coupled receptors with acceptable selectivity in flow cytometry experiments.

    PubMed

    Tripathi, Abhishek; Gaponenko, Vadim; Majetschak, Matthias

    2016-02-01

    Several previous reports suggested that many commercially available antibodies directed against G protein-coupled receptors (GPCR) lack sufficient selectivity. Accordingly, it has been proposed that receptor antibodies should be validated by at least one of several criteria, such as testing tissues or cells after knockout or silencing of the corresponding gene. Here, we tested whether 12 commercially available antibodies directed against α-adrenergic receptor (AR) subtypes (α1A/B/D, α2A/B/C), atypical chemokine receptor 3 (ACKR3), and vasopressin receptor 1A (AVPR1A) suffice these criteria. We detected in flow cytometry experiments with human vascular smooth muscle cells that the fluorescence signals from each of these antibodies were reduced by 46 ± 10 %-91 ± 2 % in cells treated with commercially available small interfering RNA (siRNA) specific for each receptor, as compared with cells that were incubated with non-targeting siRNA. The tested antibodies included anti-ACKR3 (R&D Systems, mab42273), for which specificity has previously been demonstrated. Staining with this antibody resulted in 72 ± 5 % reduction of the fluorescence signal after ACKR3 siRNA treatment. Furthermore, staining with anti-α1A-AR (Santa Cruz, sc1477) and anti-ACKR3 (Abcam, ab38089), which have previously been reported to be non-specific, resulted in 70 ± 19 % and 80 ± 4 % loss of the fluorescence signal after α1A-AR and ACKR3 siRNA treatment, respectively. Our findings demonstrate that the tested antibodies show reasonable selectivity for their receptor target under our experimental conditions. Furthermore, our observations suggest that the selectivity of GPCR antibodies depends on the method for which the antibody is employed, the species from which cells/tissues are obtained, and on the type of specimens (cell, tissue/cell homogenate, or section) tested.

  5. Processing by rhomboid protease is required for Providencia stuartii TatA to interact with TatC and to form functional homo-oligomeric complexes.

    PubMed

    Fritsch, Maximilian J; Krehenbrink, Martin; Tarry, Michael J; Berks, Ben C; Palmer, Tracy

    2012-06-01

    The twin arginine transport (Tat) system transports folded proteins across the prokaryotic cytoplasmic membrane and the plant thylakoid membrane. In Escherichia coli three membrane proteins, TatA, TatB and TatC, are essential components of the machinery. TatA from Providencia stuartii is homologous to E. coli TatA but is synthesized as an inactive pre-protein with an N-terminal extension of eight amino acids. Removal of this extension by the rhomboid protease AarA is required to activate P. stuartii TatA. Here we show that P. stuartii TatA can functionally substitute for E. coli TatA provided that the E. coli homologue of AarA, GlpG, is present. The oligomerization state of the P. stuartii TatA pro-protein was compared with that of the proteolytically activated protein and with E. coli TatA. The pro-protein still formed small homo-oligomers but cannot form large TatBC-dependent assemblies. In the absence of TatB, E. coli TatA or the processed form of P. stuartii TatA form a complex with TatC. However, this complex is not observed with the pro-form of P. stuartii TatA. Taken together our results suggest that the P. stuartii TatA pro-protein is inactive because it is unable to interact with TatC and cannot form the large TatA complexes required for transport.

  6. Novel alpha1-adrenergic receptor signaling pathways: secreted factors and interactions with the extracellular matrix.

    PubMed

    Shi, Ting; Duan, Zhong-Hui; Papay, Robert; Pluskota, Elzbieta; Gaivin, Robert J; de la Motte, Carol A; Plow, Edward F; Perez, Dianne M

    2006-07-01

    alpha1-Adrenergic receptor (alpha1-ARs) subtypes (alpha1A, alpha1B, and alpha1D) regulate multiple signal pathways, such as phospholipase C, protein kinase C (PKC), and mitogen-activated protein kinases. We employed oligonucleotide microarray technology to explore the effects of both short- (1 h) and long-term (18 h) activation of the alpha1A-AR to enable RNA changes to occur downstream of earlier well characterized signaling pathways, promoting novel couplings. Polymerase chain reaction (PCR) studies confirmed that PKC was a critical regulator of alpha1A-AR-mediated gene expression, and secreted interleukin (IL)-6 also contributed to gene expression alterations. We next focused on two novel signaling pathways that might be mediated through alpha1A-AR stimulation because of the clustering of gene expression changes for cell adhesion/motility (syndecan-4 and tenascin-C) and hyaluronan (HA) signaling. We confirmed that alpha1-ARs induced adhesion in three cell types to vitronectin, an interaction that was also integrin-, FGF7-, and PKC-dependent. alpha1-AR activation also inhibited cell migration, which was integrin- and PKC-independent but still required secretion of FGF7. alpha1-AR activation also increased the expression and deposition of HA, a glycosaminoglycan, which displayed two distinct structures: pericellular coats and long cable structures, as well as increasing expression of the HA receptor, CD44. Long cable structures of HA can bind leukocytes, which this suggests that alpha1-ARs may be involved in proinflammatory responses. Our results indicate alpha1-ARs induce the secretion of factors that interact with the extracellular matrix to regulate cell adhesion, motility and proinflammatory responses through novel signaling pathways.

  7. Hypsometric control on glacier mass balance sensitivity in Alaska

    NASA Astrophysics Data System (ADS)

    McGrath, D.; Sass, L.; Arendt, A. A.; O'Neel, S.; Kienholz, C.; Larsen, C.; Burgess, E. W.

    2015-12-01

    Mass loss from glaciers in Alaska is dominated by strongly negative surface balances, particularly on small, continental glaciers but can be highly variable from glacier to glacier. Glacier hypsometry can exert significant control on mass balance sensitivity, particularly if the equilibrium line altitude (ELA) is in a broad area of low surface slope. In this study, we explore the spatial variability in glacier response to future climate forcings on the basis of hypsometry. We first derive mass balance sensitivities (30-70 m ELA / 1° C and 40-90 m ELA / 50% decrease in snow accumulation) from the ~50-year USGS Benchmark glaciers mass balance record. We subsequently assess mean climate fields in 2090-2100 derived from the IPCC AR5/CMIP5 RCP 6.0 5-model mean. Over glaciers in Alaska, we find 2-4° C warming and 10-20% increase in precipitation relative to 2006-2015, but a corresponding 0-50% decrease in snow accumulation due to rising temperatures. We assess changes in accumulation area ratios (AAR) to a rising ELA using binned individual glacier hypsometries. For an ELA increase of 150 m, the mean statewide AAR drops by 0.45, representing a 70% reduction in accumulation area on an individual glacier basis. Small, interior glaciers are the primary drivers of this reduction and for nearly 25% of all glaciers, the new ELA exceeds the glacier's maximum elevation, portending eventual loss. The loss of small glaciers, particularly in the drier interior of Alaska will significantly modify streamflow properties (flashy hydrographs, earlier and reduced peak flows, increased interannual variability, warmer temperatures) with poorly understood downstream ecosystem and oceanographic impacts.

  8. Structure of Leishmania major methionyl-tRNA synthetase in complex with intermediate products methionyladenylate and pyrophosphate.

    PubMed

    Larson, Eric T; Kim, Jessica E; Zucker, Frank H; Kelley, Angela; Mueller, Natascha; Napuli, Alberto J; Verlinde, Christophe L M J; Fan, Erkang; Buckner, Frederick S; Van Voorhis, Wesley C; Merritt, Ethan A; Hol, Wim G J

    2011-03-01

    Leishmania parasites cause two million new cases of leishmaniasis each year with several hundreds of millions of people at risk. Due to the paucity and shortcomings of available drugs, we have undertaken the crystal structure determination of a key enzyme from Leishmania major in hopes of creating a platform for the rational design of new therapeutics. Crystals of the catalytic core of methionyl-tRNA synthetase from L. major (LmMetRS) were obtained with the substrates MgATP and methionine present in the crystallization medium. These crystals yielded the 2.0 Å resolution structure of LmMetRS in complex with two products, methionyladenylate and pyrophosphate, along with a Mg(2+) ion that bridges them. This is the first class I aminoacyl-tRNA synthetase (aaRS) structure with pyrophosphate bound. The residues of the class I aaRS signature sequence motifs, KISKS and HIGH, make numerous contacts with the pyrophosphate. Substantial differences between the LmMetRS structure and previously reported complexes of Escherichia coli MetRS (EcMetRS) with analogs of the methionyladenylate intermediate product are observed, even though one of these analogs only differs by one atom from the intermediate. The source of these structural differences is attributed to the presence of the product pyrophosphate in LmMetRS. Analysis of the LmMetRS structure in light of the Aquifex aeolicus MetRS-tRNA(Met) complex shows that major rearrangements of multiple structural elements of enzyme and/or tRNA are required to allow the CCA acceptor triplet to reach the methionyladenylate intermediate in the active site. Comparison with sequences of human cytosolic and mitochondrial MetRS reveals interesting differences near the ATP- and methionine-binding regions of LmMetRS, suggesting that it should be possible to obtain compounds that selectively inhibit the parasite enzyme.

  9. A Transform-Based Feature Extraction Approach for Motor Imagery Tasks Classification

    PubMed Central

    Khorshidtalab, Aida; Mesbah, Mostefa; Salami, Momoh J. E.

    2015-01-01

    In this paper, we present a new motor imagery classification method in the context of electroencephalography (EEG)-based brain–computer interface (BCI). This method uses a signal-dependent orthogonal transform, referred to as linear prediction singular value decomposition (LP-SVD), for feature extraction. The transform defines the mapping as the left singular vectors of the LP coefficient filter impulse response matrix. Using a logistic tree-based model classifier; the extracted features are classified into one of four motor imagery movements. The proposed approach was first benchmarked against two related state-of-the-art feature extraction approaches, namely, discrete cosine transform (DCT) and adaptive autoregressive (AAR)-based methods. By achieving an accuracy of 67.35%, the LP-SVD approach outperformed the other approaches by large margins (25% compared with DCT and 6 % compared with AAR-based methods). To further improve the discriminatory capability of the extracted features and reduce the computational complexity, we enlarged the extracted feature subset by incorporating two extra features, namely, Q- and the Hotelling’s \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$T^{2}$ \\end{document} statistics of the transformed EEG and introduced a new EEG channel selection method. The performance of the EEG classification based on the expanded feature set and channel selection method was compared with that of a number of the state-of-the-art classification methods previously reported with the BCI IIIa competition data set. Our method came second with an average accuracy of 81.38%. PMID:27170898

  10. A New Species of the Genus Kiwa (Decapoda: Anomura) from the Hydrothermal Vent of the Australia-Antarctic Ridge

    NASA Astrophysics Data System (ADS)

    Won, Y. J.; Lee, S. H.; Lee, W. K.

    2014-12-01

    Due to extreme weather conditions and remoteness to access, the great part of the Southern Ocean remains to be explored. Therefore, little is known about the Circum-Antarctic Ridge (CAR) system and its hydrothermal vent ecosystem underlying the Southern Ocean. We report the first discovery of a new deep-sea hydrothermal vent field and a new anomuran species from the Australia-Antarctic Ridge (AAR), the highest latitude (62°S; 158°E) explored in the Southern Ocean up to date. At this site, a new anomuran species which belongs to the genus Kiwa known as 'yeti crabs' was found. Morphologically, this species has characteristics of the genus Kiwa, including fifth pereopod inserted below sterna plastron, third sternite strongly produced anteriorly, and eyes extremely reduced. However, the new species differs from the other known species of Kiwa, K. hirsuta and K. puravida, showing relatively short rostrum and slender dactylus on second to fourth pereopods. Phylogenetic analysis using DNA sequences of eight genetic loci also supported the result of morphological analysis, confirming this species as a new Kiwa species, Kiwa n. sp. In addition, phylogenetic tree revealed the evolutionary relationship among the Kiwa species, presenting the Kiwa n. sp. as the sister species to K. puravida which inhabits the methane cold seep on the Pacific continental slope off Costa Rica. Considering the geography and the physicochemical environment, this unlikely result casts a mystery to be solved through further taxon sampling particularly from as-yet-unexplored vents and seeps. Discovery of the hydrothermal vent and Kiwa n. sp. from the AAR segment is significant because this site is located in the high latitude of the southern hemisphere and it is the region affected by the Antarctic Circumpolar Current (ACC). Future research on the relation of Kiwa n. sp. and the other Kiwa species affected by the ACC will provide an idea about the biogeography and the evolutionary connections of the

  11. Localization of two human autoantigen genes by PCR screening and in situ hybridization-glycyl-tRNA synthetase locates to 7p15 and Alanyl-tRNA synthetase locates to 16q22

    SciTech Connect

    Nichols, R.C.; Pai, S.I.; Liu, P.; Ge, Q.; Targoff, I.N.

    1995-11-01

    Aminoacyl-tRNA synthetases (aminoacyl-RS) catalyze the attachment of an amino acid to its cognate tRNA. Five of 20 human aminoacyl-RS (histidyl-RS, threonyl-RS, isoleucyl-RS, glycyl-RS, and alanyl-RS) have been identified as targets of autoantibodies in the autoimmune disease polymyositis/dermatomyositis (PM/DM; 9). A sixth autoantigenic amino-acyl-RS, lysyl-RS, was recently reported. The genes for histidyl-RS and threonyl-RS have been assigned to chromosome 5, as have the genes for leucyl-RS and arginyl-RS. Six other aminoacyl-RS (glutamyl-prolyl-RS, valyl-RS, cysteinyl-RS, methionyl-RS, tryptophanyl-RS, and asparaginyl-RS) were assigned to chromosomes 1, 6, 11, 12, 14, and 18, respectively. The reason for a preponderance of aminoacyl-RS genes on chromosome 5 is unknown, but it has been suggested that regulatory relatedness might be a factor. Recently the entire or partial cDNA sequences for two autoantigenic aminoacyl-RS genes, glycyl-RS (gene symbol GARS; 4) and alanyl-RS (gene symbol AARS; 1), were reported. To understand further the genesis of autoimmune responses to aminoacyl-RS and to determine whether genes for autoantigenic aminoacyl-RS colocalize to chromosome 5, we have determined the chromosomal site of the GARS and AARS genes by PCR-based screening of somatic cell hybrid panels and by fluorescence in situ hybridization (FISH) analysis. 10 refs., 1 fig.

  12. 3D VMAT Verification Based on Monte Carlo Log File Simulation with Experimental Feedback from Film Dosimetry

    PubMed Central

    Barbeiro, A. R.; Ureba, A.; Baeza, J. A.; Linares, R.; Perucha, M.; Jiménez-Ortega, E.; Velázquez, S.; Mateos, J. C.

    2016-01-01

    A model based on a specific phantom, called QuAArC, has been designed for the evaluation of planning and verification systems of complex radiotherapy treatments, such as volumetric modulated arc therapy (VMAT). This model uses the high accuracy provided by the Monte Carlo (MC) simulation of log files and allows the experimental feedback from the high spatial resolution of films hosted in QuAArC. This cylindrical phantom was specifically designed to host films rolled at different radial distances able to take into account the entrance fluence and the 3D dose distribution. Ionization chamber measurements are also included in the feedback process for absolute dose considerations. In this way, automated MC simulation of treatment log files is implemented to calculate the actual delivery geometries, while the monitor units are experimentally adjusted to reconstruct the dose-volume histogram (DVH) on the patient CT. Prostate and head and neck clinical cases, previously planned with Monaco and Pinnacle treatment planning systems and verified with two different commercial systems (Delta4 and COMPASS), were selected in order to test operational feasibility of the proposed model. The proper operation of the feedback procedure was proved through the achieved high agreement between reconstructed dose distributions and the film measurements (global gamma passing rates > 90% for the 2%/2 mm criteria). The necessary discretization level of the log file for dose calculation and the potential mismatching between calculated control points and detection grid in the verification process were discussed. Besides the effect of dose calculation accuracy of the analytic algorithm implemented in treatment planning systems for a dynamic technique, it was discussed the importance of the detection density level and its location in VMAT specific phantom to obtain a more reliable DVH in the patient CT. The proposed model also showed enough robustness and efficiency to be considered as a pre

  13. Recognition of upper airway and surrounding structures at MRI in pediatric PCOS and OSAS

    NASA Astrophysics Data System (ADS)

    Tong, Yubing; Udupa, J. K.; Odhner, D.; Sin, Sanghun; Arens, Raanan

    2013-03-01

    Obstructive Sleep Apnea Syndrome (OSAS) is common in obese children with risk being 4.5 fold compared to normal control subjects. Polycystic Ovary Syndrome (PCOS) has recently been shown to be associated with OSAS that may further lead to significant cardiovascular and neuro-cognitive deficits. We are investigating image-based biomarkers to understand the architectural and dynamic changes in the upper airway and the surrounding hard and soft tissue structures via MRI in obese teenage children to study OSAS. At the previous SPIE conferences, we presented methods underlying Fuzzy Object Models (FOMs) for Automatic Anatomy Recognition (AAR) based on CT images of the thorax and the abdomen. The purpose of this paper is to demonstrate that the AAR approach is applicable to a different body region and image modality combination, namely in the study of upper airway structures via MRI. FOMs were built hierarchically, the smaller sub-objects forming the offspring of larger parent objects. FOMs encode the uncertainty and variability present in the form and relationships among the objects over a study population. Totally 11 basic objects (17 including composite) were modeled. Automatic recognition for the best pose of FOMs in a given image was implemented by using four methods - a one-shot method that does not require search, another three searching methods that include Fisher Linear Discriminate (FLD), a b-scale energy optimization strategy, and optimum threshold recognition method. In all, 30 multi-fold cross validation experiments based on 15 patient MRI data sets were carried out to assess the accuracy of recognition. The results indicate that the objects can be recognized with an average location error of less than 5 mm or 2-3 voxels. Then the iterative relative fuzzy connectedness (IRFC) algorithm was adopted for delineation of the target organs based on the recognized results. The delineation results showed an overall FP and TP volume fraction of 0.02 and 0.93.

  14. Influence of granitoid textural parameters on sediment composition: Implications for sediment generation

    NASA Astrophysics Data System (ADS)

    Caracciolo, L.; Tolosana-Delgado, R.; Le Pera, E.; von Eynatten, H.; Arribas, J.; Tarquini, S.

    2012-12-01

    The aim of this study is to determine and characterise the control exerted by parent rock texture on sand composition as a function of grain size. The sands investigated were generated from granitoid parent rocks by the Rhone, Damma and Sidelen glaciers, which drain the Aar Massif in the Central Alps (Switzerland), and were deposited in glacial and fluvio-glacial settings. Mechanical erosion, comminution (crystal breakdown and abrasion) and hydraulic sorting are the most important processes controlling the generation of sediments in this environment, whereas chemical and/or biochemical weathering plays a negligible role. By using a GIS-based Microscopic Information System (MIS), five samples from the glacier-drained portions of the Aar basement have been analysed to determine textural parameters such as modal composition, crystal size distribution and mineral interfaces (types and lengths). Petrographic data of analysed sands include traditional point counts (Gazzi-Dickinson method, minimum of 300 points) as well as textural counts to determine interface types, frequency, and polycrystallinity in phaneritic rock fragments. According to Pettijohn's classification, grain-size dependent compositions vary from feldspathic litharenite (0φ fraction) via lithic arkose (1φ and 2φ) to arkose (3φ and 4φ). Compositional differences among our data set were compared to modern plutoniclastic sands from the Iberian Massif (Spain) and the St. Gabriel Mts. (California, USA), which allowed us to assess the role exerted by glaciers in generating sediments. By combining data from the MIS with those from petrographic analysis, we outlined the evolution of mineral interfaces from the parent rocks to the sediments.

  15. Activation of PKN mediates survival of cardiac myocytes in the heart during ischemia/reperfusion

    PubMed Central

    Takagi, Hiromitsu; Hsu, Chiao-Po; Kajimoto, Katsuya; Shao, Dan; Yang, Yanfei; Maejima, Yasuhiro; Zhai, Peiyong; Yehia, Ghassan; Yamada, Chikaomi; Zablocki, Daniela; Sadoshima, Junichi

    2011-01-01

    Rationale The function of PKN, a stress-activated protein kinase, in the heart is poorly understood. Objective We investigated the functional role of PKN during myocardial ischemia/reperfusion (I/R). Methods and Results PKN is phosphorylated at Thr774 in hearts subjected to ischemia and reperfusion. Myocardial infarction/area at risk (MI/AAR) produced by 45 min ischemia and 24 hours reperfusion was significantly smaller in transgenic mice with cardiac specific overexpression of constitutively active (CA) PKN (Tg-CAPKN) than in non-transgenic (NTg) mice (15 ± 5 vs 38 ± 5%, p<0.01). The number of TUNEL positive nuclei was significantly lower in Tg-CAPKN (0.3 ± 0.2 vs 1.0 ± 0.2%, p<0.05). Both MI/AAR (63 ± 9 vs 45 ± 8%, p<0.05) and the number of TUNEL positive cells (7.9 ± 1.0 vs 1.3 ± 0.9%, p<0.05) were greater in transgenic mice with cardiac specific overexpression of dominant negative PKN (Tg-DNPKN) than in NTg mice. Thr774 phosphorylation of PKN was also observed in response to H2O2 in cultured cardiac myocytes. Stimulation of PKN prevented, whereas inhibition of PKN aggravated cell death induced by H2O2, suggesting that the cell protective effect of PKN is cell-autonomous in cardiac myocytes. PKN induced phosphorylation of alpha B crystallin and increased cardiac proteasome activity. The infarct reducing effect in Tg-CAPKN mice was partially inhibited by epoxomicin, a proteasome inhibitor. Conclusion PKN is activated by I/R and inhibits apoptosis of cardiac myocytes, thereby protecting the heart from I/R injury. PKN mediates phosphorylation of alpha B crystallin and stimulation of proteasome activity, which in part mediates the protective effect of PKN in the heart. PMID:20595653

  16. An evaluation of Mesodon and other larger terrestrial gastropod shells for dating late Holocene and historic alluvium in the Midwestern USA

    USGS Publications Warehouse

    Rakovan, Monica T.; Rech, Jason A.; Pigati, Jeffery S.; Nekola, Jeffery C.; Wiles, Gregory C.

    2013-01-01

    Understanding the history of stream erosion and changes in channel morphology is important for managing and restoring unstable streams. One of the significant challenges in this type of research is establishing accurate dating of late Holocene and historic alluvium. Here we evaluate the potential of using 14C dating and amino acid racemization (AAR) to date large terrestrial gastropod shells that are often preserved within alluvial sediments. Many terrestrial gastropods incorporate old carbon from limestone or other carbonate rocks into their shells and therefore are unsuitable for radiocarbon dating. Recent studies, however, have shown that some taxa avoid this ‘limestone problem’ and can yield reliable 14C ages. In this study, we measured the 14C activity of specimens for the genera Mesodon, Ventridens, and Allogona collected live and from alluvial sequences dated independently by dendrochronology, 14C dating of wood, and/or 137Cs analyses. Mesodon zaletus contained old carbon in similar concentrations (up to ~ 30%) found in previous studies of other large taxa and should be avoided for 14C dating when possible. In contrast, shells of Ventridens ligera and Allogona profunda showed minimal limestone effects and therefore may be suitable for dating late Holocene alluvium. These results highlight the importance of taxonomic identification of gastropod taxa prior to their use for 14C dating and demonstrate that shell fragments that are not identifiable should be avoided. We also measured d/l ratios (n = 17) of aspartic and glutamic acid from eight different taxa of terrestrial gastropods recovered from four late Holocene and historic stratigraphic sequences. Average d/l ratios of aspartic and glutamic acid from historic sediments < 300 years old are lower in shells from younger stratigraphic units, indicating that AAR can be used to differentiate between multiple historic stratigraphic units.

  17. Variations in clique and community patterns in protein structures during allosteric communication: investigation of dynamically equilibrated structures of methionyl tRNA synthetase complexes.

    PubMed

    Ghosh, Amit; Vishveshwara, Saraswathi

    2008-11-04

    The allosteric concept has played a key role in understanding the biological functions of proteins. The rigidity or plasticity and the conformational population are the two important ideas invoked in explaining the allosteric effect. Although molecular insights have been gained from a large number of structures, a precise assessment of the ligand-induced conformational changes in proteins at different levels, ranging from gross topology to intricate details, remains a challenge. In this study, we have explored the conformational changes in the complexes of methionyl tRNA synthetase (MetRS) through novel network parameters such as cliques and communities, which identify the rigid regions in the protein structure networks (PSNs) constructed from the noncovalent interactions of amino acid side chains. MetRS belongs to the aminoacyl tRNA synthetase (aaRS) family that plays a crucial role in the translation of genetic code. These enzymes are modular with distinct domains from which extensive genetic, kinetic, and structural data are available, highlighting the role of interdomain communication. The network parameters evaluated here on the conformational ensembles of MetRS complexes, generated from molecular dynamics simulations, have enabled us to understand the interdomain communication in detail. Additionally, the characterization of conformational changes in terms of cliques and communities has also become possible, which had eluded conventional analyses. Furthermore, we find that most of the residues participating in cliques and communities are strikingly different from those that take part in long-range communication. The cliques and communities evaluated here for the first time on PSNs have beautifully captured the local geometries in detail within the framework of global topology. Here the allosteric effect is revealed at the residue level via identification of the important residues specific for structural rigidity and functional flexibility in MetRS. This ought

  18. Dating and biogeographical patterns in the sea slug genus Acanthodoris Gray, 1850 (Mollusca, Gastropoda, Nudibranchia).

    PubMed

    Hallas, Joshua M; Simison, W Brian; Gosliner, Terrence M

    2016-04-01

    Recent studies investigating vicariance and dispersal have been focused on correlating major geological events with instances of taxonomic expansion by incorporating the fossil record with molecular clock analyses. However, this approach becomes problematic for soft-bodied organisms that are poorly represented in the fossil record. Here, we estimate the phylogenetic relationships of the nudibranch genus Acanthodoris Gray, 1850 using three molecular markers (16S, COI, H3), and then test two alternative geologically calibrated molecular clock scenarios in BEAST and their effect on ancestral area reconstruction (AAR) estimates employed in LAGRANGE. The global temperate distribution of Acanthodoris spans multiple geological barriers, including the Bering Strait (∼5.32 Mya) and the Baja Peninsula (∼5.5 Mya), both of which are used in our dating estimates. The expansion of the Atlantic Ocean (∼95-105 Mya) is also used to calibrate the relationship between A. falklandica Eliot, 1905 and A. planca Fahey and Valdés, 2005, which are distributed in southern Chile and South Africa respectively. Phylogenetic analyses recovered strong biogeographical signal and recovered two major clades representing northern and southern hemispheric distributions of Acanthodoris. When all three geological events are applied to the calibration analyses, the age for Acanthodoris is estimated to be mid-Cretaceous. When the expansion of the Atlantic Ocean is excluded from our analyses, however, Acanthodoris is estimated to be much younger, with a divergence time estimate during the Miocene. Regardless of divergence estimates, our AAR suggests that Acanthodoris may have origins in the Atlantic Ocean with the Atlantic acting as a dispersal point to the northeastern Pacific. These results suggest that Acanthodoris exhibits a rare instance of western trans-arctic expansion. This study also shows that northeast Pacific specimens of A. pilosa should be regarded as A. atrogriseata and that A

  19. GPCR Ligand Dendrimer (GLiDe) Conjugates: Adenosine Receptor Interactions of a Series of Multivalent Xanthine Antagonists

    PubMed Central

    Kecskés, Angela; Tosh, Dilip K.; Wei, Qiang; Gao, Zhan-Guo; Jacobson, Kenneth A.

    2011-01-01

    Previously, G protein–coupled receptor (GPCR) agonists were tethered from polyamidoamine (PAMAM) dendrimers to provide high receptor affinity and selectivity. Here we prepared GPCR Ligand Dendrimer (GLiDe) conjugates from a potent adenosine receptor (AR) antagonist; such agents are of interest for treating Parkinson’s disease, asthma, and other conditions. Xanthine amine congener (XAC) was appended with an alkyne group on an extended C8 substituent for coupling by Cu(I)-catalyzed click chemistry to azide-derivatized G4 (fourth-generation) PAMAM dendrimers to form triazoles. These conjugates also contained triazole-linked PEG groups (8 or 22 moieties per 64 terminal positions) for increasing water-solubility and optionally prosthetic groups for spectroscopic characterization and affinity labeling. Human AR binding affinity increased progressively with the degree of xanthine substitution to reach Ki values in the nM range. The order of affinity of each conjugate was hA2AAR > hA3AR > hA1AR, while the corresponding monomer was ranked hA2AAR > hA1AR ≥ hA3AR. The antagonist activity of the most potent conjugate 14 (34 xanthines per dendrimer) was examined at the Gi-coupled A1AR. Conjugate 14 at 100 nM right-shifted the AR agonist concentration-response curve in a cyclic AMP functional assay in a parallel manner, but at 10 nM (lower than its Ki value) it significantly suppressed the maximal agonist effect in calcium mobilization. This is the first systematic probing of a potent AR antagonist tethered on a dendrimer and its activity as a function of variable loading. PMID:21539392

  20. Validation of the BARD scoring system in Polish patients with nonalcoholic fatty liver disease (NAFLD)

    PubMed Central

    2010-01-01

    Abtract Background Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver diseases, ranging from pure steatosis to nonalcoholic steatohepatitis (NASH), and eventually to liver cirrhosis with its complications. Identifying advanced fibrosis in patients is crucial to evaluating prognosis and possible therapeutic intervention. A novel, simple, and highly accurate scoring system called BARD, which identifies patients with NAFLD and without significant fibrosis, has been recently introduced and validated in North America..The aim of this study is to validate the BARD scoring system in a Polish cohort with NAFLD. Methods A group of 104 Caucasians with biopsy-proven NAFLD were included in this study. Fibrosis in liver biopsies was evaluated according to the Histological Scoring System for Nonalcoholic Fatty Liver Disease. The BARD scoring system was assessed according to Harrison et al.: BMI ≥ 28 = 1 point, AST/ALT ratio (AAR) ≥ 0.8 = 2 points, type 2 diabetes mellitus = 1point. Results Age over 50 and AAR over 0.8 showed, respectively, a moderate and strong association with advanced fibrosis. A BARD score of 2-4 points was associated with F3 or F4 stages of fibrosis with an odds ratio of 17.333 (95% Cl; 3,639 - 82.558) and negative predictive value of 97%. Conclusion Our results demonstrate that the BARD scoring system has value in the non-invasive diagnosis of advanced fibrosis in NAFLD patients. The vast majority of patients with NAFLD would avoid liver biopsy if BARD was broadly introduced into the clinic. PMID:20584330

  1. Small acidic protein 1 and SCF(TIR)(1) ubiquitin proteasome pathway act in concert to induce 2,4-dichlorophenoxyacetic acid-mediated alteration of actin in Arabidopsis roots.

    PubMed

    Takahashi, Maho; Umetsu, Kana; Oono, Yutaka; Higaki, Takumi; Blancaflor, Elison B; Rahman, Abidur

    2017-03-01

    2,4-Dichlorophenoxyacetic acid (2,4-D), a functional analogue of auxin, is used as an exogenous source of auxin as it evokes physiological responses like the endogenous auxin, indole-3-acetic acid (IAA). Previous molecular analyses of the auxin response pathway revealed that IAA and 2,4-D share a common mode of action to elicit downstream physiological responses. However, recent findings with 2,4-D-specific mutants suggested that 2,4-D and IAA might also use distinct pathways to modulate root growth in Arabidopsis. Using genetic and cellular approaches, we demonstrate that the distinct effects of 2,4-D and IAA on actin filament organization partly dictate the differential responses of roots to these two auxin analogues. 2,4-D but not IAA altered the actin structure in long-term and short-term assays. Analysis of the 2,4-D-specific mutant aar1-1 revealed that small acidic protein 1 (SMAP1) functions positively to facilitate the 2,4-D-induced depolymerization of actin. The ubiquitin proteasome mutants tir1-1 and axr1-12, which show enhanced resistance to 2,4-D compared with IAA for inhibition of root growth, were also found to have less disrupted actin filament networks after 2,4-D exposure. Consistently, a chemical inhibitor of the ubiquitin proteasome pathway mitigated the disrupting effects of 2,4-D on the organization of actin filaments. Roots of the double mutant aar1-1 tir1-1 also showed enhanced resistance to 2,4-D-induced inhibition of root growth and actin degradation compared with their respective parental lines. Collectively, these results suggest that the effects of 2,4-D on actin filament organization and root growth are mediated through synergistic interactions between SMAP1 and SCF(TIR)(1) ubiquitin proteasome components.

  2. Optimal Duration of Coronary Ligation and Reperfusion for Reperfusion Injury Study in a Rat Model

    PubMed Central

    Chang, Shih-Tai; Chu, Chi-Ming; Yang, Teng-Yao; Hung, Li-Man; Pan, Kuo-Li; Cherng, Wen-Jin

    2016-01-01

    Background Reperfusion injury (RI) has an important impact on the clinical prognosis for patients with acute myocardial injury who had their coronary blood flow reestablished. However, no studies to date have investigated the timeframe of coronary occlusion and reperfusion effects on RI. Methods A total of 100 rats were divided into 4 groups based on the coronary ligation period: 30, 60, 120, and 180 min, and each group was further divided into 5 subgroups with different reperfusion periods: 0, 30, 60, 120, and 180 min. R0 was the baseline of each subgroup. All animals received the same protocols for designed ligation and reperfusion periods. Evans blue and 2,3,5-triphenyltetrazolium chloride were used to distinguish different myocardial injury areas: area at risk (AAR) and myocardial necrosis. The differences of the ratios of the necrotic area to AAR between each subgroup and baseline were further averaged to calculate an overall value of each heart. Results The relative RI percentages showed significant differences (0.8 ± 2.3%, 4.9 ± 3.3%, 10.8 ± 3.1%, and 20.3 ± 3.6% respectively, p < 0.001) at different time points of reperfusion but not at different time points of ligation (p = 0.593). The effects of different time courses in RI showed that the L120R180 group (43.4 ± 2.3%) had the highest RI difference with the baseline group. Conclusions Maximal RI occurred at the timeframe of L120R180 in our animal model. This result may be utilized to assess the substantial benefits of RI therapies in an experimental rat model setting. PMID:27471363

  3. Chemistry of Hydrothermal Plumes at 159°E on the Australian-Antarctic Ridge

    NASA Astrophysics Data System (ADS)

    Hahm, D.; Baker, E. T.; Rhee, T. S.; Lupton, J. E.; Resing, J. A.; Park, S. H.

    2014-12-01

    The Australian-Antarctic Ridge (AAR) is one of the largest unexplored regions of the global mid-ocean ridge system. In the present contribution, we present the geochemistry of the hydrothermal plumes over the KR1, an AAR segment at 159ºE and 62ºS. In 2011, we collected 48 Miniature Autonomous Plume Recorder profiles, measuring optical back scatter and oxidation-reduction potential, and identified the area between 158.5 and 159ºE as the densest concentration of active hydrothermal sites. In order to further characterize the chemistry of the hydrothermal plumes over the area, named 'Mujin', we conducted intensive vertical and tow-yo CTD casts in 2013. The maximum concentrations of the chemical tracers 3He, CH4, H2, and dissolved Mn, were 7.47 fmol/kg, 19.6 nmol/kg, 8.8 nmol/kg, 94.3 nmol/L, respectively. The CH4/3He (1 -10) and CH4/Mn (0.01 - 0.2) ratios were significantly lower than many ultra-mafic hosted systems, which are often found in slow spreading ridges. The lower ratios are consistent with a basaltic-hosted system, typical of the intermediate spreading rate of 6.8 cm/yr of KR1. Additionally, some of the plume samples collected around 158.6 and 158.8ºE exhibited slightly higher ratios of H2/3He than the others. Assuming that H2 is produced from the reduction of water by reduced iron compounds in the rock, the higher ratios suggest that those plumes are supported by a younger hydrothermal system, which may have experienced a recent eruption.

  4. The Alfvén Mission for the ESA M5 Call: Mission Concept

    NASA Astrophysics Data System (ADS)

    Fazakerley, Andrew; Berthomier, Matthieu; Pottelette, Raymond; Forsyth, Colin

    2016-04-01

    This poster will present the proposed Alfvén mission concept and is complemented by a presentation of the mission scientific goals planned for the ST1.5 session. The Alfvén mission has the scientific objective of studying particle acceleration and other forms of electromagnetic energy conversion in a collisionless low beta plasma. The mission is proposed to operate in the Earth's Auroral Acceleration Region (AAR), the most accessible laboratory for investigating plasmas at an interface where ideal magneto-hydrodynamics does not apply. Alfvén is designed to answer questions about where and how the particles that create the aurorae are accelerated, how and why they emit auroral kilometric radiation, what creates and maintains large scale electric fields aligned with the magnetic field, and to elucidate the ion outflow processes which are slowly removing the Earth's atmosphere. The mission will provide the required coordinated two-spacecraft observations within the AAR several times a day. From well designed separations along or across the magnetic field lines, using a comprehensive suite of inter-calibrated particles and field instruments, it will measure the parallel electric fields, variations in particle flux, and wave energy that will answer open questions on energy conversion. It will use onboard auroral imagers to determine how this energy conversion occurs in the regional context and, together with its orbit design, this makes the mission ideally suited to resolving spatio-temporal ambiguities that have plagued previous auroral satellite studies. The spacecraft observations will be complemented by coordinated observations with the existing dense network of ground based observatories, for more detailed ionospheric and auroral information when Alfvén overflights occur.

  5. Efficacy of Electronic Foramen Locators in Controlling Root Canal Working Length during Rotary Instrumentation.

    PubMed

    Parente, Lorena Arruda; Levin, Martin D; Vivan, Rodrigo Ricci; Bernardes, Ricardo Affonso; Duarte, Marco Antonio Hungaro; Vasconcelos, Bruno Carvalho de

    2015-10-01

    The present study evaluated the efficacy of electronic foramen locators (EFLs) to control root canal working length during rotary instrumentation and to assess possible reliability variations of different working lengths. Forty-eight human mandibular bicuspids were randomly divided in 2 groups according to the used device, Root ZX II (RZX) and Propex II (PRO). They were further subdivided in 2 subgroups according to the root canal preparation level (0.0 and -1.0). Preparation was performed with the Protaper rotary system using a crown-down technique. RZX was employed on its automatic auto-reverse mode (AAR) and PRO was used with the MPAS-10R contra-angle to monitor the preparation. The last used file (F3) was fixed, and the apical portion of the teeth was worn buccolingually, allowing to measure the extent between the file tip and the apical foramen (AF). The precision values of 0.0 mm and -1.0 mm were 100% and 0.0% for RZX, and 100% and 66.7% for PRO, respectively, with a range of ±0.5 mm. Statistical analysis showed no differences between the groups at 0.0 mm. However, at -1.0 mm, RZX showed the poorest results (0.96±0.11 mm), followed by PRO (0.43±0.23 mm). The difference between RZX and PRO was statistically significant. The EFLs were precise in maintaining the working length during rotary preparation when reaching the AF, but when their penetration was limited, both devices showed decreased precision; the RZX AAR failed in all instances.

  6. Adenosine and protection from acute kidney injury

    PubMed Central

    Yap, Steven C.; Lee, H. Thomas

    2012-01-01

    Purpose of Review Acute Kidney Injury (AKI) is a major clinical problem without effective therapy. Development of AKI among hospitalized patients drastically increases mortality, and morbidity. With increases in complex surgical procedures together with a growing elderly population, the incidence of AKI is rising. Renal adenosine receptor (AR) manipulation may have great therapeutic potential in mitigating AKI. In this review, we discuss renal AR biology and potential clinical therapies for AKI. Recent Findings The 4 AR subtypes (A1AR, A2AAR, A2BAR and A3AR) have diverse effects on the kidney. The pathophysiology of AKI may dictate the specific AR subtype activation needed to produce renal protection. The A1AR activation in renal tubules and endothelial cells produces beneficial effects against ischemia and reperfusion (IR) injury by modulating metabolic demand, decreasing necrosis, apoptosis and inflammation. The A2AAR protects against AKI by modulating leukocyte-mediated renal and systemic inflammation whereas the A2BAR activation protects by direct activation of renal parenchymal ARs. In contrast, the A1AR antagonism may play a protective role in nephrotoxic AKI and radiocontrast induced nephropathy by reversing vascular constriction and inducing naturesis and diuresis. Furthermore, as the A3AR-activation exacerbates apoptosis and tissue damage due to renal IR, selective A3AR antagonism may hold promise to attenuate renal IR injury. Finally, renal A1AR activation also protects against renal endothelial dysfunction caused by hepatic IR injury. Summary Despite the current lack of therapies for the treatment and prevention of AKI, recent research suggests that modulation of renal ARs holds promise in treating AKI and extrarenal injury. PMID:22080856

  7. Mechanisms Underlying Activation of α1-Adrenergic Receptor-Induced Trafficking of AQP5 in Rat Parotid Acinar Cells under Isotonic or Hypotonic Conditions

    PubMed Central

    Bragiel, Aneta M.; Wang, Di; Pieczonka, Tomasz D.; Shono, Masayuki; Ishikawa, Yasuko

    2016-01-01

    Defective cellular trafficking of aquaporin-5 (AQP5) to the apical plasma membrane (APM) in salivary glands is associated with the loss of salivary fluid secretion. To examine mechanisms of α1-adrenoceptor (AR)-induced trafficking of AQP5, immunoconfocal microscopy and Western blot analysis were used to analyze AQP5 localization in parotid tissues stimulated with phenylephrine under different osmolality. Phenylephrine-induced trafficking of AQP5 to the APM and lateral plasma membrane (LPM) was mediated via the α1A-AR subtype, but not the α1B- and α1D-AR subtypes. Phenylephrine-induced trafficking of AQP5 was inhibited by ODQ and KT5823, inhibitors of nitric oxide (NO)-stimulated guanylcyclase (GC) and protein kinase (PK) G, respectively, indicating the involvement of the NO/ soluble (c) GC/PKG signaling pathway. Under isotonic conditions, phenylephrine-induced trafficking was inhibited by La3+, implying the participation of store-operated Ca2+ channel. Under hypotonic conditions, phenylephrine-induced trafficking of AQP5 to the APM was higher than that under isotonic conditions. Under non-stimulated conditions, hypotonicity-induced trafficking of AQP5 to the APM was inhibited by ruthenium red and La3+, suggesting the involvement of extracellular Ca2+ entry. Thus, α1A-AR activation induced the trafficking of AQP5 to the APM and LPM via the Ca2+/ cyclic guanosine monophosphate (cGMP)/PKG signaling pathway, which is associated with store-operated Ca2+ entry. PMID:27367668

  8. Fuzzylot: a novel self-organising fuzzy-neural rule-based pilot system for automated vehicles.

    PubMed

    Pasquier, M; Quek, C; Toh, M

    2001-10-01

    This paper presents part of our research work concerned with the realisation of an Intelligent Vehicle and the technologies required for its routing, navigation, and control. An automated driver prototype has been developed using a self-organising fuzzy rule-based system (POPFNN-CRI(S)) to model and subsequently emulate human driving expertise. The ability of fuzzy logic to represent vague information using linguistic variables makes it a powerful tool to develop rule-based control systems when an exact working model is not available, as is the case of any vehicle-driving task. Designing a fuzzy system, however, is a complex endeavour, due to the need to define the variables and their associated fuzzy sets, and determine a suitable rule base. Many efforts have thus been devoted to automating this process, yielding the development of learning and optimisation techniques. One of them is the family of POP-FNNs, or Pseudo-Outer Product Fuzzy Neural Networks (TVR, AARS(S), AARS(NS), CRI, Yager). These generic self-organising neural networks developed at the Intelligent Systems Laboratory (ISL/NTU) are based on formal fuzzy mathematical theory and are able to objectively extract a fuzzy rule base from training data. In this application, a driving simulator has been developed, that integrates a detailed model of the car dynamics, complete with engine characteristics and environmental parameters, and an OpenGL-based 3D-simulation interface coupled with driving wheel and accelerator/ brake pedals. The simulator has been used on various road scenarios to record from a human pilot driving data consisting of steering and speed control actions associated to road features. Specifically, the POPFNN-CRI(S) system is used to cluster the data and extract a fuzzy rule base modelling the human driving behaviour. Finally, the effectiveness of the generated rule base has been validated using the simulator in autopilot mode.

  9. A Myocardial Slice Culture Model Reveals Alpha-1A-Adrenergic Receptor Signaling in the Human Heart

    PubMed Central

    Thomas, R. Croft; Singh, Abhishek; Cowley, Patrick; Myagmar, Bat-Erdene; Montgomery, Megan D.; Swigart, Philip M.; De Marco, Teresa; Baker, Anthony J.; Simpson, Paul C.

    2016-01-01

    Background Translation of preclinical findings could benefit from a simple, reproducible, high throughput human model to study myocardial signaling. Alpha-1A-adrenergic receptors (ARs) are expressed at very low levels in the human heart, and it is unknown if they function. Objectives To develop a high throughput human myocardial slice culture model, and to test the hypothesis that alpha-1A- ARs are functional in the human heart. Methods Cores of LV free wall 8 mm diameter were taken from 52 hearts (18 failing and 34 nonfailing). Slices 250 μm thick were cut with a Krumdieck apparatus and cultured using a rotating incubation unit. Results About 60 slices were cut from each LV core, and a typical study could use 96 slices. Myocyte morphology was maintained, and diffusion into the slice center was rapid. Slice viability was stable for at least 3 days in culture by ATP and MTT assays. The beta-AR agonist isoproterenol stimulated phospholamban phosphorylation, and the alpha-1A-AR agonist A61603 stimulated ERK phosphorylation, with nanomolar EC50 values in slices from both failing and nonfailing hearts. Strips cut from the slices were used to quantify activation of contraction by isoproterenol, A61603, and phenylephrine. The slices supported transduction by adenovirus. Conclusions We have developed a simple, high throughput LV myocardial slice culture model to study signaling in the human heart. This model can be useful for translational studies, and we show for the first time that the alpha-1A-AR is functional in signaling and contraction in the human heart. PMID:27453955

  10. Modeling debris-covered glaciers: response to steady debris deposition

    NASA Astrophysics Data System (ADS)

    Anderson, Leif S.; Anderson, Robert S.

    2016-05-01

    Debris-covered glaciers are common in rapidly eroding alpine landscapes. When thicker than a few centimeters, surface debris suppresses melt rates. If continuous debris cover is present, ablation rates can be significantly reduced leading to increases in glacier length. In order to quantify feedbacks in the debris-glacier-climate system, we developed a 2-D long-valley numerical glacier model that includes englacial and supraglacial debris advection. We ran 120 simulations on a linear bed profile in which a hypothetical steady state debris-free glacier responds to a step increase of surface debris deposition. Simulated glaciers advance to steady states in which ice accumulation equals ice ablation, and debris input equals debris loss from the glacier terminus. Our model and parameter selections can produce 2-fold increases in glacier length. Debris flux onto the glacier and the relationship between debris thickness and melt rate strongly control glacier length. Debris deposited near the equilibrium-line altitude, where ice discharge is high, results in the greatest glacier extension when other debris-related variables are held constant. Debris deposited near the equilibrium-line altitude re-emerges high in the ablation zone and therefore impacts melt rate over a greater fraction of the glacier surface. Continuous debris cover reduces ice discharge gradients, ice thickness gradients, and velocity gradients relative to initial debris-free glaciers. Debris-forced glacier extension decreases the ratio of accumulation zone to total glacier area (AAR). Our simulations reproduce the "general trends" between debris cover, AARs, and glacier surface velocity patterns from modern debris-covered glaciers. We provide a quantitative, theoretical foundation to interpret the effect of debris cover on the moraine record, and to assess the effects of climate change on debris-covered glaciers.

  11. Lightweight deformable mirrors for future space telescopes

    NASA Astrophysics Data System (ADS)

    Patterson, Keith

    This thesis presents a concept for ultra-lightweight deformable mirrors based on a thin substrate of optical surface quality coated with continuous active piezopolymer layers that provide modes of actuation and shape correction. This concept eliminates any kind of stiff backing structure for the mirror surface and exploits micro-fabrication technologies to provide a tight integration of the active materials into the mirror structure, to avoid actuator print-through effects. Proof-of-concept, 10-cm-diameter mirrors with a low areal density of about 0.5 kg/m2 have been designed, built and tested to measure their shape-correction performance and verify the models used for design. The low cost manufacturing scheme uses replication techniques, and strives for minimizing residual stresses that deviate the optical figure from the master mandrel. It does not require precision tolerancing, is lightweight, and is therefore potentially scalable to larger diameters for use in large, modular space telescopes. Other potential applications for such a laminate could include ground-based mirrors for solar energy collection, adaptive optics for atmospheric turbulence, laser communications, and other shape control applications. The immediate application for these mirrors is for the Autonomous Assembly and Reconfiguration of a Space Telescope (AAReST) mission, which is a university mission under development by Caltech, the University of Surrey, and JPL. The design concept, fabrication methodology, material behaviors and measurements, mirror modeling, mounting and control electronics design, shape control experiments, predictive performance analysis, and remaining challenges are presented herein. The experiments have validated numerical models of the mirror, and the mirror models have been used within a model of the telescope in order to predict the optical performance. A demonstration of this mirror concept, along with other new telescope technologies, is planned to take place during

  12. Yeast mitochondrial threonyl-tRNA synthetase recognizes tRNA isoacceptors by distinct mechanisms and promotes CUN codon reassignment

    SciTech Connect

    Ling, Jiqiang; Peterson, Kaitlyn M.; Simonovic, Ivana; Cho, Chris; Soll, Dieter; Simonovic, Miljan

    2014-03-12

    Aminoacyl-tRNA synthetases (aaRSs) ensure faithful translation of mRNA into protein by coupling an amino acid to a set of tRNAs with conserved anticodon sequences. Here, we show that in mitochondria of Saccharomyces cerevisiae, a single aaRS (MST1) recognizes and aminoacylates two natural tRNAs that contain anticodon loops of different size and sequence. Besides a regular ?? with a threonine (Thr) anticodon, MST1 also recognizes an unusual ??, which contains an enlarged anticodon loop and an anticodon triplet that reassigns the CUN codons from leucine to threonine. Our data show that MST1 recognizes the anticodon loop in both tRNAs, but employs distinct recognition mechanisms. The size but not the sequence of the anticodon loop is critical for ?? recognition, whereas the anticodon sequence is essential for aminoacylation of ??. The crystal structure of MST1 reveals that, while lacking the N-terminal editing domain, the enzyme closely resembles the bacterial threonyl-tRNA synthetase (ThrRS). A detailed structural comparison with Escherichia coli ThrRS, which is unable to aminoacylate ??, reveals differences in the anticodon-binding domain that probably allow recognition of the distinct anticodon loops. Finally, our mutational and modeling analyses identify the structural elements in MST1 (e.g., helix {alpha}11) that define tRNA selectivity. Thus, MTS1 exemplifies that a single aaRS can recognize completely divergent anticodon loops of natural isoacceptor tRNAs and that in doing so it facilitates the reassignment of the genetic code in yeast mitochondria.

  13. Spatial variability in mass loss of glaciers in the Everest region, central Himalayas, between 2000 and 2015

    NASA Astrophysics Data System (ADS)

    King, Owen; Quincey, Duncan J.; Carrivick, Jonathan L.; Rowan, Ann V.

    2017-02-01

    Region-wide averaging of Himalayan glacier mass change has masked any catchment or glacier-scale variability in glacier recession; thus the role of a number of glaciological processes in glacier wastage remains poorly understood. In this study, we quantify mass loss rates over the period 2000-2015 for 32 glaciers across the Everest region and assess how future ice loss is likely to differ depending on glacier hypsometry. The mean mass balance of all 32 glaciers in our sample was -0.52 ± 0.22 m water equivalent (w.e.) a-1. The mean mass balance of nine lacustrine-terminating glaciers (-0.70 ± 0.26 m w.e. a-1) was 32 % more negative than land-terminating, debris-covered glaciers (-0.53 ± 0.21 m w.e. a-1). The mass balance of lacustrine-terminating glaciers is highly variable (-0.45 ± 0.13 to -0.91 ± 0.22 m w.e. a-1), perhaps reflecting glacial lakes at different stages of development. To assess the importance of hypsometry on glacier response to future temperature increases, we calculated current (Dudh Koshi - 0.41, Tama Koshi - 0.43, Pumqu - 0.37) and prospective future glacier accumulation area Ratios (AARs). IPCC AR5 RCP 4.5 warming (0.9-2.3 °C by 2100) could reduce AARs to 0.29 or 0.08 in the Tama Koshi catchment, 0.27 or 0.17 in the Dudh Koshi catchment and 0.29 or 0.18 in the Pumqu catchment. Our results suggest that glacial lake expansion across the Himalayas could expedite ice mass loss and the prediction of future contributions of glacial meltwater to river flow will be complicated by spatially variable glacier responses to climate change.

  14. The three α1-adrenoceptor subtypes show different spatio-temporal mechanisms of internalization and ERK1/2 phosphorylation.

    PubMed

    Perez-Aso, M; Segura, V; Montó, F; Barettino, D; Noguera, M A; Milligan, G; D'Ocon, P

    2013-10-01

    We analyzed the kinetic and spatial patterns characterizing activation of the MAP kinases ERK 1 and 2 (ERK1/2) by the three α1-adrenoceptor (α1-AR) subtypes in HEK293 cells and the contribution of two different pathways to ERK1/2 phosphorylation: protein kinase C (PKC)-dependent ERK1/2 activation and internalization-dependent ERK1/2 activation. The different pathways of phenylephrine induced ERK phosphorylation were determined by western blot, using the PKC inhibitor Ro 31-8425, the receptor internalization inhibitor concanavalin A and the siRNA targeting β-arrestin 2. Receptor internalization properties were studied using CypHer5 technology and VSV-G epitope-tagged receptors. Activation of α1A- and α1B-ARs by phenylephrine elicited rapid ERK1/2 phosphorylation that was directed to the nucleus and inhibited by Ro 31-8425. Concomitant with phenylephrine induced receptor internalization α1A-AR, but not α1B-AR, produced a maintained and PKC-independent ERK phosphorylation, which was restricted to the cytosol and inhibited by β-arrestin 2 knockdown or concanavalin A treatment. α1D-AR displayed constitutive ERK phosphorylation, which was reduced by incubation with prazosin or the selective α1D antagonist BMY7378. Following activation by phenylephrine, α1D-AR elicited rapid, transient ERK1/2 phosphorylation that was restricted to the cytosol and not inhibited by Ro 31-8425. Internalization of the α1D-AR subtype was not observed via CypHer5 technology. The three α1-AR subtypes present different spatio-temporal patterns of receptor internalization, and only α1A-AR stimulation translates to a late, sustained ERK1/2 phosphorylation that is restricted to the cytosol and dependent on β-arrestin 2 mediated internalization.

  15. The second extracellular loop of GPCRs determines subtype-selectivity and controls efficacy as evidenced by loop exchange study at A2 adenosine receptors.

    PubMed

    Seibt, Benjamin F; Schiedel, Anke C; Thimm, Dominik; Hinz, Sonja; Sherbiny, Farag F; Müller, Christa E

    2013-05-01

    The second extracellular loop (EL2) of G protein-coupled receptors (GPCRs), which represent important drug targets, may be involved in ligand recognition and receptor activation. We studied the closely related adenosine receptor (AR) subtypes A2A and A2B by exchanging the complete EL2 of the human A2BAR for the EL2 of the A2AAR. Furthermore, single amino acid residues (Asp148(45.27), Ser149(45.28), Thr151(45.30), Glu164(45.43), Ser165(45.44), and Val169(45.48)) in the EL2 of the A2BAR were exchanged for alanine. The single mutations did not lead to any major effects, except for the T151A mutant, at which NECA showed considerably increased efficacy. The loop exchange entailed significant effects: The A2A-selective agonist CGS21680, while being completely inactive at A2BARs, showed high affinity for the mutant A2B(EL2-A2A)AR, and was able to fully activate the receptor. Most strikingly, all agonists investigated (adenosine, NECA, BAY60-6583, CGS21680) showed strongly increased efficacies at the mutant A2B(EL2-A2A) as compared to the wt AR. Thus, the EL2 of the A2BAR appears to have multiple functions: besides its involvement in ligand binding and subtype selectivity it modulates agonist-bound receptor conformations thereby controlling signalling efficacy. This role of the EL2 is likely to extend to other members of the GPCR family, and the EL2 of GPCRs appears to be an attractive target structure for drugs.

  16. A coupled groundwater-flow-modelling and vulnerability-mapping methodology for karstic terrain management

    NASA Astrophysics Data System (ADS)

    Kavouri, Konstantina P.; Karatzas, George P.; Plagnes, Valérie

    2017-02-01

    A coupled groundwater-flow-modelling and vulnerability-mapping methodology for the management of karst aquifers with spatial variability is developed. The methodology takes into consideration the duality of flow and recharge in karst and introduces a simple method to integrate the effect of temporal storage in the unsaturated zone. In order to investigate the applicability of the developed methodology, simulation results are validated against available field measurement data. The criteria maps from the PaPRIKa vulnerability-mapping method are used to document the groundwater flow model. The FEFLOW model is employed for the simulation of the saturated zone of Palaikastro-Chochlakies karst aquifer, in the island of Crete, Greece, for the hydrological years 2010-2012. The simulated water table reproduces typical karst characteristics, such as steep slopes and preferred drain axes, and is in good agreement with field observations. Selected calculated error indicators—Nash-Sutcliffe efficiency (NSE), root mean squared error (RMSE) and model efficiency (E')—are within acceptable value ranges. Results indicate that different storage processes take place in different parts of the aquifer. The north-central part seems to be more sensitive to diffuse recharge, while the southern part is affected primarily by precipitation events. Sensitivity analysis is performed on the parameters of hydraulic conductivity and specific yield. The methodology is used to estimate the feasibility of artificial aquifer recharge (AAR) at the study area. Based on the developed methodology, guidelines were provided for the selection of the appropriate AAR scenario that has positive impact on the water table.

  17. A Versatile Platform for Single- and Multiple-Unnatural Amino Acid Mutagenesis in Escherichia coli

    PubMed Central

    Chatterjee, Abhishek; Sun, Sophie B.; Furman, Jennifer L.; Xiao, Han; Schultz, Peter G.

    2013-01-01

    To site-specifically incorporate an unnatural amino acid (UAA) into target proteins in Escherichia coli, we use a suppressor plasmid that provides an engineered suppressor tRNA and an aminoacyl-tRNA synthetase (aaRS) specific for the UAA of interest. The continuous drive to further improve UAA incorporation efficiency in E. coli has resulted in several generations of suppressor plasmids. Here we describe a new, highly efficient suppressor plasmid, pUltra, harboring a single copy each of the tRNA and aaRS expression cassettes that exhibits higher suppression activity than its predecessors. This system is able to efficiently incorporate up to three UAAs within the same protein at levels up to 30% of the level of wild-type protein expression. Its unique origin of replication (CloDF13) and antibiotic resistance marker (spectinomycin) allow pUltra to be used in conjunction with the previously reported pEVOL suppressor plasmid, each encoding a distinct tRNA/aaRS pair, to simultaneously insert two different UAAs into the same protein. We demonstrate the utility of this system by efficiently incorporating two bio-orthogonal UAAs containing keto and azido side chains into ketosteroid isomerase and subsequently derivatizing these amino acid residues with two distinct fluorophores, capable of Förster resonance energy transfer interaction. Finally, because of its minimal composition, two different tRNA/aaRS pairs were encoded in pUltra, allowing the generation of a single plasmid capable of dual suppression. The high suppression efficiency and the ability to harbor multiple tRNA/aaRS pairs make pUltra a useful system for conducting single- and multiple-UAA mutagenesis in E. coli. PMID:23379331

  18. Identification and functional characterization of an endoplasmic reticulum oxidoreductin 1-α gene in Litopenaeus vannamei.

    PubMed

    Zhang, Ze-Zhi; Yuan, Kai; Yue, Hai-Tao; Yuan, Feng-Hua; Bi, Hai-Tao; Weng, Shao-Ping; He, Jian-Guo; Chen, Yi-Hong

    2016-04-01

    In the current study, full-length sequence of endoplasmic reticulum oxidoreductin 1-α (LvERO1-α) was cloned from Litopenaeus vannamei. Real-time RT-PCR results showed that LvERO1-α was highly expressed in hemocytes, gills, and intestines. White spot syndrome virus (WSSV) challenge was performed, and the expression of LvERO1-α and two other downstream genes of the double-stranded RNA-activated protein kinase-like ER kinase-eIF2α (PERK-α) pathway, namely, homocysteine-induced endoplasmic reticulum protein (LvHERP) and acylamino-acid-releasing enzyme (LvAARE), strongly increased in the hemocytes. Flow cytometry assay results indicated that the apoptosis rate of L. vannamei hemocytes in the LvERO1-α knockdown group was significantly lower than that of the controls. Moreover, shrimps with knockdown expression of LvERO1-α exhibited decreased cumulative mortality upon WSSV infection. Downregulation of L. vannamei immunoglobulin-binding protein (LvBip), which had been proven to induce unfolded protein response (UPR) in L. vannamei, did not only upregulate LvERO1-α, LvHERP, and LvAARE in hemocytes, but also increased their apoptosis rate, as well as the shrimp cumulative mortality. Furthermore, reporter gene assay results showed that the promoter of LvERO1-α was activated by L. vannamei activating transcription factor 4, thereby confirming that LvERO1-α was regulated by the PERK-eIF2α pathway. These results suggested that LvERO1-α plays a critical role in WSSV-induced apoptosis, which likely occurs through the WSSV-activated PERK-eIF2α pathway.

  19. Fat segmentation on chest CT images via fuzzy models

    NASA Astrophysics Data System (ADS)

    Tong, Yubing; Udupa, Jayaram K.; Wu, Caiyun; Pednekar, Gargi; Subramanian, Janani Rajan; Lederer, David J.; Christie, Jason; Torigian, Drew A.

    2016-03-01

    Quantification of fat throughout the body is vital for the study of many diseases. In the thorax, it is important for lung transplant candidates since obesity and being underweight are contraindications to lung transplantation given their associations with increased mortality. Common approaches for thoracic fat segmentation are all interactive in nature, requiring significant manual effort to draw the interfaces between fat and muscle with low efficiency and questionable repeatability. The goal of this paper is to explore a practical way for the segmentation of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) components of chest fat based on a recently developed body-wide automatic anatomy recognition (AAR) methodology. The AAR approach involves 3 main steps: building a fuzzy anatomy model of the body region involving all its major representative objects, recognizing objects in any given test image, and delineating the objects. We made several modifications to these steps to develop an effective solution to delineate SAT/VAT components of fat. Two new objects representing interfaces of SAT and VAT regions with other tissues, SatIn and VatIn are defined, rather than using directly the SAT and VAT components as objects for constructing the models. A hierarchical arrangement of these new and other reference objects is built to facilitate their recognition in the hierarchical order. Subsequently, accurate delineations of the SAT/VAT components are derived from these objects. Unenhanced CT images from 40 lung transplant candidates were utilized in experimentally evaluating this new strategy. Mean object location error achieved was about 2 voxels and delineation error in terms of false positive and false negative volume fractions were, respectively, 0.07 and 0.1 for SAT and 0.04 and 0.2 for VAT.

  20. Simulated performance of biomass gasification based combined power and refrigeration plant for community scale application

    NASA Astrophysics Data System (ADS)

    Chattopadhyay, S.; Mondal, P.; Ghosh, S.

    2016-07-01

    Thermal performance analysis and sizing of a biomass gasification based combined power and refrigeration plant (CPR) is reported in this study. The plant is capable of producing 100 kWe of electrical output while simultaneously producing a refrigeration effect, varying from 28-68 ton of refrigeration (TR). The topping gas turbine cycle is an indirectly heated all-air cycle. A combustor heat exchanger duplex (CHX) unit burns producer gas and transfer heat to air. This arrangement avoids complex gas cleaning requirements for the biomass-derived producer gas. The exhaust air of the topping GT is utilized to run a bottoming ammonia absorption refrigeration (AAR) cycle via a heat recovery steam generator (HRSG), steam produced in the HRSG supplying heat to the generator of the refrigeration cycle. Effects of major operating parameters like topping cycle pressure ratio (rp) and turbine inlet temperature (TIT) on the energetic performance of the plant are studied. Energetic performance of the plant is evaluated via energy efficiency, required biomass consumption and fuel energy savings ratio (FESR). The FESR calculation method is significant for indicating the savings in fuel of a combined power and process heat plant instead of separate plants for power and process heat. The study reveals that, topping cycle attains maximum power efficiency of 30%in pressure ratio range of 8-10. Up to a certain value of pressure ratio the required air flow rate through the GT unit decreases with increase in pressure ratio and then increases with further increase in pressure ratio. The capacity of refrigeration of the AAR unit initially decreases up to a certain value of topping GT cycle pressure ratio and then increases with further increase in pressure ratio. The FESR is found to be maximized at a pressure ratio of 9 (when TIT=1100°C), the maximum value being 53%. The FESR is higher for higher TIT. The heat exchanger sizing is also influenced by the topping cycle pressure ratio and GT-TIT.

  1. Effects by silodosin on the partially obstructed rat ureter in vivo and on human and rat isolated ureters

    PubMed Central

    Villa, L; Buono, R; Fossati, N; Rigatti, P; Montorsi, F; Benigni, F; Hedlund, P

    2013-01-01

    Background and Purpose α1-adrenoceptor (-AR) antagonists may facilitate ureter stone passage in humans. We aimed to study effects by the α1A-AR selective antagonist silodosin (compared to tamsulosin and prazosin) on ureter pressures in a rat model of ureter obstruction, and on contractions of human and rat isolated ureters. Experimental Approach After ethical approval, ureters of male rats were cannulated beneath the kidney pelvis for in vivo ureteral intraluminal recording of autonomous peristaltic pressure waves. A partial ureter obstruction was applied to the distal ureter. Mean arterial blood pressure (MAP) was recorded. Approximate clinical and triple clinical doses of the α1-AR antagonists were given intravenously. Effects by the α1-AR antagonists on isolated human and rat ureters were studied in organ baths. Key Results Intravenous silodosin (0.1–0.3 mg kg−1) or prazosin (0.03–0.1 mg kg−1) reduced obstruction-induced increases in intraluminal ureter pressures by 21–37% or 18–40% respectively. Corresponding effects by tamsulosin (0.01 or 0.03 mg kg−1) were 9–20%. Silodosin, prazosin and tamsulosin reduced MAP by 10–12%, 25–26% (P < 0.05), or 18–25% (P < 0.05) respectively. When effects by the α1A-AR antagonists on obstruction-induced ureter pressures were expressed as a function of MAP, silodosin had six- to eightfold and 2.5- to eightfold better efficacy than tamsulosin or prazosin respectively. Silodosin effectively reduced contractions of both human and rat isolated ureters. Conclusions and Implications Silodosin inhibits contractions of the rat and human isolated ureters and has excellent functional selectivity in vivo to relieve pressure-load of the rat obstructed ureter. Silodosin as pharmacological ureter stone expulsive therapy should be clinically further explored. PMID:23373675

  2. T3 enhances Ang2 in rat aorta in myocardial I/R: comparison with left ventricle.

    PubMed

    Sabatino, Laura; Kusmic, Claudia; Nicolini, Giuseppina; Amato, Rosario; Casini, Giovanni; Iervasi, Giorgio; Balzan, Silvana

    2016-10-01

    Angiogenesis is important for recovery after tissue damage in myocardial ischemia/reperfusion, and tri-iodothyronine (T3) has documented effects on angiogenesis. The angiopoietins 1/2 and tyrosine kinase receptor represent an essential system in angiogenesis controlling endothelial cell survival and vascular maturation. Recently, in a 3-day ischemia/reperfusion rat model, the infusion of a low dose of T3 improved the post-ischemic recovery of cardiac function.Adopting this model, our study aimed to investigate the effects of T3 on the capillary index and the expression of angiogenic genes as the angiopoietins 1/2 and tyrosine kinase receptor system, in the thoracic aorta and in the left ventricle. In the thoracic aorta, T3 infusion significantly improved the angiogenic sprouting and angiopoietin 2 expression. Instead, Sham-T3 group did not show any significant increment of capillary density and angiopoietin 2 expression. In the area at risk (AAR) of the left ventricle, T3 infusion did not increase capillary density but restored levels of angiopoietin 1, which were reduced in I/R group. Angiopoietin 2 levels were similar to Sham group and unchanged by T3 administration. In the remote zone, T3 induced a significant increment of both angiopoietin 1/2. In conclusion, T3 infusion induced a different response of angiopoietin 1/2 between the ventricle (the AAR and the remote zone) and the thoracic aorta, probably reflecting the different action of angiopoietin 1/2 in cardiomyocytes and endothelial cells. Overall, these data suggest a new aspect of T3-mediated cardioprotection through angiogenesis.

  3. High magnitude and rapid incision from river capture: Rhine River, Switzerland

    NASA Astrophysics Data System (ADS)

    Yanites, Brian J.; Ehlers, Todd A.; Becker, Jens K.; Schnellmann, Michael; Heuberger, Stefan

    2013-06-01

    Landscape evolution is controlled by the development and organization of drainage basins. As a landscape evolves, drainage reorganization events can occur via river capture or piracy, whereby one river basin grows at the expense of another. The river downstream of a capture location will generate a transient topographic response as the added water discharge increases sediment transport and erosion efficiency. This erosional response will propagate upstream through both the captured and original river basins. Here we focus on quantifying the impact of drainage reorganization along the Rhine/Aare River system (~45,000 km2) during the late Pliocene/early Pleistocene, where gravel remnants indicate total incision of ~650 m during the last ~4.2 Myr in the region of the recent Aare-Rhine confluence. We develop a numerical model of drainage capture to quantify the range of possible magnitudes of erosion and the transient river response resulting from the reorganization of the Rhine River. The model accounts for both fluvial incision and sediment transport. Our model estimates 400-800 m of river elevation change (lowering profiles) during the last ~4 Myr due to river capture events, providing an important component to the recent exhumation budget of the Swiss Alpine Foreland. The model indicates a rapid response to capture events (re-equilibration timescale of ~1 Myr). The predicted incision magnitudes are consistent with incision measured from the elevation of Pliocene and early Pleistocene river gravels, suggesting that across northern Switzerland, a significant amount of incision can be explained by drainage reorganization.

  4. 3D VMAT Verification Based on Monte Carlo Log File Simulation with Experimental Feedback from Film Dosimetry.

    PubMed

    Barbeiro, A R; Ureba, A; Baeza, J A; Linares, R; Perucha, M; Jiménez-Ortega, E; Velázquez, S; Mateos, J C; Leal, A

    2016-01-01

    A model based on a specific phantom, called QuAArC, has been designed for the evaluation of planning and verification systems of complex radiotherapy treatments, such as volumetric modulated arc therapy (VMAT). This model uses the high accuracy provided by the Monte Carlo (MC) simulation of log files and allows the experimental feedback from the high spatial resolution of films hosted in QuAArC. This cylindrical phantom was specifically designed to host films rolled at different radial distances able to take into account the entrance fluence and the 3D dose distribution. Ionization chamber measurements are also included in the feedback process for absolute dose considerations. In this way, automated MC simulation of treatment log files is implemented to calculate the actual delivery geometries, while the monitor units are experimentally adjusted to reconstruct the dose-volume histogram (DVH) on the patient CT. Prostate and head and neck clinical cases, previously planned with Monaco and Pinnacle treatment planning systems and verified with two different commercial systems (Delta4 and COMPASS), were selected in order to test operational feasibility of the proposed model. The proper operation of the feedback procedure was proved through the achieved high agreement between reconstructed dose distributions and the film measurements (global gamma passing rates > 90% for the 2%/2 mm criteria). The necessary discretization level of the log file for dose calculation and the potential mismatching between calculated control points and detection grid in the verification process were discussed. Besides the effect of dose calculation accuracy of the analytic algorithm implemented in treatment planning systems for a dynamic technique, it was discussed the importance of the detection density level and its location in VMAT specific phantom to obtain a more reliable DVH in the patient CT. The proposed model also showed enough robustness and efficiency to be considered as a pre

  5. Pharmacological blockade of small conductance Ca(2+)-activated K(+) channels by ICA reduces arrhythmic load in rats with acute myocardial infarction.

    PubMed

    Hundahl, Laura A; Sattler, Stefan M; Skibsbye, Lasse; Diness, Jonas G; Tfelt-Hansen, Jacob; Jespersen, Thomas

    2017-03-11

    Acute myocardial infarction (AMI) with development of ventricular fibrillation (VF) is a common cause of sudden cardiac death (SCD). At present, no pharmacological treatment has successfully been able to prevent VF in the acute stage of AMI. This study investigates the antiarrhythmic effect of inhibiting small conductance Ca(2+)-activated K(+) (SK) channels using the pore blocker N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) in AMI rats. Acute coronary ligation was performed in 26 anesthetized rats, and ECG, monophasic action potentials (MAPs), and ventricular effective refractory period (vERP) were recorded. Rats were randomized into four groups: (i) 3 mg/kg i.v. ICA with AMI (AMI-ICA-group, n = 9), (ii) vehicle with AMI (AMI-vehicle-group, n = 9), (iii) vehicle with sham operation (sham-vehicle-group, n = 8), and (iv) 3 mg/kg i.v. ICA with sham operation (sham-ICA-group, n = 6). At the end of experiments, hearts were stained for the non-perfused area at risk (AAR). AMI resulted in the development of ventricular tachycardia (VT) in all AMI-vehicle and AMI-ICA rats; however, ICA significantly decreased VT duration. VF occurred in 44% of AMI-vehicle rats but not in AMI-ICA rats. Monophasic action potential duration at 80% repolarization (MAPD80) in the ischemic area decreased rapidly in both AMI-vehicle and AMI-ICA rats. However, 5 min after occlusion, MAPD80 returned to baseline in AMI-ICA rats but not in AMI-vehicle rats. The vERP was prolonged in the AMI-ICA group compared to AMI-vehicle after ligation. AAR was similar between the AMI-vehicle group and the AMI-ICA group. In rats with AMI, ICA reduces the burden of arrhythmia.

  6. Frequencies, mechanisms and climate forcing of paleofloods in the Bernese Alps (Switzerland) inferred from natural, historical, and instrumental time series

    NASA Astrophysics Data System (ADS)

    Schulte, Lothar; Peña, Juan Carlos; Carvalho, Filipe; Julià, Ramon; Gómez-Bolea, Antonio; Burjachs, Francesc; Llorca, Jaime; Rubio, Patricio; Veit, Heinz

    2015-04-01

    The aim of this contribution is the reconstruction of a 2600-yr long flood series generated from high-resolution deltaplain sediments of the Hasli-Aare and Lütschine delta, which reproduces the fluvial dynamic and related mechanisms, including trends, clusters and gaps of floods in alpine catchments. Paleofloods frequencies were reconstructed from geoarchives particularly by sedimentary, geochemical (XRF-core scan, conventional XRF, LOI and grain size), mineralogical, geomorphological, pollen and lichenometric records. An important issue is the question if these paleofloods can be calibrated (exact dating) by data series from historical sources (textual and factual) and by instrumental data. Not less than 12 of 14 severe and catastrophic events before the termination of the River Aare Correction in 1867, are detected during the last 700 years also by coarse-grained flood layers, ln(Zr/Ti) peaks and Factor 1 scores. Spectral analysis of the geochemical and pollen time series and climate proxies (δ14C, TSI, δ18O isotopes from the Greenland ice, temperatures and precipitation reconstruction from tree-rings, NAO, SNAO) evidence similar periodicities of 60, 85, 105, 120 and 200 yrs during the two last Millennia. Thus, the mechanisms of the flood processes are strongly influenced by the North Atlantic dynamics and solar forcing. The composite 2600-yr sedimentary floodplain record illustrates that periods of organic soil formation and deposition of phyllosilicates (medium high catchment area) match very clearly to maxima of Total Solar Irradiance (Steinhilber et al., 2009) pointing to reduced flood activity during warmer climate pulses. The aggradation of the paleoflood clusters (e.g. 1300-1350, 1420-1480, 1550-1620, 1650-1720 and 1811-1851 cal yr AD) with contribution of siliciclasts from highest catchment area (plutonic bedrock) occurred predominantly during periods with cooler summer temperature, reduced solar irradiance and phases of drier spring climate (B

  7. The history of Cesium-137 liquid emissions by Mühleberg Nuclear Power Plant (Switzerland) is recorded in Lake Biel sediments

    NASA Astrophysics Data System (ADS)

    Girardclos, Stéphanie; Faessler, Jérôme; Loizeau, Jean-Luc; Zehringer, Markus

    2014-05-01

    Lake sediments record changes happening in their upstream river catchment and regional environment which includes traces of artificial radionuclides emissions deriving from human activities. 137Cs emissions started worldwide in the early 1950's and peaked in 1963-64 due to nuclear bomb tests in the high atmosphere. A second 137Cs activity peak, due to the 1986 Chernobyl catastrophe is recorded in sediment archives from central Europe. These two events (1963/64 and 1986) serve routinely as time markers for recent lake records. Nuclear Power Plants (NPPs) are often constructed along river course for cooling purposes. Since 1972, Mühleberg NPP (central Switzerland) lies 18 km upstream Lake Biel and releases radioactive liquid emissions into the Aare river which adds to the diffuse - above mentioned - radioactive pollution, as revealed by Albrecht et al. (1995; 1998) and recently confirmed by Thevenon et al. (2013) from Lake Biel sediments. The water of Lake Biel is used as drinking water for ca. 60'000 inhabitants and its outflowing water is further used by downstream cities lying on the Aare-Rhine course such as Basel (200'000 inhab.) In this study, the 137Cs activity curve of a 90-cm-long sediment core (BIE10-8), retrieved in April 2010 from the central Lake Biel basin at ca. 50 m depth, and measured by gamma ray spectrometry using high resolution germanium detectors, confirms previous work and reveals a new peak for the year 1998-2000, as observed by Thevenon et al. (2013). This peak is most certainly due to Mühleberg NPP as shown by the good correlation with declared 137Cs liquid emissions indicating a significant increase in 1998-99. Decay corrected activity data, converted into 137Cs fluxes, point to water pollution by Mühleberg NPP in 1975-1985 as being similar to those linked to the catastrophic events in 1963-64 and 1986 (about 75%). As former study showed that Lake Biel sediments scavenge only a portion of the total radionuclide in water, i.e. 30-55% for

  8. Suitability of alkaline leaching and etching experiments in the quantification of ASR potential of quartz-rich rocks

    NASA Astrophysics Data System (ADS)

    Kuchařová, Aneta; Šachlová, Šárka; Pertold, Zdeněk; Přikryl, Richard

    2015-04-01

    Three groups of methods are conventionally applied in the assessment of the susceptibility of aggregates used in concrete to be affected by alkali-silica reaction (ASR). The most frequently employed expansion tests (accelerated mortar bar test and concrete prism test, e.g. ASTM C1260, RILEM AAR2, RILEM AAR4.1) quantify ASR potential of aggregates according to the expansion values of mortar bars (resp. concrete prisms) measured after certain testing time period. Petrographic methods are based on the quantification of alkali-reactive phases by polarizing microscopy (e.g. RILEM AAR1). Chemical methods quantify ASR potential according to the amount of Si4+ dissolved into alkaline solution combined with the reduction of alkalinity of the solution (e.g. ASTM C289). The current study focused on the comparison of three approaches: the alkaline etching of polished rock sections and standard chemical method (following ASTM C289) with the measuring of expansion values of mortar bars (following ASTM C1260). Various types of quartz and amorphous SiO2 used for the experiments were separated from rock samples of orthoquartzite, quartz meta-greywacke, pegmatite, phyllite, chert, and flint. Polished rock sections (resp. crushed fraction 0.125/0.250) were used and subjected to leaching in 1M NaOH solution at 80°C for 14 days (resp. 24 hours). After alkaline etching in alkaline solution, the rock sections were analyzed by scanning electron microscopy combined with energy dispersive spectrometer. Representative areas were documented in back scattered electron images and quantified using fully-automatic petrographic image analysis. ASR potential of the polished rock sections was evaluated by the vol. % of area affected by alkaline etching. ASR potential of crushed aggregate was estimated by measurements of Si4+ dissolved into the solution versus the reduction of alkalinity of the solution (following ASTM C289). Classification according to the ASTM C289 indicated three of investigated

  9. Heritable and cancer risks of exposures to anticancer drugs: inter-species comparisons of covalent deoxyribonucleic acid-binding agents.

    PubMed

    Vogel, E W; Barbin, A; Nivard, M J; Stack, H F; Waters, M D; Lohman, P H

    1998-05-25

    In the past years, several methodologies were developed for potency ranking of genotoxic carcinogens and germ cell mutagens. In this paper, we analyzed six sub-classes of covalent deoxyribonucleic acid (DNA) binding antineoplastic drugs comprising a total of 37 chemicals and, in addition, four alkyl-epoxides, using four approaches for the ranking of genotoxic agents on a potency scale: the EPA/IARC genetic activity profile (GAP) database, the ICPEMC agent score system, and the analysis of qualitative and quantitative structure-activity and activity-activity relationships (SARs, AARs) between types of DNA modifications and genotoxic endpoints. Considerations of SARs and AARs focused entirely on in vivo data for mutagenicity in male germ cells (mouse, Drosophila), carcinogenicity (TD50s) and acute toxicity (LD50s) in rodents, whereas the former two approaches combined the entire database on in vivo and in vitro mutagenicity tests. The analysis shows that the understanding and prediction of rank positions of individual genotoxic agents requires information on their mechanism of action. Based on SARs and AARs, the covalent DNA binding antineoplastic drugs can be divided into three categories. Category 1 comprises mono-functional alkylating agents that primarily react with N7 and N3 moieties of purines in DNA. Efficient DNA repair is the major protective mechanism for their low and often not measurable genotoxic effects in repair-competent germ cells, and the need of high exposure doses for tumor induction in rodents. Due to cell type related differences in the efficiency of DNA repair, a strong target cell specificity in various species regarding the potency of these agents for adverse effects is found. Three of the four evaluation systems rank category 1 agents lower than those of the other two categories. Category 2 type mutagens produce O-alkyl adducts in DNA in addition to N-alkyl adducts. In general, certain O-alkyl DNA adducts appear to be slowly repaired, or

  10. Annual and seasonal mass balances of Chhota Shigri Glacier (benchmark glacier, Western Himalaya), India

    NASA Astrophysics Data System (ADS)

    Mandal, Arindan; Ramanathan, Alagappan; Farooq Azam, Mohd; Wagnon, Patrick; Vincent, Christian; Linda, Anurag; Sharma, Parmanand; Angchuk, Thupstan; Bahadur Singh, Virendra; Pottakkal, Jose George; Kumar, Naveen; Soheb, Mohd

    2015-04-01

    Several studies on Himalayan glaciers have been recently initiated as they are of particular interest in terms of future water supply, regional climate change and sea-level rise. In 2002, a long-term monitoring program was initiated on Chhota Shigri Glacier (15.7 square km, 9 km long, 6263-4050 m a.s.l.) located in Lahaul and Spiti Valley, Himachal Pradesh, India. This glacier lies in the monsoon-arid transition zone (western Himalaya) and is a representative glacier in Lahaul and Spiti Valley. While annual mass balances have been measured continuously since 2002 using the glaciological method, seasonal scale observations began in 2009. The annual and seasonal mass balances were then analyzed along with meteorological conditions in order to understand the role of winter and summer balances on annual glacier-wide mass balance of Chhota Shigri glacier. During the period 2002-2013, the glacier experienced a negative glacier-wide mass balance of -0.59±0.40 m w.e. a-1 with a cumulative glaciological mass balance of -6.45 m w.e. Annual glacier-wide mass balances were negative except for four years (2004/05, 2008/09, 2009/10 and 2010/11) where it was generally close to balanced conditions. Equilibrium line altitude (ELA) for steady state condition is calculated as 4950 m a.s.l. corresponding to an accumulation area ratio (AAR) of 62% using annual glacier-wide mass balance, ELA and AAR data between 2002 and 2013. The winter glacier-wide mass balance between 2009 and 2013 ranges from a maximum value of 1.38 m w.e. in 2009/10 to a minimum value of 0.89 in 2012/13 year whereas the summer glacier-wide mass balance varies from the highest value of -0.95 m w.e. in 2010/11 to the lowest value of -1.72 m w.e. in 2011/12 year. The mean vertical mass balance gradient between 2002 and 2013 was 0.66 m w.e. (100 m)-1 quite similar to Alps, Nepalese Himalayas etc. Over debris covered area, the gradients are highly variable with a negative mean value of -2.15 m w.e. (100 m)-1 over 2002

  11. Reconstructed glacier geometry and inferred Equilibrium Line Altitude changes during the Late Pleistocene deglaciation in the Retezat Mountains, Southern Carpathians

    NASA Astrophysics Data System (ADS)

    Madarász, Balázs; Ruszkiczay-Rüdiger, Zsófia; Kern, Zoltán; Urdea, Petru

    2016-04-01

    Quaternary glaciations had a major imprint on the landscape and topography of the Southern Carpathians. Their transitional position between continental and Mediterranean climate zones arouses special interest concerning the timing and pattern of glaciations in this area. Probably the Retezat Mts hosted the most extended glaciation during the Late Pleistocene within this range. The peak elevations of the study area reach 2500 m asl, and the most extended glaciers descended to 1040 m in the northern and to 1130 m on the southern valleys. Major cirque floors are typically situated at 2000-2100 m asl. Glacial landforms have been mapped in order to reconstruct the past ice bodies and the elevation shifts of the paleo equilibrium line altitudes (ELA) during several deglaciation phases of the Last Glacial Maximum (LGM) and Lateglacial in the Retezat Mts. On the basis of published 10Be exposure age data on the northern valleys of the study area, deglaciation of the Retezat Mts occurred at least in five phases between ~21.0 ka and 13.5 ka [1]. Various methods (THAR, AAR, AABR) have been tested using a GIS tool to estimate the ELA of the reconstructed paleoglaciers [2] and paleo ELAs were calculated for each of the deglaciation phases. Preliminary estimates of regional LGM paleoELA employing the simplest THAR method (with a ratio of 0.5) ranged from ~1670 m during the LGM to ~2210 m for the smallest cirque glacier at 13.5 ka, respectively. The AAR and AABR methods provide somewhat higher ELAs for each phase. The obtained paleoELAs were compared to ELA reconstructions available from other Carpathian ranges and also to the Alps and Dinarides. Our data will contribute to a more accurate ELA distribution during the LGM, which may be indicative of the past state of the climate system (moisture gradient, circulation regimes). Thanks to OTKA PD83610, PD104899; NKM-96/2014, NKM-31/2015; OMAA 90öu17; LP2012-27/2012. References: [1] Ruszkiczay-Rüdiger et al. 2016 Quat. Int. (in

  12. Interpretation of fluid inclusions in quartz deformed by weak ductile shearing: Reconstruction of differential stress magnitudes and pre-deformation fluid properties

    NASA Astrophysics Data System (ADS)

    Diamond, Larryn W.; Tarantola, Alexandre

    2015-05-01

    A well developed theoretical framework is available in which paleofluid properties, such as chemical composition and density, can be reconstructed from fluid inclusions in minerals that have undergone no ductile deformation. The present study extends this framework to encompass fluid inclusions hosted by quartz that has undergone weak ductile deformation following fluid entrapment. Recent experiments have shown that such deformation causes inclusions to become dismembered into clusters of irregularly shaped relict inclusions surrounded by planar arrays of tiny, new-formed (neonate) inclusions. Comparison of the experimental samples with a naturally sheared quartz vein from Grimsel Pass, Aar Massif, Central Alps, Switzerland, reveals striking similarities. This strong concordance justifies applying the experimentally derived rules of fluid inclusion behaviour to nature. Thus, planar arrays of dismembered inclusions defining cleavage planes in quartz may be taken as diagnostic of small amounts of intracrystalline strain. Deformed inclusions preserve their pre-deformation concentration ratios of gases to electrolytes, but their H2O contents typically have changed. Morphologically intact inclusions, in contrast, preserve the pre-deformation composition and density of their originally trapped fluid. The orientation of the maximum principal compressive stress (σ1) at the time of shear deformation can be derived from the pole to the cleavage plane within which the dismembered inclusions are aligned. Finally, the density of neonate inclusions is commensurate with the pressure value of σ1 at the temperature and time of deformation. This last rule offers a means to estimate magnitudes of shear stresses from fluid inclusion studies. Application of this new paleopiezometer approach to the Grimsel vein yields a differential stress (σ1-σ3) of ˜ 300 MPa at 390 ± 30 °C during late Miocene NNW-SSE orogenic shortening and regional uplift of the Aar Massif. This differential

  13. Aminostratigraphy of surface and subsurface Quaternary sediments, North Carolina coastal plain, USA

    USGS Publications Warehouse

    Wehmiller, J. F.; Thieler, E.R.; Miller, D.; Pellerito, V.; Bakeman, Keeney V.; Riggs, S.R.; Culver, S.; Mallinson, D.; Farrell, K.M.; York, L.L.; Pierson, J.; Parham, P.R.

    2010-01-01

    The Quaternary stratigraphy and geochronology of the Albemarle Embayment of the North Carolina (NC) Coastal Plain is examined using amino acid racemization (AAR) in marine mollusks, in combination with geophysical, lithologic, and biostratigraphic analysis of 28 rotasonic cores drilled between 2002 and 2006. The Albemarle Embayment is bounded by structural highs to the north and south, and Quaternary strata thin westward toward the Suffolk paleoshoreline, frequently referred to as the Suffolk Scarp. The Quaternary section is up to ???90. m thick, consists of a variety of estuarine, shelf, back-barrier, and lagoonal deposits, and has been influenced by multiple sea-level cycles. The temporal resolution of the amino acid racemization method is tested statistically and with the stratigraphic control provided by this geologic framework, and it is then applied to the correlation and age estimation of subsurface units throughout the region. Over 500 specimens (primarily Mercenaria and Mulinia) from the subsurface section have been analyzed using either gas chromatographic (GC) or reverse-phase liquid chromatographic (RPLC) techniques. The subsurface stratigraphic data are compared with AAR results from numerous natural or excavated exposures from the surrounding region, as well as results from NC beach collections, to develop a comprehensive aminostratigraphic database for the entire Quaternary record within the NC coastal system. Age mixing, recognized in the beach collections, is also seen in subsurface sections, usually where major seismic reflections or core lithology indicate the presence of stratigraphic discontinuities. Kinetic models for racemization are tested within the regional stratigraphic framework, using either radiocarbon or U-series calibrations or comparison with regional biostratigraphy. Three major Pleistocene aminozones [AZ2, AZ3, and AZ4] are found throughout the region, all being found in superposition in several cores. Each can be subdivided

  14. Properties of Alfven waves in the magnetotail below 9 R(E) and their relation to auroral acceleration and major geomagnetic storms

    NASA Astrophysics Data System (ADS)

    Dombeck, John Paul

    The presented studies investigate the characteristics of Alfvén wave events in the geomagnetic tail on the plasma sheet boundary layer (PSBL) and possibly well within the plasma sheet during substorms and major geomagnetic storms (<- 200 Dst). Such storms are rare but dramatically affect the state of the magnetosphere in ways that we have only recently been capable of investigating with sufficient in situ instrumentation. The first comparative study of major storm PSBL Alfvén waves events is presented. Properties of eight substorm and ten major storm events are compared using a new method, providing new insights into the phenomena, their interactions in the auroral acceleration region (AAR), and their generation. Direct comparison between Polar and FAST indicating a decrease (increase) in low-(high-)frequency shear (kinetic) earthward Alfvénic Poynting flux and an increase in earthward electron energy flux strongly suggests transfer of shear Alfvén wave Poynting flux to kinetic Alfvén waves which then accelerate auroral electrons. Polar observations also suggest a broadband source and indicate that small-scale, temporally/spatially variable factors, likely including density cavities and ionospheric conductivity structure, strongly affect the reflectivity/dissipation properties, as the waves in each frequency band contain a mixture of earthward, tailward, reflecting and incoherent wave intervals. Averages of these properties are consistent with theory, but the detailed structure has not been predicted. Tailward intervals also suggest ionospheric field line shear. Most major storm events were found have similar properties to substorm events with a few notable differences, consistent with effects related to the extended duration of storms. Low-latitude broadband auroral electrons and high-frequency Alfvén waves along with properties of a unique Alfvén wave event, related to a major storm tail reconfiguration, with very intense Poynting flux and the first

  15. The response of debris-covered glaciers to climate change: A numerical modeling approach

    NASA Astrophysics Data System (ADS)

    Anderson, Leif S.; Anderson, Robert S.

    2016-04-01

    Debris-covered glaciers are common in rapidly-eroding alpine landscapes. When thicker than a few centimeters, surface debris suppresses melt rates. Continuous debris cover can therefore reduce the mass balance gradient in the ablation zone, leading to increases in glacier length. In order to quantify feedbacks in the debris-glacier-climate system, we developed a 2D long-valley numerical glacier model that includes deposition of debris on the glacier surface, and both englacial and supraglacial debris advection. We ran 120 simulations in which a steady state debris-free glacier responds to a step increase of surface debris deposition. Simulated glaciers advance to new steady states in which ice accumulation equals ice ablation, and debris input equals debris loss from the glacier. The debris flux onto the glacier surface, and the details of the relationship between debris thickness and melt rate strongly control glacier length. Debris deposited near the equilibrium-line altitude, where ice discharge is high, results in the greatest glacier extension when other debris-related variables are held constant. Continuous debris cover reduces ice discharge gradients, ice thickness gradients, and velocity gradients relative to debris-free glaciers forced by the same climate. Debris-forced glacier extension decreases the ratio of accumulation zone to total glacier area (AAR). The model reproduces first-order relationships between debris cover, AARs, and glacier surface velocities reported from glaciers in High Asia. We also explore the response of debris-covered glaciers to increases in the equilibrium-line altitude (climate warming). We highlight the conditions required to generate a low surface velocity 'dead' ice terminal reach during a warming climate, and the associated increase of fractional glacier surface debris. We also compare our debris-covered glacier climate response results with data from glaciers in High Asia. Our model provides a quantitative, theoretical

  16. Zooplankton Growth, Respiration and Grazing on the Australian Margins of the Tropical Indian and Pacific Oceans.

    PubMed

    McKinnon, A David; Doyle, Jason; Duggan, Samantha; Logan, Murray; Lønborg, Christian; Brinkman, Richard

    2015-01-01

    The specific activity of aminoacyl-tRNA synthetases (spAARS), an index of growth rate, and of the electron transport system (spETS), an index of respiration, was measured in three size fractions (73-150 μm, >150 μm and >350 μm) of zooplankton during five cruises to tropical coastal waters of the Kimberley coast (North West Australia) and four cruises to waters of the Great Barrier Reef (GBR; North East Australia). The N-specific biomass of plankton was 3-4-fold higher in the Kimberley than on the GBR in all 3 size classes: Kimberley 1.27, 3.63, 1.94 mg m-3; GBR 0.36, 0.88 and 0.58 mg m-3 in the 73-150 μm, >150 μm and >350 μm size classes, respectively. Similarly, spAARS activity in the Kimberley was greater than that of the GBR: 88.4, 132.2, and 147.6 nmol PPi hr-1 mg protein -1 in the Kimberley compared with 71.7, 82.0 and 83.8 nmol PPi hr-1 mg protein -1 in the GBR, for the 73-150 μm, >150 μm and >350 μm size classes, respectively. Specific ETS activity showed similar differences in scale between the two coasts: 184.6, 148.8 and 92.2 μL O2 hr-1 mg protein-1 in the Kimberley, against 86.5, 88.3 and 71.3 μL O2 hr-1 mg protein-1 in the GBR. On the basis of these measurements, we calculated that >150 μm zooplankton grazing accounted for 7% of primary production in the Kimberley and 8% in GBR waters. Area-specific respiration by >73 μm zooplankton was 7-fold higher in the Kimberley than on the GBR and production by >150 μm zooplankton was of the order of 278 mg C m-2 d-1 in the Kimberley and 42 mg C m-2 d-1 on the GBR. We hypothesize that the much stronger physical forcing on the North West shelf is the principal driver of higher rates in the west than in the east of the continent.

  17. Comparing reconstructed Pleistocene equilibrium-line altitudes in the tropical Andes of central Peru

    NASA Astrophysics Data System (ADS)

    Ramage, Joan M.; Smith, Jacqueline A.; Rodbell, Donald T.; Seltzer, Geoffrey O.

    2005-10-01

    Glacier equilibrium-line altitude (ELA), and the difference between modern and palaeo-ELA can be interpreted as a proxy for climate change. One issue in ELA reconstruction is that different methods of ELA reconstruction may produce a range of results for the same palaeoglacier. When a range of methods is used to reconstruct ELAs across a region, resulting variations may be related to the method rather than the past climate. Palaeoclimatic interpretation of ELAs that were reconstructed by different methods may prompt spurious inferences if the ELA range is the result of methodological differences rather than climatic variation. We address the relationship and degree of variation between methods by comparing terminus-to-headwall-altitude ratio (THAR), accumulation-area ratio (AAR), and accumulation-area balance ratio (AABR) methods for palaeoglaciers in four valleys in the tropical Andes. Valleys in the eastern cordillera of the Peruvian Andes bordering the Junin Plain (11° S, 76° W, ca. 4100 m a.s.l.) are presently ice-free but were glaciated repeatedly during the Pleistocene. We use a combination of 90-m shuttle radar topography mission (SRTM) data, 15-m Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) data, and 1:25 000 topographic maps to reconstruct ELAs. Within each of three groups of moraines, map-based THAR and AABR estimates of ELA tend to be highest, followed by DEM-derived THAR ELAs, with AAR-reconstructed ELAs somewhat lower in this region. ELA estimates for the local Last Glacial Maximum (LLGM) range from ca. 4250 to 4570 m a.s.l., with ELAs of ca. -220 to -550 m (depending on valley and method used). Within individual valleys, ELAs for the same palaeoglaciers calculated by different methods vary by +/- 100 m. ELAs of the LLGM glaciers and those of the largest glaciers to occupy the Junin valleys (> 65 ka) are not markedly different from each other, regardless of the method used in their calculation, which is largely a reflection

  18. Monitoring temporal variations in water resources across the Arabian Peninsula and identification of their controlling factors

    NASA Astrophysics Data System (ADS)

    Ahmed, M.; Sultan, M.; Othman, A.

    2015-12-01

    Assessment, monitoring, and development of the fresh water resources in the Arabian Peninsula (AP) are critical for the sustenance of the AP's growing population and water consumption. Monthly (01/2003-12/2013) Gravity Recovery and Climate Experiment (GRACE) data along with other relevant climatic, geologic, hydrogeologic, and remote sensing datasets were used to monitor the spatiotemporal variability in the AP's water resources and to investigate the causes of those variations. Four regions were selected; in our selection, we tried to cover major aquifers, follow political boundaries, and exceed GRACE footprint (~0.20×106 km2) to minimize uncertainties. The selected regions are: (1) Northern Saudi Arabia and Jordan (area: 0.53×106 km2), (2) Southern Saudi Arabia, Qatar and United Arab Emiratis (area: 0.97×106 km2), (3) Yemen (area: 0.45×106 km2), and (4) Oman (area: 0.32×106 km2). Results indicate: (1) Northern Saudi Arabia and Jordan area is experiencing large depletions (-8.76±0.94 mm/yr; -4.68±0.50 km3/yr) in GRACE-derived terrestrial water storage (TWS) that is largely related to groundwater extraction as well as decrease in rainfall rates throughout the investigated period compared to the preceding period (average annual rainfall [AAR]: 2003-2013: 58 mm; 1979-2002: 103 mm), (2) Southern Saudi Arabia, Qatar and United Arab Emiratis area is experiencing a moderate depletion (-2.73±1.0 mm/yr; -2.63±0.96 km3/yr) in TWS that might be related to groundwater/oil extraction as well as a moderate decrease in rainfall rates (AAR: 2003-2013: 61 mm; 1979-2002: 82 mm), (3) Yemen is experiencing a slight depletion (-0.82±0.30 mm/yr; -0.36±0.13 km3/yr) in TWS that might be related groundwater extraction, and (4) Oman is experiencing slight increase (+0.78±0.30 mm/yr; +0.25±0.09 km3/yr) in TWS that might be related an increase in rainfall rates. Our preliminary results are being further examined by: (1) extracting temporal variations in groundwater storage by

  19. Characterization of cDNAs and genomic DNAs for human threonyl- and cysteinyl-tRNA synthetases

    SciTech Connect

    Cruzen, M.E.

    1993-01-01

    Techniques of molecular biology were used to clone, sequence and map two human aminoacyl-tRNA synthetase (aaRS) cDNAs: threonyl-tRNA synthetase (ThrRS) a class II enzyme and cysteinyl-tRNA synthetase (CysRS) a class I enzyme. The predicted protein sequence of human ThrRS is highly homologous to that of lower eukaryotic and prokaryotic ThRSs, particularly in the regions containing the three structural motifs common to all class II synthetases. Signature regions 1 and 2, which characterize the class IIa subgroup (SerRS, ThrRS and HisRS) are highly conserved from bacteria to human. Structural predictions for human ThrRS based on the known structure of the closely related SerRS from E.coli implicate strongly conserved residues in the signature sequences to be important in substrate binding. The amino terminal 100 residues of the deduced amino acid sequence of ThrRS shares structural similarity to SerRS consistent with forming an antiparallel helix implicated in tRNA binding. The 5' untranslated sequence of the human ThrRS gene shares short stretches of common sequence with the gene for hamster HisRS including a binding site for the promoter specific transcription factor sp-1. The deduced amino acid sequence of human CysRS has a high degree of sequence identify to E. coli CysRS. Human CysRS possesses the classic characteristics of a class I synthetase and is most closely related to the MetRS subgroup. The amino terminal half of human CysRS can be modeled as a nucleotide binding fold and shares significant sequence and structural similarity to the other enzymes in this subgroup. The CysRS structural gene (CARS) was mapped to human chromosome 11p15.5 by fluorescent in situ hybridization. CARS is the first aaRS gene to be mapped to chromosome 11. The steady state of both CysRS and ThrRs mRNA were quantitated in several human tissues. Message levels for these enzymes appear to be subjected to differential regulation in different cell types.

  20. Ground state of bilayer hα-silica: mechanical and electronic properties

    NASA Astrophysics Data System (ADS)

    Han, Yang; Hu, Ming

    2015-12-01

    The family of two-dimensional (2D) crystals was recently joined by silica, one of the most abundant resources on earth. So far two different polymorphs of this material, namely a tetrahedra-shaped monolayer and a fully saturated bilayer structure, have been synthesized on various metal substrates and their fascinating properties enable 2D silica to hold promise in nanoelectronic device applications. In this paper a new ground state of bilayer—AAr-stacking hα-silica—has been discovered by first principles calculations. The new structure is featured with a formation of Si-Si bonds between all sp3 hybridized SiO3 triangular pyramids, lying respectively in different silica layers, with an intrinsic rotational angle of about 12.5° along the out-of-plane Si-Si bond. Due to the doubled number of Si-Si bonds in the new structure, the system energy is lowered by nearly three times more than that reported recently in literature (0.8 eV) (Özçelik et al 2014 Phys. Rev. Lett. 112 246803), when compared with the single layer hα-silica. A mechanical property investigation shows that the AAr-stacking bilayer hα-silica possesses high in-plane stiffness and a negative Poisson’s ratio, which stems from the intrinsic rotational angle of the SiO3 triangular pyramids. Strikingly, the negative Poisson’s ratio evolves into positive at a critical tensile strain ɛ ≈ 1.2%. Such negative-to-positive evolvement is associated with the adaptation of the rotational angle to the applied strain and the structure transition into the nearby valley of the energy landscape. The detailed transition process has been thoroughly analyzed. The electronic properties of the new ground state are also calculated, along with their response to the external strain. Our new ground state structure introduces a new member to the family of 2D bilayer silica materials and is expected to facilitate experimental studies identifying the related structures and exploring further physical and chemical

  1. Aminostratigraphy of surface and subsurface Quaternary sediments, North Carolina coastal plain, USA

    USGS Publications Warehouse

    Wehmiller, John F.; Thieler, E. Robert; Miller, D.; Pellerito, V.; Bakeman, Keeney V.; Riggs, S.R.; Culver, S.; Mallinson, D.; Farrell, K.M.; York, L.L.; Pierson, J.; Parham, P.R.

    2010-01-01

    The Quaternary stratigraphy and geochronology of the Albemarle Embayment of the North Carolina (NC) Coastal Plain is examined using amino acid racemization (AAR) in marine mollusks, in combination with geophysical, lithologic, and biostratigraphic analysis of 28 rotasonic cores drilled between 2002 and 2006. The Albemarle Embayment is bounded by structural highs to the north and south, and Quaternary strata thin westward toward the Suffolk paleoshoreline, frequently referred to as the Suffolk Scarp. The Quaternary section is up to ∼90 m thick, consists of a variety of estuarine, shelf, back-barrier, and lagoonal deposits, and has been influenced by multiple sea-level cycles. The temporal resolution of the amino acid racemization method is tested statistically and with the stratigraphic control provided by this geologic framework, and it is then applied to the correlation and age estimation of subsurface units throughout the region. Over 500 specimens (primarily Mercenaria and Mulinia) from the subsurface section have been analyzed using either gas chromatographic (GC) or reverse-phase liquid chromatographic (RPLC) techniques. The subsurface stratigraphic data are compared with AAR results from numerous natural or excavated exposures from the surrounding region, as well as results from NC beach collections, to develop a comprehensive aminostratigraphic database for the entire Quaternary record within the NC coastal system. Age mixing, recognized in the beach collections, is also seen in subsurface sections, usually where major seismic reflections or core lithology indicate the presence of stratigraphic discontinuities. Kinetic models for racemization are tested within the regional stratigraphic framework, using either radiocarbon or U-series calibrations or comparison with regional biostratigraphy. Three major Pleistocene aminozones [AZ2, AZ3, and AZ4] are found throughout the region, all being found in superposition in several cores. Each can be subdivided

  2. Potentially functional polymorphisms in aminoacyl-tRNA synthetases genes are associated with breast cancer risk in a Chinese population.

    PubMed

    He, Yisha; Gong, Jianhang; Wang, Yanru; Qin, Zhenzhen; Jiang, Yue; Ma, Hongxia; Jin, Guangfu; Chen, Jiaping; Hu, Zhibin; Guan, Xiaoxiang; Shen, Hongbing

    2015-07-01

    Aminoacyl-tRNA synthetases (ARSs) are responsible for cellular protein synthesis and cell viability involving in various process of tumorigenesis. We hypothesized that genetic variants in core ARSs genes may play an important role in the development of breast cancer. Thus, we conducted a case-control study including 1064 breast cancer cases and 1073 cancer-free controls to evaluate the associations of 28 potentially functional polymorphisms in 12 core ARSs genes (AARS, CARS, EPRS, HARS, KARS, LARS, MARS, QARS, RARS, VARS, WARS, and YARS) with breast cancer risk. We found significant associations with the risk of breast cancer for rs34087264 in AARS [odds ratio (OR) = 1.15, 95% confidence interval (CI) = 1.01-1.31], rs801186 in HARS (OR = 1.29, 95% CI = 1.08-1.54), rs193466 in RARS (OR = 1.17, 95% CI = 1.02-1.35), and rs2273802 in WARS (OR = 1.14, 95% CI = 1.01-1.30). We further observed significant interactions between rs2273802 and age at the first live birth (P = 0.041), and between rs801186 and age on breast cancer risk (P = 0.018). Combined analysis of these four SNPs showed a significant allele-dosage association between the number of risk alleles and breast cancer risk (Ptrend  = 2.00 × 10(-4) ). Compared with individuals with "0-2" risk alleles, those carrying "3," "4," or "5 or more" risk alleles had a 1.32 (95% CI = 1.07-1.64), 1.48 (95% CI = 1.45-1.91), or 1.60 folds (95% CI = 1.06-2.41) risk of breast cancer, respectively. These findings indicate that genetic variants in core ARSs genes may modify the individual susceptibility to breast cancer in Chinese population.

  3. Late Holocene climate change at Goat Lake, Kenai Mountains, south-central Alaska

    NASA Astrophysics Data System (ADS)

    Daigle, T. A.; Kaufman, D. S.

    2006-12-01

    Lake sediments, glacier extents, and tree rings were used to reconstruct late Holocene climate changes from Goat Lake in the Kenai Mountains, south-central Alaska (60° 14' N/149° 54' W). Two sediment cores (3.7 and 5.6 m long) were dated with 16 AMS 14C ages and record changes in watershed (organic- matter content) and within-lake (biogenic silica) productivity since ~9500 cal yr BP. Sediment analyses focused on the last 1000 yr; this interval includes a sharp transition from gyttja to inorganic mud at ~1660 AD, which marks the fist time since Pleistocene deglaciation that the north goat outlet glacier (NGO) of the Harding Icefield overtopped the drainage divide at 590 m asl to spill meltwater into Goat Lake. One 14C age of ~1535 AD from a subfossil log in the NGO valley requires ~125 yr for the NGO to thicken 150 m to the elevation of the drainage divide where it remained until ~1930. Since ~1930, the NGO has thinned 150 m and retreated 1.4 km. Equilibrium-line altitudes (ELA) were reconstructed for 12 cirque glaciers nearby Goat Lake based on the accumulation-area ratio (AAR) method following field mapping of ice-marginal features formed during the maximum Little Ice Age (LIA) in the 19th century. Maximum LIA ELA data (AAR = 0.58) were compared with 1950 ELA and yield an average lowering of 50 ± 20 m. Application of the local lapse rate of 0.47°C/100 m indicates an average ablation-season temperature reduction of 0.3°C during the maximum LIA compared to 1950, assuming no change in winter precipitation. A new tree-ring chronology from 27 hemlock trees in the Goat Lake watershed correlates with mean March through August temperature from Kenai airport (r = 0.35) and a 207 yr reconstruction indicates an average temperature reduction of 1.0°C from 1800-1900 compared with 1930-1950. Assuming no change in winter precipitation, then a 1°C cooling should have been associated with an ELA lowering by 200 m. This did not occur, and we suggest that some degree of

  4. Motor unit potential morphology differences in individuals with non-specific arm pain and lateral epicondylitis

    PubMed Central

    Calder, Kristina M; Stashuk, Daniel W; McLean, Linda

    2008-01-01

    Background The pathophysiology of non-specific arm pain (NSAP) is unclear and the diagnosis is made by excluding other specific upper limb pathologies, such as lateral epicondylitis or cervical radiculopathy. The purpose of this study was to determine: (i) if the quantitative parameters related to motor unit potential morphology and/or motor unit firing patterns derived from electromyographic (EMG) signals detected from an affected muscle of patients with NSAP are different from those detected in the same muscle of individuals with lateral epicondylitis (LE) and/or control subjects and (ii) if the quantitative EMG parameters suggest that the underlying pathophysiology in NSAP is either myopathic or neuropathic in nature. Methods Sixteen subjects with NSAP, 11 subjects with LE, eight subjects deemed to be at-risk for developing a repetitive strain injury, and 37 control subjects participated. A quantitative electromyography evaluation was completed using decomposition-based quantitative electromyography (DQEMG). Needle- and surface-detected EMG signals were collected during low-level isometric contractions of the extensor carpi radialis brevis (ECRB) muscle. DQEMG was used to extract needle-detected motor unit potential trains (MUPTs), and needle-detected motor unit potential (MUP) and surface detected motor unit potential (SMUP) morphology and motor unit (MU) firing rates were compared among the four groups using one-way analysis of variance (ANOVA). Post hoc analyses were performed using Tukey's pairwise comparisons. Results Significant group differences were found for all MUP variables and for MU firing rate (p < 0.006). The post-hoc analyses revealed that patients with NSAP had smaller MUP amplitude and SMUP amplitude and area compared to the control and LE groups (p < 0.006). MUP duration and AAR values were significantly larger in the NSAP, LE and at-risk groups compared to the control group (p < 0.006); while MUP amplitude, duration and AAR values were

  5. Performance of several simple, noninvasive models for assessing significant liver fibrosis in patients with chronic hepatitis B

    PubMed Central

    Zeng, Xianghua; Xu, Cheng; He, Dengming; Li, Maoshi; Zhang, Huiyan; Wu, Quanxin; Xiang, Dedong; Wang, Yuming

    2015-01-01

    Aim To compare the performance of several simple, noninvasive models comprising various serum markers in diagnosing significant liver fibrosis in the same sample of patients with chronic hepatitis B (CHB) with the same judgment standard. Methods A total of 308 patients with CHB who had undergone liver biopsy, laboratory tests, and liver stiffness measurement (LSM) at the Southwest Hospital, Chongqing, China between March 2010 and April 2014 were retrospectively studied. Receiver operating characteristic (ROC) curves and area under ROC curves (AUROCs) were used to analyze the results of the models, which incorporated age-platelet (PLT) index (API model), aspartate transaminase (AST) to alanine aminotransferase (ALT) ratio (AAR model), AST to PLT ratio index (APRI model), γ-glutamyl transpeptidase (GGT) to PLT ratio index (GPRI model), GGT-PLT-albumin index (S index model), age-AST-PLT-ALT index (FIB-4 model), and age-AST-PLT-ALT-international normalized ratio index (Fibro-Q model). Results The AUROCs of the S index, GPRI, FIB-4, APRI, API, Fibro-Q, AAR, and LSM for predicting significant liver fibrosis were 0.726 (P < 0.001), 0.726 (P < 0.001), 0.621 (P = 0.001), 0.619 (P = 0.001), 0.580 (P = 0.033), 0.569 (P = 0.066), 0.495 (P = 0.886), and 0.757 (P < 0.001), respectively. The S index and GPRI had the highest correlation with histopathological scores (r = 0.373, P < 0.001; r = 0.372, P < 0.001, respectively) and LSM values (r = 0.516, P < 0.001; r = 0.513, P < 0.001, respectively). When LSM was combined with S index and GPRI, the AUROCs were 0.753 (P < 0.001) and 0.746 (P < 0.001), respectively. Conclusion S index and GPRI had the best diagnostic performance for significant liver fibrosis and were robust predictors of significant liver fibrosis in patients with CHB for whom transient elastography was unavailable. PMID:26088852

  6. XCALIBUR: a Vertical Takeoff TSTO RLV Concept with a HEDM Upperstage and a Scram-Rocket Booster

    NASA Astrophysics Data System (ADS)

    Bradford, J.

    2002-01-01

    A new 3rd generation, two-stage-to-orbit (TSTO) reusable launch vehicle (RLV) has been designed. The Xcalibur concept represents a novel approach due to its integration method for the upperstage element of the system. The vertical-takeoff booster, which is powered by rocket-based combined-cycle (RBCC) engines, carries the upperstage internally in the aft section of the airframe to a Mach 15 staging condition. The upperstage is released from the booster and carries the 6,820 kg of payload to low earth orbit (LEO) using its high energy density matter (HEDM) propulsion system. The booster element is capable of returning to the original launch site in a ramjet-cruise propulsion mode. Both the booster and the upperstage utilize advanced technologies including: graphite-epoxy tanks, metal-matrix composites, UHTC TPS materials, electro- mechanical actuators (EMAs), and lightweight subsystems (avionics, power distribution, etc.). The booster system is enabled main propulsion system which utilizes four RBCC engines. These engines operate in four distinct modes: air- augmented rocket (AAR), ramjet, scram-rocket, and all-rocket. The booster operates in AAR mode from takeoff to Mach 3, with ramjet mode operation from Mach 3 to Mach 6. The rocket re-ignition for scram-rocket mode occurs at Mach 6, with all-rocket mode from Mach 14 to the staging condition. The extended utilization of the scram-rocket mode greatly improves vehicle performance by providing superior vehicle acceleration when compared to the scramjet mode performance over the same flight region. Results indicate that the specific impulse penalty due to the scram-rocket mode operation is outweighed by the reduced flight time, smaller vehicle size due to increased mixture ratio, and lower allowable maximum dynamic pressure. A complete vehicle system life-cycle analysis was performed in an automated, multi-disciplinary design environment. Automated disciplinary performance analysis tools include: trajectory (POST

  7. An Interglacial Polar Bear and an Early Weichselian Glaciation at Poolepynten, Western Svalbard

    NASA Astrophysics Data System (ADS)

    Ingolfsson, O.; Alexanderson, H.

    2012-12-01

    Recent discovery of a subfossil polar bear (Ursus maritimus) jawbone in the Poolepynten coastal cliff sequence, western Svalbard (Ingolfsson & Wiig, 2009), and its implications for the natural history of the polar bear (Lindqvist et al. 2010; Miller et al. 2012), motivated an effort to better constrain the environmental history and age envelope of the Poolepynten sediment sequence, particularly the lithostratigraphy of the coastal cliffs with emphasis on re-dating the sequence using the optically stimulated luminescence (OSL) dating technique. We report a revised lithostratigraphy and nine new OSL ages. It is concluded that the Poolepynten sequence holds evidence of four regional glaciation events, recorded in the strata as erosional unconformities and/or glacial deposits followed by shallow-marine deposition signifying transgressions and subsequent glacio-isostatic rebound and regression. Our OSL ages refine previous age determinations (14C and IRSL) and support the interpretation that the subfossil polar bear jawbone is of last interglacial (Eemian) age (Alexanderson et al. in press). References: Alexanderson, H., Ingolfsson, O., Murray, A.S. & Dudek, J. in press. An Interglacial Polar Bear and an Early Weichselian Glaciation at Poolepynten, Western Svalbard. Boreas 00, 000-000. Ingolfsson, O. & Wiig, O. 2009. Late Pleistocene fossil find in Svalbard: the oldest remains of a polar bear (Ursus maritimus Phipps, 1744) ever discovered. Polar Research 28, 455-466. Lindqvist, C., Schuster, S. C., Sun, Y., Talbot, S. L., Qi, J., Ratan, A., Tomsho, L. P., Kasson, L., Zeyl, E., Aars, J., Miller, W., Ingólfsson, Ó., Bachmann, L. & Wiig, Ø. 2010. Complete mitochondrial genome of a Pleistocene jawbone unveils the origin of polar bear. Proceedings of the National Academy of Sciences 107, 5053-5057. Miller, W., Schuster, S. C., Welch, A. J., Ratan, A., Bedoya-Reina, O. C., Zhao, F., Kim, H. L., Burhans, R.C., Drautz, D.I., Wittekindt, N.E., Tomsho, L.P., Ibarra-Laclette, E

  8. Zooplankton Growth, Respiration and Grazing on the Australian Margins of the Tropical Indian and Pacific Oceans

    PubMed Central

    McKinnon, A. David; Doyle, Jason; Duggan, Samantha; Logan, Murray; Lønborg, Christian; Brinkman, Richard

    2015-01-01

    The specific activity of aminoacyl-tRNA synthetases (spAARS), an index of growth rate, and of the electron transport system (spETS), an index of respiration, was measured in three size fractions (73–150 μm, >150 μm and >350 μm) of zooplankton during five cruises to tropical coastal waters of the Kimberley coast (North West Australia) and four cruises to waters of the Great Barrier Reef (GBR; North East Australia). The N-specific biomass of plankton was 3–4-fold higher in the Kimberley than on the GBR in all 3 size classes: Kimberley 1.27, 3.63, 1.94 mg m-3; GBR 0.36, 0.88 and 0.58 mg m-3 in the 73–150 μm, >150 μm and >350 μm size classes, respectively. Similarly, spAARS activity in the Kimberley was greater than that of the GBR: 88.4, 132.2, and 147.6 nmol PPi hr-1 mg protein -1 in the Kimberley compared with 71.7, 82.0 and 83.8 nmol PPi hr-1 mg protein -1 in the GBR, for the 73–150 μm, >150 μm and >350 μm size classes, respectively. Specific ETS activity showed similar differences in scale between the two coasts: 184.6, 148.8 and 92.2 μL O2 hr-1 mg protein-1 in the Kimberley, against 86.5, 88.3 and 71.3 μL O2 hr-1 mg protein-1 in the GBR. On the basis of these measurements, we calculated that >150 μm zooplankton grazing accounted for 7% of primary production in the Kimberley and 8% in GBR waters. Area-specific respiration by >73 μm zooplankton was 7-fold higher in the Kimberley than on the GBR and production by >150 μm zooplankton was of the order of 278 mg C m-2 d-1 in the Kimberley and 42 mg C m-2 d-1 on the GBR. We hypothesize that the much stronger physical forcing on the North West shelf is the principal driver of higher rates in the west than in the east of the continent. PMID:26469275

  9. Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis

    PubMed Central

    Hsu, Cheng-Lung; Liu, Jai-Shin; Wu, Po-Long; Guan, Hong-Hsiang; Chen, Yuh-Ling; Lin, An-Chi; Ting, Huei-Ju; Pang, See-Tong; Yeh, Shauh-Der; Ma, Wen-Lung; Chen, Chung-Jung; Wu, Wen-Guey; Chang, Chawnshang

    2014-01-01

    Treatment with individual anti-androgens is associated with the development of hot-spot mutations in the androgen receptor (AR), including T877A (hydroxyflutamide [HF]) and W741(C/L) (bicalutamide [CDX]). Here, we found that anti-androgens bound mt-ARs (HF-T877A-AR-LBD and CDX-W741L-AR-LBD) have similar binary structure to the 5α-dihydrotestosterone (DHT) bound wild type (wt) AR (DHT-wt-AR-LBD). Phage display revealed that these ARs bound to similar peptides, including BUD31, containing an Fxx(F/H/L/W/Y)Y motif cluster with Tyr in the +5 position. Structural analyses of the AR-LBD-BUD31 complex at 2.1 Å resolution revealed formation of an extra hydrogen bond between the Tyr+5 residue of the peptide and Gln733 of the AR AF2 domain, suggesting that peptides with Fxx(F/H/L/W/Y)Y motifs can interact with wt or mutated ARs. Functional studies showed that BUD31-related peptides suppressed transactivation of both DHT-wt-AR and HF-T877A-AR by interrupting AR N- and C-terminal interactions, thereby inhibiting wt and mutant AR-mediated prostate cancer cell growth. Collectively, these results suggest the combination of peptide screening and X-ray structure analysis as a new strategy for developing anti-androgens that simultaneously suppress both wt and mutated AR function. PMID:25091737

  10. Bioisosteric phentolamine analogs as potent alpha-adrenergic antagonists.

    PubMed

    Hong, Seoung-Soo; Bavadekar, Supriya A; Lee, Sang-Il; Patil, Popat N; Lalchandani, S G; Feller, Dennis R; Miller, Duane D

    2005-11-01

    The synthesis and biological evaluation of a new series of bioisosteric phentolamine analogs are described. Replacement of the carbon next to the imidazoline ring of phentolamine with a nitrogen atom provides compounds (2, 3) that are about 1.6 times and 4.1 times more potent functionally than phentolamine on rat alpha1-adrenergic receptors, respectively. In receptor binding assays, the affinities of phentolamine and its bioisosteric analogs were determined on the human embryonic kidney (HEK) and Chinese Hamster ovary (CHO) cell lines expressing the human alpha1- and alpha2-AR subtypes, respectively. Analogs 2 and 3, both, displayed higher binding affinities at the alpha2- versus the alpha1-ARs, affinities being the least at the alpha1B-AR. Binding affinities of the methoxy ether analog 2 were greater than those of the phenolic analog 3 at all six alpha-AR subtypes. One of the nitrogen atoms in the imidazoline ring of phentolamine was replaced with an oxygen atom to give compounds 4 and 5, resulting in a 2-substituted oxazoline ring. The low functional antagonist activity on rat aorta, and binding potencies of these two compounds on human alpha1A- and alpha2A-AR subtypes indicate that a basic functional group is important for optimum binding to the alpha1- and alpha2A-adrenergic receptors.

  11. The Relationship between Inflammatory Marker Levels and Hepatitis C Virus Severity

    PubMed Central

    He, Qitian; He, Quan; Qin, Xue; Li, Shan; Li, Taijie; Xie, Li; Deng, Yan; He, Yu

    2016-01-01

    Background. Red cell distribution width (RDW) and platelet-lymphocyte ratio (PLR) have been studied in a variety of etiological diseases. We aim to investigate the relationship between RDW and PLR and the severity of hepatitis C virus- (HCV-) related liver disease. Methods. We included fifty-two chronic HCV and 42 HCV-related cirrhosis patients and 84 healthy controls. Hematological and virological parameters and liver function biomarkers of HCV-related patients at admission were recorded. Results. RDW, RDW-to-platelet (RPR), and 1/PLR values in HCV-related cirrhosis patients were significantly higher than in chronic HCV patients and healthy controls (all P < 0.001). The aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), AST-to-platelet ratio index (APRI), and fibrosis index based on the four factors (FIB-4) scores in HCV-related cirrhosis patients were significantly higher than in chronic HCV patients (all P < 0.001). The areas under the curve of the RDW, RPR, and 1/PLR for predicting cirrhosis were 0.791, 0.960, and 0.713, respectively. Bivariate logistic regression analysis showed that RDW could independently predict the presence of cirrhosis in chronic HCV patients. Conclusions. RDW, RPR, and PLR may be potential markers for estimating HCV severity. PMID:28090206

  12. Sesamin protects against renal ischemia reperfusion injury by promoting CD39-adenosine-A2AR signal pathway in mice.

    PubMed

    Li, Ke; Gong, Xia; Kuang, Ge; Jiang, Rong; Wan, Jingyuan; Wang, Bin

    2016-01-01

    Ischemia reperfusion injury (IRI) is a leading cause of acute kidney injury with high morbidity and mortality due to limited therapy. Here, we examine whether sesamin attenuates renal IRI in an animal model and explore the underlying mechanisms. Male mice were subjected to right renal ischemia for 30 min followed by reperfusion for 24 h with sesamin (100 mg/kg) during which the left kidney was removed. Renal damage and function were assessed subsequently. The results showed that sesamin reduced kidney ischemia reperfusion injury, as assessed by decreased serum creatinine (Scr) and Blood urea nitrogen (BUN), alleviated tubular damage and apoptosis. In addition, sesamin inhibited neutrophils infiltration and pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β production in IR-preformed kidney. Notably, sesamin promoted the expression of CD39, A2A adenosine receptor (A2AAR), and A2BAR mRNA and protein as well as adenosine production. Furthermore, CD39 inhibitor or A2AR antagonist abolished partly the protection of sesamin in kidney IRI. In conclusion, sesamin could effectively protect kidney from IRI by inhibiting inflammatory responses, which might be associated with promoting the adenosine-CD39-A2AR signaling pathway.

  13. Sesamin protects against renal ischemia reperfusion injury by promoting CD39-adenosine-A2AR signal pathway in mice

    PubMed Central

    Li, Ke; Gong, Xia; Kuang, Ge; Jiang, Rong; Wan, Jingyuan; Wang, Bin

    2016-01-01

    Ischemia reperfusion injury (IRI) is a leading cause of acute kidney injury with high morbidity and mortality due to limited therapy. Here, we examine whether sesamin attenuates renal IRI in an animal model and explore the underlying mechanisms. Male mice were subjected to right renal ischemia for 30 min followed by reperfusion for 24 h with sesamin (100 mg/kg) during which the left kidney was removed. Renal damage and function were assessed subsequently. The results showed that sesamin reduced kidney ischemia reperfusion injury, as assessed by decreased serum creatinine (Scr) and Blood urea nitrogen (BUN), alleviated tubular damage and apoptosis. In addition, sesamin inhibited neutrophils infiltration and pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β production in IR-preformed kidney. Notably, sesamin promoted the expression of CD39, A2A adenosine receptor (A2AAR), and A2BAR mRNA and protein as well as adenosine production. Furthermore, CD39 inhibitor or A2AR antagonist abolished partly the protection of sesamin in kidney IRI. In conclusion, sesamin could effectively protect kidney from IRI by inhibiting inflammatory responses, which might be associated with promoting the adenosine-CD39-A2AR signaling pathway. PMID:27347331

  14. Synthesis, crystal structure, biological evaluation, and molecular docking studies of quinoline-arylpiperazine derivative as potent α1A-adrenoceptor antagonist

    NASA Astrophysics Data System (ADS)

    Xu, Wei; Jiang, Renwang; Yuan, Mu

    2017-02-01

    Arylpiperazine derivatives received special attention owing to their antagonist potency on α1-adrenoceptors (α1-ARs). In this work, quinoline-arylpiperazine derivative (1) was synthesized and its structural properties were investigated using single crystal X-ray diffraction analysis and theoretical calculations. Biological evaluation in vitro revealed that compound 1 exhibited a 3-fold higher selectivity for α1A-AR over than α1B subtype when compared to non-selective antagonist prazosin. Molecular docking studies shed light on the antagonistic activity of both 1 and prazosin on α1A and α1B-AR. The docking results suggested that residues Gln177, Phe86, Phe288, Phe308, Phe312 and Tyr316 were identified as the major sites for the two agents binding to the α1A receptor. As depicted by pharmacophoric model, 1 was deemed to be the α1A-selective antagonist on the basis of pharmacophoric features. Our present work may provide valuable information for better drug design of subtype-selective α1-AR antagonists.

  15. Cigarette Smoke Impairs A2A Adenosine Receptor Mediated Wound Repair through Up-regulation of Duox-1 Expression

    PubMed Central

    Tian, Zhi; Zhang, Hui; Dixon, Jendayi; Traphagen, Nicole; Wyatt, Todd A.; Kharbanda, Kusum; Simet Chadwick, Samantha; Kolliputi, Narasaiah; Allen-Gipson, Diane S.

    2017-01-01

    Cigarette smoke (CS) exposure and intrinsic factors such as the NADPH oxidases produce high levels of reactive oxygen species (ROS), ensuing inflammatory tissue injury. We previously demonstrated that CS-generated ROS, particularly hydrogen peroxide (H2O2), impaired adenosine stimulated wound repair. We hypothesized that CS exposure modulates expression of Dual oxidase 1 (Duox-1), a NADPH oxidases known to generate H2O2. To test this hypothesis, we used human bronchial epithelial cell line Nuli-1 and C57BL/6 mice. Cells were treated with 5% CS extract (CSE) for various periods of time, and mice were exposed to whole body CS for six weeks. Both CSE and CS treatment induced increased expression of Duox-1, and silencing of Doux-1 improved the rate of cell wound repair induced by CSE treatment. Nuli-1 cells pretreated with thapsigargin but not calcium ionophore exhibited increased Duox-1 mRNA expression. CSE treatment stimulated PKCα activation, which was effectively blocked by pretreatment with diphenylene iodonium, a NADPH oxidase inhibitor. Compared to control, lungs from CS-exposed mice showed a significant increase in PKCα activity and Duox-1 expression. Collectively, the data demonstrated that CS exposure upregulates expression of Duox-1 protein. This further leads to H2O2 production and PKCα activation, inhibiting A2AAR-stimulated wound repair. PMID:28337995

  16. Autonomous Aerial Refueling Ground Test Demonstration—A Sensor-in-the-Loop, Non-Tracking Method

    PubMed Central

    Chen, Chao-I; Koseluk, Robert; Buchanan, Chase; Duerner, Andrew; Jeppesen, Brian; Laux, Hunter

    2015-01-01

    An essential capability for an unmanned aerial vehicle (UAV) to extend its airborne duration without increasing the size of the aircraft is called the autonomous aerial refueling (AAR). This paper proposes a sensor-in-the-loop, non-tracking method for probe-and-drogue style autonomous aerial refueling tasks by combining sensitivity adjustments of a 3D Flash LIDAR camera with computer vision based image-processing techniques. The method overcomes the inherit ambiguity issues when reconstructing 3D information from traditional 2D images by taking advantage of ready to use 3D point cloud data from the camera, followed by well-established computer vision techniques. These techniques include curve fitting algorithms and outlier removal with the random sample consensus (RANSAC) algorithm to reliably estimate the drogue center in 3D space, as well as to establish the relative position between the probe and the drogue. To demonstrate the feasibility of the proposed method on a real system, a ground navigation robot was designed and fabricated. Results presented in the paper show that using images acquired from a 3D Flash LIDAR camera as real time visual feedback, the ground robot is able to track a moving simulated drogue and continuously narrow the gap between the robot and the target autonomously. PMID:25970254

  17. Theoretical exploration of the cooperative effect in NMF-NMF-amino acid residue hydrogen bonding system.

    PubMed

    Li, Xichen; Liu, Wenlan; Sun, Kening; Wang, Yan; Tan, Hongwei; Chen, Guangju

    2008-09-28

    This paper presents a theoretical study of the cooperative effect in sixteen linearly-arranged trimer systems consisting of N-methylformamide dimer and an extra amino acid residue. These trimer systems, NMF-NMF-AAR, in short, have been systematically investigated by full optimization at B3LYP/cc-pVTZ level and subsequent electronic energy calculations at PBE1PBE/cc-pVTZ, HF/cc-pVTZ and MP2/cc-pVTZ, respectively. Obvious spatial transformation due to energetic factors has been found in almost all the trimers. Systematic analysis in weak interaction energy components has shown that: (1) in these trimer systems, the bonding structure and the cooperative effect combine to determine the stability of both HB1 and HB2. For HB2, the structure of the constituent amino acid residue also plays a crucial role by interfering with the neighboring moieties; (2) the large contribution of the cooperative effect to the overall hydrogen bonding energy has claimed the importance of cooperativity in our systems; (3) the non-hydrogen bonding weak interaction components are found to be non-negligible in these trimer systems; (4) moreover, the cooperative effect between these non-hydrogen bonding components is always found to be positive. The good performances of PBE1PBE and PM6 have been established by comparisons between these methods.

  18. Allosteric regulation of rhomboid intramembrane proteolysis.

    PubMed

    Arutyunova, Elena; Panwar, Pankaj; Skiba, Pauline M; Gale, Nicola; Mak, Michelle W; Lemieux, M Joanne

    2014-09-01

    Proteolysis within the lipid bilayer is poorly understood, in particular the regulation of substrate cleavage. Rhomboids are a family of ubiquitous intramembrane serine proteases that harbour a buried active site and are known to cleave transmembrane substrates with broad specificity. In vitro gel and Förster resonance energy transfer (FRET)-based kinetic assays were developed to analyse cleavage of the transmembrane substrate psTatA (TatA from Providencia stuartii). We demonstrate significant differences in catalytic efficiency (kcat/K0.5) values for transmembrane substrate psTatA (TatA from Providencia stuartii) cleavage for three rhomboids: AarA from P. stuartii, ecGlpG from Escherichia coli and hiGlpG from Haemophilus influenzae demonstrating that rhomboids specifically recognize this substrate. Furthermore, binding of psTatA occurs with positive cooperativity. Competitive binding studies reveal an exosite-mediated mode of substrate binding, indicating allostery plays a role in substrate catalysis. We reveal that exosite formation is dependent on the oligomeric state of rhomboids, and when dimers are dissociated, allosteric substrate activation is not observed. We present a novel mechanism for specific substrate cleavage involving several dynamic processes including positive cooperativity and homotropic allostery for this interesting class of intramembrane proteases.

  19. Entamoeba lysyl-tRNA synthetase contains a cytokine-like domain with chemokine activity towards human endothelial cells.

    PubMed

    Castro de Moura, Manuel; Miro, Francesc; Han, Jung Min; Kim, Sunghoon; Celada, Antonio; Ribas de Pouplana, Lluís

    2011-11-01

    Immunological pressure encountered by protozoan parasites drives the selection of strategies to modulate or avoid the immune responses of their hosts. Here we show that the parasite Entamoeba histolytica has evolved a chemokine that mimics the sequence, structure, and function of the human cytokine HsEMAPII (Homo sapiens endothelial monocyte activating polypeptide II). This Entamoeba EMAPII-like polypeptide (EELP) is translated as a domain attached to two different aminoacyl-tRNA synthetases (aaRS) that are overexpressed when parasites are exposed to inflammatory signals. EELP is dispensable for the tRNA aminoacylation activity of the enzymes that harbor it, and it is cleaved from them by Entamoeba proteases to generate a standalone cytokine. Isolated EELP acts as a chemoattractant for human cells, but its cell specificity is different from that of HsEMAPII. We show that cell specificity differences between HsEMAPII and EELP can be swapped by site directed mutagenesis of only two residues in the cytokines' signal sequence. Thus, Entamoeba has evolved a functional mimic of an aaRS-associated human cytokine with modified cell specificity.

  20. Enhancing Alkane Production in Cyanobacterial Lipid Droplets: A ModeFl Platform for Industrially Relevant Compound Production

    PubMed Central

    Peramuna, Anantha; Morton, Ray; Summers, Michael L.

    2015-01-01

    Cyanobacterial lipid droplets (LDs) are packed with hydrophobic energy-dense compounds and have great potential for biotechnological expression and the compartmentalization of high value compounds. Nostoc punctiforme normally accumulates LDs containing neutral lipids, and small amounts of heptadecane, during the stationary phase of growth. In this study, we further enhanced heptadecane production in N. punctiforme by introducing extrachromosomal copies of aar/adc genes, and report the discovery of a putative novel lipase encoded by Npun_F5141, which further enhanced alkane production. Extra copies of all three genes in high light conditions resulted in a 16-fold higher accumulation of heptadecane compared to the wild type strain in the exponential phase. LD accumulation during exponential phase also increased massively to accommodate the heptadecane production. A large number of small, less fluorescent LDs were observed at the cell periphery in exponential growth phase, whereas fewer number of highly fluorescent, much larger LDs were localized towards the center of the cell in the stationary phase. These advances demonstrate that cyanobacterial LDs are an ideal model platform to make industrially relevant compounds, such as alkanes, during exponential growth, and provide insight into LD formation in cyanobacteria. PMID:25821934

  1. FGF19 (fibroblast growth factor 19) as a novel target gene for activating transcription factor 4 in response to endoplasmic reticulum stress.

    PubMed

    Shimizu, Makoto; Li, Juan; Maruyama, Ryuto; Inoue, Jun; Sato, Ryuichiro

    2013-02-15

    FGF19 (fibroblast growth factor 19), expressed in the small intestine, acts as an enterohepatic hormone by mediating inhibitory effects on the bile acid synthetic pathway and regulating carbohydrate and lipid metabolism. In an attempt to identify novel agents other than bile acids that induce increased FGF19 expression, we found that some ER (endoplasmic reticulum) stress inducers were effective. When intestinal epithelial Caco-2 cells were incubated with thapsigargin, marked increases were observed in the mRNA and secreted protein levels of FGF19. This was not associated with the farnesoid X receptor. Reporter gene analyses using the 5'-promoter region of FGF19 revealed that a functional AARE (amino-acid-response element) was localized in this region, and this site was responsible for inducing its transcription through ATF4 (activating transcription factor 4), which is activated in response to ER stress. EMSAs (electrophoretic mobility-shift assays) and ChIP (chromatin immunoprecipitation) assays showed that ATF4 bound to this site and enhanced FGF19 expression. Overexpression of ATF4 in Caco-2 cells induced increased FGF19 mRNA expression, whereas shRNA (short hairpin RNA)-mediated depletion of ATF4 significantly attenuated a thapsigargin-induced increase in FGF19 mRNA.

  2. Glaciological and hydrological sensitivities in the Hindu Kush - Himalaya

    NASA Astrophysics Data System (ADS)

    Shea, Joseph; Immerzeel, Walter

    2016-04-01

    Glacier responses to future climate change will affect hydrology at subbasin-scales. The main goal of this study is to assess glaciological and hydrological sensitivities of sub-basins throughout the Hindu Kush - Himalaya (HKH) region. We use a simple geometrical analysis based on a full glacier inventory and digital elevation model (DEM) to estimate sub-basin equilibrium line altitudes (ELA) from assumptions of steady-state accumulation area ratios (AARs). The ELA response to an increase in temperature is expressed as a function of mean annual precipitation, derived from a range of high-altitude studies. Changes in glacier contributions to streamflow in response to increased temperatures are examined for scenarios of both static and adjusted glacier geometries. On average, glacier contributions to streamflow increase by approximately 50% for a +1K warming based on a static geometry. Large decreases (-60% on average) occur in all basins when glacier geometries are instantaneously adjusted to reflect the new ELA. Finally, we provide estimates of sub-basin glacier response times that suggest a majority of basins will experience declining glacier contributions by the year 2100.

  3. Two siblings with homozygous pathogenic splice-site variant in mitochondrial asparaginyl-tRNA synthetase (NARS2).

    PubMed

    Vanlander, Arnaud V; Menten, Björn; Smet, Joél; De Meirleir, Linda; Sante, Tom; De Paepe, Boel; Seneca, Sara; Pearce, Sarah F; Powell, Christopher A; Vergult, Sarah; Michotte, Alex; De Latter, Elien; Vantomme, Lies; Minczuk, Michal; Van Coster, Rudy

    2015-02-01

    A homozygous missense mutation (c.822G>C) was found in the gene encoding the mitochondrial asparaginyl-tRNA synthetase (NARS2) in two siblings born to consanguineous parents. These siblings presented with different phenotypes: one had mild intellectual disability and epilepsy in childhood, whereas the other had severe myopathy. Biochemical analysis of the oxidative phosphorylation (OXPHOS) complexes in both siblings revealed a combined complex I and IV deficiency in skeletal muscle. In-gel activity staining after blue native-polyacrylamide gel electrophoresis confirmed the decreased activity of complex I and IV, and, in addition, showed the presence of complex V subcomplexes. Considering the consanguineous descent, homozygosity mapping and whole-exome sequencing were combined revealing the presence of one single missense mutation in the shared homozygous region. The c.822G>C variant affects the 3' splice site of exon 7, leading to skipping of the whole exon 7 and a part of exon 8 in the NARS2 mRNA. In EBV-transformed lymphoblasts, a specific decrease in the amount of charged mt-tRNA(Asn) was demonstrated as compared with controls. This confirmed the pathogenic nature of the variant. To conclude, the reported variant in NARS2 results in a combined OXPHOS complex deficiency involving complex I and IV, making NARS2 a new member of disease-associated aaRS2.

  4. A Comparative Investigation on the Capability of Modified Zerilli-Armstrong and Arrhenius-Type Constitutive Models to Describe Flow Behavior of BFe10-1-2 Cupronickel Alloy at Elevated Temperature

    NASA Astrophysics Data System (ADS)

    Cai, Jun; Lei, Ying; Wang, Kuaishe; Zhang, Xiaolu; Miao, Chengpeng; Li, Wenbing

    2016-05-01

    True stress and true strain data obtained from isothermal compression tests on a Gleeble-3800 thermo-mechanical simulator, in a wide range of temperatures (1073-1323 K) and strain rates (0.001-10 s-1), has been used to evaluate the material constants of two constitutive models: the modified Zerilli-Armstrong and the strain compensation Arrhenius-type models. Furthermore, a comparative study was conducted on the capabilities of the two models in order to represent the elevated temperature flow behavior of BFe10-1-2 cupronickel alloy. The suitability levels of these two models were evaluated by comparing the accuracy of their predictions of deformation behavior, correlation coefficient ( R), average absolute relative error ( AARE), relative errors of prediction, and the number of material constants. The results show that the predicted values of these two models agree well with the experimental values of BFe10-1-2 cupronickel alloy except at the temperature of 1123 K and the strain rate of 1 s-1. Meanwhile, the strain compensated Arrhenius-type model can track the deformation behavior of BFe10-1-2 cupronickel alloy more accurately throughout the entire temperature and strain rate range, while fewer material constants are involved in the modified Zerilli-Armstrong model.

  5. A3 adenosine receptor agonist reduces brain ischemic injury and inhibits inflammatory cell migration in rats.

    PubMed

    Choi, In-Young; Lee, Jae-Chul; Ju, Chung; Hwang, Sunyoung; Cho, Geum-Sil; Lee, Hyuk Woo; Choi, Won Jun; Jeong, Lak Shin; Kim, Won-Ki

    2011-10-01

    A3 adenosine receptor (A3AR) is recognized as a novel therapeutic target for ischemic injury; however, the mechanism underlying anti-ischemic protection by the A3AR agonist remains unclear. Here, we report that 2-chloro-N(6)-(3-iodobenzyl)-5'-N-methylcarbamoyl-4'-thioadenosine (LJ529), a selective A3AR agonist, reduces inflammatory responses that may contribute to ischemic cerebral injury. Postischemic treatment with LJ529 markedly reduced cerebral ischemic injury caused by 1.5-hour middle cerebral artery occlusion, followed by 24-hour reperfusion in rats. This effect was abolished by the simultaneous administration of the A3AR antagonist MRS1523, but not the A2AAR antagonist SCH58261. LJ529 prevented the infiltration/migration of microglia and monocytes occurring after middle cerebral artery occlusion and reperfusion, and also after injection of lipopolysaccharides into the corpus callosum. The reduced migration of microglia by LJ529 could be related with direct inhibition of chemotaxis and down-regulation of spatiotemporal expression of Rho GTPases (including Rac, Cdc42, and Rho), rather than by biologically relevant inhibition of inflammatory cytokine/chemokine release (eg, IL-1β, TNF-α, and MCP-1) or by direct inhibition of excitotoxicity/oxidative stress (not affected by LJ529). The present findings indicate that postischemic activation of A3AR and the resultant reduction of inflammatory response should provide a promising therapeutic strategy for the treatment of ischemic stroke.

  6. Improving alkane synthesis in Escherichia coli via metabolic engineering.

    PubMed

    Song, Xuejiao; Yu, Haiying; Zhu, Kun

    2016-01-01

    Concerns about energy security and global petroleum supply have made the production of renewable biofuels an industrial imperative. The ideal biofuels are n-alkanes in that they are chemically and structurally identical to the fossil fuels and can "drop in" to the transportation infrastructure. In this work, an Escherichia coli strain that produces n-alkanes was constructed by heterologous expression of acyl-acyl carrier protein (ACP) reductase (AAR) and aldehyde deformylating oxygenase (ADO) from Synechococcus elongatus PCC7942. The accumulation of alkanes ranged from 3.1 to 24.0 mg/L using different expressing strategies. Deletion of yqhD, an inherent aldehyde reductase in E. coli, or overexpression of fadR, an activator for fatty acid biosynthesis, exhibited a nearly twofold increase in alkane titers, respectively. Combining yqhD deletion and fadR overexpression resulted in a production titer of 255.6 mg/L in E. coli, and heptadecene was the most abundant product.

  7. Integrative function of adrenaline receptors for glucagon-like peptide-1 exocytosis in enteroendocrine L cell line GLUTag.

    PubMed

    Harada, Kazuki; Kitaguchi, Tetsuya; Tsuboi, Takashi

    2015-05-15

    Adrenaline reacts with three types of adrenergic receptors, α1, α2 and β-adrenergic receptors (ARs), inducing many physiological events including exocytosis. Although adrenaline has been shown to induce glucagon-like peptide-1 (GLP-1) secretion from intestinal L cells, the precise molecular mechanism by which adrenaline regulates GLP-1 secretion remains unknown. Here we show by live cell imaging that all types of adrenergic receptors are stimulated by adrenaline in enteroendocrine L cell line GLUTag cells and are involved in GLP-1 exocytosis. We performed RT-PCR analysis and found that α1B-, α2A-, α2B-, and β1-ARs were expressed in GLUTag cells. Application of adrenaline induced a significant increase of intracellular Ca(2+) and cAMP concentration ([Ca(2+)]i and [cAMP]i, respectively), and GLP-1 exocytosis in GLUTag cells. Blockade of α1-AR inhibited adrenaline-induced [Ca(2+)]i increase and exocytosis but not [cAMP]i increase, while blockade of β1-AR inhibited adrenaline-induced [cAMP]i increase and exocytosis but not [Ca(2+)]i increase. Furthermore, overexpression of α2A-AR suppressed the adrenaline-induced [cAMP]i increase and exocytosis. These results suggest that the fine-turning of GLP-1 secretion from enteroendocrine L cells is established by the balance between α1-, α2-, and β-ARs activation.

  8. Alpine Post-Collisional Orogeny: topics of debate and possible targets for AlpArray research

    NASA Astrophysics Data System (ADS)

    Kissling, Edi

    2016-04-01

    In all aspects, the Alps are by far the best documented orogen. Within their only 1000km lengths from Nice to Vienna, the Alps exhibit an extraordinary variation in structure along strike and from surface to great depth. The modern well-accepted mountain building concept calls for a material flux carefully balanced by mantle flow, plate convergence, subduction, crustal delamination, surface topography, uplift and erosion. The Alpine data set provides a basis to relate subduction processes with Penninic nappes evolution and overthrusting of Austroalpine lid, collision and oceanic slab break-off with build-up of topography, and post-collisional slab rollback and isostatic rebound due to erosional unloading to exhumation of deep European basement structures such as Tauern and Aar massiv. Temporal and spatial variations and relative importance of these processes and their relation to the overall convergence between the Adriatic/Africa and European continental plates, however, are still poorly understood and remain matters of debate. While the AlpArray Seismic Experiment will provide new geophysical information of unprecedented resolution and reliability, discussions and interdisciplinary earth science research among AlpArray community targeted at key questions will lead to a better understanding of collisional orogeny in general and Alpine evolution in particular.

  9. Genetically expanded cell-free protein synthesis using endogenous pyrrolysyl orthogonal translation system.

    PubMed

    Chemla, Yonatan; Ozer, Eden; Schlesinger, Orr; Noireaux, Vincent; Alfonta, Lital

    2015-08-01

    Cell-free protein synthesis offers a facile and rapid method for synthesizing, monitoring, analyzing, and purifying proteins from a DNA template. At the same time, genetic code expansion methods are gaining attention due to their ability to site-specifically incorporate unnatural amino acids (UAAs) into proteins via ribosomal translation. These systems are based on the exogenous addition of an orthogonal translation system (OTS), comprising an orthogonal tRNA, and orthogonal aminoacyl tRNA synthetase (aaRS), to the cell-free reaction mixture. However, these components are unstable and their preparation is labor-intensive, hence introducing a major challenge to the system. Here, we report on an approach that significantly reduces the complexity, effort and time needed to express UAA-containing proteins while increasing stability and realizing maximal suppression efficiency. We demonstrate an endogenously introduced orthogonal pair that enables the use of the valuable yet insoluble pyrrolysyl-tRNA synthetase in a cell-free system, thereby expanding the genetic repertoire that can be utilized in vitro and enabling new possibilities for bioengineering. With the high stability and efficiency of our system, we offer an improved and accessible platform for UAA incorporation into proteins.

  10. Pharmacological Profiles of Alpha 2 Adrenergic Receptor Agonists Identified Using Genetically Altered Mice and Isobolographic Analysis

    PubMed Central

    Fairbanks, Carolyn A.; Stone, Laura S.; Wilcox, George L.

    2009-01-01

    Endogenous, descending noradrenergic fibers convey powerful analgesic control over spinal afferent circuitry mediating the rostrad transmission of pain signals. These fibers target alpha 2 adrenergic receptors (α2ARs) on both primary afferent terminals and secondary neurons, and their activation mediates substantial inhibitory control over this transmission, rivaling that of opioid receptors which share similar a similar pattern of distribution. The terminals of primary afferent nociceptive neurons and secondary spinal dorsal horn neurons express α2AAR and α2CAR subtypes, respectively. Spinal delivery of these agents serves to reduce their side effects, which are mediated largely at supraspinal sites, by concentrating the drugs at the spinal level. Targeting these spinal α2ARs with one of five selective therapeutic agonists, clonidine, dexmedetomidine, brimonidine, ST91 and moxonidine, produces significant antinociception that can work in concert with opioid agonists to yield synergistic antinociception. Application of several genetically altered mouse lines had facilitated identification of the primary receptor subtypes that likely mediate the antinociceptive effects of these agents. This review provides first an anatomical description of the localization of the three subtypes in the central nervous system, second a detailed account of the pharmacological history of each of these six primary agonists, and finally a comprehensive report of the specific interactions of other GPCR agonists with each of the six principal α2AR agonists featured. PMID:19393691

  11. Two-dimensional cross-section sensitivity and uncertainty analysis of the LBM (Lithium Blanket Module) experiments at LOTUS

    SciTech Connect

    Davidson, J.W.; Dudziak, D.J.; Pelloni, S.; Stepanek, J.

    1988-01-01

    In a recent common Los Alamos/PSI effort, a sensitivity and nuclear data uncertainty path for the modular code system AARE (Advanced Analysis for Reactor Engineering) was developed. This path includes the cross-section code TRAMIX, the one-dimensional finite difference S/sub N/-transport code ONEDANT, the two-dimensional finite element S/sub N/-transport code TRISM, and the one- and two-dimensional sensitivity and nuclear data uncertainty code SENSIBL. Within the framework of the present work a complete set of forward and adjoint two-dimensional TRISM calculations were performed both for the bare, as well as for the Pb- and Be-preceeded, LBM using MATXS8 libraries. Then a two-dimensional sensitivity and uncertainty analysis for all cases was performed. The goal of this analysis was the determination of the uncertainties of a calculated tritium production per source neutron from lithium along the central Li/sub 2/O rod in the LBM. Considered were the contributions from /sup 1/H, /sup 6/Li, /sup 7/Li, /sup 9/Be, /sup nat/C, /sup 14/N, /sup 16/O, /sup 23/Na, /sup 27/Al, /sup nat/Si, /sup nat/Cr, /sup nat/Fe, /sup nat/Ni, and /sup nat/Pb. 22 refs., 1 fig., 3 tabs.

  12. ORNL RAIL BARGE DB

    SciTech Connect

    Johnson, P. )

    1991-07-01

    The Oak Ridge National Laboratory (ORNL) Rail and Barge Network Database is a representation of the rail and barge system of the United States. The network is derived from the Federal Rail Administration (FRA) rail database. The database consists of 96 subnetworks. Each of the subnetworks represent an individual railroad, a waterway system, or a composite group of small railroads. Two subnetworks represent waterways; one being barge/intercoastal, and the other coastal merchant marine with access through the Great Lakes/Saint Lawrence Seaway, Atlantic and Gulf Coasts, the Panama Canal, and Pacific Coast. Two other subnetworks represent small shortline railroads and terminal railroad operations. One subnetwork is maintained for the representation of Amtrak operations. The remaining 91 subnetworks represent individual or corporate groups of railroads. Coordinate locations are included as part of the database. The rail portion of the database is similar to the original FRA rail network. The waterway coordinates are greatly enhanced in the current release. Inland waterway representation was extracted from the 1:2,000,000 United States Geological Survey data. An important aspect of the database is the transfer file. This file identifies where two railroads interline traffic between their systems. Also included are locations where rail/waterway intermodal transfers could occur. Other files in the database include a translation table between Association of American Railroad (AAR) codes to the 96 subnetworks in the database, a list of names of the 96 subnetworks, and a file of names for a large proportion of the nodes in the network.

  13. ORNL RAIL & BARGE DB. Network Database

    SciTech Connect

    Johnson, P.

    1991-07-01

    The Oak Ridge National Laboratory (ORNL) Rail and Barge Network Database is a representation of the rail and barge system of the United States. The network is derived from the Federal Rail Administration (FRA) rail database. The database consists of 96 subnetworks. Each of the subnetworks represent an individual railroad, a waterway system, or a composite group of small railroads. Two subnetworks represent waterways; one being barge/intercoastal, and the other coastal merchant marine with access through the Great Lakes/Saint Lawrence Seaway, Atlantic and Gulf Coasts, the Panama Canal, and Pacific Coast. Two other subnetworks represent small shortline railroads and terminal railroad operations. One subnetwork is maintained for the representation of Amtrak operations. The remaining 91 subnetworks represent individual or corporate groups of railroads. Coordinate locations are included as part of the database. The rail portion of the database is similar to the original FRA rail network. The waterway coordinates are greatly enhanced in the current release. Inland waterway representation was extracted from the 1:2,000,000 United States Geological Survey data. An important aspect of the database is the transfer file. This file identifies where two railroads interline traffic between their systems. Also included are locations where rail/waterway intermodal transfers could occur. Other files in the database include a translation table between Association of American Railroad (AAR) codes to the 96 subnetworks in the database, a list of names of the 96 subnetworks, and a file of names for a large proportion of the nodes in the network.

  14. ORNL RAIL & BARGE DB. Network Database

    SciTech Connect

    Johnson, P.

    1992-03-16

    The Oak Ridge National Laboratory (ORNL) Rail and Barge Network Database is a representation of the rail and barge system of the United States. The network is derived from the Federal Rail Administration (FRA) rail database. The database consists of 96 subnetworks. Each of the subnetworks represent an individual railroad, a waterway system, or a composite group of small railroads. Two subnetworks represent waterways; one being barge/intercoastal, and the other coastal merchant marine with access through the Great Lakes/Saint Lawrence Seaway, Atlantic and Gulf Coasts, the Panama Canal, and Pacific Coast. Two other subnetworks represent small shortline railroads and terminal railroad operations. One subnetwork is maintained for the representation of Amtrak operations. The remaining 91 subnetworks represent individual or corporate groups of railroads. Coordinate locations are included as part of the database. The rail portion of the database is similar to the original FRA rail network. The waterway coordinates are greatly enhanced in the current release. Inland waterway representation was extracted from the 1:2,000,000 United States Geological Survey data. An important aspect of the database is the transfer file. This file identifies where two railroads interline traffic between their systems. Also included are locations where rail/waterway intermodal transfers could occur. Other files in the database include a translation table between Association of American Railroad (AAR) codes to the 96 subnetworks in the database, a list of names of the 96 subnetworks, and a file of names for a large proportion of the nodes in the network.

  15. Identification of potent inhibitors of the Trypanosoma brucei methionyl-tRNA synthetase via high-throughput orthogonal screening.

    PubMed

    Pedró-Rosa, Laura; Buckner, Frederick S; Ranade, Ranae M; Eberhart, Christina; Madoux, Franck; Gillespie, J Robert; Koh, Cho Yeow; Brown, Steven; Lohse, Jacqueline; Verlinde, Christophe L M; Fan, Erkang; Bannister, Thomas; Scampavia, Louis; Hol, Wim G J; Spicer, Timothy; Hodder, Peter

    2015-01-01

    Improved therapies for the treatment of Trypanosoma brucei, the etiological agent of the neglected tropical disease human African trypanosomiasis, are urgently needed. We targeted T. brucei methionyl-tRNA synthetase (MetRS), an aminoacyl-tRNA synthase (aaRS), which is considered an important drug target due to its role in protein synthesis, cell survival, and its significant differences in structure from its mammalian ortholog. Previous work using RNA interference of MetRS demonstrated growth inhibition of T. brucei, further validating it as an attractive target. We report the development and implementation of two orthogonal high-throughput screening assays to identify inhibitors of T. brucei MetRS. First, a chemiluminescence assay was implemented in a 1536-well plate format and used to monitor adenosine triphosphate depletion during the aminoacylation reaction. Hit confirmation then used a counterscreen in which adenosine monophosphate production was assessed using fluorescence polarization technology. In addition, a miniaturized cell viability assay was used to triage cytotoxic compounds. Finally, lower throughput assays involving whole parasite growth inhibition of both human and parasite MetRS were used to analyze compound selectivity and efficacy. The outcome of this high-throughput screening campaign has led to the discovery of 19 potent and selective T. brucei MetRS inhibitors.

  16. Heterologous biosynthesis and manipulation of alkanes in Escherichia coli.

    PubMed

    Cao, Ying-Xiu; Xiao, Wen-Hai; Zhang, Jin-Lai; Xie, Ze-Xiong; Ding, Ming-Zhu; Yuan, Ying-Jin

    2016-11-01

    Biosynthesis of alkanes in microbial foundries offers a sustainable and green supplement to traditional fossil fuels. The dynamic equilibrium of fatty aldehydes, key intermediates, played a critical role in microbial alkanes production, due to the poor catalytic capability of aldehyde deformylating oxygenase (ADO). In our study, exploration of competitive pathway together with multi-modular optimization was utilized to improve fatty aldehydes balance and consequently enhance alkanes formation in Escherichia coli. Endogenous fatty alcohol formation was supposed to be competitive with alkane production, since both of the two routes consumed the same intermediate-fatty aldehyde. Nevertheless, in our case, alkanes production in E. coli was enhanced from trace amount to 58.8mg/L by the facilitation of moderate fatty alcohol biosynthesis, which was validated by deletion of endogenous aldehyde reductase (AHR), overexpression of fatty alcohol oxidase (FAO) and consequent transcriptional assay of aar, ado and adhP genes. Moreover, alkanes production was further improved to 81.8mg/L, 86.6mg/L or 101.7mg/L by manipulation of fatty acid biosynthesis, lipids degradation or electron transfer system modules, which directly referenced to fatty aldehydes dynamic pools. A titer of 1.31g/L alkanes was achieved in 2.5L fed-batch fermentation, which was the highest reported titer in E. coli. Our research has offered a reference for chemical overproduction in microbial cell factories facilitated by exploring competitive pathway.

  17. Cloning, expression, crystallization and preliminary X-ray crystallographic analysis of glutamyl-tRNA synthetase (Xoo1504) from Xanthomonas oryzae pv. oryzae.

    PubMed

    Doan, Thanh Thi Ngoc; Natarajan, Sampath; Kim, Hyesoon; Ahn, Yeh-Jin; Kim, Jeong-Gu; Lee, Byoung-Moo; Kang, Lin-Woo

    2009-01-01

    The gltX gene from Xanthomonas oryzae pv. oryzae (Xoo1504) encodes glutamyl-tRNA synthetase (GluRS), one of the most important enzymes involved in bacterial blight (BB), which causes huge production losses of rice worldwide. GluRS is a class I-type aminoacyl-tRNA synthetase (aaRS) that is primarily responsible for the glutamylation of tRNA(Glu). It plays an essential role in protein synthesis, as well as the regulation of cells, in all organisms. As it represents an important target for the development of new antibacterial drugs against BB, determination of the three-dimensional structure of GluRS is essential in order to understand its catalytic mechanism. In order to analyze its structure and function, the gltX gene was cloned and the GluRS enzyme was expressed, purified and then crystallized. A GluRS crystal belonging to the monoclinic space group C2 diffracted to 2.8 A resolution and had unit-cell parameters a = 186.8, b = 108.4, c = 166.1 A, beta = 96.3 degrees . The unit-cell volume of the crystal allowed the presence of six to eight monomers in the asymmetric unit, with a corresponding Matthews coefficient (V(M)) range of 2.70-2.02 A(3) Da(-1) and a solvent-content range of 54.5-39.3%.

  18. Increased IGFBP-1 phosphorylation in response to leucine deprivation is mediated by CK2 and PKC.

    PubMed

    Malkani, Niyati; Biggar, Kyle; Shehab, Majida Abu; Li, Shawn Shun-Cheng; Jansson, Thomas; Gupta, Madhulika B

    2016-04-15

    Insulin-like growth factor binding protein-1 (IGFBP-1), secreted by fetal liver, is a key regulator of IGF-I bioavailability and fetal growth. IGFBP-1 phosphorylation decreases IGF-I bioavailability and diminishes its growth-promoting effects. Growth-restricted fetuses have decreased levels of circulating essential amino acids. We recently showed that IGFBP-1 hyperphosphorylation (pSer101/119/169) in response to leucine deprivation is regulated via activation of the amino acid response (AAR) in HepG2 cells. Here we investigated nutrient-sensitive protein kinases CK2/PKC/PKA in mediating IGFBP-1 phosphorylation in leucine deprivation. We demonstrated that leucine deprivation stimulated CK2 activity (enzymatic assay) and induced IGFBP-1 phosphorylation (immunoblotting/MRM-MS). Inhibition (pharmacological/siRNA) of CK2/PKC, but not PKA, prevented IGFBP-1 hyperphosphorylation in leucine deprivation. PKC inhibition also prevented leucine deprivation-stimulated CK2 activity. Functionally, leucine deprivation decreased IGF-I-induced-IGF-1R autophosphorylation when CK2/PKC were not inhibited. Our data strongly support that PKC promotes leucine deprivation-induced IGFBP-1 hyperphosphorylation via CK2 activation, mechanistically linking decreased amino acid availability and reduced fetal growth.

  19. Modeling the Hot Deformation Behaviors of As-Extruded 7075 Aluminum Alloy by an Artificial Neural Network with Back-Propagation Algorithm

    NASA Astrophysics Data System (ADS)

    Quan, Guo-zheng; Zou, Zhen-yu; Wang, Tong; Liu, Bo; Li, Jun-chao

    2017-01-01

    In order to investigate the hot deformation behaviors of as-extruded 7075 aluminum alloy, the isothermal compressive tests were conducted at the temperatures of 573, 623, 673 and 723 K and the strain rates of 0.01, 0.1, 1 and 10 s-1 on a Gleeble 1500 thermo-mechanical simulator. The flow behaviors showing complex characteristics are sensitive to strain, strain rate and temperature. The effects of strain, temperature and strain rate on flow stress were analyzed and dynamic recrystallization (DRX)-type softening characteristics of the flow behaviors with single peak were identified. An artificial neural network (ANN) with back-propagation (BP) algorithm was developed to deal with the complex deformation behavior characteristics based on the experimental data. The performance of ANN model has been evaluated in terms of correlation coefficient (R) and average absolute relative error (AARE). A comparative study on Arrhenius-type constitutive equation and ANN model for as-extruded 7075 aluminum alloy was conducted. Finally, the ANN model was successfully applied to the development of processing map and implanted into finite element simulation. The results have sufficiently articulated that the well-trained ANN model with BP algorithm has excellent capability to deal with the complex flow behaviors of as-extruded 7075 aluminum alloy and has great application potentiality in hot deformation processes.

  20. A Characterization for the Hot Flow Behaviors of As-extruded 7050 Aluminum Alloy

    NASA Astrophysics Data System (ADS)

    Quan, Guo-zheng; Liu, Jin; Mao, An; Liu, Bo; Zhang, Jin-sheng

    2015-11-01

    The deep understanding of flow behaviors of as-extruded 7050 aluminum alloy significantly contributes to the accuracy simulation for its various plastic forming processes. In order to obtain the improved Arrhenius-type equation with variable parameters for this alloy, a series of compression tests were performed at temperatures of 573 K, 623 K, 673 K, 723 K and strain rates of 0.01 s-1, 0.1 s-1, 1 s-1, 10 s-1 with a height reduction of 60% on Gleeble-1500 thermo-mechanical simulator. It is obvious that strain rate, strain and temperature all have a significant effect on the hot flow behaviors, and the true stress-true strain curves indicate three types after the peak value: decreasing gradually to a steady state with sustaining DRX softening till a balance with work hardening, decreasing continuously with sustaining increasing DRX softening beyond work hardening and maintaining higher stress level after the peak value with a balance between work hardening and DRV softening. Based on the experimental data, the improved Arrhenius-type constitutive model was established to predict the high temperature flow stress of as-extruded 7050 aluminum alloy. The accuracy and reliability of the improved Arrhenius-type model were further evaluated in terms of the correlation coefficient (R), here 0.98428, the average absolute relative error (AARE), here 3.5%. The results indicate that the improved Arrhenius-type constitutive model presents a good predictable ability.

  1. Design Considerations of ISTAR Hydrocarbon Fueled Combustor Operating in Air Augmented Rocket, Ramjet and Scramjet Modes

    NASA Technical Reports Server (NTRS)

    Andreadis, Dean; Drake, Alan; Garrett, Joseph L.; Gettinger, Christopher D.; Hoxie, Stephen S.

    2003-01-01

    The development and ground test of a rocket-based combined cycle (RBCC) propulsion system is being conducted as part of the NASA Marshall Space Flight Center (MSFC) Integrated System Test of an Airbreathing Rocket (ISTAR) program. The eventual flight vehicle (X-43B) is designed to support an air-launched self-powered Mach 0.7 to 7.0 demonstration of an RBCC engine through all of its airbreathing propulsion modes - air augmented rocket (AAR), ramjet (RJ), and scramjet (SJ). Through the use of analytical tools, numerical simulations, and experimental tests the ISTAR program is developing and validating a hydrocarbon-fueled RBCC combustor design methodology. This methodology will then be used to design an integrated RBCC propulsion system that produces robust ignition and combustion stability characteristics while maximizing combustion efficiency and minimizing drag losses. First order analytical and numerical methods used to design hydrocarbon-fueled combustors are discussed with emphasis on the methods and determination of requirements necessary to establish engine operability and performance characteristics.

  2. Design Considerations of Istar Hydrocarbon Fueled Combustor Operating in Air Augmented Rocket, Ramjet and Scramjet Modes

    NASA Technical Reports Server (NTRS)

    Andreadis, Dean; Drake, Alan; Garrett, Joseph L.; Gettinger, Christopher D.; Hoxie, Stephen S.

    2002-01-01

    The development and ground test of a rocket-based combined cycle (RBCC) propulsion system is being conducted as part of the NASA Marshall Space Flight Center (MSFC) Integrated System Test of an Airbreathing Rocket (ISTAR) program. The eventual flight vehicle (X-43B) is designed to support an air-launched self-powered Mach 0.7 to 7.0 demonstration of an RBCC engine through all of its airbreathing propulsion modes - air augmented rocket (AAR), ramjet (RJ), and scramjet (SJ). Through the use of analytical tools, numerical simulations, and experimental tests the ISTAR program is developing and validating a hydrocarbon-fueled RBCC combustor design methodology. This methodology will then be used to design an integrated RBCC propulsion system thai: produces robust ignition and combustion stability characteristics while maximizing combustion efficiency and minimizing drag losses. First order analytical and numerical methods used to design hydrocarbon-fueled combustors are discussed with emphasis on the methods and determination of requirements necessary to establish engine operability and performance characteristics.

  3. Spectromicroscopy Mapping of Colloidal/Particulate Organic Matter in Lake Brienz, Switzerland

    SciTech Connect

    Schäfer,T.; Chanudet, V.; Claret, F.; Filella, M.

    2007-01-01

    Transmission electron microscopy (TEM), soft X-ray scanning transmission X-ray microscopy (STXM), and {mu}-FTIR spectromicroscopy were used to map colloidal/particulate material in an ultra-oligotrophic lake, Lake Brienz, Switzerland, with a special focus on organic functionality. Within the statistical margin of error and the uncertainties arising from the representativeness of the results, the research reveals that organic material was associated with potassium-rich inorganic colloids present in surface and deep water (depths of 1 and 100 m, respectively), which indicates a vertical transfer of aggregates by sedimentation. Pure organic colloids could only be detected in surface waters. In addition, correlation map analysis of synchrotron-based {mu}-FTIR and carbon K-edge STXM spectromicroscopic data using spectra from the Luetschine and Aare Rivers as target spectra revealed spectral similarities with organic components from both tributary rivers in deeper regions (100 m) of the lake. The results prove that STXM and {mu}-FTIR can characterize colloidal and particulate organic material in low organic carbon systems.

  4. Comparative Study on the Cellular and Systemic Nutrient Sensing and Intermediary Metabolism after Partial Replacement of Fishmeal by Meat and Bone Meal in the Diet of Turbot (Scophthalmus maximus L.).

    PubMed

    Song, Fei; Xu, Dandan; Mai, Kangsen; Zhou, Huihui; Xu, Wei; He, Gen

    2016-01-01

    This study was designed to examine the cellular and systemic nutrient sensing mechanisms as well as the intermediary metabolism responses in turbot (Scophthalmus maximus L.) fed with fishmeal diet (FM diet), 45% of FM replaced by meat and bone meal diet (MBM diet) or MBM diet supplemented with essential amino acids to match the amino acid profile of FM diet (MBM+AA diet). During the one month feeding trial, feed intake was not affected by the different diets. However, MBM diet caused significant reduction of specific growth rate and nutrient retentions. Compared with the FM diet, MBM diet down-regulated target of rapamycin (TOR) and insulin-like growth factor (IGFs) signaling pathways, whereas up-regulated the amino acid response (AAR) signaling pathway. Moreover, MBM diet significantly decreased glucose and lipid anabolism, while increased muscle protein degradation and lipid catabolism in liver. MBM+AA diet had no effects on improvement of MBM diet deficiencies. Compared with fasted, re-feeding markedly activated the TOR signaling pathway, IGF signaling pathway and glucose, lipid metabolism, while significantly depressed the protein degradation signaling pathway. These results thus provided a comprehensive display of molecular responses and a better explanation of deficiencies generated after fishmeal replacement by other protein sources.

  5. Ecotoxicological effects extrapolation models

    SciTech Connect

    Suter, G.W. II

    1996-09-01

    One of the central problems of ecological risk assessment is modeling the relationship between test endpoints (numerical summaries of the results of toxicity tests) and assessment endpoints (formal expressions of the properties of the environment that are to be protected). For example, one may wish to estimate the reduction in species richness of fishes in a stream reach exposed to an effluent and have only a fathead minnow 96 hr LC50 as an effects metric. The problem is to extrapolate from what is known (the fathead minnow LC50) to what matters to the decision maker, the loss of fish species. Models used for this purpose may be termed Effects Extrapolation Models (EEMs) or Activity-Activity Relationships (AARs), by analogy to Structure-Activity Relationships (SARs). These models have been previously reviewed in Ch. 7 and 9 of and by an OECD workshop. This paper updates those reviews and attempts to further clarify the issues involved in the development and use of EEMs. Although there is some overlap, this paper does not repeat those reviews and the reader is referred to the previous reviews for a more complete historical perspective, and for treatment of additional extrapolation issues.

  6. Clinical and genetic characterization of leukoencephalopathies in adults.

    PubMed

    Lynch, David S; Rodrigues Brandão de Paiva, Anderson; Zhang, Wei Jia; Bugiardini, Enrico; Freua, Fernando; Tavares Lucato, Leandro; Macedo-Souza, Lucia Inês; Lakshmanan, Rahul; Kinsella, Justin A; Merwick, Aine; Rossor, Alexander M; Bajaj, Nin; Herron, Brian; McMonagle, Paul; Morrison, Patrick J; Hughes, Deborah; Pittman, Alan; Laurà, Matilde; Reilly, Mary M; Warren, Jason D; Mummery, Catherine J; Schott, Jonathan M; Adams, Matthew; Fox, Nick C; Murphy, Elaine; Davagnanam, Indran; Kok, Fernando; Chataway, Jeremy; Houlden, Henry

    2017-03-02

    Leukodystrophies and genetic leukoencephalopathies are a rare group of disorders leading to progressive degeneration of cerebral white matter. They are associated with a spectrum of clinical phenotypes dominated by dementia, psychiatric changes, movement disorders and upper motor neuron signs. Mutations in at least 60 genes can lead to leukoencephalopathy with often overlapping clinical and radiological presentations. For these reasons, patients with genetic leukoencephalopathies often endure a long diagnostic odyssey before receiving a definitive diagnosis or may receive no diagnosis at all. In this study, we used focused and whole exome sequencing to evaluate a cohort of undiagnosed adult patients referred to a specialist leukoencephalopathy service. In total, 100 patients were evaluated using focused exome sequencing of 6100 genes. We detected pathogenic or likely pathogenic variants in 26 cases. The most frequently mutated genes were NOTCH3, EIF2B5, AARS2 and CSF1R. We then carried out whole exome sequencing on the remaining negative cases including four family trios, but could not identify any further potentially disease-causing mutations, confirming the equivalence of focused and whole exome sequencing in the diagnosis of genetic leukoencephalopathies. Here we provide an overview of the clinical and genetic features of these disorders in adults.

  7. Fibro markers for prediction of hepatocellular carcinoma in egyptian patients with chronic liver disease.

    PubMed

    Mobarak, Lamiaa; Omran, Dalia; Nabeel, Mohammed M; Zakaria, Zeinab

    2016-10-21

    It is well known that hepatocellular carcinoma (HCC) develops as a consequence of hepatic fibrosis progression. In this study, we aimed to evaluate the inflammatory and fibrosis markers as predictors for HCC development among patients with hepatitis C virus (HCV) related chronic liver disease to help in early diagnosis and management of HCC. A total of 280 patients with chronic liver disease were included in this retrospective study, out of them 140 had liver cirrhosis with HCC and 140 had cirrhosis without HCC. Eight readily available blood indices King score, Fibro Q, AST-ALT ratio (AAR), APRI, LOK index, Goteborg University Cirrhosis Index (GUCI), fibro alpha, and Biotechnology Research Center (BRC) were constructed to compare the accuracies of these non invasive scores in predicting HCC development. All fibrosis scores except APRI were significantly higher in HCC. We found that Fibro alpha and BRC had superior diagnostic performance in prediction of HCC based on area under curve of 0.91 and 0.93, respectively compared to other scores with area under curve ranged from poor to failure (0.59-0.66). Almost all cirrhotic cases were secondary to HCV (93.6%), while HBV was detected in 2.1% of cases only. Anti-HCV positive was reported in 100% of HCC cases (P = 0.002). Fibro alpha and BRC scores can be used for prediction of HCC. J. Med. Virol. © 2016 Wiley Periodicals, Inc.

  8. Comparative Study on the Cellular and Systemic Nutrient Sensing and Intermediary Metabolism after Partial Replacement of Fishmeal by Meat and Bone Meal in the Diet of Turbot (Scophthalmus maximus L.)

    PubMed Central

    Mai, Kangsen; Zhou, Huihui; Xu, Wei; He, Gen

    2016-01-01

    This study was designed to examine the cellular and systemic nutrient sensing mechanisms as well as the intermediary metabolism responses in turbot (Scophthalmus maximus L.) fed with fishmeal diet (FM diet), 45% of FM replaced by meat and bone meal diet (MBM diet) or MBM diet supplemented with essential amino acids to match the amino acid profile of FM diet (MBM+AA diet). During the one month feeding trial, feed intake was not affected by the different diets. However, MBM diet caused significant reduction of specific growth rate and nutrient retentions. Compared with the FM diet, MBM diet down-regulated target of rapamycin (TOR) and insulin-like growth factor (IGFs) signaling pathways, whereas up-regulated the amino acid response (AAR) signaling pathway. Moreover, MBM diet significantly decreased glucose and lipid anabolism, while increased muscle protein degradation and lipid catabolism in liver. MBM+AA diet had no effects on improvement of MBM diet deficiencies. Compared with fasted, re-feeding markedly activated the TOR signaling pathway, IGF signaling pathway and glucose, lipid metabolism, while significantly depressed the protein degradation signaling pathway. These results thus provided a comprehensive display of molecular responses and a better explanation of deficiencies generated after fishmeal replacement by other protein sources. PMID:27802317

  9. Synthesis and Anti-Renal Fibrosis Activity of Conformationally Locked Truncated 2-Hexynyl-N6-Substituted-(N)-Methanocarba-nucleosides as A3 Adenosine Receptor Antagonists and Partial Agonists

    PubMed Central

    2015-01-01

    Truncated N6-substituted-(N)-methanocarba-adenosine derivatives with 2-hexynyl substitution were synthesized to examine parallels with corresponding 4′-thioadenosines. Hydrophobic N6 and/or C2 substituents were tolerated in A3AR binding, but only an unsubstituted 6-amino group with a C2-hexynyl group promoted high hA2AAR affinity. A small hydrophobic alkyl (4b and 4c) or N6-cycloalkyl group (4d) showed excellent binding affinity at the hA3AR and was better than an unsubstituted free amino group (4a). A3AR affinities of 3-halobenzylamine derivatives 4f–4i did not differ significantly, with Ki values of 7.8–16.0 nM. N6-Methyl derivative 4b (Ki = 4.9 nM) was a highly selective, low efficacy partial A3AR agonist. All compounds were screened for renoprotective effects in human TGF-β1-stimulated mProx tubular cells, a kidney fibrosis model. Most compounds strongly inhibited TGF-β1-induced collagen I upregulation, and their A3AR binding affinities were proportional to antifibrotic effects; 4b was most potent (IC50 = 0.83 μM), indicating its potential as a good therapeutic candidate for treating renal fibrosis. PMID:24456490

  10. Long-term retention of skilled visual search following severe traumatic brain injury

    PubMed Central

    PAVAWALLA, SHITAL P.; SCHMITTER-EDGECOMBE, MAUREEN

    2007-01-01

    We examined the long-term retention of a learned automatic cognitive process in 17 severe TBI participants and 10 controls. Participants had initially received extensive consistent-mapping (CM) training (i.e., 3600 trials) in a semantic category visual search task (Schmitter-Edgecombe & Beglinger, 2001). Following CM training, TBI and control groups demonstrated dramatic performance improvements and the development of an automatic attention response (AAR), indicating task-specific and stimulus-specific skill learning. After a 5- or 10-month retention interval, participants in this study performed a New CM task and the originally trained CM task to assess for retention of task-specific and stimulus-specific visual search skills, respectively. No significant group differences were found in the level of retention for either skill type, indicating that individuals with severe TBI were able to retain the learned skills over a long-term retention interval at a level comparable to controls. Exploratory analyses revealed that TBI participants who returned at the 5-month retention interval showed nearly complete skill retention, and greater skill retention than TBI participants who returned at the 10-month interval, suggesting that “booster” or retraining sessions may be needed when a skill is not continuously in use. PMID:17064444

  11. The MIS 5 palaeoenvironmental record in the SE Mediterranean coast of the Iberian Peninsula (Río Antas, Almería, Spain)

    NASA Astrophysics Data System (ADS)

    Torres, T.; Ortiz, J. E.; Blázquez, A. M.; Ruiz Zapata, B.; Gil, M. J.; Martín, T.; Sánchez-Palencia, Y.

    2015-08-01

    Landwards of a MIS5 bar, a borehole core (SRA) was analyzed to establish the relationship between the lagoonal record and the raised beach deposits in the surroundings of the Antas river mouth and to reconstruct the Pleistocene palaeoenvironmental evolution of the southern Mediterranean coast of the Iberian Peninsula. 63 samples were recovered for amino acid racemization dating, 86 samples for sedimentological and paleontological determination, 37 samples for pollen identification and 54 for biomarker analysis. AAR revealed that the borehole record contains MIS11, MIS6 and MIS5 deposits, the latter extensively represented. During the end of MIS6 and MIS5, a sand barrier developed and created a shallow lagoon with alternating terrestrial inputs this process being common in other Mediterranean realms. Litho- and biofacies allowed the identification of distinct paleoenvironments through time, with the presence of a lagoonal environment alternating with alluvial fan progradation. Biomarkers indicated constant input from terrestrial plants, together with variable development of aquatic macrophytes. The palynological content allowed the reconstruction of the paleoclimatological conditions during MIS6 and 5, with evidence of seven scenarios characterized by alternating arid and relatively humid conditions.

  12. Biscrolling nanotube sheets and functional guests into yarns

    NASA Astrophysics Data System (ADS)

    Baughman, Ray

    2011-03-01

    Multifunctional applications of textiles have been limited by the inability to spin important materials into yarns. Generically applicable methods are demonstrated for producing weavable yarns comprising up to 95 wt % of otherwise unspinnable particulate or nanofiber powders that remain highly functional. Scrolled 50 nm thick carbon nanotube sheets confine these powders in the galleries of irregular scroll sacks, whose observed complex structures are related to twist-dependent extension of Archimedean spirals, Fermat spirals, or spiral pairs into scrolls. The strength and electronic connectivity of a small weight fraction of scrolled carbon nanotube sheet enables yarn weaving, sewing, knotting, braiding, and charge collection. This technology is used to make yarns of superconductors, Li-ion battery materials, graphene ribbons, catalytic nanofibers for fuel cells, and Ti O2 for photocatalysis. Work done in collaboration with Shaoli Fang, Xavier Lepro-Chavez, Chihye Lewis, Raquel Ovalle-Robles, Javier Carratero-Gonzalez, Elisabet Castillo-Martinez, Mikhail Kozlov, Jiyoung Oh, Neema Rawat, Carter Haines, Mohammed Haque, Vaishnavi Aare, Stephanie Stoughton, Anvar Zakhidov, and Ray Baughman, The University of Texas at Dallas / Alan G. MacDiarmid NanoTech Institute.

  13. Characterization factors for thermal pollution in freshwater aquatic environments.

    PubMed

    Verones, Francesca; Hanafiah, Marlia Mohd; Pfister, Stephan; Huijbregts, Mark A J; Pelletier, Gregory J; Koehler, Annette

    2010-12-15

    To date the impact of thermal emissions has not been addressed in life cycle assessment despite the narrow thermal tolerance of most aquatic species. A method to derive characterization factors for the impact of cooling water discharges on aquatic ecosystems was developed which uses space and time explicit integration of fate and effects of water temperature changes. The fate factor is calculated with a 1-dimensional steady-state model and reflects the residence time of heat emissions in the river. The effect factor specifies the loss of species diversity per unit of temperature increase and is based on a species sensitivity distribution of temperature tolerance intervals for various aquatic species. As an example, time explicit characterization factors were calculated for the cooling water discharge of a nuclear power plant in Switzerland, quantifying the impact on aquatic ecosystems of the rivers Aare and Rhine. The relative importance of the impact of these cooling water discharges was compared with other impacts in life cycle assessment. We found that thermal emissions are relevant for aquatic ecosystems compared to other stressors, such as chemicals and nutrients. For the case of nuclear electricity investigated, thermal emissions contribute between 3% and over 90% to Ecosystem Quality damage.

  14. ISAP: ISO Spectral Analysis Package

    NASA Astrophysics Data System (ADS)

    Ali, Babar; Bauer, Otto; Brauher, Jim; Buckley, Mark; Harwood, Andrew; Hur, Min; Khan, Iffat; Li, Jing; Lord, Steve; Lutz, Dieter; Mazzarella, Joe; Molinari, Sergio; Morris, Pat; Narron, Bob; Seidenschwang, Karla; Sidher, Sunil; Sturm, Eckhard; Swinyard, Bruce; Unger, Sarah; Verstraete, Laurent; Vivares, Florence; Wieprecht, Ecki

    2014-03-01

    ISAP, written in IDL, simplifies the process of visualizing, subsetting, shifting, rebinning, masking, combining scans with weighted means or medians, filtering, and smoothing Auto Analysis Results (AARs) from post-pipeline processing of the Infrared Space Observatory's (ISO) Short Wavelength Spectrometer (SWS) and Long Wavelength Spectrometer (LWS) data. It can also be applied to PHOT-S and CAM-CVF data, and data from practically any spectrometer. The result of a typical ISAP session is expected to be a "simple spectrum" (single-valued spectrum which may be resampled to a uniform wavelength separation if desired) that can be further analyzed and measured either with other ISAP functions, native IDL functions, or exported to other analysis package (e.g., IRAF, MIDAS) if desired. ISAP provides many tools for further analysis, line-fitting, and continuum measurements, such as routines for unit conversions, conversions from wavelength space to frequency space, line and continuum fitting, flux measurement, synthetic photometry and models such as a zodiacal light model to predict and subtract the dominant foreground at some wavelengths.

  15. Optimization of a green extraction method for the recovery of polyphenols from olive leaf using cyclodextrins and glycerin as co-solvents.

    PubMed

    Mourtzinos, Ioannis; Anastasopoulou, Eleni; Petrou, Athanasios; Grigorakis, Spyros; Makris, Dimitris; Biliaderis, Costas G

    2016-11-01

    Olive leaf, an agricultural by-product, was studied for the valorization of its biophenols using green extraction techniques; i.e. non-toxic and eco-friendly extraction solvents were used, involving water and glycerol. 2-hydroxypropyl-β-cyclodextrin (CD), was also employed as an enhancer of the extraction, since cyclodextrins (CD's) are known to improve the extractability of olive leaf polyphenols by forming water soluble inclusion complexes. The process was optimized by implementing a central composite (Box-Behnken) experimental design and response surface methodology, taking into consideration the following independent variables: glycerol concentration (Cgl), CD concentration (CCD) and temperature (T). The evaluation of the extraction model was based on two responses: the total polyphenol yield (YTP) and the antiradical activity (AAR). Optimum values for the extraction process were obtained at 60% (w/v) glycerol content, T = 60 °C and 7% (w/v) CD content. LC-MS analysis was also applied in order to characterize the polyphenolic composition of extracts containing cyclodextrins. The main polyphenols present were oleuropein and oleuropein derivatives. Olive leaf aqueous extracts containing glycerol and cyclodextrins may be used as raw materials/ingredients for several end-users in the food, cosmetic and pharmaceutical industries.

  16. Study of the Binding Energies between Unnatural Amino Acids and Engineered Orthogonal Tyrosyl-tRNA Synthetases

    PubMed Central

    Ren, Wei; Truong, Tan M.; Ai, Hui-wang

    2015-01-01

    We utilized several computational approaches to evaluate the binding energies of tyrosine (Tyr) and several unnatural Tyr analogs, to several orthogonal aaRSes derived from Methanocaldococcus jannaschii and Escherichia coli tyrosyl-tRNA synthetases. The present study reveals the following: (1) AutoDock Vina and ROSETTA were able to distinguish binding energy differences for individual pairs of favorable and unfavorable aaRS-amino acid complexes, but were unable to cluster together all experimentally verified favorable complexes from unfavorable aaRS-Tyr complexes; (2) MD-MM/PBSA provided the best prediction accuracy in terms of clustering favorable and unfavorable enzyme-substrate complexes, but also required the highest computational cost; and (3) MM/PBSA based on single energy-minimized structures has a significantly lower computational cost compared to MD-MM/PBSA, but still produced sufficiently accurate predictions to cluster aaRS-amino acid interactions. Although amino acid-aaRS binding is just the first step in a complex series of processes to acylate a tRNA with its corresponding amino acid, the difference in binding energy, as shown by MD-MM/PBSA, is important for a mutant orthogonal aaRS to distinguish between a favorable unnatural amino acid (unAA) substrate from unfavorable natural amino acid substrates. Our computational study should assist further designing and engineering of orthogonal aaRSes for the genetic encoding of novel unAAs. PMID:26220470

  17. Constitutive Modeling of Hot Deformation Behavior of High-Strength Armor Steel

    NASA Astrophysics Data System (ADS)

    Bobbili, Ravindranadh; Madhu, Vemuri

    2016-05-01

    The hot isothermal compression tests of high-strength armor steel under a wide range of deformation temperatures (1100-1250 °C) and strain rates of (0.001-1/s) were performed. Based on the experimental data, constitutive models were established using the original Johnson-Cook (JC) model, modified JC model, and strain-compensated Arrhenius model, respectively. The modified JC model considers the coupled effects of strain hardening, strain rate hardening, and thermal softening. Moreover, the prediction accuracy of these developed models was determined by estimating the correlation coefficient ( R) and average absolute relative error (AARE). The results demonstrate that the flow behavior of high-strength armor steel is considerably influenced by the strain rate and temperature. The original JC model is inadequate to provide good description on the flow stress at evaluated temperatures. The modified JC model and strain-compensated Arrhenius model significantly enhance the predictability. It is also observed from the microstructure study that at low strain rates (0.001-0.01/s) and high temperatures (1200-1250 °C), a typical dynamic recrystallization (DRX) occurs.

  18. A Comparative Study on Johnson Cook, Modified Zerilli-Armstrong and Arrhenius-Type Constitutive Models to Predict High-Temperature Flow Behavior of Ti-6Al-4V Alloy in α + β Phase

    NASA Astrophysics Data System (ADS)

    Cai, Jun; Wang, Kuaishe; Han, Yingying

    2016-03-01

    True stress and true strain values obtained from isothermal compression tests over a wide temperature range from 1,073 to 1,323 K and a strain rate range from 0.001 to 1 s-1 were employed to establish the constitutive equations based on Johnson Cook, modified Zerilli-Armstrong (ZA) and strain-compensated Arrhenius-type models, respectively, to predict the high-temperature flow behavior of Ti-6Al-4V alloy in α + β phase. Furthermore, a comparative study has been made on the capability of the three models to represent the elevated temperature flow behavior of Ti-6Al-4V alloy. Suitability of the three models was evaluated by comparing both the correlation coefficient R and the average absolute relative error (AARE). The results showed that the Johnson Cook model is inadequate to provide good description of flow behavior of Ti-6Al-4V alloy in α + β phase domain, while the predicted values of modified ZA model and the strain-compensated Arrhenius-type model could agree well with the experimental values except under some deformation conditions. Meanwhile, the modified ZA model could track the deformation behavior more accurately than other model throughout the entire temperature and strain rate range.

  19. Flow Behavior and Constitutive Equation of Ti-6.5Al-2Sn-4Zr-4Mo-1W-0.2Si Titanium Alloy

    NASA Astrophysics Data System (ADS)

    Yang, Xuemei; Guo, Hongzhen; Liang, Houquan; Yao, Zekun; Yuan, Shichong

    2016-04-01

    In order to get a reliable constitutive equation for the finite element simulation, flow behavior of Ti-6.5Al-2Sn-4Zr-4Mo-1W-0.2Si alloy under high temperature was investigated by carrying a series of isothermal compression tests at temperatures of 1153-1293 K and strain rates of 0.01-10.0 s-1 on the Gleeble-1500 simulator. Results showed that the true stress-strain curves exhibited peaks at small strains, after which the flow stress decreased monotonically. Ultimately, the flow curves reached steady state at the strain of 0.6, showing a dynamic flow softening phenomenon. The effects of strain rate, temperature, and strain on the flow behavior were researched by establishing a constitutive equation. The relations among stress exponent, deformation activation energy, and strain were preliminarily discussed by using strain rate sensitivity exponent and dynamic recrystallization kinetics curve. Stress values predicted by the modified constitutive equation showed a good agreement with the experimental ones. The correlation coefficient ( R) and average absolute relative error (AARE) were 98.2% and 4.88%, respectively, which confirmed that the modified constitutive equation could give an accurate estimation of the flow stress for BT25y titanium alloy.

  20. Autonomous Aerial Refueling Ground Test Demonstration--A Sensor-in-the-Loop, Non-Tracking Method.

    PubMed

    Chen, Chao-I; Koseluk, Robert; Buchanan, Chase; Duerner, Andrew; Jeppesen, Brian; Laux, Hunter

    2015-05-11

    An essential capability for an unmanned aerial vehicle (UAV) to extend its airborne duration without increasing the size of the aircraft is called the autonomous aerial refueling (AAR). This paper proposes a sensor-in-the-loop, non-tracking method for probe-and-drogue style autonomous aerial refueling tasks by combining sensitivity adjustments of a 3D Flash LIDAR camera with computer vision based image-processing techniques. The method overcomes the inherit ambiguity issues when reconstructing 3D information from traditional 2D images by taking advantage of ready to use 3D point cloud data from the camera, followed by well-established computer vision techniques. These techniques include curve fitting algorithms and outlier removal with the random sample consensus (RANSAC) algorithm to reliably estimate the drogue center in 3D space, as well as to establish the relative position between the probe and the drogue. To demonstrate the feasibility of the proposed method on a real system, a ground navigation robot was designed and fabricated. Results presented in the paper show that using images acquired from a 3D Flash LIDAR camera as real time visual feedback, the ground robot is able to track a moving simulated drogue and continuously narrow the gap between the robot and the target autonomously.

  1. Ground penetrating radar (GPR) measurements at Mittivakkat Gletscher, Southeast Greenland

    NASA Astrophysics Data System (ADS)

    Clement Yde, Jacob; Løland, Ronny; Ruud, Henry; Mernild, Sebastian H.; Riger-Kusk, Mette; de Villiers, Simon; Tvis Knudsen, N.; Malmros, Jeppe K.

    2014-05-01

    Here, we present ground penetrating radar (GPR) measurements conducted on the surface of Mittivakkat Gletscher in Southeast Greenland (the only long-term mass balance observed glacier in Greenland) and estimate the change in ice volume over an 18 year period. Between a previous direct volume survey in 1994 and the new GPR survey in 2012, the glacier has changed its volume from 2.02 ± 0.10 to 1.50 ± 0.08 km3 while the study area has decreased from 17.6 to 15.8 km2. These results are in accordance with the cumulative mass loss observed by long-term mass balance measurements (1995/1996 - 2011/2012) at Mittivakkat Gletscher and confirms that the glacier is in severe climatic disequilibrium (AAR = 0.17). The observed volume-area scaling exponent γ and coefficient c are outside the range of global scaling parameters, but are sensitive to small uncertainties. As Mittivakkat Gletscher is generally considered as representative of glaciers in Southeast Greenland, these findings could indicate that a regional volume-area scaling approach would provide a more accurate total glacier volume estimate for Greenland than using parameters given by global scaling relationships.

  2. Comparison of relaxation responses of cavernous and trigonal smooth muscles from rabbits by alpha1-adrenoceptor antagonists; prazosin, terazosin, doxazosin, and tamsulosin.

    PubMed Central

    Seo, K. K.; Lee, M. Y.; Lim, S. W.; Kim, S. C.

    1999-01-01

    Alpha1a-adrenergic receptor (AR) primarily mediates the contraction of the prostatic and cavernous smooth muscles. Among clinically available alpha1-AR antagonists for the medical management of benign prostatic hyperplasia (BPH), tamsulosin has a modest selectivity for alpha1A- and alpha1D- over alpha1B-ARs. To compare the effects of various alpha1-AR antagonists on relaxation responses of cavernous and trigonal smooth muscles, isometric tension studies with relatively selective (tamsulosin) and non-selective (prazosin, doxazosin, and terazosin) alpha1A-AR antagonists, were conducted in the cavernous and trigonal muscle strips of rabbits (n=10 each). Tamsulosin had the strongest inhibitory effect on contraction of trigonal smooth muscle among the various alpha1-AR antagonists, and the inhibitory activities of prazosin, doxazosin, and terazosin were not statistically different. All alpha1-AR antagonists caused concentration-dependent relaxation of the cavernous muscle strips. Tamsulosin was shown to have greater potency than prazosin (more than 100-fold), doxazosin (more than 1000-fold), and terazosin (more than 1000-fold), in relaxation of cavernous smooth muscle. In conclusion, tamsulosin might be the most effective drug among the four commonly used alpha1-AR antagonists for the medical management of BPH. Tamsulosin might be a potential substitute for phentolamine in combination with vasoactive agents as an intracavernous injection therapy for patients with erectile dysfunction. PMID:10102527

  3. Optical Remote Sensing of Glacier Characteristics: A Review with Focus on the Himalaya

    PubMed Central

    Racoviteanu, Adina E.; Williams, Mark W.; Barry, Roger G.

    2008-01-01

    The increased availability of remote sensing platforms with appropriate spatial and temporal resolution, global coverage and low financial costs allows for fast, semi-automated, and cost-effective estimates of changes in glacier parameters over large areas. Remote sensing approaches allow for regular monitoring of the properties of alpine glaciers such as ice extent, terminus position, volume and surface elevation, from which glacier mass balance can be inferred. Such methods are particularly useful in remote areas with limited field-based glaciological measurements. This paper reviews advances in the use of visible and infrared remote sensing combined with field methods for estimating glacier parameters, with emphasis on volume/area changes and glacier mass balance. The focus is on the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) sensor and its applicability for monitoring Himalayan glaciers. The methods reviewed are: volumetric changes inferred from digital elevation models (DEMs), glacier delineation algorithms from multi-spectral analysis, changes in glacier area at decadal time scales, and AAR/ELA methods used to calculate yearly mass balances. The current limitations and on-going challenges in using remote sensing for mapping characteristics of mountain glaciers also discussed, specifically in the context of the Himalaya. PMID:27879883

  4. Evolution of translation machinery in recoded bacteria enables multi-site incorporation of nonstandard amino acids

    PubMed Central

    Amiram, Miriam; Haimovich, Adrian D; Fan, Chenguang; Wang, Yane-Shih; Aerni, Hans-Rudolf; Ntai, Ioanna; Moonan, Daniel W; Ma, Natalie J; Rovner, Alexis J; Hong, Seok Hoon; Kelleher, Neil L; Goodman, Andrew L; Jewett, Michael C; Söll, Dieter; Rinehart, Jesse; Isaacs, Farren J

    2016-01-01

    Expansion of the genetic code with nonstandard amino acids (nsAAs) has enabled biosynthesis of proteins with diverse new chemistries. However, this technology has been largely restricted to proteins containing a single or few nsAA instances. Here we describe an in vivo evolution approach in a genomically recoded Escherichia coli strain for the selection of orthogonal translation systems capable of multi-site nsAA incorporation. We evolved chromosomal aminoacyl-tRNA synthetases (aaRSs) with up to 25-fold increased protein production for p-acetyl-L-phenylalanine and p-azido-L-phenylalanine (pAzF). We also evolved aaRSs with tunable specificities for 14 nsAAs, including an enzyme that efficiently charges pAzF while excluding 237 other nsAAs. These variants enabled production of elastin-like-polypeptides with 30 nsAA residues at high yields (~50 mg/L) and high accuracy of incorporation (>95%). This approach to aaRS evolution should accelerate and expand our ability to produce functionalized proteins and sequence-defined polymers with diverse chemistries. PMID:26571098

  5. The profile of antibiotics resistance and integrons of extended-spectrum beta-lactamase producing thermotolerant coliforms isolated from the Yangtze River basin in Chongqing.

    PubMed

    Chen, Hao; Shu, Weiqun; Chang, Xiaosong; Chen, Ji-an; Guo, Yebin; Tan, Yao

    2010-07-01

    The spreading of extended-spectrum beta-lactamases (ESBL)-producing thermotolerant coliforms (TC) in the water environment is a threat to human health but little is known about ESBL-producing TCs in the Yangtze River. We received 319 ESBL-producing stains obtained from the Chongqing basin and we investigated antibiotic susceptibility, bla gene types and the presence of integrons and gene cassettes. 16.8% of TC isolates were ESBL-producing bacteria and bla(TEM+CTx-M) was the predominant ESBL type. 65.2% of isolates contained class 1 integrons, but only 3 carried intI 2. Gene cassettes were amplified and sequenced. aadA, drfA, cmlA, sat1, aar3 and two ORF cassettes were found. In conclusion, Yangtze River is heavily polluted by ESBL-producing TC bacteria and the combined bla gene type could enhance antibiotic resistance. Class 1 integrons were widespread in ESBL-producing isolates and play an important role in multi-drug resistance. Characterization of gene cassettes could reveal the dissemination of antibiotic resistance genes.

  6. Turbulent transport and production/destruction of ozone in a boundary layer over complex terrain

    NASA Technical Reports Server (NTRS)

    Greenhut, Gary K.; Jochum, Anne M.; Neininger, Bruno

    1994-01-01

    The first Intensive Observation Period (IOP) of the Swiss air pollution experiment POLLUMET took place in 1990 in the Aare River Valley between Bern and Zurich. During the IOP, fast response measurements of meteorological variables and ozone concentration were made within the boundary layer aboard a motorglider. In addition, mean values of meteorological variables and the concentrations of ozone and other trace species were measured using other aircraft, pilot balloons, tethersondes, and ground stations. Turbulent flux profiles of latent and sensible heat and ozone are calculated from the fast response data. Terms in the ozone mean concentration budget (time rate of change of mean concentration, horizontal advection, and flux divergence) are calculated for stationary time periods both before and after the passage of a cold front. The source/sink term is calculated as a residual in the budget, and its sign and magnitude are related to the measured concentrations of reactive trace species within the boundary layer. Relationships between concentration ratios of trace species and ozone concentration are determined in order to understand the influence of complex terrain on the processes that produce and destroy ozone.

  7. Definition and automatic anatomy recognition of lymph node zones in the pelvis on CT images

    NASA Astrophysics Data System (ADS)

    Liu, Yu; Udupa, Jayaram K.; Odhner, Dewey; Tong, Yubing; Guo, Shuxu; Attor, Rosemary; Reinicke, Danica; Torigian, Drew A.

    2016-03-01

    Currently, unlike IALSC-defined thoracic lymph node zones, no explicitly provided definitions for lymph nodes in other body regions are available. Yet, definitions are critical for standardizing the recognition, delineation, quantification, and reporting of lymphadenopathy in other body regions. Continuing from our previous work in the thorax, this paper proposes a standardized definition of the grouping of pelvic lymph nodes into 10 zones. We subsequently employ our earlier Automatic Anatomy Recognition (AAR) framework designed for body-wide organ modeling, recognition, and delineation to actually implement these zonal definitions where the zones are treated as anatomic objects. First, all 10 zones and key anatomic organs used as anchors are manually delineated under expert supervision for constructing fuzzy anatomy models of the assembly of organs together with the zones. Then, optimal hierarchical arrangement of these objects is constructed for the purpose of achieving the best zonal recognition. For actual localization of the objects, two strategies are used -- optimal thresholded search for organs and one-shot method for the zones where the known relationship of the zones to key organs is exploited. Based on 50 computed tomography (CT) image data sets for the pelvic body region and an equal division into training and test subsets, automatic zonal localization within 1-3 voxels is achieved.

  8. Growth inhibition in Chinese cabbage (Brassica rapa var. chinensis) growth exposed to di-n-butyl phthalate.

    PubMed

    Liao, Chien-Sen; Yen, Jui-Hung; Wang, Yei-Shung

    2009-04-30

    The toxicity and effects of di-n-butyl phthalate (DBP), an endocrine disruptor, on the growth of Chinese cabbage (Brassica rapa var. chinensis) were studied. Etiolation occurred on leaves of Chinese cabbage plant treated with 50mg/L of DBP for 42 d. DBP even below 1mg/L had a significant effect on the concentration of chlorophyll in Chinese cabbage and the biomass showed a severe decrease under treatment with more than 30 mg/L of DBP. At a concentration below 1mg/L of DBP, no significant difference in accumulation was found, but treatments with concentration exceeding 10, 30, 50 and 100mg/L all resulted in significant accumulation of DBP. Six protein spots extracted from leaf tissue of DBP-treated Chinese cabbage displaying a differential expression are shown in 2-DE maps. According to proteome level studies, three protein spots were found to increase and were identified, respectively, as acyl-[acyl-carrier-protein] desaturase (acyl-ACP desaturase), root phototropism protein 3 (RPT3) and ferredoxin-nitrite reductase (Fd-NiR). The other three protein spots were found to decrease and were identified respectively as dihydroflavonol-4-reductase (DFR), aminoacyl-tRNA synthetase (aaRS) and ATP synthase subunit beta. The key finding is that the other closely related plant, Bok choy (Brassica rapa subsp. chinensis), the subspecies of Chinese cabbage, respond differently to the same chemicals.

  9. MD Simulations of tRNA and Aminoacyl-tRNA Synthetases: Dynamics, Folding, Binding, and Allostery

    PubMed Central

    Li, Rongzhong; Macnamara, Lindsay M.; Leuchter, Jessica D.; Alexander, Rebecca W.; Cho, Samuel S.

    2015-01-01

    While tRNA and aminoacyl-tRNA synthetases are classes of biomolecules that have been extensively studied for decades, the finer details of how they carry out their fundamental biological functions in protein synthesis remain a challenge. Recent molecular dynamics (MD) simulations are verifying experimental observations and providing new insight that cannot be addressed from experiments alone. Throughout the review, we briefly discuss important historical events to provide a context for how far the field has progressed over the past few decades. We then review the background of tRNA molecules, aminoacyl-tRNA synthetases, and current state of the art MD simulation techniques for those who may be unfamiliar with any of those fields. Recent MD simulations of tRNA dynamics and folding and of aminoacyl-tRNA synthetase dynamics and mechanistic characterizations are discussed. We highlight the recent successes and discuss how important questions can be addressed using current MD simulations techniques. We also outline several natural next steps for computational studies of AARS:tRNA complexes. PMID:26184179

  10. Anisotropic Andreev reflection in ferromagnet/s-wave superconductors (FS)

    NASA Astrophysics Data System (ADS)

    Hoegl, Petra; Matos Abiague, Alex; Zutic, Igor; Fabian, Jaroslav

    2015-03-01

    Andreev reflection in FS junctions is a sensitive probe of the junction interface as well as of the spin polarization of the F region. By performing analytical and numerical calculations on widely accepted model systems, with interfacial Rashba and Dresselhaus spin-orbit fields, we show that Andreev reflection spectroscopy is also a sensitive tool of the interfacial spin-orbit coupling. In particular, we find a finite subgap conductance even in half-metallic systems due to the spin-flip Andreev reflection, imposing a triplet proximity effect. Furthermore, we predict a giant magnetic anisotropy of the Andreev reflection--anisotropic Andreev reflection (AAR)--with respect to the orientation of the F magnetization. We analyze the effects of the tunnel barrier strength, the F spin polarization, and the effective mass and Fermi wave vector mismatch. Our results should also have implications for designing Majorana states in semiconductor junctions with superconductors. This work has been supported by DFG SFB 689 and the International Doctorate Program Topological Insulators of the Elite Network of Bavaria.

  11. ADCK4 mutations promote steroid-resistant nephrotic syndrome through CoQ10 biosynthesis disruption

    PubMed Central

    Ashraf, Shazia; Gee, Heon Yung; Woerner, Stephanie; Xie, Letian X.; Vega-Warner, Virginia; Lovric, Svjetlana; Fang, Humphrey; Song, Xuewen; Cattran, Daniel C.; Avila-Casado, Carmen; Paterson, Andrew D.; Nitschké, Patrick; Bole-Feysot, Christine; Cochat, Pierre; Esteve-Rudd, Julian; Haberberger, Birgit; Allen, Susan J.; Zhou, Weibin; Airik, Rannar; Otto, Edgar A.; Barua, Moumita; Al-Hamed, Mohamed H.; Kari, Jameela A.; Evans, Jonathan; Bierzynska, Agnieszka; Saleem, Moin A.; Böckenhauer, Detlef; Kleta, Robert; El Desoky, Sherif; Hacihamdioglu, Duygu O.; Gok, Faysal; Washburn, Joseph; Wiggins, Roger C.; Choi, Murim; Lifton, Richard P.; Levy, Shawn; Han, Zhe; Salviati, Leonardo; Prokisch, Holger; Williams, David S.; Pollak, Martin; Clarke, Catherine F.; Pei, York; Antignac, Corinne; Hildebrandt, Friedhelm

    2013-01-01

    Identification of single-gene causes of steroid-resistant nephrotic syndrome (SRNS) has furthered the understanding of the pathogenesis of this disease. Here, using a combination of homozygosity mapping and whole human exome resequencing, we identified mutations in the aarF domain containing kinase 4 (ADCK4) gene in 15 individuals with SRNS from 8 unrelated families. ADCK4 was highly similar to ADCK3, which has been shown to participate in coenzyme Q10 (CoQ10) biosynthesis. Mutations in ADCK4 resulted in reduced CoQ10 levels and reduced mitochondrial respiratory enzyme activity in cells isolated from individuals with SRNS and transformed lymphoblasts. Knockdown of adck4 in zebrafish and Drosophila recapitulated nephrotic syndrome-associated phenotypes. Furthermore, ADCK4 was expressed in glomerular podocytes and partially localized to podocyte mitochondria and foot processes in rat kidneys and cultured human podocytes. In human podocytes, ADCK4 interacted with members of the CoQ10 biosynthesis pathway, including COQ6, which has been linked with SRNS and COQ7. Knockdown of ADCK4 in podocytes resulted in decreased migration, which was reversed by CoQ10 addition. Interestingly, a patient with SRNS with a homozygous ADCK4 frameshift mutation had partial remission following CoQ10 treatment. These data indicate that individuals with SRNS with mutations in ADCK4 or other genes that participate in CoQ10 biosynthesis may be treatable with CoQ10. PMID:24270420

  12. How to identify carbonate rock reactions in concrete

    SciTech Connect

    Katayama, Tetsuya . E-mail: katayamat@kge.co.jp

    2004-11-15

    This paper summarizes the modern petrographic techniques used to diagnose carbonate rock reactions in concrete. Concrete microbar specimens of the prototype RILEM AAR-5 test, provided by the Austrian Cement Research Institute, and typical Canadian concrete that had undergone alkali-carbonate reaction (ACR) were examined. Scanning electron microscopy, element mapping and quantitative analysis using electron-probe microanalyzer with energy-dispersive spectrometry (EPMA/EDS: around x 2000, <0.1 nA) were made of polished thin sections after completing polarizing microscopy. Dedolomitization produced a myrmekitic texture, composed of spotted brucite (<3 {mu}m) and calcite within the reaction rim, along with a carbonate halo of calcite in the surrounding cement paste. However, no evidence was detected that dedolomitization had produced the expansion cracks in the cement paste, while the classical definition of alkali-carbonate reaction postulates their development. It was found that the alkali-silica reaction (ASR) due to cryptocrystalline quartz hidden in the matrix, always associated with dedolomitization in all the carbonate aggregates tested, was responsible for the expansion of both the laboratory and field concretes, even with the Canadian dolomitic limestone from Kingston, the reference material for alkali-carbonate reaction. It is suggested that the term alkali-carbonate reaction is misleading.

  13. Alkali-silica reactivity of expanded glass granules in structure of lightweight concrete

    NASA Astrophysics Data System (ADS)

    Bumanis, G.; Bajare, D.; Locs, J.; Korjakins, A.

    2013-12-01

    Main component in the lightweight concrete, which provides its properties, is aggregate. A lot of investigations on alkali silica reaction (ASR) between cement and lightweight aggregates have been done with their results published in the academic literature. Whereas expanded glass granules, which is relatively new product in the market of building materials, has not been a frequent research object. Therefore lightweight granules made from waste glass and eight types of cement with different chemical and mineralogical composition were examined in this research. Expanded glass granules used in this research is commercially available material produced by Penostek. Lightweight concrete mixtures were prepared by using commercial chemical additives to improve workability of concrete. The aim of the study is to identify effect of cement composition to the ASR reaction which occurs between expanded glass granules and binder. Expanded glass granules mechanical and physical properties were determined. In addition, properties of fresh and hardened concrete were determined. The ASR test was processed according to RILEM AAR-2 testing recommendation. Tests with scanning electron microscope and microstructural investigations were performed for expanded glass granules and hardened concrete specimens before and after exposing them in alkali solution.

  14. Study of the Binding Energies between Unnatural Amino Acids and Engineered Orthogonal Tyrosyl-tRNA Synthetases

    NASA Astrophysics Data System (ADS)

    Ren, Wei; Truong, Tan M.; Ai, Hui-Wang

    2015-07-01

    We utilized several computational approaches to evaluate the binding energies of tyrosine (Tyr) and several unnatural Tyr analogs, to several orthogonal aaRSes derived from Methanocaldococcus jannaschii and Escherichia coli tyrosyl-tRNA synthetases. The present study reveals the following: (1) AutoDock Vina and ROSETTA were able to distinguish binding energy differences for individual pairs of favorable and unfavorable aaRS-amino acid complexes, but were unable to cluster together all experimentally verified favorable complexes from unfavorable aaRS-Tyr complexes; (2) MD-MM/PBSA provided the best prediction accuracy in terms of clustering favorable and unfavorable enzyme-substrate complexes, but also required the highest computational cost; and (3) MM/PBSA based on single energy-minimized structures has a significantly lower computational cost compared to MD-MM/PBSA, but still produced sufficiently accurate predictions to cluster aaRS-amino acid interactions. Although amino acid-aaRS binding is just the first step in a complex series of processes to acylate a tRNA with its corresponding amino acid, the difference in binding energy, as shown by MD-MM/PBSA, is important for a mutant orthogonal aaRS to distinguish between a favorable unnatural amino acid (unAA) substrate from unfavorable natural amino acid substrates. Our computational study should assist further designing and engineering of orthogonal aaRSes for the genetic encoding of novel unAAs.

  15. Investigation of source location determination from Magsat magnetic anomalies: The Euler method approach

    NASA Technical Reports Server (NTRS)

    Ravat, Dhananjay

    1996-01-01

    The applicability of the Euler method of source location determination was investigated on several model situations pertinent to satellite-data scale situations as well as Magsat data of Europe. Our investigations enabled us to understand the end-member cases for which the Euler method will work with the present satellite magnetic data and also the cases for which the assumptions implicit in the Euler method will not be met by the present satellite magnetic data. These results have been presented in one invited lecture at the Indo-US workshop on Geomagnetism in Studies of the Earth's Interior in August 1994 in Pune, India, and at one presentation at the 21st General Assembly of the IUGG in July 1995 in Boulder, CO. A new method, called Anomaly Attenuation Rate (AAR) Method (based on the Euler method), was developed during this study. This method is scale-independent and is appropriate to locate centroids of semi-compact three dimensional sources of gravity and magnetic anomalies. The method was presented during 1996 Spring AGU meeting and a manuscript describing this method is being prepared for its submission to a high-ranking journal. The grant has resulted in 3 papers and presentations at national and international meetings and one manuscript of a paper (to be submitted shortly to a reputable journal).

  16. A novel autoregulatory loop between the Gcn2-Atf4 pathway and L-Proline metabolism controls stem cell identity

    PubMed Central

    D'Aniello, C; Fico, A; Casalino, L; Guardiola, O; Di Napoli, G; Cermola, F; De Cesare, D; Tatè, R; Cobellis, G; Patriarca, E J; Minchiotti, G

    2015-01-01

    Increasing evidence indicates that metabolism is implicated in the control of stem cell identity. Here, we demonstrate that embryonic stem cell (ESC) behaviour relies on a feedback loop that involves the non-essential amino acid L-Proline (L-Pro) in the modulation of the Gcn2-Eif2α-Atf4 amino acid starvation response (AAR) pathway that in turn regulates L-Pro biosynthesis. This regulatory loop generates a highly specific intrinsic shortage of L-Pro that restricts proliferation of tightly packed domed-like ESC colonies and safeguards ESC identity. Indeed, alleviation of this nutrient stress condition by exogenously provided L-Pro induces proliferation and modifies the ESC phenotypic and molecular identity towards that of mesenchymal-like, invasive pluripotent stem cells. Either pharmacological inhibition of the prolyl-tRNA synthetase by halofuginone or forced expression of Atf4 antagonises the effects of exogenous L-Pro. Our data provide unprecedented evidence that L-Pro metabolism and the nutrient stress response are functionally integrated to maintain ESC identity. PMID:25857264

  17. Automatic anatomy recognition in whole-body PET/CT images

    SciTech Connect

    Wang, Huiqian; Udupa, Jayaram K. Odhner, Dewey; Tong, Yubing; Torigian, Drew A.; Zhao, Liming

    2016-01-15

    Purpose: Whole-body positron emission tomography/computed tomography (PET/CT) has become a standard method of imaging patients with various disease conditions, especially cancer. Body-wide accurate quantification of disease burden in PET/CT images is important for characterizing lesions, staging disease, prognosticating patient outcome, planning treatment, and evaluating disease response to therapeutic interventions. However, body-wide anatomy recognition in PET/CT is a critical first step for accurately and automatically quantifying disease body-wide, body-region-wise, and organwise. This latter process, however, has remained a challenge due to the lower quality of the anatomic information portrayed in the CT component of this imaging modality and the paucity of anatomic details in the PET component. In this paper, the authors demonstrate the adaptation of a recently developed automatic anatomy recognition (AAR) methodology [Udupa et al., “Body-wide hierarchical fuzzy modeling, recognition, and delineation of anatomy in medical images,” Med. Image Anal. 18, 752–771 (2014)] to PET/CT images. Their goal was to test what level of object localization accuracy can be achieved on PET/CT compared to that achieved on diagnostic CT images. Methods: The authors advance the AAR approach in this work in three fronts: (i) from body-region-wise treatment in the work of Udupa et al. to whole body; (ii) from the use of image intensity in optimal object recognition in the work of Udupa et al. to intensity plus object-specific texture properties, and (iii) from the intramodality model-building-recognition strategy to the intermodality approach. The whole-body approach allows consideration of relationships among objects in different body regions, which was previously not possible. Consideration of object texture allows generalizing the previous optimal threshold-based fuzzy model recognition method from intensity images to any derived fuzzy membership image, and in the process

  18. Morphology, sedimentology and stratigraphic implication of debris-covered glacier deposits from the LGM and Lateglacial (Eastern Alps, Austria)

    NASA Astrophysics Data System (ADS)

    Reitner, Jürgen M.; Seidl, Sabrina; Wagreich, Michael

    2013-04-01

    Understanding the genesis of Quaternary sediments is crucial for establishing a climato-stratigraphy and, further on, to infer paleoclimatic conditions, if possible. Especially diamictons in the high-mountain environment may be formed by variety of processes, i.e. glacial, periglacial and gravitational. On the other hand, the interpretation of morphological features might be ambiguous as for example ridges may document latero-frontal dump moraines, flow of a rock avalanche event or constituents of a rock-glacier. In addition, equilibrium line altitudes (ELAs) of paleo-glaciers are mostly based on calculations using the reconstructed glacier size and applying a more or less fixed accumulation area ration (e.g. AAR - method). However, such ELAs are of no use for stratigraphic correlations and climatic considerations, if the former glacial system was strongly influenced by supraglacial debris deriving from steep back walls of cirques. We present two examples of reconstructed debris-covered or more specifically debris-mantled paleo-glaciers, their geological and morphological setting as well as their documented sedimentology and morphology. The first example is from the easternmost part of the European Alps (Northern Calcareous Alps / Schneeberg mountains / Puchberg) where an up to 60 m high moraine systems of LGM age shows some striking morphological similarities with relict rock glacier. However, based especially on lithofacies analyses as well as on the lithology of the matrix a glacial genesis could be proven. Lateglacial glacier deposits from the interior of the Alps (Lienz Dolomites / area of Karlsbader Hütte) display a quite similar glacial system. The geometry of the deposits in relation to proglacial sturzstrom sediments, showing typical indications of dynamic fragmentation, and the amount of angular, passively transported clasts in the till point to a rock avalanche event which had hit the glacier surface during a glacier advance. As the glacial system shows

  19. An anisotropy- based inclination shallowing correction of the Shepody Fm. of New Brunswick and Nova Scotia and the Deer Lake Group of Newfoundland, Canada.

    NASA Astrophysics Data System (ADS)

    Bilardello, D.; Kodama, K. P.

    2006-12-01

    The North American apparent polar wander path (APWP) for the upper Paleozoic is dominated by red beds, which have been reported to suffer from deposition-/ compaction- induced magnetic inclination shallowing. To apply a correction for inclination shallowing, experiments to measure the magnetic fabric of hematite have been designed and performed together with paleo-magnetic investigations on Lower Carboniferous red beds from the Shepody Fm of New Brunswick and Nova Scotia and from the Deer Lake Group of Newfoundland. The corrected poles have been plotted on the existing APWPs for comparison. In a previous anisotropy of magnetic susceptibility (AMS)-based, inclination correction of the Shepody Fm, IRM acquisition, Lowrie and fold tests revealed secondary maghemite, goethite and primary hematite as magnetic carriers, thus indicating that AMS would measure a composite fabric rather than that of hematite only. These results were confirmed by further anisotropy measurements. Anisotropy of Anhysteretic Remanence (AAR) measurements revealed an absence of fabric for maghemite, while high field (5 T) isothermal remanent magnetization (hf-IRM) anisotropy, cleaned of the low coercivity components, revealed a very distinct depositional fabric for primary hematite. An inclination correction performed using the hf-IRM anisotropy gave a similar result to the AMS-based correction (mean corrected inclinations: 29.1° for AMS and 28.8° for hf-IRM indicating respectively 11.1° and 8° of inclination shallowing). These values are consistent with results obtained from three other hematite and magnetite- bearing Lower Carboniferous rocks from North America: the A95 for the four North American paleopoles decreases from an uncorrected value of 12° to a corrected value of 4.6°. These corrections imply a ~ 6° increase in co-latitude for the average Lower Carboniferous paleopole. To determine the corrected inclinations, individual magnetic particle anisotropy of hematite must be measured

  20. Transfusion of Plasma Collected at Late Phase after Preconditioning Reduces Myocardial Infarct Size Induced by Ischemia-reperfusion in Rats In vivo

    PubMed Central

    Zhao, Yang; Zheng, Zhi-Nan; Cheung, Chi-Wai; Zuo, Zhi-Yi; Jin, San-Qing

    2017-01-01

    Background: Plasma transfusion is a common clinical practice. Remote ischemic preconditioning (RIPC) protects organs against ischemia-reperfusion (IR) injury. Whether preconditioned plasma (PP), collected at late phase after RIPC, could protect organs against IR injury in vivo is unknown. This study explored whether transfusion of PP could reduce myocardial infarct size (IS) after IR in rat in vivo. Methods: Eighty Lewis rats were randomized to eight groups (n = 10 for each group). Two groups of plasma donor rats donated plasma at 48 h after transient limb ischemia (PP) or control protocol (nonpreconditioned plasma [NPP]). Six groups of recipient rats received normal saline (NS; NS-IR 1, and NS-IR 24 groups), NPP (NPP-IR 1 and NPP-IR 24 groups), or PP (PP-IR 1 and PP-IR 24 groups) at one or 24 h before myocardial IR. Myocardial IR consisted of 30-min left anterior descending (LAD) coronary artery occlusion and 180-min reperfusion. The area at risk (AAR) and infarct area were determined by double-staining with Evans blue and triphenyltetrazolium chloride. IS was calculated by infarct area divided by AAR. This was a 3 × 2 factorial design study, and factorial analysis was used to evaluate the data. If an interaction between the fluid and transfusion time existed, one-way analysis of variance with Bonferroni correction for multiple comparisons was used to analyze the single effects of fluid type when the transfusion time was fixed. Results: IS in the NPP-IR 1 and PP-IR 1 groups was smaller than in the NS-IR 1 group (F = 6.838, P = 0.005; NPP-IR 1: 57 ± 8% vs. NS-IR1: 68 ± 6%, t = 2.843, P = 0.020; PP-IR 1: 56 ± 8% vs. NS-IR 1: 68 ± 6%, t = 3.102, P = 0.009), but no significant difference was detected between the NPP-IR 1 and PP-IR 1 groups (57 ± 8% vs. 56 ± 8%, t = 0.069, P = 1.000). IS in the NPP-IR 24 and PP-IR 24 groups was smaller than in the NS-IR 24 group (F = 24.796, P < 0.001; NPP-IR 24: 56% ± 7% vs. NS-IR 24: 68 ± 7%, t = 3.102, P = 0.026; PP-IR 24