Sample records for kriis tnis kanger

  1. The use of neutrons for the detection of explosives in Civil Security Applications

    SciTech Connect

    Pesente, S.; Fabris, D.; Lunardon, M.; Moretto, S.; Nebbia, G.; Viesti, G.


    The search for hidden explosives has been simulated in laboratory conditions by using our Tagged Neutron Inspection System (TNIS). Applications of the TNIS concept to Civil Security problems are discussed in the light of our projects for cargo container inspections. Moreover, neutron attenuation and scattering can be used to search in real time for large quantity of explosive hidden in vehicles.

  2. Molecular evolution of troponin I and a role of its N-terminal extension in nematode locomotion

    PubMed Central

    Barnes, Dawn E.; Hwang, Hyundoo; Ono, Kanako; Lu, Hang; Ono, Shoichiro


    Summary The troponin complex, composed of troponin T (TnT), troponin I (TnI), and troponin C (TnC), is the major calcium-dependent regulator of muscle contraction, which is present widely in both vertebrates and invertebrates. Little is known about evolutionary aspects of troponin in the animal kingdom. Using a combination of data mining and functional analysis of TnI, we report evidence that an N-terminal extension of TnI is present in most of bilaterian animals as a functionally important domain. Troponin components have been reported in species in most of representative bilaterian phyla. Comparison of TnI sequences shows that the core domains are conserved in all examined TnIs, and that N- and C-terminal extensions are variable among isoforms and species. In particular, N-terminal extensions are present in all protostome TnIs and chordate cardiac TnIs but lost in a subset of chordate TnIs including vertebrate skeletal-muscle isoforms. Transgenic rescue experiments in C. elegans striated muscle show that the N-terminal extension of TnI (UNC-27) is required for coordinated worm locomotion but not in sarcomere assembly and single muscle-contractility kinetics. These results suggest that N-terminal extensions of TnIs are retained from a TnI ancestor as a functional domain. PMID:26849746

  3. Development of the EURITRACK tagged neutron inspection system

    NASA Astrophysics Data System (ADS)

    Perot, B.; Carasco, C.; Bernard, S.; Mariani, A.; Szabo, J.-L.; Mercier, E.; Sannie, G.; Viesti, G.; Nebbia, G.; Pesente, S.; Lunardon, M.; Moretto, S.; Fabris, D.; Zenoni, A.; Bonomi, G.; Donzella, A.; Fontana, A.; Boghen, G.; Valkovic, V.; Sudac, D.; Moszynski, M.; Batsch, T.; Gierlik, M.; Woski, D.; Klamra, W.; Isaksson, P.; Le Tourneur, P.; Lhuissier, M.; Colonna, A.; Tintori, C.; Peerani, P.; Sequeira, V.; Salvato, M.


    The EURopean Illicit TRAfficing Countermeasures Kit (EURITRACK) project is part of the 6th European Union Framework Program. It aims at developing a Tagged Neutron Inspection System (TNIS) to detect illicit materials, such as explosives and narcotics, in cargo containers. Fast neutron induced reactions produce specific gamma-rays used to determine the chemical composition of the inspected material. The associated particle technique is employed to precisely locate the interaction points of the neutrons. A new deuterium-tritium neutron generator has been developed, including a pixelized alpha particle detector. The TNIS also comprises high-efficiency fast neutron and gamma-ray detectors, a dedicated front-end electronics and an integrated software to entirely drive the system and automatically process the data. Most components have been integrated during last months at Institute Ruder Boskovic, in Zagreb, Croatia. An overview of the TNIS and of its preliminary performances is presented.

  4. The slow isoform of Xenopus troponin I is expressed in developing skeletal muscle but not in the heart.


    Warkman, Andrew S; Atkinson, Burr G


    In birds and mammals three isoforms of troponin I (TnI) exist; a slow (TnIs), a fast (TnIf) and a cardiac (TnIc). Although each of these isoforms is expressed in the adult forms of these organisms in a muscle fiber-type-specific manner, the gene encoding TnIs is also expressed within the developing heart of these vertebrates. Herein, our results demonstrate that the developing heart of Xenopus laevis, unlike its counterpart in birds and mammals, does not express the gene encoding the TnIs isoform and that the expression of this gene, as well as the one encoding the Xenopus TnIf isoform, is restricted to skeletal muscle.

  5. Nerve-responsive troponin I slow promoter does not respond to unloading

    NASA Technical Reports Server (NTRS)

    Criswell, D. S.; Hodgson, V. R.; Hardeman, E. C.; Booth, F. W.


    We examined the regulation of the troponin I slow (TnIs) promoter during skeletal muscle unloading-induced protein isoform transition, by using a transgenic mouse line harboring the -4,200 to +12 base pairs region of the human TnIs promoter. Eighteen female transgenic mice ( approximately 30 g body mass) were randomly divided into two groups: weight-bearing (WB) controls (n = 9) and hindlimb unloaded (HU; n = 9). The HU mice were tail suspended for 7 days. Body mass was unchanged in the WB group but was reduced (-6%; P < 0.05) after the HU treatment. Absolute soleus muscle mass (-25%) and soleus mass relative to body mass (-16%) were both lower (P < 0.05) in the HU group compared with the WB mice. Northern blot analyses indicate that 7 days of HU result in a 64% decrease (P < 0.05) in the abundance of endogenous TnIs mRNA (microg/mg muscle) in the mouse soleus. Furthermore, there is a trend for the abundance of the fast troponin I mRNA to be increased (+34%). Analysis of transgenic chloramphenicol acetyltransferase activity in the soleus muscle revealed no difference (P > 0.05) between WB and HU groups. We conclude that additional elements are necessary for the TnIs gene to respond to an unloading-induced, slow-to-fast isoform transition stimulus.

  6. Electron Resonance Decay into a Biological Function: Decrease in Viability of E. coli Transformed by Plasmid DNA Irradiated with 0.5-18 eV Electrons.


    Kouass Sahbani, S; Cloutier, P; Bass, A D; Hunting, D J; Sanche, L


    Transient negative ions (TNIs) are ubiquitous in electron-molecule scattering at low electron impact energies (0-20 eV) and are particularly effective in damaging large biomolecules. Because ionizing radiation generates mostly 0-20 eV electrons, TNIs are expected to play important roles in cell mutagenesis and death during radiotherapeutic cancer treatment, although this hypothesis has never been directly verified. Here, we measure the efficiency of transforming E. coli bacteria by inserting into the cells, pGEM-3ZfL(-) plasmid DNA that confers resistance to the antibiotic ampicillin. Before transformation, plasmids are irradiated with electrons of specific energies between 0.5 and 18 eV. The loss of transformation efficiency plotted as a function of irradiation energy reveals TNIs at 5.5 and 9.5 eV, corresponding to similar states observed in the yields of DNA double strand breaks. We show that TNIs are detectable in the electron-energy dependence of a biological process and can decrease cell viability.

  7. Symposium Proceedings on Intervention Programs Aimed at Increasing Minority Participation in Mathematics-Based Fields Held in Washington, DC on 27-28 May 1988

    DTIC Science & Technology


    scientists and engineers in tnis country (Employed Scientists and Engineeris in the U.S., National Science Foundation, 1985). A recent report of the...Pre-school Behavior. Genetic Psychology Monographs, 75, 43-88. (1968). An Exploratory Study of Socialization Effects on Black Children: Some Black

  8. ARBAT Flat Trajectory Study Report.

    DTIC Science & Technology


    per secona. Tnis Aas a rii.nner azimutn rate than the ARSAT System han. Tnhis m-iane use of an increase in tnet number of pulses per, frame not...position. The ARSAT radar system, in the present conficuration shall be exercised to achieve the intercept and track of the above targets. At the end of

  9. Criteria for Reconstitution of Forces.

    DTIC Science & Technology


    proposed. ,.. nceS’ F For NTIS CQ𔃽*! DTI~C Vi LI Just If .ut - . ion_ .. ".. D 1lI T . .. .. .. ... AVAt 1 " t’ ’. Dist SIRCURITY CLASSIFICATION OF TNIS...the CGSC sample had combat experience, an average of 14 months. Only 4 percent of the Advanced Course respondents, who were mostly captains , reported

  10. Nerve-responsive troponin I slow promoter does not respond to unloading

    NASA Technical Reports Server (NTRS)

    Criswell, D. S.; Hodgson, V. R.; Hardeman, E. C.; Booth, F. W.


    We examined the regulation of the troponin I slow (TnIs) promoter during skeletal muscle unloading-induced protein isoform transition, by using a transgenic mouse line harboring the -4,200 to +12 base pairs region of the human TnIs promoter. Eighteen female transgenic mice ( approximately 30 g body mass) were randomly divided into two groups: weight-bearing (WB) controls (n = 9) and hindlimb unloaded (HU; n = 9). The HU mice were tail suspended for 7 days. Body mass was unchanged in the WB group but was reduced (-6%; P < 0.05) after the HU treatment. Absolute soleus muscle mass (-25%) and soleus mass relative to body mass (-16%) were both lower (P < 0.05) in the HU group compared with the WB mice. Northern blot analyses indicate that 7 days of HU result in a 64% decrease (P < 0.05) in the abundance of endogenous TnIs mRNA (microg/mg muscle) in the mouse soleus. Furthermore, there is a trend for the abundance of the fast troponin I mRNA to be increased (+34%). Analysis of transgenic chloramphenicol acetyltransferase activity in the soleus muscle revealed no difference (P > 0.05) between WB and HU groups. We conclude that additional elements are necessary for the TnIs gene to respond to an unloading-induced, slow-to-fast isoform transition stimulus.

  11. Adaptive Processing for Low RCS Targets

    DTIC Science & Technology


    EDITION OF NOV 61$ SOLETE UNCLASSIFIED SECURITY CLASSIFICATION OF THIS PAGE (Whom Dote EniOWe) IL-~ -- .. - k UNCLASSIFIED SCr%1TY CLASIFICATION OF TNIS...the matched-signal concept, whether in the time or frequency domain, the purpose should be kept in mind . The idea is to enhance returns from targets

  12. Repair, Evaluation, Maintenance, and Rehabilitation Research Program. Lubricants for Hydraulic Structures

    DTIC Science & Technology


    not unally list additives, instead, they indicate characteristics such as good antiwear cualities , goo’ water resistance, or 37 good oxidation...34ASTM Industrial Fluid Lubricants. Saybolt Visco ly Grade Number Detailed physical health and safety normation on tnis product is availahle on...Zinc, P.P.M., Max. 10 10 10 10 "ASTM Industrial Fluid Lubricants, Saybolt Viscosity Grade Number. I Detailed physical, health andi safety information

  13. Distributed Hypothesis Formation in Distributed Sensor Networks

    DTIC Science & Technology


    the processing architecture at each node in the DSN. Each node contains the Generalized Tracker/Classifier for processing of (Continued) - DD 1473...TIM Olr TNiS PAG Iwhn D-le Ine 4e.) local sensor data, an information fusion module to integrate processed information from various nodes, and an...OF EACH PROCESSING NODE .. ............ 10 2.2.1 Local Processing of the Sensor Data. ......... 12 2.2.2 Information Fusion. .. ................ 12

  14. Low-Level Convergence and the Prediction of Convective Precipitation in South Florida.

    DTIC Science & Technology


    Af" -Ao97 55 ILLINOIS STATE WATER SURVEY URBANA F/6 4/2 LOWLEVEL CONVERGENCE AND THE PREDICTION OF CONVECTIVE PRECIPIT-ETC(U) FEB 81 A I WATSON. R L...not be construed as an official Department of the Army position, policy, or decision, unless so designated by other documentation. IS. KEY WORDS ...varying meteorological cond’tions and ti: == UNCLASSIFIED of day. SECURITY CLASSIFICATIOR OF TNIS PAGE (Whven Data Etered) State Water Survey

  15. A Microcomputer System for Target Information in the Fire Support Coordination Center: A Data Base Approach.

    DTIC Science & Technology


    space and lie speed of access to secondary storaee and. the requirement for an e..eftive interactive system for a non-sopbisticated user. The desian of...operator woriine in the SACC operational spaces uses tne QUEST data base query language to access targets and target information from the data base. Requests...display unit in the SACC. The report printouts are available from a printer located in the main computer spaces . During tnis period, the TIO is

  16. Semidiurnal Hough Mode Extensions in the Thermosphere and Their Application

    DTIC Science & Technology


    OF TNIS PAGE (11t~n Veto Rnforod) ..- q4ITY CLASSIFICATION OF THIS PAGE(Whan Dae EFneld) 20. Abstract (Continued) solar cycle. This note gives the...will vary with solar cycle insofar as ion drag (proportional to electron density) and neutral temperature vary with the solar cycle. To present the...Reidel, Dordrecht, Holland, 200 pp. 2. Hong, S., and R. S. Lindzen, 1976, Solar Semidiurnal Tide in the Thermosphere. J. Atmos. Sci., a, in press. 3

  17. Scanning Cargo Containers with Tagged Neutrons

    SciTech Connect

    Viesti, G.; Botosso, C.; Fabris, D.; Lunardon, M.; Moretto, S.; Nebbia, G.; Pesente, S.; Zenoni, A.; Donzella, A.; Perot, B.; Carasco, C.; Bernard, S.; Mariani, A.; Szabo, J.-L.; Sannie, G.; Valkovic, V.; Sudac, D.; Nad, K.; Peerani, P.; Sequeira, V.


    A new Tagged Neutron Inspection System (TNIS) able to detect illicit materials such as explosives and narcotics in cargo containers has been developed within the EURopean Illicit TRAfficing Countermeasures Kit (EURITRACK) project. After the R and D phase, the inspection portal has been installed and commissioned at the Rijeka seaport in Croatia, where it has been operated in connection with the existing X-ray scanner for a first two-month demonstration campaign. Results obtained are presented and discussed in this paper.

  18. Scanning Cargo Containers with Tagged Neutrons

    NASA Astrophysics Data System (ADS)

    Viesti, G.; Botosso, C.; Fabris, D.; Lunardon, M.; Moretto, S.; Nebbia, G.; Pesente, S.; Zenoni, A.; Donzella, A.; Perot, B.; Carasco, C.; Bernard, S.; Mariani, A.; Szabo, J.-L.; Sannie, G.; Valkovic, V.; Sudac, D.; Nad, K.; Peerani, P.; Sequeira, V.; Salvato, M.; Moszynski, M.; Gierlik, M.; Klamra, W.; Le Tourneur, P.; Lhuissier, M.; Colonna, A.; Tintori, C.


    A new Tagged Neutron Inspection System (TNIS) able to detect illicit materials such as explosives and narcotics in cargo containers has been developed within the EURopean Illicit TRAfficing Countermeasures Kit (EURITRACK) project. After the R&D phase, the inspection portal has been installed and commissioned at the Rijeka seaport in Croatia, where it has been operated in connection with the existing X-ray scanner for a first two-month demonstration campaign. Results obtained are presented and discussed in this paper.

  19. Logic Design of a Shared Disk System in a Multi-Micro Computer Environment.

    DTIC Science & Technology


    thesis was essential to the project. Chapter II addresses tne system arcnitecture. Detailed discussion is eiven of all major hardware components as...tne development of tne vicropoiis interface design. A eeneral understandin? of tnis structure is an essential prerequiste to an understanding of,bin_dec,dec_asc • subroutine prints out at tne console a bulation of user supplied input and tne calling program

  20. Prehistoric Cultural Resources within the Right-of-Way of the Proposed Little Blue River Channel, Jackson County, Missouri. Part 1.

    DTIC Science & Technology


    Kenneth L. Brown Rebecca Filer James E. King Robert J. Ziegler Alfred E. Johnson, Principal Investigator An Archaeological Project Conducted for the Kansas...Funds for this investigation and report were provided by the U.S. Army Corps of Engineers. The Corps may not necessarily agree with the contents of this...1473 EovTloas or NPOV 6S IS OBSOLETE tn 1 zi- SECURITY CLASSIFICATION OF TNIS PA .E (114 [lots Entere’t) % ABSTRACT This report describes archaeological

  1. A Plan for the Automation of the DE 1052 Class of Naval Surface Ships

    DTIC Science & Technology


    tnis device. Secondly, the main computer main- tains a file of simulation and diagnostic programs that can test the operability of any component...contains all operating systems, calculation procedures and program logic, and communication interfaces. Inputs to this controller system are control center. A minimum of main computer Inputs and outputs have been used to reduce system complexity and enhance the system’s reliability

  2. Transcriptional control of muscle plasticity: differential regulation of troponin I genes by electrical activity.


    Calvo, S; Stauffer, J; Nakayama, M; Buonanno, A


    Plasticity of the skeletal muscle phenotype can result from the selective repression and activation of gene expression in response to innervation patterns. Motoneurons, eliciting different patterns of depolarization, regulate the contractile properties of the myofibers they innervate by selectively activating expression of genes encoding fiber-type-specific (fast vs. slow) contractile proteins. We have analyzed the regulation of the troponin I slow (TnIs) and fast (TnIf) genes as a model to study the molecular mechanisms regulating fiber-type plasticity. We found that expression of the two TnI isoforms is downregulated by denervation. Moreover, TnI expression is upregulated by specific patterns of electrical activity [10 Hz vs. 100 Hz] used to depolarize muscle. We previously isolated the rat TnIs gene and demonstrated that regulatory sequences reside in its upstream region and second intron [Banerjee-Basu S, Buonanno A (1993), Mol Cell Biol 12:5024-5032]. Using transgenic mice, we show that the upstream region of the TnIs gene extending from -949 to +50 is sufficient to confer transcription specifically in slowtwitch muscles. Serial deletions of the TnIs upstream and intronic regions were generated in a CAT reporter vector to delineate transcriptional regulatory elements in transiently transfected Sol8 myotubes. Sequences necessary to confer the highest levels of TnIs transcription mapped to the upstream region between -0.95 and -0.72 kb, and to a 56 bp sequence located in the second intron. Comparison of the at sequence between -0.95 and -0.72 to the human TnIs gene identified a highly homologous region of 128 bp that we named the TnI SURE (slow upstream regulatory element). Alignment of these two SURE sequences with the quail TnI fast intronic regulatory element identified common motifs, namely, two A/T-rich sequences (A/T1 and A/T2) with homology to homeotic protein and MEF2 binding sites, a CACC box, an E box, and a novel motif (GCAGGCA) that we denoted the

  3. Compilation of Reprints Number 58, Office of Naval Research.

    DTIC Science & Technology


    CLASSIFICATION OF TNIS PAG Elhon Does Fvtorod) K1, K2 , and K3 are constants that depend on the optical properties of the water. The constants are...sections of the fairing are shown assembled in Figure 2 on a steel load-bearing cable. Each fairing is approximately 10 cm high, 2 cm thick and 15 cm long... thickness 8 in which the surface temperature was determined by extrapo- the transfer of heat and momentum is primarily by lation of nearly adiabatic

  4. Synthesis of Some 4-Quinolones and Related Structures for Evaluation as Potential Antimalarial Agents

    DTIC Science & Technology


    evaluation new com- pounds related to either endochin (2-methyl-3-heptyl-7-.nethoxy-4(lH)- quino - lone) or the 3-carbomethoxy-4(lH)-quinolones that had shown...of aliphatic aldehydes with 2-methyl-4(lH)- quino - lones to give the 3(1-alkenyl) derivatives proved its generality, since it pro- ceeds when both...yields. Tnis facile reaction indicates, once more, the activated nature of the 3 position in the ’(lDOi- quino - lone ring system. 0 0 + CH20 ) CCHYN(CH3

  5. The Toxicity of Nitroguanidine and Photolyzed Nitroguandine to Freshwater Aquatic Organisms

    DTIC Science & Technology


    Paratanytarsus dissimlils), and aquatic worms ( Lumbriculus variegatus ). The. IN) tWS UCLASSIFIED SEURIY4T CLAISIPICAtIOW OF TNIS PAGE (1160 Date U40*4. I. II...2868 0 ( Lumbriculus variegatue ) 1785 0 (1.49 0 a. The high, low, and control NGu concentrations are listed for each test. The top concentration tested...Bailey, H.C. and D.H.W. Liu. 1980. Lumbriculus variegatus , a benthic oligochaete, as a bioassay organism. In: A.L. Buikema and J. Cairns, Jr., eds

  6. An Infrared Study of Ambient Temperature Chloroaluminates as a Function of Melt Acidity.

    DTIC Science & Technology


    8217D- 4 T N4 I.E 1 -D’ 1ARIN .-..PRAUR M ~ rMO I , nT’TT’E TVo E 11111IL25 11111_L6 MI= UNCLASSIFIED 51CURITY CLASSIFICATION OF TnIS PAGE ’UIte., Dae...4000 cm- Data Collection A Happ -Genzel apodization function was applied to the double- sided interferogram. The collection parameters used to obtain...corresponding to the transformation: m + CC-N CH-C=N+ For instance, l-n-butyl-2-methyl-tetrahydropyridine absorbs at 1649 -1cm In the base form and 1684 cm" as

  7. Porosity and Crack Initiation During Low Cycle Fatigue

    DTIC Science & Technology


    in the pore-induced local plastic zones extend at least one pore radius into the material. Given a typical pore diameter of 30 . m , tnis implies a strip...of the number of cycles to initiate a 15 . m crack in the presence of porosity during LCF. REFERENCES 1. H. A. Kuhn and C. L. Downey, Int. J. of...39 (1974). 3. H. E. Exner and D. Pohl, Powder Metal. Int., 10(4), 193-196 (1979). 4. R. Haynes, Powder Metal., 1, pp. 17-20 (1977). 5. M . Eudier

  8. Decision Support for Attack Submarine Commanders.

    DTIC Science & Technology



  9. The Ecology of the Benthic and Endolithic Communities of a Rocky Reef in the Kelp Beds off Del Monte Beach, Monterey, California.

    DTIC Science & Technology


    RECIPIENT’S CATALOG NUMMER 4. TITLCj~ T.egj max-& ~vRC eocology of the !nthic and %Ser’S hes is,4 .1ndo RLthic ommunities of a lcky eef S EFRIGOG EOTNNE 0 t...1 . CONTRACT OR GRANT mumB90R( s ) 9. PER11FORMING ORGANIZATION NAME ANC ACORESS 10. PROGRAM EL9EMENT. PROJE01CT. TASKC AREA &WORK UNIT MBER’S Naval...COITION OF IMOV goIsSOSL6T7NLSSFE9 ~ ) 41 S /N@10014550 ISECURITY CLASSFICATION OF TNIS PAGE66 IMN Doe ete") UNCLASSIFIED 󈧘. (continued) the level of

  10. Lock and Dam 13 Major Rehabilitation Whiteside County, Illinois, Clinton County, Iowa.

    DTIC Science & Technology


    Tnis oermit does not authorize the disposal of crecged material in an Imoortant Resource Area wh-ich has Deen cesionated as such by the illinois...Illinois," approved June 10, 1911, as amenoed. (Illinois Revised Statutes, Cnapter 19, paragraphs 52 et seq.) 2. This oermit does not convey title to, organics 2. Laboratory testing was performed in accordance with EN 1110-2-1906 dated 30 Nov 70, revised 1 Nay 80 and 20 Aug 86. All samples were

  11. The Role of Passive Film Growth Kinetics and Properties in Stress Corrosion and Crevice Corrosion Susceptibility

    DTIC Science & Technology


    super ,qiosing Pourbaix diagrams (6), it :an be seen that molybdate is not an oxidizer of ferrous ion (Fig. 8). Experimentally, tnis has been proved by...are 10" . and 10 M4, respectively. These diagrams are not ful consistent, particularly with regard to the selection of AGO values for 4O . Pourbaix et...electrochemically inert with respect to di~solved iron species, we can construct an E-pH diagram for e in a � solution. Fig. 9 represents an E-pH diagram for

  12. Application of Advanced Decision-Analytic Technology to Rapid Deployment Joint Task Force Problems

    DTIC Science & Technology


    60 4 E F I T 20 0 2U 40 60 s0 100 CO3T Figure A-1 BENEFIT/COST CURVE A-4 This is not an approach that DDI uses unilaterally to study and recommend...UNCLASSIFIED SICURITv CLAS.IPICATION OP TNIS PA@e(hm bets goIu .... useful product in the near term. This problem concerned the provision of programs, permit rapid ex- ploration of the usefulness of new proposed base options, and add to under- standing whether and how decision

  13. 2250-MHz High Efficiency Microwave Power Amplifier (HEMPA)

    NASA Technical Reports Server (NTRS)

    Sims, W. Herbert; Bell, Joseph L. (Technical Monitor)


    Tnis paper will focus on developing an exotic switching technique that enhances the DC-to-RF conversion efficiency of microwave power amplifiers. For years, switching techniques implemented in the 10 kHz to 30 MHz region have resulted in DC-to-RF conversion efficiencies of 90-95-percent. Currently amplifier conversion efficiency, in the 2-3 GHz region approaches, 10-20-percent. Using a combination of analytical modeling and hardware testing, a High Efficiency Microwave Power Amplifier was built that demonstrated conversion efficiencies four to five times higher than current state of the art.

  14. Army Vocational Guidance in Two-Year Colleges

    DTIC Science & Technology


    motivation) apparently remains the preferred tool for "teasing" tnis data out. From the literature, Factor II is best explained by Maslow’s " needs hierarchy ...34 ( Maslow , 1954, 1970) where the lower end of his scale includes very basic needs related to personal security (survival). In job terms, this...seeker and those As an employer, the U.S. Army competes with pri ate (E-2) or private first class i E-3). There is of the service many other public and

  15. Interface Characterization of Cu-Cu and Cu-Ag-Cu Low Temperature Solid State Bonds.

    DTIC Science & Technology


    produce low -. 0 onnos s boniecnstrated, the thrust o: tnis texann a ecne: onaractorlstics as a function c.: 4 time, temperature and pressure . The...conducted under y hyrostatic pressure to avoid deformation of the tensile specimen. At 2Cksi the tensile yield strength of the silver has been exceeded by...A19i 915 INTERFACE CHARACTERIZATION OF CU-CU AND CU-AG-CU LOW 1/1 TEMPERATURE SOLID STATE BONDS(U) NAVAL POSTGRADUATE SCHOO0L MONTEREY CA R Z DALBEY

  16. Thermodynamics of High Temperature Materials.

    DTIC Science & Technology


    Department of Commerce 23 -1A , /7 National Bureau of Standards A102 Washington, D.C. 20234 ______________ I I. CONTROLLING OFFICE NAME AND ADDRESS Air...DISTRIBUTION STATEMENT (of this Report) r ~Appro-,’. f’or public re r-: e ; 17. DISTRIBUTION STATEMENT (of the abstract entered in Block 20, It different from...8SOLETE SCRT SEUIYCLASSIFICATION OF TNIS PAGE " e aoEtr AEOST.1-0443 THERMODYNAMICS OF HIGH TEMPERATURE MATERIALS Annual Report for the Period of 1 October

  17. A Laser Trap for Neutral Atoms.

    DTIC Science & Technology


    alexandrite laser operating in DO , 1473 OITIow OFr I NOV ’IS 13 OBSOLETE S/N 0 102- I.F- 0 14- 6601 SECURITY CLASSIFICATION OF TNIS PAGE (WhenOnt...development and characterization of the new alexandrite laser, demonstration of the trap at low densities, and deter- mination of the spatial and...range and the trap depth down by vr). We have used spa- tial filtering to reliably and stabily operate our new cw alexandrite laser as well as argon and

  18. Development of Passive Diver Thermal Protection System

    DTIC Science & Technology


    underwater swims .,(- /A *vi t S/N 01 2- IFP- 014- 6401 SUCURITY CLAWFIICATIO" OFr TNIS PAQUIP10t1 DW BOOV04• I ~~~/ / ", NCSC TM 378-83 SUMMARY Cold water...independent suit inflation source, inflation hoses, a Diver Urine Collection System (DUCS) for long duration missions, fin guards to prevent loss of swim ...dry suits were tested for comparative mobility by the Department of Kinesiology , University of California, Los Angeles. 3 Experienced divers evaluated

  19. MCNP calculations for container inspection with tagged neutrons

    NASA Astrophysics Data System (ADS)

    Boghen, G.; Donzella, A.; Filippini, V.; Fontana, A.; Lunardon, M.; Moretto, S.; Pesente, S.; Zenoni, A.


    We are developing an innovative tagged neutrons inspection system (TNIS) for cargo containers: the system will allow us to assay the chemical composition of suspect objects, previously identified by a standard X-ray radiography. The operation of the system is extensively being simulated by using the MCNP Monte Carlo code to study different inspection geometries, cargo loads and hidden threat materials. Preliminary simulations evaluating the signal and the signal over background ratio expected as a function of the system parameters are presented. The results for a selection of cases are briefly discussed and demonstrate that the system can operate successfully in different filling conditions.

  20. Array I Photo Imagery Analysis.

    DTIC Science & Technology


    stereo scan Ssearcn, was -ated 2s oeina: Detectaole i-I - rti iy Detectac’e 1 - ’ ion etectaole .A ’Ile Ŕ" rating means that one is capable of detecting...tures on a ohotograph. Another term "minimum ground seoaration ," :cmes into context for tnis iiscussion. This is the ininimum distance oetween ions sroula be notedi: 1. The brightness of the mine to be resolved; 2. The uniformity of the target background; and 3. The extent of the uniform

  1. Rigid-Flex Printed Circuit Manufacturing process. A Project of the Manufacturing Technology Program.

    DTIC Science & Technology


    002- L -0146601SECURITY CLASSIFICATION OF TNIS PAGE (011ioe Data Bntered) UNCLASSIFIED SUc~hfTY cLAIsaicooricoi OF THIS PACE (IIo "a Mu9.,erva...n I irt I Olut I Av- ’ji L ~ iii1’_ t PREFACE Advances in manufacturing technology are continuing to be made as both new materials and processing...Peel, Laminate Exhibit 10 6 5 4 1 2 3 Cost 5 6 3 4 2 1 L Facility Rating 4 5 2 6 3 1 Indicates Failure/Test Requirements I/ Indicates After Etching T

  2. Analysis of Air Force Academy Nonrevenue Intercollegiate Athletic Program

    DTIC Science & Technology


    majority of the men’s competition is in Division I and women’s is in Division II . The value and benefits derived from each sport is based on three factors... Division II , or Division III for certain legislative and competitive purposes" (5:127). This manual further states that an institutions women’s program...Division I for men, and Division II for women. The effect of tnis designation does not restrict any nonrevenue teams from. competing against other divisions

  3. Identification of MDMB-FUBINACA in commercially available e-liquid formulations sold for use in electronic cigarettes.


    Peace, Michelle R; Krakowiak, Rose I; Wolf, Carl E; Poklis, Alphonse; Poklis, Justin L


    MDMB-FUBINACA (aka MDMB(N)-Bz-F), chemical name Methyl (S)-2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3,3-dimethylbutanoate, a designer drug or a new psychoactive substance (NPS), was identified in three commercially available e-liquids formulated for electronic cigarette use. The e-liquids were evaluated using direct analysis in real time ion source attached to a time of flight mass spectrometer (DART-MS) and gas chromatograph mass spectrometer (GC-MS) to identify active ingredients/drugs, flavorants, and other possible constituents. The e-liquids were also evaluated for alcohol content by headspace gas chromatography with flame ionization detector (HS-GC-FID). The aerosol produced from the e-liquids by use of an e-cigarette was analyzed by solid phase micro-extraction gas chromatography mass spectrometry (SPME-GC-MS) to ensure delivery of the active ingredient/drug. Propylene glycol, vegetable glycerin, MDMB-FUBINACA, alcohol content and a flavor profile were determined for each of the e-liquids. MDMB-FUBINACA was determined to be the major active ingredient in all three e-liquids and was successfully detected by SPME-GC-MS in the aerosol generated by a KangerTech Aerotank clearomizer/electronic cigarette.

  4. Tau-positive nuclear indentations in P301S tauopathy mice.


    Fernández-Nogales, Marta; Santos-Galindo, María; Merchán-Rubira, Jesús; Hoozemans, Jeroen J M; Rábano, Alberto; Ferrer, Isidro; Avila, Jesús; Hernández, Félix; Lucas, José J


    Increased incidence of neuronal nuclear indentations is a well-known feature of the striatum of Huntington's disease (HD) brains and, in Alzheimer's disease (AD), neuronal nuclear indentations have recently been reported to correlate with neurotoxicity caused by improper cytoskeletal/nucleoskeletal coupling. Initial detection of rod-shaped tau immunostaining in nuclei of cortical and striatal neurons of HD brains and in hippocampal neurons of early Braak stage AD led us to coin the term "tau nuclear rods (TNRs)." Although TNRs traverse nuclear space, they in fact occupy narrow cytoplasmic extensions that fill indentations of the nuclear envelope and we will here refer to this histological hallmark as Tau-immunopositive nuclear indentations (TNIs). We reasoned that TNI formation is likely secondary to tau alterations as TNI detection in HD correlates with an increase in total tau, particularly of the isoforms with four tubulin binding repeats (4R-tau). Here we analyze transgenic mice that overexpress human 4R-tau with a frontotemporal lobar degeneration-tau point mutation (P301S mice) to explore whether tau alteration is sufficient for TNI formation. Immunohistochemistry with various tau antibodies, immunoelectron microscopy and double tau-immunofluorescence/DAPI-nuclear counterstaining confirmed that excess 4R-tau in P301S mice is sufficient for the detection of abundant TNIs that fill nuclear indentations. Interestingly, this does not correlate with an increase in the number of nuclear indentations, thus suggesting that excess total tau or an isoform imbalance in favor of 4R-tau facilitates tau detection inside preexisting nuclear indentations but does not induce formation of the latter. In summary, here we demonstrate that tau alteration is sufficient for TNI detection and our results suggest that the neuropathological finding of TNIs becomes a possible indicator of increased total tau and/or increased 4R/3R-tau ratio in the affected neurons apart from being an

  5. Dynamic Color Scanner System

    DTIC Science & Technology


    wm^^mrmm JlilJJLUJJ.l, UM *•* ". «^^~mw^-r mmmmmmmem DYNAMIC COLOR SCANNER SYSTEM L. T. Hunkler ITT Aerospaco/Gpticai Division S Fort Wayne ...Division, a division of International Telephone and Tele- graph Corporation, Fort Wayne , Indiana, under contract F33615-72- C-2071 for research and...iliKriiBiröfiiii-1, ■ ^ii ■"»*-—™""tWi "!—i^^^P«^ ^3 <o lil r^ ■ i u o o 0) (0 n •H Q (U ri 0) l-i 3 tP •H 20 SO-Z^H •— ■■■■I

  6. Experimental validation of MCNP simulations for the EURITRACK Tagged Neutron Inspection System

    NASA Astrophysics Data System (ADS)

    Donzella, A.; Bodini, I.; Zenoni, A.; Fontana, A.; Perot, B.; Bernard, S.; Carasco, C.; Mariani, A.; Sudac, D.; Valkovic, V.


    The detection of illicit trafficking such as explosive materials inside large commercial payloads is today an important worldwide problem. Differently from the X- or γ-ray based systems, neutron interrogation allows the elemental composition of inspected materials to be measured. A container interrogation device based on the Tagged Neutron Inspection System (TNIS) has been developed within the EURITRACK (EURopean Illicit TRAfficking Countermeasures Kit) project of the 6th Framework Program of the European Union. A prototype of such system has been integrated at the Ruder Boskovic Institute (IRB) of Zagreb, Croatia, and performance tests have been carried out. A detailed simulation of the IRB experimental set-up has been performed. Comparison of the Monte Carlo predictions with collected experimental data is presented.

  7. The crater-facies kimberlite system of Tokapal, Bastar District, Chhattisgarh, India

    NASA Astrophysics Data System (ADS)

    Mainkar, Datta; Lehmann, Bernd; Haggerty, Stephen E.


    Discovery of diamondiferous kimberlites in the Mainpur Kimberlite Field, Raipur District, Chhattisgarh in central India, encouraged investigation of similar bodies in other parts of the Bastar craton. The earlier known Tokapal ultramafic intrusive body, located beyond the 19-km milestone in Tokapal village along the Jagdalpur-Geedam road, was reinterpreted as crater-facies kimberlite. Its stratigraphic position in the Meso-Neoproterozoic intracratonic sedimentary Indravati basin makes it one of the oldest preserved crater-facies kimberlite systems. Ground and limited subsurface data (dug-, tube-wells and exploratory boreholes) have outlined an extensive surface area (>550 ha) of the kimberlite. The morphological and surface color features of this body on enhanced satellite images suggest that there is a central feeder surrounded by a collar and wide pyroclastic apron. Exploration drilling indicates that the central zone probably corresponds to a vent overlain by resedimented volcaniclastic (epiclastic) rocks that are surrounded by a 2-km-wide spread of pyroclastic rocks (lapilli tuff, tuff/ash beds and volcaniclastic breccia). Drill-holes also reveal that kimberlitic lapilli tuffs and tuffs are sandwiched between the Kanger and Jagdalpur Formations and also form sills within the sedimentary sequence of the Indravati basin. The lapilli tuffs are commonly well stratified and display slumping. Base surges and lava flows occur in the southern part of the Tokapal system. The geochemistry and petrology of the rock correspond to average Group I kimberlite with a moderate degree of contamination. However, the exposed rock is intensely weathered and altered with strong leaching of mobile elements (Ba, Rb, Sr). Layers of vesicular fine-grained glassy material represent kimberlitic lava flows. Tuffs containing juvenile lapilli with pseudomorphed olivine macrocrysts are set in a talc-serpentine-carbonate matrix with locally abundant spinel and sphene. Garnet has not been

  8. Greenland elders and high school students offer perspectives on climate change and science

    NASA Astrophysics Data System (ADS)

    Showstack, Randy


    KANGERLUSSUAQ, GREENLAND—This small town in central western Greenland, which has a population of about 650 and a major airstrip dating from World War II, is a center for scientific research and a starting point for scientists working in the region and on Greenland's ice sheet to study climate change and other issues. The town, just north of the Arctic Circle, sits at the edge of the 190-kilometer-long Kangerlussuaq Fjord and straddles the Qinnguata Kuussua River estuary, whose source water is the Russell Glacier, about 20 kilometers to the east. Between Kanger—as some refer to the town—and the glacier, some Eskimo-Kalaallit elders held a traditional gathering last month and also offered their perspectives on climate change during an impromptu 14 July meeting with high school students and other visitors. The evening before that meeting, Ole Olsvig, Kurt Olsen, Avaruna Mathaeussen, and other high schoolers from Greenland were in a makeshift classroom at the back of a renovated former U.S. Army barracks in Kanger, which had served as a U.S. military base. The students, who said they care deeply about their traditional culture and also are very aware of recent changes in climate, were helping to make presentations about their summer science projects. A total of 16 high schoolers from Greenland, 3 from Denmark, and 5 from the United States were there, participating in Joint Science Education Project (JSEP) activities; JSEP is an international collaborative polar science education effort between Greenland, Denmark, and the United States that receives support from the U.S. National Science Foundation (NSF).

  9. Impact of e-liquid flavors on nicotine intake and pharmacology of e-cigarettes.


    St Helen, Gideon; Dempsey, Delia A; Havel, Christopher M; Jacob, Peyton; Benowitz, Neal L


    To describe the effect of e-liquid flavors on nicotine intake and pharmacology of e-cigarettes. 11 males and 3 females participated in a 3-day inpatient crossover study with strawberry, tobacco, and their usual flavor e-liquid. Nicotine levels were nominally 18mg/mL in the strawberry (pH 8.29) and tobacco (pH 9.10) e-liquids and ranged between 3-18mg/mL in the usual brands (mean pH 6.80). Each day consisted of a 15-puff session followed by 4h of abstinence, then 90min of ad libitum use. Subjects used a KangerTech mini ProTank 3. After 15 puffs, the amount of nicotine inhaled and systemically retained were not significantly different between the strawberry and tobacco e-liquids but plasma AUC(0→180) was significantly higher with the strawberry e-liquid. While not significantly different, Cmax was 22% higher and various early time point AUCs to measure rate of rise of nicotine in blood ranged between 17 and 23% higher with the strawberry e-liquid compared to the tobacco e-liquid. During ad libitum use, systemic exposure to nicotine (AUC(0→90)) was the same for the tobacco and usual brand e-liquids but were both significantly lower than after using the strawberry e-liquid. The usual flavors were more liked and satisfying than the strawberry and tobacco e-liquids. Flavors influence nicotine exposure through flavor liking, may affect rate of nicotine absorption possibly through pH effects, and contribute to heart rate acceleration and subjective effects of e-cigarettes. E-cigarette users titrate their nicotine exposure but the extent of titration may vary across flavors. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Irradiation of 4''x4'' NaI(Tl) detector by the 14 MeV neutrons.


    Sudac, D; Valkovic, V


    Within the EURopean Illicit TRAfficking Countermeasures Kit (EURITRACK) project, a new Tagged Neutron Inspection System (TNIS) has been developed and installed in the Port of Rijeka in Croatia. The system was based on the examination of sea containers with the 14 MeV neutron beam. During the operation the characteristic gamma rays were produced and measured by several 5''x5''x10'' NaI(Tl) detectors. During this procedure some of the detectors were exposed to an intensive neutron beam radiation. It was necessary to check for possible radiation damage of the NaI(Tl) scintillator during the gamma detector selection phase of the project. The 4''x4'' NaI(Tl) detector was exposed to 14 MeV neutrons for 20 h. From the presented results on energy resolution and activation measurements it could be concluded that there are no significant differences in energy resolution before and after the irradiation by 4.7x10(11) of 14 MeV neutrons. The only problem could be the high level of medium and long term induced activity in the energy region below 2 MeV.

  11. Re II and other exotic spectra in HD 65949

    NASA Astrophysics Data System (ADS)

    Cowley, C. R.; Hubrig, S.; Wahlgren, G. M.


    Powerful astronomical spectra reveal an urgent need for additional work on atomic lines, levels, and oscillator strengths. The star HD 65949 provides some excellent examples of species rarely identified in stellar spectra. For example, the Re II spectrum is well developed, with 17 lines between 3731 Å and 4904 Å, attributed wholly or partially to ReII. Classifications and oscillator strengths are lacking for a number of these lines. The spectrum of Os II is well identified. Of 14 lines attributed wholly or partially to Os II, only one has an entry in the VALD database. We find strong evidence that Te II is present. There are no Te II lines in the VALD database. Ru II is clearly present, but oscillator strengths for lines in the visual are lacking. There is excellent to marginal evidence for a number of less commonly identified species, including KrII, Nb II, Sb II, Xe II, PrIII, Ho III, AuII, and Pt II (probably 198Pt), to be present in the spectrum of HD 65949. The line HgII λ3984 is of outstanding strength, and all three lines of Multiplet 1 of HgI are present, even though the surface temperature of HD 65949 is relatively high. Finally, we present the case of an unidentified line at 3859.63 Å of 24 mÅ equivalent width, which could be the same feature seen in magnetic chemically peculiar stars. It is typically blended with a putative U II line used in cosmochronology.

  12. Cost-effectiveness of a standard intervention versus a navigated intervention on colorectal cancer screening use in primary care.


    Lairson, David R; Dicarlo, Melissa; Deshmuk, Ashish A; Fagan, Heather B; Sifri, Randa; Katurakes, Nora; Cocroft, James; Sendecki, Jocelyn; Swan, Heidi; Vernon, Sally W; Myers, Ronald E


    Colorectal cancer (CRC) screening is cost-effective but underused. The objective of this study was to determine the cost-effectiveness of a mailed standard intervention (SI) and tailored navigation interventions (TNIs) to increase CRC screening use in the context of a randomized trial among primary care patients. Participants (n = 945) were randomized either to a usual care control group (n = 317), to an SI group (n = 316), or to a TNI group (n = 312). The SI group was sent both colonoscopy instructions and stool blood tests irrespective of baseline preference. TNI group participants were sent instructions for scheduling a colonoscopy, a stool blood test, or both based on their test preference, as determined at baseline; then, they received a navigation telephone call. Activity cost estimation was used to determine the cost of each intervention and to compute incremental cost-effectiveness ratios. Statistical uncertainty within the base case was assessed with 95% confidence intervals derived from net benefit regression analysis. The effects of uncertain parameters, such as the cost of planning, training, and involvement of those receiving "investigator salaries," were assessed with sensitivity analyses. Program costs of the SI were $167 per participant. The average cost of the TNI was $289 per participant. The TNI was more effective than the SI but substantially increased the cost per additional individual screened. Decision-makers need to consider cost structure, level of planning, and training required to implement these 2 intervention strategies and their willingness to pay for additional individuals screened to determine whether a tailored navigation would be justified and feasible. © 2013 American Cancer Society.

  13. Spectroscopic and ITC study of the conformational change upon Ca{sup 2+}-binding in TnC C-lobe and TnI peptide complex from Akazara scallop striated muscle

    SciTech Connect

    Yumoto, Fumiaki; Tanaka, Hiroyuki; Nagata, Koji; Miyauchi, Yumiko; Miyakawa, Takuya; Ojima, Takao; Tanokura, Masaru


    Akazara scallop (Chlamys nipponensis akazara) troponin C (TnC) of striated adductor muscle binds only one Ca{sup 2+} ion at the C-terminal EF-hand motif (Site IV), but it works as the Ca{sup 2+}-dependent regulator in adductor muscle contraction. In addition, the scallop troponin (Tn) has been thought to regulate muscle contraction via activating mechanisms that involve the region spanning from the TnC C-lobe (C-lobe) binding site to the inhibitory region of the TnI, and no alternative binding of the TnI C-terminal region to TnC because of no similarity between second TnC-binding regions of vertebrate and the scallop TnIs. To clarify the Ca{sup 2+}-regulatory mechanism of muscle contraction by scallop Tn, we have analyzed the Ca{sup 2+}-binding properties of the complex of TnC C-lobe and TnI peptide, and their interaction using isothermal titration microcalorimetry, nuclear magnetic resonance, circular dichroism, and gel filtration chromatography. The results showed that single Ca{sup 2+}-binding to the Site IV leads to a structural transition not only in Site IV but also Site III through the structural network in the C-lobe of scallop TnC. We therefore assumed that the effect of Ca{sup 2+}-binding must lead to a change in the interaction mode between the C-lobe of TnC and the TnI peptide. The change should be the first event of the transmission of Ca{sup 2+} signal to TnI in Tn ternary complex.

  14. Formation and stabilization of C6- by radiative electron attachment

    NASA Astrophysics Data System (ADS)

    Chandrasekaran, Vijayanand; Prabhakaran, Aneesh; Kafle, Bhim; Rubinstein, Hilel; Heber, Oded; Rappaport, Michael; Toker, Yoni; Zajfman, Daniel


    Radiative electron attachment (REA) plays an important role in forming molecular anions in various astrophysical environments. In this work, we determined the rate coefficient for the formation of C6- by REA based on a detailed balance approach. C6- ions are stored in an electrostatic ion beam trap and are photoexcited above their adiabatic detachment energy (4.18 eV). Due to fast internal conversion and intramolecular vibrational redistribution, photoexcitation leads to the formation of temporary negative ions (TNIs), the same as those one formed by the electron attachment. Absolute vibrational autodetachment and recurrent (or Poincaré) fluorescence (RF) rate coefficients have already been reported [V. Chandrasekaran et al., J. Phys. Chem. Lett. 5, 4078 (2014)]. Knowing the branching ratios of the various competing rate coefficients is decisive to the understanding of the formation probability of anions via REA. The radiative stabilization rate of C6-, shown to be dominated by RF, was determined to be 5 × 104 s-1 at the electron detachment energy, i.e., at least a factor of 100 faster than the stabilization by infrared transitions. The RF is found to very effectively stabilize the TNI formed by electron attachment. Using detailed balance to link the measured delayed detachment rate to the rate of electron attachment, we estimate the REA rate leading to the formation of C6- to be 3 × 10-7 cm3 s-1 at 300 K in agreement with theory (1.7 × 10-7 cm3 s-1 [R. Terzieva and E. Herbst, Int. J. Mass Spectrom. 201, 135 (2000)]). Such a high rate for REA to C6 indicates that REA may play a prominent role in the formation of anions in the interstellar medium.

  15. Cooperative regulation of myosin-S1 binding to actin filaments by a continuous flexible Tm-Tn chain.


    Mijailovich, Srboljub M; Kayser-Herold, Oliver; Li, Xiaochuan; Griffiths, Hugh; Geeves, Michael A


    The regulation of striated muscle contraction involves cooperative interactions between actin filaments, myosin-S1 (S1), tropomyosin (Tm), troponin (Tn), and calcium. These interactions are modeled by treating overlapping tropomyosins as a continuous flexible chain (CFC), weakly confined by electrostatic interactions with actin. The CFC is displaced locally in opposite directions on the actin surface by the binding of either S1 or Troponin I (TnI) to actin. The apparent rate constants for myosin and TnI binding to and detachment from actin are then intrinsically coupled via the CFC model to the presence of neighboring bound S1s and TnIs. Monte Carlo simulations at prescribed values of the CFC stiffness, the CFC's degree of azimuthal confinement, and the angular displacements caused by the bound proteins were able to predict the stopped-flow transients of S1 binding to regulated F-actin. The transients collected over a large range of calcium concentrations could be well described by adjusting a single calcium-dependent parameter, the rate constant of TnI detachment from actin, k(-I). The resulting equilibrium constant K(B) ≡ 1/K(I) varied sigmoidally with the free calcium, increasing from 0.12 at low calcium (pCa >7) to 12 at high calcium (pCa <5.5) with a Hill coefficient of ~2.15. The similarity of the curves for excess-actin and excess-myosin data confirms their allosteric relationship. The spatially explicit calculations confirmed variable sizes for the cooperative units and clustering of bound myosins at low calcium concentrations. Moreover, inclusion of negative cooperativity between myosin units predicted the observed slowing of myosin binding at excess-myosin concentrations.

  16. Catecholamine-Dependent β-Adrenergic Signaling in a Pluripotent Stem Cell Model of Takotsubo Cardiomyopathy.


    Borchert, Thomas; Hübscher, Daniela; Guessoum, Celina I; Lam, Tuan-Dinh D; Ghadri, Jelena R; Schellinger, Isabel N; Tiburcy, Malte; Liaw, Norman Y; Li, Yun; Haas, Jan; Sossalla, Samuel; Huber, Mia A; Cyganek, Lukas; Jacobshagen, Claudius; Dressel, Ralf; Raaz, Uwe; Nikolaev, Viacheslav O; Guan, Kaomei; Thiele, Holger; Meder, Benjamin; Wollnik, Bernd; Zimmermann, Wolfram-Hubertus; Lüscher, Thomas F; Hasenfuss, Gerd; Templin, Christian; Streckfuss-Bömeke, Katrin


    Takotsubo syndrome (TTS) is characterized by an acute left ventricular dysfunction and is associated with life-threating complications in the acute phase. The underlying disease mechanism in TTS is still unknown. A genetic basis has been suggested to be involved in the pathogenesis. The aims of the study were to establish an in vitro induced pluripotent stem cell (iPSC) model of TTS, to test the hypothesis of altered β-adrenergic signaling in TTS iPSC-cardiomyocytes (CMs), and to explore whether genetic susceptibility underlies the pathophysiology of TTS. Somatic cells of patients with TTS and control subjects were reprogrammed to iPSCs and differentiated into CMs. Three-month-old CMs were subjected to catecholamine stimulation to simulate neurohumoral overstimulation. We investigated β-adrenergic signaling and TTS cardiomyocyte function. Enhanced β-adrenergic signaling in TTS-iPSC-CMs under catecholamine-induced stress increased expression of the cardiac stress marker NR4A1; cyclic adenosine monophosphate levels; and cyclic adenosine monophosphate-dependent protein kinase A-mediated hyperphosphorylation of RYR2-S2808, PLN-S16, TNI-S23/24, and Cav1.2-S1928, and leads to a reduced calcium time to transient 50% decay. These cellular catecholamine-dependent responses were mainly mediated by β1-adrenoceptor signaling in TTS. Engineered heart muscles from TTS-iPSC-CMs showed an impaired force of contraction and a higher sensitivity to isoprenaline-stimulated inotropy compared with control subjects. In addition, altered electrical activity and increased lipid accumulation were detected in catecholamine-treated TTS-iPSC-CMs, and were confirmed by differentially expressed lipid transporters CD36 and CPT1C. Furthermore, we uncovered genetic variants in different key regulators of cardiac function. Enhanced β-adrenergic signaling and higher sensitivity to catecholamine-induced toxicity were identified as mechanisms associated with the TTS phenotype. (International