54 results on '"M. M. Koza"'
Search Results
2. Quantum critical spin-liquid-like behavior in the S=12 quasikagome-lattice compound CeRh1−xPdxSn investigated using muon spin relaxation and neutron scattering
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Rajesh Tripathi, D. T. Adroja, C. Ritter, Shivani Sharma, Chongli Yang, A. D. Hillier, M. M. Koza, F. Demmel, A. Sundaresan, S. Langridge, Wataru Higemoto, Takashi U. Ito, A. M. Strydom, G. B. G. Stenning, A. Bhattacharyya, David Keen, H. C. Walker, R. S. Perry, Francis Pratt, Qimiao Si, and T. Takabatake
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- 2022
3. Strong renormalization of Ba vibrations in thermoelectric type-IX clathrate Ba24Ge100
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R. Viennois, M. Beaudhuin, and M. M. Koza
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- 2022
4. Muon spin rotation and neutron scattering investigations of the B -site ordered double perovskite Sr2DyRuO6
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Duc Le, Ronald I. Smith, M. M. Koza, A. Sundaresan, Adrian D. Hillier, Sean Langridge, Shivani Sharma, D. T. Adroja, C. V. Tomy, C. Ritter, and Ravi Pratap Singh
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Physics ,Magnetic moment ,Condensed matter physics ,Magnetic structure ,Relaxation (NMR) ,02 engineering and technology ,Muon spin spectroscopy ,021001 nanoscience & nanotechnology ,01 natural sciences ,Magnetic susceptibility ,Paramagnetism ,Spin wave ,0103 physical sciences ,Antiferromagnetism ,010306 general physics ,0210 nano-technology - Abstract
The magnetic ground state of the B -site ordered double perovskite S r 2 DyRu O 6 has been investigated using muon spin rotation and relaxation (µSR), neutron powder diffraction (NPD), and inelastic neutron scattering (INS), in addition to heat capacity and magnetic susceptibility (AC and DC) measurements. A clear signature of a long-range ordered magnetic ground state has been observed in the heat capacity data, which exhibits two sharp anomalies at 39.5 and 36 K found as well in the magnetic data. Further supporting evidence consistent with long-range magnetic ordering comes from a sharp drop in the muon initial asymmetry and a peak in the relaxation rate at 40 K, along with a weak anomaly near 36 K. Based on temperature dependent NPD, the low temperature magnetic structure contains two interpenetrating lattices of D y 3 + and Ru 5 + , forming an antiferromagnetic ground state below 39.5 K with magnetic propagation vector k = ( 0 , 0 , 0 ) . The magnetic moments of D y 3 + and Ru 5 + at 3.5 K are pointing along the crystallographic b axis with values of μ Dy = 4.92 ( 10 ) μ B and μ Ru = 1.94 ( 7 ) μ B , respectively. The temperature dependence of the Ru 5 + moments follows a mean field type behavior, while that of the D y 3 + moments exhibits a deviation indicating that the primary magnetic ordering is induced by the order of the 4 d electrons of Ru 5 + rather than that of the proper 4 f D y 3 + electrons. The origin of the second anomaly observed in the heat capacity data at 36 K must be connected to a very small spin reorientation as the NPD studies do not reveal any clear change in the observed magnetic Bragg peaks’ positions or intensities between these two transitions. INS measurements reveal the presence of crystal field excitations (CEF) in the paramagnetic state with overall CEF splitting of 73.8 meV, in agreement with the point change model calculations, and spin wave excitations below 9 meV at 7 K. Above T N , the spin wave excitations transform into a broad diffuse scattering indicating the presence of short-range dynamic magnetic correlations.
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- 2020
5. Self- and interdiffusion in dilute liquid germanium-based alloys
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H, Weis, F, Kargl, M, Kolbe, M M, Koza, T, Unruh, and A, Meyer
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Self- and inter-diffusion coefficients in liquid Ge and dilute Ge-based Ge-Si, Ge-Au, Ge-In, Ge-Ce and Ge-Gd alloys-containing 2 at% additions, respectively, are measured using a comprehensive approach of measuring techniques: quasi-elastic neutron scattering, in situ long-capillary experiments combined with x-ray radiography, and a long-capillary experiment under microgravity conditions. Resulting inter- and Ge self-diffusion coefficients are equal within error bars for each investigated alloy. The interdiffusion coefficients are smaller for the alloys containing Ce and Gd, However, no dependence of the atomic mass of the minor additions, that varies by about a factor of seven between Si and Au, on the diffusion coefficients could be observed. This demonstrates that in a loosely-packed metallic liquid with fast diffusive dynamics the diffusion mechanism is highly collective in nature.
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- 2019
6. Vibrational dynamics of the type-I clathrates A8Sn44□2 (A = Cs, Rb, K) from lattice-dynamics calculations, inelastic neutron scattering, and specific heat measurements
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Christophe Candolfi, Yu. Grin, M. M. Koza, Wilder Carrillo-Cabrera, Frank Steglich, Michael Baitinger, Umut Aydemir, Aydemir, Umut (ORCID 0000-0003-1164-1973 & YÖK ID 58403), Candolfi, C., Koza, M. M., Carrillo-Cabrera, W., Grin, Yu., Steglich, F., Baitinger, M., Koç University AKKİM Boron-Based Materials & High-technology Chemicals Research & Application Center (KABAM) / Koç Üniversitesi AKKİM Bor Tabanlı Malzemeler ve İleri Teknoloji Kimyasallar Uygulama ve Araştırma Merkezi (KABAM), College of Sciences, and Department of Chemistry
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Physics, applied ,010302 applied physics ,Materials science ,Phonon ,Clathrate hydrate ,Ab initio ,General Physics and Astronomy ,chemistry.chemical_element ,02 engineering and technology ,021001 nanoscience & nanotechnology ,Alkali metal ,01 natural sciences ,Molecular physics ,Spectral line ,Inelastic neutron scattering ,Disorder phase-transition ,Electronic band-structure ,Thermal-conductivity ,Thermoelectric properties ,Microscopic dynamics ,Raman-spectroscopy ,Crystal ,Excitations ,Efficiency ,Condensed Matter::Materials Science ,chemistry ,Caesium ,Vacancy defect ,0103 physical sciences ,Physics::Atomic and Molecular Clusters ,0210 nano-technology - Abstract
We report on a joint theoretical and experimental study of the vibrational dynamics of the type-I clathrates A(8)Sn(44)square (2) (A=K, Rb, Cs, and square stands for a vacancy) by high-resolution inelastic neutron scattering experiments combined with low-temperature specific heat measurements (2-300K). Ab initio lattice dynamics calculations were performed on hypothetical vacancy-free A(8)Sn(46) clathrates in order to determine the phonon dispersions and vibrational density of states Z ( omega ). The temperature dependence of the generalized vibrational density of states (GVDOS) was traced from 420K down to 50K, paying particular attention to the low-energy region of the GVDOS spectra. In the Cs and Rb compounds, the inelastic signal at low energies is dominated by several peaks mainly associated with the dynamics of the alkali metal atoms A in the polyhedral cages of the clathrate structure. In contrast, the low-energy spectrum of the K compound features a more pronounced contribution of the weighed modes of the framework Sn atoms. Upon cooling, the A-weighted modes soften regardless of the nature of the alkali element. The shift observed is similar for the three compounds and of small amplitude, suggestive of a dominant quasi-harmonic behavior above 50K. The distinct dynamics of the K atoms in comparison to Cs and Rb is further demonstrated by the analyses of the low-temperature specific heat data, indicating that the low-energy Sn-weighted modes cannot be described by a Debye model with Einstein-like contributions., CNRS-MPG Program
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- 2020
7. Absence of a long-range ordered magnetic ground state in Pr
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Harikrishnan S, Nair, Michael O, Ogunbunmi, S K, Ghosh, D T, Adroja, M M, Koza, T, Guidi, and A M, Strydom
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Signatures of absence of a long-range ordered magnetic ground state down to 0.36 K are observed in magnetic susceptibility, specific heat, thermal/electrical transport and inelastic neutron scattering data of the quasi-skutterudite compound Pr
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- 2018
8. Understanding the magnetism in noncentrosymmetric CeIrGe3: Muon spin relaxation and neutron scattering studies
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Gilles André, Pascal Manuel, M. M. Koza, D. T. Adroja, Adrian D. Hillier, Stéphane Rols, Dmitry D. Khalyavin, and V. K. Anand
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Physics ,Magnetic structure ,Magnetic moment ,Condensed matter physics ,Strongly Correlated Electrons (cond-mat.str-el) ,Condensed Matter - Superconductivity ,Neutron diffraction ,FOS: Physical sciences ,02 engineering and technology ,021001 nanoscience & nanotechnology ,01 natural sciences ,Heat capacity ,Magnetic susceptibility ,Inelastic neutron scattering ,Superconductivity (cond-mat.supr-con) ,Condensed Matter - Strongly Correlated Electrons ,0103 physical sciences ,Antiferromagnetism ,010306 general physics ,0210 nano-technology ,Controlling collective states ,Energy (signal processing) - Abstract
The magnetic properties of a pressure induced noncentrosymmetric heavy-fermion superconductor CeIrGe$_3$ have been investigated by muon spin relaxation ($\mu$SR), powder neutron diffraction (ND) and inelastic neutron scattering (INS) techniques at ambient pressure. For completeness we have also measured the ac magnetic susceptibility $\chi_{\rm ac}(T)$, dc magnetic susceptibility $\chi(T)$, dc isothermal magnetization $M(H)$ and heat capacity $C_{\rm p}(T,H)$ down to 2 K. CeIrGe$_{3}$ is known to exhibit pressure induced superconductivity ($T_{\rm c}\approx 1.5$ K) at a pressure of 20 GPa and antiferromagnetic ordering at 8.7 K, 4.7 K and 0.7 K at ambient pressure. Our $\chi_{\rm ac}(T)$ and $\chi(T)$ data show an additional anomaly near 6.2 K which is also captured in $C_{\rm p}(T)$ data. From $\chi_{\rm ac}(T)$, $\chi(T)$ and $C_{\rm p}(T)$ measurements we infer three antiferromagnetic transitions above 2 K at $T_{\rm N1}= 8.5$ K, $T_{\rm N2}= 6.0$ K and $T_{\rm N3}= 4.6$ K. Our $\mu$SR study also confirms the presence of three transitions through the observation of one frequency for $T_{\rm N2} < T\leq T_{\rm N1}$, two frequencies for $T_{\rm N3} < T\leq T_{\rm N2}$ and three frequencies for $T\leq T_{\rm N3}$ in the oscillatory asymmetry. The ND data reveal an incommensurate nature of the magnetic ordering at $T=7$ K with the propagation vector k = (0,0,0.688(3)), and a commensurate magnetic structure at $T=1.5$ K with the propagation vector locked to the value k = (0,0,2/3) and magnetic moments oriented along the $c$ axis. The commensurate structure couples a macroscopic ferromagnetic component, resulting in a strong dependence of the lock-in transition temperature on external magnetic field. The INS data show two well defined crystal electric field (CEF) excitations arising from the CEF-split Kramers doublet ground state of Ce$^{3+}$., Comment: 13 pages, 16 figures, 1 table
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- 2018
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9. Energy Landscapes of Human Acetylcholinesterase and Its Huperzine A-Inhibited Counterpart
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Flynn R. Hill, Lambert van Eijck, Marcus Trapp, M M Koza, Moeava Tehei, Judith Peters, Patrick Masson, Florian Nachon, Martin Weik, and Marie Trovaslet
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chemistry.chemical_classification ,Chemistry ,Molecular Dynamics Simulation ,Acetylcholinesterase ,Recombinant Proteins ,Surfaces, Coatings and Films ,Orders of magnitude (entropy) ,chemistry.chemical_compound ,Alkaloids ,Enzyme ,Biochemistry ,Catalytic Domain ,Materials Chemistry ,medicine ,Biophysics ,Humans ,Thermodynamics ,Cholinesterase Inhibitors ,Physical and Theoretical Chemistry ,Sesquiterpenes ,Huperzine A ,Protein Binding ,medicine.drug - Abstract
Enzymes are animated by a hierarchy of motions occurring on time scales that span more than 15 orders of magnitude from femtoseconds (10(-15) s) to several minutes. As a consequence, an enzyme is characterized by a large number of conformations, so-called conformational substates that interconvert via molecular motions. The energy landscapes of these macromolecules are very complex, and many conformations are separated by only small energy barriers. Movements at this level are fast thermal atomic motions occurring on a time scale between 10(-7) and 10(-12) s, which are experimentally accessible by incoherent neutron scattering techniques. They correspond to local fluctuations within the molecule and are believed to act as coupling links for larger, conformational changes. Several questions related to this hierarchy of motions are a matter of very active research: which of the motions are involved in the biological functions of the macromolecule and are motions of different energy (and thus time) scale correlated? How does the distribution of motions change when an enzyme is inhibited? We report here on investigations of the enzyme human acetylcholinesterase, unliganded and in complex with the noncovalent inhibitor Huperzine A, by incoherent neutron scattering. Different time scales are explored to shed light on the interplay of enzyme activity, dynamics, and inhibition. Surprisingly the average molecular dynamics do not seem to be altered by the presence of the inhibitor used in this study within the considered time scales. The activation energy for the free and the inhibited form of the enzyme is moreover found to be almost identical despite changes of interactions inside the gorge, which leads to the active site of the enzyme.
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- 2012
10. Contrasting effect of La substitution on the magnetic moment direction in the Kondo semiconductorsCeT2Al10(T=Ru,Os)
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Adrian D. Hillier, M. M. Koza, Jo Kawabata, Dmitry D. Khalyavin, P. Peratheepan, Toshiro Takabatake, D. T. Adroja, André M. Strydom, B. Fåk, Y. Okada, Jon W. Taylor, Amitava Bhattacharyya, Yuji Muro, C. Ritter, and Yoshihiro Yamada
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Physics ,Magnetic anisotropy ,Condensed matter physics ,Magnetic moment ,Kondo insulator ,Order (ring theory) ,Antiferromagnetism ,Muon spin spectroscopy ,Condensed Matter Physics ,Ground state ,Inelastic neutron scattering ,Electronic, Optical and Magnetic Materials - Abstract
The opening of a spin gap in the orthorhombic compounds CeT$_2$Al$_{10}$ (T = Ru and Os) is followed by antiferromagnetic ordering at $T_N$ = 27 K and 28.5 K, respectively, with a small ordered moment (0.29$-$0.34$\mu_B$) along the $c-$axis, which is not an easy axis of the crystal field (CEF). In order to investigate how the moment direction and the spin gap energy change with 10\% La doping in Ce$_{1-x}$La$_x$T$_2$Al$_{10}$ (T = Ru and Os) and also to understand the microscopic nature of the magnetic ground state, we here report on magnetic, transport, and thermal properties, neutron diffraction (ND) and inelastic neutron scattering (INS) investigations on these compounds. Our INS study reveals the persistence of spin gaps of 7 meV and 10 meV in the 10\% La-doped T = Ru and Os compounds, respectively. More interestingly our ND study shows a very small ordered moment of 0.18 $\mu_B$ along the $b-$axis (moment direction changed compared with the undoped compound), in Ce$_{0.9}$La$_{0.1}$Ru$_2$Al$_{10}$, however a moment of 0.23 $\mu_B$ still along the $c-$axis in Ce$_{0.9}$La$_{0.1}$Os$_2$Al$_{10}$. This contrasting behavior can be explained by a different degree of hybridization in CeRu$_2$Al$_{10}$ and CeOs$_2$Al$_{10}$, being stronger in the latter than in the former. Muon spin rotation ($\mu$SR) studies on Ce$_{1-x}$La$_x$Ru$_2$Al$_{10}$ ($x$ = 0, 0.3, 0.5 and 0.7), reveal the presence of coherent frequency oscillations indicating a long$-$range magnetically ordered ground state for $x$ = 0 to 0.5, but an almost temperature independent Kubo$-$Toyabe response between 45 mK and 4 K for $x$ = 0.7. We will compare the results of the present investigations with those reported on the electron and hole$-$doping in CeT$_2$Al$_{10}$.
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- 2015
11. Muon spin rotation and neutron scattering study of the noncentrosymmetric tetragonal compoundCeAuAl3
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M. M. Koza, Alberto Fraile, Adrian D. Hillier, A. del Moral, J. W. Taylor, Enrique Burzurí, C. de la Fuente, J. I. Arnaudas, Winfried Kockelmann, Aziz Daoud-Aladine, D. T. Adroja, Fernando Luis, Science and Technology Facilities Council (UK), European Commission, Diputación General de Aragón, and Ministerio de Ciencia e Innovación (España)
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Physics ,Strongly Correlated Electrons (cond-mat.str-el) ,Condensed matter physics ,FOS: Physical sciences ,Muon spin spectroscopy ,Condensed Matter Physics ,Coupling (probability) ,Magnetic susceptibility ,Heat capacity ,Inelastic neutron scattering ,Electronic, Optical and Magnetic Materials ,Condensed Matter - Strongly Correlated Electrons ,Paramagnetism ,Antiferromagnetism ,Condensed Matter::Strongly Correlated Electrons ,Energy (signal processing) - Abstract
Under the terms of the Creative Commons Attribution License 3.0 (CC-BY).-- et al., We have investigated the noncentrosymmetric tetragonal heavy fermion compound CeAuAl3 using muon spin rotation (μSR), neutron diffraction (ND), and inelastic neutron scattering (INS) measurements. We have also revisited the magnetic, transport, and thermal properties. The magnetic susceptibility reveals an antiferromagnetic transition at 1.1 K with, possibly, another magnetic transition near 0.18 K. The heat capacity shows a sharp λ-type anomaly at 1.1 K in zero field, which broadens and moves to a higher temperature in an applied magnetic field. Our zero-field μSR and ND measurements confirm the existence of a long-range magnetic ground state below 1.2 K. Further, the ND study reveals an incommensurate magnetic order with a magnetic propagation vector k=(0,0,0.52(1)) and a spiral structure of Ce moments coupled ferromagnetically within the ab plane. Our INS study reveals the presence of two well-defined crystal electric field (CEF) excitations at 5.1 and 24.6 meV in the paramagnetic phase of CeAuAl3 that can be explained on the basis of the CEF theory and the Kramer's theorem for a Ce ion having a 4f1 electronic state. Furthermore, low energy quasielastic excitations show a Gaussian line shape below 30 K compared to a Lorentzian line shape above 30 K, indicating a slowdown of spin fluctuations below 30 K. We have estimated a Kondo temperature of TK=3.5K from the quasielastic linewidth, which is in good agreement with that estimated from the heat capacity. This study also indicates the absence of any CEF-phonon coupling unlike that observed in isostructural CeCuAl3 The CEF parameters, energy level scheme, and their wave functions obtained from the analysis of INS data explain satisfactorily the single crystal susceptibility in the presence of two-ion anisotropic exchange interaction in CeAuAl3., We are grateful for funding by the Centre for Materials Physics and chemistry-Science and technology facilities council (CPMC-STFC) (Grant No. CMPC-09108), EU-FEDER (Grants No. MAT2009-10040, No. MAT2012-31309, and No. DGA-E81) and Fondo Social Europeo.
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- 2015
12. Unusual non-Fermi liquid behavior in
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Adrian D. Hillier, M. M. Koza, D. T. Adroja, Herwig Michor, Martin Rotter, G. Hilscher, Ernst-Wilhelm Scheidt, Pascal Manuel, Eve Bauer, S Manalo, Peter Rogl, U. Killer, Robert Bewley, Michael Reissner, and D. Dobozanov
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Materials science ,Condensed matter physics ,Relaxation (NMR) ,Muon spin spectroscopy ,Condensed Matter Physics ,Magnetic susceptibility ,Inelastic neutron scattering ,Electronic, Optical and Magnetic Materials ,Paramagnetism ,Crystal field theory ,Condensed Matter::Strongly Correlated Electrons ,Fermi liquid theory ,Electrical and Electronic Engineering ,Ground state - Abstract
We report on unusual non-Fermi liquid features of the ternary compound CeNi 9 Ge 4 which exhibits the largest ever recorded value of the electronic specific heat C / T ≃ 5.5 J / mol K 2 at T = 0.08 K in a purely paramagnetic system. The latter is confirmed by μ SR measurements down to 30 mK revealing a rather slow simple exponential muon spin depolarisation in zero-field and thus a spatially homogeneous paramagnetic state. The ground state properties and crystal field (CF) splitting of CeNi 9 Ge 4 have been studied by specific heat, magnetic susceptibility as well as muon spin relaxation ( μ SR) and inelastic neutron spectroscopy (INS).
- Published
- 2006
13. Crystalline electric field splitting in YbNi4 P2 measured by inelastic neutron scattering
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Zita Huesges, Cornelius Krellner, Frank Steglich, Oliver Stockert, Christoph Geibel, and M. M. Koza
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Materials science ,Condensed matter physics ,Ferromagnetism ,Condensed Matter::Strongly Correlated Electrons ,Crystal structure ,Neutron scattering ,Inelastic scattering ,Condensed Matter Physics ,Anisotropy ,Inelastic neutron scattering ,Excitation ,Electronic, Optical and Magnetic Materials ,Ion - Abstract
The heavy fermion (HF) compound YbNi4P2 is a promising new system for the study of ferromagnetic quantum criticality. Its particular crystal structure in which the Yb ions form chains along the c-axis might cause quasi-1D magnetic interactions. In thermodynamic and transport measurements, highly anisotropic behaviour has been observed. To clarify the role of the crystalline electric field (CEF) on this anisotropy, we have measured its level scheme by inelastic neutron scattering. We observed a broad magnetic excitation feature between 7 and 13 meV that is composed of two or three CEF transitions. We discuss the probability of an additional CEF level at either very high or very low energy.
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- 2013
14. Correlation of the dynamics of native human acetylcholinesterase and its inhibited huperzine A counterpart from sub-picoseconds to nanoseconds
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Judith Peters, Florian Nachon, Patrick Masson, Marcus Trapp, Moeava Tehei, M M Koza, Martin Weik, Marie Trovaslet, N Martinez, Thomas, Frank, Institute of human genetics, Medical University Graz, Biocomplexité des écosystèmes coralliens de l'Indo-Pacifique (CoReUS2), Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut Laue-Langevin (ILL), ILL, Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)
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MESH: Enzyme Activation ,[SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,Statistics as Topic ,Biomedical Engineering ,Biophysics ,Thermal fluctuations ,Bioengineering ,Neutron scattering ,Molecular Dynamics Simulation ,Biochemistry ,Inelastic neutron scattering ,Catalysis ,Biomaterials ,Molecular dynamics ,Alkaloids ,MESH: Alkaloids ,Humans ,MESH: Protein Binding ,MESH: Molecular Dynamics Simulation ,Research Articles ,MESH: Statistics as Topic ,Binding Sites ,MESH: Humans ,MESH: Kinetics ,[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,Chemistry ,Relaxation (NMR) ,MESH: Models, Chemical ,Nanosecond ,MESH: Acetylcholinesterase ,MESH: Catalysis ,Enzyme Activation ,Crystallography ,Kinetics ,Models, Chemical ,MESH: Binding Sites ,Chemical physics ,Picosecond ,Density of states ,Acetylcholinesterase ,MESH: Sesquiterpenes ,Cholinesterase Inhibitors ,MESH: Cholinesterase Inhibitors ,Sesquiterpenes ,Biotechnology ,Protein Binding - Abstract
It is a long debated question whether catalytic activities of enzymes, which lie on the millisecond timescale, are possibly already reflected in variations in atomic thermal fluctuations on the pico- to nanosecond timescale. To shed light on this puzzle, the enzyme human acetylcholinesterase in its wild-type form and complexed with the inhibitor huperzine A were investigated by various neutron scattering techniques and molecular dynamics simulations. Previous results on elastic neutron scattering at various timescales and simulations suggest that dynamical processes are not affected on average by the presence of the ligand within the considered time ranges between 10 ps and 1 ns. In the work presented here, the focus was laid on quasi-elastic (QENS) and inelastic neutron scattering (INS). These techniques give access to different kinds of individual diffusive motions and to the density of states of collective motions at the sub-picoseconds timescale. Hence, they permit going beyond the first approach of looking at mean square displacements. For both samples, the autocorrelation function was well described by a stretched-exponential function indicating a linkage between the timescales of fast and slow functional relaxation dynamics. The findings of the QENS and INS investigation are discussed in relation to the results of our earlier elastic incoherent neutron scattering and molecular dynamics simulations.
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- 2014
15. Muon spin relaxation and neutron scattering investigations of the noncentrosymmetric heavy-fermion antiferromagnet CeRhGe3
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K.A. McEwen, B.D. Rainford, Jon W. Taylor, Adrian D. Hillier, V. K. Anand, M. M. Koza, Pascal Manuel, and D. T. Adroja
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Physics ,Magnetic anisotropy ,Magnetic moment ,Neutron magnetic moment ,Condensed matter physics ,Order (ring theory) ,Condensed Matter::Strongly Correlated Electrons ,Neutron scattering ,Condensed Matter Physics ,Heat capacity ,Magnetic susceptibility ,Inelastic neutron scattering ,Electronic, Optical and Magnetic Materials - Abstract
The magnetic ground state of CeRhGe${}_{3}$ has been investigated using magnetic susceptibility, heat capacity, neutron diffraction, muon spin relaxation (\ensuremath{\mu}SR), and inelastic neutron scattering (INS) techniques. Our \ensuremath{\mu}SR study clearly reveals the presence of two frequencies below T${}_{\mathrm{N}2}$ $=$ 7 K and three frequencies between 7 K and T${}_{\mathrm{N}1}$ $=$ 14.5 K, indicating long-range magnetic ordering of the Ce${}^{3+}$ moment. The temperature dependence of the highest frequency follows a mean-field order parameter. Our powder neutron diffraction study at 1.5 K reveals the presence of magnetic Bragg peaks, indexed by the propagation vector k $=$ (0, 0, 3/4) with the Ce${}^{3+}$ magnetic moment \ensuremath{\sim}0.45(9) ${\ensuremath{\mu}}_{\mathrm{B}}$ along the $c$ axis. INS studies at 18 K (i.e., above T${}_{\mathrm{N}1}$) show the presence of two well-defined crystal-field (CEF) excitations at 7.5 and 18 meV. At 10 and 4.5 K, a very small increase has been observed in the CEF excitation energies. At 100 K, both CEF excitations broaden and a broad quasielastic component has also been observed. Further, the low-energy INS study reveals the presence of a nearly temperature-independent quasielastic linewidth between 16 and 60 K, which indicates a Kondo temperature T${}_{\mathrm{K}}$ $=$ 12.6(3) K. The presence of well-defined CEF excitations in CeRhGe${}_{3}$ suggests local moment magnetism and may explain the absence of pressure-induced superconductivity. Analyzing the INS data based on a CEF model, we have evaluated the CEF ground-state wave functions and ground-state moment. The observed small value of the ordered moment along the $c$ axis, deduced from the neutron diffraction data, contrasts with the ab-plane moment direction predicted by the single-ion CEF anisotropy and indicates the presence of two-ion anisotropic magnetic exchange interactions, which govern the direction of the moment.
- Published
- 2012
16. Inelastic neutron scattering study of the lattice dynamics in the clathrate compound BaGe5
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Frank Steglich, M. M. Koza, Michael Baitinger, Yu. Grin, Christophe Candolfi, and Umut Aydemir
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Lattice dynamics ,Range (particle radiation) ,Materials science ,Phonon ,Clathrate hydrate ,Clathrate compound ,Nanotechnology ,Crystal structure ,Condensed Matter Physics ,Molecular physics ,Inelastic neutron scattering ,chemistry.chemical_compound ,chemistry ,General Materials Science ,Crystallite - Abstract
We report inelastic neutron scattering (INS) measurements on the polycrystalline oP60-type clathrate BaGe_5, whose crystal structure is related to the type-I clathrate Ba8Ge_(43□3) and to the cP124-clathrate Ba_6Ge_(25). Our results show that BaGe_5 exhibits a similar phonon density of states (PDOS) in the energy range 0–40 meV with respect to Ba8Ge_(43□3). The low-energy region of the PDOS spectrum (0–10 meV) consists of two peaks at 4.1 and 6.2 meV likely related to Ba-weighted modes. Compared to Ba8Ge_(43□3), the low-energy region of the phonon spectrum of BaGe_5 shows a more complex structure, likely reflecting the presence of three distinct crystallographic sites for Ba. The specific heat data of BaGe_5, reexamined in light of the INS results, indicate that the Ba-weighted modes dominate the low-temperature behavior of C_p.
- Published
- 2015
17. Vibrational dynamics of the filled skutteruditesM1−xFe4Sb12(M=Ca, Sr, Ba, and Yb): Temperature response, dispersion relation, and material properties
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Mark R. Johnson, Andreas Leithe-Jasper, Lucia Capogna, Hannu Mutka, Yuri Grin, Michael Krisch, M. M. Koza, Helge Rosner, and Walter Schnelle
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Physics ,Brillouin zone ,Degree (graph theory) ,Condensed matter physics ,Scattering ,Dynamic structure factor ,Density of states ,Neutron scattering ,Inelastic scattering ,Atomic physics ,Condensed Matter Physics ,Inelastic neutron scattering ,Electronic, Optical and Magnetic Materials - Abstract
The vibrational dynamics of the ternary Ca${}_{1\ensuremath{-}x}$Fe${}_{4}$Sb${}_{12}$, Ba${}_{1\ensuremath{-}x}$Fe${}_{4}$Sb${}_{12}$, Sr${}_{1\ensuremath{-}x}$Fe${}_{4}$Sb${}_{12}$, and Yb${}_{1\ensuremath{-}x}$Fe${}_{4}$Sb${}_{12}$ compounds is studied for its temperature dependence, dispersion relations, and material properties by experiments and ab initio powder-averaged lattice-dynamics (PALD) calculations. The experimental techniques used are high-resolution inelastic neutron scattering (INS) and inelastic x-ray scattering (IXS). Vibrational properties of polycrystalline material have been mapped out in an extensive energy-momentum phase space facilitating the study of powder-averaged phonon-dispersion relations within the first and second Brillouin zones. Qualitatively, the experimental dynamic structure factor $S(Q,\ensuremath{\omega})$ matches, to a high degree, PALD calculations allowing different schemes of collective vibrational eigenmodes to be evaluated. From the PALD calculations, quantitative values of velocity of sound, Debye temperatures, and elastic, bulk, and Young's moduli are computed. The variation of the generalized density of states $G(\ensuremath{\omega})$ with temperature is studied experimentally in the range from 2 to 600 K. No particular anomalies in the collective dynamics are observed apart from a global softening of $G(\ensuremath{\omega})$ upon heating.
- Published
- 2011
18. Evolution of quantum criticality in the system CeNi9Ge4
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C. Gold, Adrian D. Hillier, Herwig Michor, M. M. Koza, S Manalo, L. Peyker, D. T. Adroja, and Ernst-Wilhelm Scheidt
- Subjects
Physics ,History ,Field (physics) ,Condensed matter physics ,Strongly Correlated Electrons (cond-mat.str-el) ,FOS: Physical sciences ,Neutron scattering ,01 natural sciences ,7. Clean energy ,010305 fluids & plasmas ,Computer Science Applications ,Education ,Crystal ,Paramagnetism ,Condensed Matter - Strongly Correlated Electrons ,Electrical resistivity and conductivity ,Quantum critical point ,0103 physical sciences ,ddc:530 ,Condensed Matter::Strongly Correlated Electrons ,010306 general physics ,Ground state ,Scaling - Abstract
The heavy fermion system CeNi9Ge4 exhibits a paramagnetic ground state with remarkable features such as: a record value of the electronic specific heat coefficient in systems with a paramagnetic ground state, \gamma = C/T \simeq 5.5 J/molK^2 at 80 mK, a temperature-dependent Sommerfeld-Wilson ratio, R=\chi/\gamma, below 1 K and an approximate single ion scaling of the 4f-magnetic specific heat and susceptibility. These features are related to a rather small Kondo energy scale of a few Kelvin in combination with a quasi-quartet crystal field ground state. Tuning the system towards long range magnetic order is accomplished by replacing a few at.% of Ni by Cu or Co. Specific heat, susceptibility and resistivity studies reveal T_N \sim 0.2 K for CeNi8CuGe4 and T_N \sim 1 K for CeNi8CoGe4. To gain insight whether the transition from the paramagnetic NFL state to the magnetically ordered ground state is connected with a heavy fermion quantum critical point we performed specific heat and ac susceptibility studies and utilized the \mu SR technique and quasi-elastic neutron scattering., Comment: 8 pages, 3 figures, will be published in J.Phys.: Conf. Series (Proceedings of the International & Interdisciplinary Workshop on Novel Phenomena in Intergrated Comples Sciences: From Living to Non-living Systems, Japan, held in Kyoto, October 11-14, 2010)
- Published
- 2011
- Full Text
- View/download PDF
19. Vibrational dynamics of the type-I clathrateBa8ZnxGe46−x−y◻y(x=0,2,4,6,8)
- Author
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A. Grytsiv, Martin Rotter, Mark R. Johnson, Navida Nasir, M. M. Koza, Hannu Mutka, and Peter Rogl
- Subjects
Quasielastic scattering ,Materials science ,Quasielastic neutron scattering ,Clathrate hydrate ,Neutron scattering ,Biological small-angle scattering ,Atomic physics ,Inelastic scattering ,Condensed Matter Physics ,Small-angle neutron scattering ,Inelastic neutron scattering ,Electronic, Optical and Magnetic Materials - Published
- 2010
20. Vibrational dynamics of filled skutteruditesM1−xFe4Sb12(M=Ca, Sr, Ba, and Yb)
- Author
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Mark R. Johnson, M. M. Koza, Yuri Grin, Lucia Capogna, Andreas Leithe-Jasper, Helge Rosner, Clemens Ritter, Walter Schnelle, and Hannu Mutka
- Subjects
Physics ,Ionic radius ,Condensed matter physics ,Inelastic scattering ,Neutron scattering ,engineering.material ,Condensed Matter Physics ,Omega ,Electronic, Optical and Magnetic Materials ,Crystallography ,Quasielastic neutron scattering ,Density of states ,engineering ,Skutterudite ,Ternary operation - Abstract
First-principles density-functional theory and lattice-dynamics calculations were performed to study the vibrational dynamics and related observables of the ternary compounds ${\text{Ca}}_{1\ensuremath{-}x}{\text{Fe}}_{4}{\text{Sb}}_{12}$, ${\text{Sr}}_{1\ensuremath{-}x}{\text{Fe}}_{4}{\text{Sb}}_{12}$, ${\text{Ba}}_{1\ensuremath{-}x}{\text{Fe}}_{4}{\text{Sb}}_{12}$. and ${\text{Yb}}_{1\ensuremath{-}x}{\text{Fe}}_{4}{\text{Sb}}_{12}$. The calculation results are supported by experimental data, which were obtained from neutron inelastic scattering, neutron-diffraction, and heat-capacity measurements. Within the calculation approach based on the theory of harmonic solids all observables are linked to the phonon density of states $Z(\ensuremath{\omega})$. The good agreement with experimental data shows that the vibrational dynamics of the ternary skutterudite structures can be described by a set of normal modes. Features in the experimentally obtained density of states $G(\ensuremath{\omega})$ reflecting the variation in properties (mass, ionic radius) of the cations Ca, Sr, Ba, and Yb are reproduced by the calculations. The quality of the inelastic neutron experiments enables the detection of at least two mode peaks at 4.9 and 5.7 meV with a pronounced spectral weight of ytterbium.
- Published
- 2010
21. Charge disproportionation and collinear magnetic order in the frustrated triangular antiferromagnetAgNiO2
- Author
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Martin Jansen, Richard M. Ibberson, M. M. Koza, Radu Coldea, Paolo G. Radaelli, E. M. Wheeler, E. Wawrzynska, and Timo Sörgel
- Subjects
Physics ,Valence (chemistry) ,Condensed matter physics ,Magnetic structure ,Ferromagnetism ,Octahedron ,Phonon ,Neutron diffraction ,Antiferromagnetism ,Condensed Matter::Strongly Correlated Electrons ,Hexagonal lattice ,Condensed Matter Physics ,Electronic, Optical and Magnetic Materials - Abstract
We report a high-resolution neutron diffraction study of the crystal and magnetic structure of the orbitally degenerate frustrated metallic magnet ${\text{AgNiO}}_{2}$. At high temperatures the structure is hexagonal with a single crystallographic Ni site, low-spin ${\text{Ni}}^{3+}$ with spin 1/2 and twofold orbital degeneracy, arranged in an antiferromagnetic triangular lattice with frustrated spin and orbital order. A structural transition occurs upon cooling below 365 K to a tripled hexagonal unit cell containing three crystallographically distinct Ni sites with expanded and contracted ${\text{NiO}}_{6}$ octahedra, naturally explained by spontaneous charge order on the Ni triangular layers. No Jahn-Teller distortions occur, suggesting that charge order occurs in order to lift the orbital degeneracy. Symmetry analysis of the inferred Ni charge order pattern and the observed oxygen displacement pattern suggests that the transition could be mediated by charge fluctuations at the Ni sites coupled to a soft oxygen optical phonon breathing mode. At low temperatures the electron-rich Ni sublattice (assigned to a valence close to ${\text{Ni}}^{2+}$ with $S=1$) orders magnetically into a collinear stripe structure of ferromagnetic rows ordered antiferromagnetically in the triangular planes. We discuss the stability of this uncommon spin order pattern in the context of an easy-axis triangular antiferromagnet with additional weak second-neighbor interactions and interlayer couplings.
- Published
- 2008
22. Experimental evidence supported by simulations of a very high H2 diffusion in metal organic framework materials
- Author
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F, Salles, H, Jobic, G, Maurin, M M, Koza, P L, Llewellyn, T, Devic, C, Serre, and G, Ferey
- Abstract
Quasielastic neutron scattering measurements are combined with molecular dynamics simulations to extract the self-diffusion coefficient of hydrogen in the metal organic frameworks MIL-47(V) and MIL-53(Cr). We find that the diffusivity of hydrogen at low loading is about 2 orders of magnitude higher than in zeolites. Such a high mobility has never been experimentally observed before in any nanoporous materials, although it was predicted in carbon nanotubes. Either 1D or 3D diffusion mechanisms are elucidated depending on the chemical features of the MIL framework.
- Published
- 2008
23. Neutron Scattering on Frustrated Magnets
- Author
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A. Krimmel, V. Tsurkan, A. Loidl, H. Mutka, M. M. Koza, Amitabha Ghoshray, and Bilwadal Bandyopadhyay
- Subjects
Physics ,Condensed matter physics ,Magnetic structure ,media_common.quotation_subject ,Spinel ,Degrees of freedom (physics and chemistry) ,Frustration ,Nanotechnology ,engineering.material ,Neutron scattering ,Ion ,Coupling (physics) ,engineering ,Condensed Matter::Strongly Correlated Electrons ,media_common ,Spin-½ - Abstract
Frustration denotes the inability of a system to satisfy all pairwise interactions and enables a large variety of fascinating ground states that depend on the very details of the interactions involved. The focus will be on neutron scattering studies of spinel compounds AB2X4. It is well known that the B‐site ions form a pyrochlore lattice with inherent strong geometric frustration (GF). Among these compounds, heavy fermion‐like behaviour of LiV2O4 and new kinds of magneto‐elastic coupling phenomena in chromate spinels will be considered. Recently, also the A‐site spinels has been shown to be subject to strong frustration effects, not only for the spin sector but also for the orbital and structural degrees of freedom. Corresponding ordering phenomena in MAl2O4 (M = Mn,Fe,Co) will be discussed.
- Published
- 2008
24. Ferromagnetic fluctuations in YbNi4P2 measured by inelastic neutron scattering
- Author
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Giovanna G. Simeoni, Jan Peter Embs, M. M. Koza, Zita Huesges, Cornelius Krellner, Oliver Stockert, Tom Fennell, and C. Geibel
- Subjects
History ,Materials science ,Condensed matter physics ,Inelastic scattering ,Neutron scattering ,Small-angle neutron scattering ,Inelastic neutron scattering ,Computer Science Applications ,Education ,Neutron spectroscopy ,Condensed Matter::Materials Science ,Ferromagnetism ,Quasielastic neutron scattering ,Curie temperature ,Condensed Matter::Strongly Correlated Electrons - Abstract
YbNi4P2 is one of the very few heavy-fermion systems which allow the study of ferromagnetic quantum criticality. The Curie temperature TC=0.17 K can be suppressed by substituting arsenic on the phosphorus site, without changing the ferromagnetic nature of the ordered state. The ordered moment, even of the unsubstituted compound, is only around 0.05 μB, which hinders elastic neutron scattering experiments. To gain microscopic insight into the nature of the interactions, we have studied the magnetic excitations of polycrystalline YbNi4P2 by time-of-flight neutron spectroscopy. For momentum transfers larger than about 0.6 A−1 we find a quasi-elastic response whose width at low temperatures is limited by the Kondo effect. In contrast, the low-energy magnetic response is distinctly different for Q approaching zero: At low temperatures, but still in the paramagnetic phase, susceptibility and lifetime of the spin fluctuations are strongly enhanced, indicating the proximity of ferromagnetism.
- Published
- 2015
25. Magnetic ordering and spin excitations in the frustrated magnetMnSc2S4
- Author
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Alois Loidl, Vladimir Tsurkan, Susan D. Horn, Denis Sheptyakov, Hannu Mutka, A. Krimmel, M. M. Koza, M. Mücksch, and Clemens Ritter
- Subjects
Physics ,Magnetic structure ,Condensed matter physics ,Spin polarization ,media_common.quotation_subject ,Magnon ,Frustration ,Condensed Matter Physics ,Inelastic neutron scattering ,Electronic, Optical and Magnetic Materials ,Resonant inelastic X-ray scattering ,Spin ice ,Spin wave ,media_common - Abstract
The $A$-site spinel compound $\mathrm{Mn}{\mathrm{Sc}}_{2}{\mathrm{S}}_{4}$ exhibits strong frustration effects with a low ordering temperature $({T}_{N}=2.3\phantom{\rule{0.3em}{0ex}}\mathrm{K})$. Detailed neutron-scattering investigations have been performed to study the magnetic ordering process and the associated magnetic excitations. The magnetic structure found at $T=1.5\phantom{\rule{0.3em}{0ex}}\mathrm{K}$ is a spiral within the $a\text{\ensuremath{-}}b$ plane characterized by a propagation vector of $\mathbf{q}=(3∕4,3∕4,0)$. The magnetic ordering process is spectroscopically reflected by a change from a purely quasielastic to an inelastic response. The quasielastic line width corresponds to a magnetic energy scale of $\ensuremath{\approx}1\phantom{\rule{0.3em}{0ex}}\mathrm{meV}$ which is consistent with the spin wave stiffness as determined from the magnon dispersion at low temperatures.
- Published
- 2006
26. Vibronic and magnetic excitations in the spin-orbital liquid state of FeSc2S4
- Author
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A, Krimmel, M, Mücksch, V, Tsurkan, M M, Koza, H, Mutka, and A, Loidl
- Abstract
Inelastic neutron scattering results on the spin-orbital liquid in FeSc2S4 are presented. This sulfospinel reveals strong geometric frustration in the spin and in the orbital sector. In the present experiments the orbital liquid is evidenced by a clear spectroscopic signature of a dynamic Jahn-Teller effect with a vibronic splitting 3Gamma approximately 2 meV in agreement with theoretical estimates. The excitations of the spin liquid reveal strong dispersion and can be characterized as cooperative spin excitations in a supercooled paramagnet with a spin gap of Delta approximately 0.2 meV.
- Published
- 2004
27. Magnetisation dynamics of YbIr2Si2
- Author
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A. Hiess, Zakir Hossain, M. M. Koza, C. Geibel, and Oliver Stockert
- Subjects
Quantum phase transition ,Range (particle radiation) ,Materials science ,Condensed matter physics ,Scattering ,Intermetallic ,Inelastic scattering ,Condensed Matter Physics ,Inelastic neutron scattering ,Electronic, Optical and Magnetic Materials ,Condensed Matter::Materials Science ,Paramagnetism ,Magnetization ,Condensed Matter::Strongly Correlated Electrons ,Electrical and Electronic Engineering - Abstract
The two crystallographic modifications of YbIr2Si2 are supposed to be located on either side of a quantum phase transition. We here report on inelastic neutron scattering experiments investigating the magnetisation dynamics in the paramagnetic state. The observed magnetic scattering in the energy range of about 15–40 meV has been attributed to crystalline electric field (CEF) transitions. We relate our findings to the magnetic properties of the non-Fermi-liquid (NFL) YbRh2Si2.
- Published
- 2006
28. Crystalline electric field excitations of the non-Fermi-liquid
- Author
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Frank Steglich, C. Geibel, J. Ferstl, Oliver Stockert, A. P. Murani, and M. M. Koza
- Subjects
Physics ,Condensed matter physics ,Inelastic scattering ,Condensed Matter Physics ,Inelastic neutron scattering ,Electronic, Optical and Magnetic Materials ,Ion ,Spin wave ,Excited state ,Fermi liquid theory ,Electrical and Electronic Engineering ,Atomic physics ,Ground state ,Excitation - Abstract
We report on inelastic neutron scattering experiments on YbRh 2 Si 2 powder to study the magnetic excitation spectrum. The high-energy magnetic response at T = 1.5 K extends beyond 55 meV and is dominated by crystalline electric field excitations of the Yb 3 + ions. The measurements yield a doublet ground state and three excited doublet states at approximately 17 , 25 , and 43 meV.
- Published
- 2006
29. Absence of molecular mobility on nano-second time scales in amorphous ice phases.
- Author
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M. M. Koza, B. Geil, H. Schober, and F. Natali
- Published
- 2005
30. Experimental determination of the phonon density of states in filled skutterudites: evidence for a localized mode of the filling atom.
- Author
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R. Viennois, L. Girard, M. M. Koza, H. Mutka, D. Ravot, F. Terki, S. Charar, and J.-C. Tedenac
- Published
- 2005
31. Inelastic neutron scattering study of the lattice dynamics in the clathrate compound BaGe5.
- Author
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C Candolfi, U Aydemir, M M Koza, M Baitinger, Yu Grin, and F Steglich
- Published
- 2015
- Full Text
- View/download PDF
32. Temperature-dependent dynamic structure factors for liquid water inferred from inelastic neutron scattering measurements.
- Author
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Noguere G, Scotta JP, Xu S, Farhi E, Ollivier J, Calzavarra Y, Rols S, Koza M, and Marquez Damian JI
- Abstract
Temperature-dependent dynamic structure factors S(Q, ω) for liquid water have been calculated using a composite model, which is based on the decoupling approximation of the mean square displacement of the water molecules into diffusion and solid-like vibrational parts. The solid-like vibrational part S
vib (Q, ω) is calculated with the phonon expansion method established in the framework of the incoherent Gaussian approximation. The diffusion part Sdiff (Q, ω) relies on the Egelstaff-Schofield translational diffusion model corrected for jump diffusions and rotational diffusions with the Singwi-Sjölander random model and Sears expansion, respectively. Systematics of the model parameters as a function of temperature were deduced from quasi-elastic neutron scattering data analysis reported in the literature and from molecular dynamics (MD) simulations relying on the TIP4P/2005f model. The resulting S(Q, ω) values are confronted by means of Monte Carlo simulations to inelastic neutron scattering data measured with IN4, IN5, and IN6 time-of-flight spectrometers of the Institut Laue-Langevin (ILL) (Grenoble, France). A modest range of temperatures (283-494 K) has been investigated with neutron wavelengths corresponding to incident neutron energies ranging from 0.57 to 67.6 meV. The neutron-weighted multiphonon spectra deduced from the ILL data indicate a slight overestimation by the MD simulations of the frequency shift and broadening of the librational band. The descriptive power of the composite model was suited for improving the comparison to experiments via Bayesian updating of prior model parameters inferred from MD simulations. The reported posterior temperature-dependent densities of state of hydrogen in H2 O would represent valuable insights for studying the collective coupling interactions in the water molecule between the inter- and intramolecular degrees of freedom.- Published
- 2021
- Full Text
- View/download PDF
33. Lattice dynamics in intermetallic Mg2Ge and Mg2Si.
- Author
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Bessas D, Simon RE, Friese K, Koza M, and Hermann RP
- Abstract
The lattice dynamics of polycrystalline Mg(2)Ge and Mg(2)Si are compared using both microscopic and macroscopic measurements as well as theoretical calculations. The volume thermal expansion coefficient between 200 and 300 K was found to be 4.37(5) · 10(-5) K(-1) in Mg(2)Ge, compared to 3.69(5) · 10(-5) K(-1) in Mg(2)Si. Inelastic neutron scattering measurements yield densities of phonon states which are in line with theoretical calculations. The microscopic data were corroborated with macroscopic calorimetry measurements and provide quantified values for anharmonicity. The estimated macroscopic Grüneisen parameter is, γ(Mg(2)Si) = 1.17(5) and γ(Mg(2)Ge) = 1.46(5) at 295 K, in excellent agreement with Raman scattering data. Although the element specific mean force constants are practically the same, in Mg(2)Ge and Mg(2)Si, a mass homology relation alone cannot reproduce the difference in the partial densities of vibrational states in these compounds and differences in elemental bonding should be taken into account.
- Published
- 2014
- Full Text
- View/download PDF
34. Liquid 1-propanol studied by neutron scattering, near-infrared, and dielectric spectroscopy.
- Author
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Sillrén P, Matic A, Karlsson M, Koza M, Maccarini M, Fouquet P, Götz M, Bauer T, Gulich R, Lunkenheimer P, Loidl A, Mattsson J, Gainaru C, Vynokur E, Schildmann S, Bauer S, and Böhmer R
- Subjects
- Dielectric Spectroscopy, Neutron Diffraction, Scattering, Small Angle, Spectroscopy, Near-Infrared, 1-Propanol chemistry
- Abstract
Liquid monohydroxy alcohols exhibit unusual dynamics related to their hydrogen bonding induced structures. The connection between structure and dynamics is studied for liquid 1-propanol using quasi-elastic neutron scattering, combining time-of-flight and neutron spin-echo techniques, with a focus on the dynamics at length scales corresponding to the main peak and the pre-peak of the structure factor. At the main peak, the structural relaxation times are probed. These correspond well to mechanical relaxation times calculated from literature data. At the pre-peak, corresponding to length scales related to H-bonded structures, the relaxation times are almost an order of magnitude longer. According to previous work [C. Gainaru, R. Meier, S. Schildmann, C. Lederle, W. Hiller, E. Rössler, and R. Böhmer, Phys. Rev. Lett. 105, 258303 (2010)] this time scale difference is connected to the average size of H-bonded clusters. The relation between the relaxation times from neutron scattering and those determined from dielectric spectroscopy is discussed on the basis of broad-band permittivity data of 1-propanol. Moreover, in 1-propanol the dielectric relaxation strength as well as the near-infrared absorbance reveal anomalous behavior below ambient temperature. A corresponding feature could not be found in the polyalcohols propylene glycol and glycerol.
- Published
- 2014
- Full Text
- View/download PDF
35. Translational and rotational diffusion in water in the Gigapascal range.
- Author
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Bove LE, Klotz S, Strässle T, Koza M, Teixeira J, and Saitta AM
- Abstract
First measurements of the self-dynamics of liquid water in the GPa range are reported. The GPa range has here become accessible through a new setup for the Paris-Edinburgh press specially conceived for quasielastic neutron scattering studies. A direct measurement of both the translational and rotational diffusion coefficients of water along the 400 K isotherm up to 3 GPa, corresponding to the melting point of ice VII, is provided and compared with molecular dynamics simulations. The translational diffusion is observed to strongly decrease with pressure, though its variation slows down for pressures higher than 1 GPa and decouples from that of the shear viscosity. The rotational diffusion turns out to be insensitive to pressure. Through comparison with structural data and molecular dynamics simulations, we show that this is a consequence of the rigidity of the first neighbors shell and of the invariance of the number of hydrogen bonds of a water molecule under high pressure. These results show the inadequacy of the Stokes-Einstein-Debye equations to predict the self-diffusive behavior of water at high temperature and high pressure, and challenge the usual description of hot dense water behaving as a simple liquid.
- Published
- 2013
- Full Text
- View/download PDF
36. Observation of a superfluid component within solid helium.
- Author
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Lauter H, Apaja V, Kalinin I, Kats E, Koza M, Krotscheck E, Lauter VV, and Puchkov AV
- Abstract
We demonstrate by neutron scattering that a localized superfluid component exists at high pressures within solid helium in aerogel. Its existence is deduced from the observation of two sharp phonon-roton spectra which are clearly distinguishable from modes in bulk superfluid helium. These roton excitations exhibit different roton gap parameters than the roton observed in the bulk fluid at freezing pressure. One of the roton modes disappears after annealing the samples. Comparison with theoretical calculations suggests that the model that reproduces the observed data best is that of superfluid double layers within the solid and at the helium-substrate interface.
- Published
- 2011
- Full Text
- View/download PDF
37. Dynamics in confinement.
- Author
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Frick B, Koza M, and Zorn R
- Published
- 2003
- Full Text
- View/download PDF
38. Strong renormalization of phonon frequencies in Mg(1-x)Al(x)B2.
- Author
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Renker B, Bohnen KB, Heid R, Ernst D, Schober H, Koza M, Adelmann P, Schweiss P, and Wolf T
- Abstract
The phonon spectrum of Mg(1-x)Al(x)B2 shows a strong dependence on the aluminum content x. This is experimentally demonstrated by both Raman and inelastic neutron scattering and theoretically predicted by first-principles calculations. The observed changes in the phonon spectrum are put into perspective with respect to the superconducting properties within this family of materials.
- Published
- 2002
- Full Text
- View/download PDF
39. Anesthesia-related periodic involuntary movement in an obstetrical patient for cesarean section under epidural anesthesia: a case report.
- Author
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Martinez LP and Koza M
- Subjects
- Female, Humans, Leg, Periodicity, Pregnancy, Spinal Cord anatomy & histology, Spinal Cord drug effects, Spinal Cord physiology, Anesthesia, Epidural, Anesthesia, Obstetrical, Cesarean Section, Movement
- Abstract
Anesthesia-related periodic involuntary movements in a patient with regional anesthesia or etomidate anesthesia can be alarming. This case report describes anesthesia-related periodic involuntary movement in a patient undergoing cesarean section with epidural anesthesia. The anesthesia-related periodic involuntary movement occurred postoperatively in the recovery room. The discussion includes a brief review of spinal cord anatomy and physiology, as well as a review of the literature describing similar events.
- Published
- 1997
40. Flow cytometric evaluation of the effect of various thrombin inhibitors on platelet activation in whole blood.
- Author
-
Kaiser B, Koza M, Walenga JM, and Fareed J
- Subjects
- Adenosine Diphosphate pharmacology, Amino Acid Sequence, Arachidonic Acid pharmacology, Collagen pharmacology, Evaluation Studies as Topic, Humans, Molecular Sequence Data, Recombinant Proteins pharmacology, Reference Values, Thromboplastin pharmacology, Enzyme Inhibitors pharmacology, Flow Cytometry, Platelet Activation drug effects, Thrombin antagonists & inhibitors
- Abstract
In an in vitro study the effect of various thrombin inhibitors (argatroban, efegatran, DuP 714, recombinant hirudin and PEG-hirudin) on platelet activation in whole blood was investigated. Blood was drawn from normal human volunteers using the double syringe technique without use of a tourniquet to avoid autoaggregation of platelets. Blood was anticoagulated with either argatroban, efegatran, DuP 714, hirudin or PEG-hirudin at final concentrations of 10 micrograms/ml. Blood samples were then incubated at 37 degrees C either with saline, r-tissue factor, arachidonic acid, adenosine diphosphate or collagen. At definite times (1, 2.5, 5, 10 min) aliquots were taken and after various steps of fixative procedure the percentage of platelet activation was measured using fluorescent monoclonal antibodies to platelet surface receptors GPIIIa (CD-61) and P-selectin (CD-62). Flow cytometric analysis showed a platelet activation after all agonists used. All thrombin inhibitors studied caused a nearly complete inhibition of r-tissue factor-mediated platelet activation. In contrast, after activation with the other agonists an increased percent CD-62 expression was found with a maximum after 2.5 to 5 min. The results show that in whole blood thrombin inhibitors are effective in preventing platelet activation induced by r-tissue factor. The formation of active serine proteases including thrombin may be effectively inhibited by these agents. The observations further suggest that while thrombin inhibitors may control serine proteases, these agents do not inhibit the activation of platelets mediated by other agonists.
- Published
- 1996
- Full Text
- View/download PDF
41. Impact of biotechnology in the diagnostic and therapeutic management of cardiovascular disorders.
- Author
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Fareed J, Hoppensteadt D, Iyer L, Koza M, Walenga JM, and Bermes E Jr
- Subjects
- Amino Acid Sequence, Antibodies, Monoclonal, Anticoagulants therapeutic use, Biomarkers, Cardiovascular Diseases physiopathology, Hirudin Therapy, Hirudins genetics, Humans, Lipoproteins genetics, Lipoproteins therapeutic use, Molecular Sequence Data, Recombinant Proteins genetics, Recombinant Proteins therapeutic use, Risk Factors, Thromboplastin antagonists & inhibitors, Biotechnology, Cardiovascular Diseases diagnosis, Cardiovascular Diseases therapy
- Abstract
Although biotechnology has been useful in the development of new diagnostic methods and drugs for the management of cardiovascular disorders, there are several issues which raise certain questions on the global use of biotechnology based drugs and diagnostic methods (Piascik, 1991; Fareed, 1993a; Fareed, 1994a). The cost is rather prohibitive in the development of this type of technology. Most diagnostic methods and drugs developed utilizing biotechnology based methods are relatively expensive. The second important consideration is the equivalence of the newer biotechnology derived drugs to the natural products. Many of the biotechnology derived drugs are obtained in prokaryotic systems (E. coli). Post-transcriptional modifications such as glycosylation are often important in determining the function of various proteins. On the other hand, biotechnology based diagnostic methods exhibit somewhat different specificity in comparison to conventional methods. Thus, it is rather important to assess the developments in this area in a careful manner. Furthermore, validation of the clinical, diagnostic and therapeutic efficacy of biotechnology derived diagnostic devices and drugs is a prerequisite for their use in cardiovascular medicine.
- Published
- 1995
- Full Text
- View/download PDF
42. Procoagulant and anticoagulant effects of intravascular contrast media as assessed by thromboelastography.
- Author
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Iqbal O, Jeske W, Hoppensteadt D, Koza M, Walenga JM, Fareed J, and Moncada R
- Subjects
- Contrast Media adverse effects, Diatomaceous Earth pharmacology, Disease Susceptibility, Humans, Iohexol adverse effects, Iopamidol adverse effects, Ioxaglic Acid adverse effects, Blood Coagulation drug effects, Contrast Media pharmacology, Iohexol pharmacology, Iopamidol pharmacology, Ioxaglic Acid pharmacology, Thrombelastography
- Published
- 1995
- Full Text
- View/download PDF
43. Utility of the Heptest and a chromogenic substrate method to assess anticoagulation in patients refractory to heparinization by the activated partial thromboplastin time method.
- Author
-
Messmore HL, Koza M, Farid S, and Wehrmacher WH
- Subjects
- Chromogenic Compounds, Heparin blood, Humans, Male, Partial Thromboplastin Time, Blood Coagulation Tests, Heparin therapeutic use
- Published
- 1994
- Full Text
- View/download PDF
44. Studies on the pharmacokinetics and pharmacodynamics of recombinant hirudin (rHV2-Lys 47) after intravenous and subcutaneous administration in dogs.
- Author
-
Iyer L, Koza M, Iqbal O, Calabria R, and Fareed J
- Subjects
- Animals, Biological Availability, Cattle, Chromogenic Compounds metabolism, Enzyme-Linked Immunosorbent Assay, Hirudins administration & dosage, Hirudins blood, Hirudins pharmacokinetics, Hirudins pharmacology, Injections, Intravenous, Injections, Subcutaneous, Male, Oligopeptides metabolism, Partial Thromboplastin Time, Recombinant Fusion Proteins administration & dosage, Recombinant Fusion Proteins blood, Recombinant Fusion Proteins pharmacokinetics, Recombinant Fusion Proteins pharmacology, Recombinant Proteins administration & dosage, Recombinant Proteins blood, Recombinant Proteins pharmacokinetics, Recombinant Proteins pharmacology, Thrombin Time, Hirudins analogs & derivatives
- Abstract
In recent years, the pharmacological and biochemical characterization of hirudins has taken a major upswing due to the availability of this natural polypeptide in recombinant form. Despite this, the current knowledge on the pharmacokinetics and pharmacodynamics of recombinant hirudin (rH) appears to be incomplete. The present study was designed to investigate the relationship between plasma concentrations of rH with corresponding antithrombin responses after intravenous (i.v.) and subcutaneous (s.c.) administration in dogs. Four male, Mongrel dogs were each injected with an i.v. (bolus) dose (1 mg/kg) of one specific variant of rH, i.e. rH with a lysine residue in position 47 (rHV2-Lys 47). The dogs were injected with a s.c. dose (1 mg/kg) of rHV2-Lys 47 after one week. After each dose, blood was collected at different time intervals, plasma separated and stored at -70 degrees C. Plasma concentrations of rHV2-Lys 47 were determined using an enzyme-linked immunosorbent assay (ELISA) method and pharmacokinetic parameters were determined using standard non-compartmental methods. The ex vivo antithrombin activity of the drug was measured using activated partial thromboplastin time (APTT), calcium-thrombin time (Ca++TT) and a chromogenic anti-IIa assay. The results from this study indicate that the pharmacokinetic behavior of rHV2-Lys 47 is strongly influenced by the route of administration. In all three functional assays used, a significant correlation was obtained after i.v. administration between plasma concentrations and corresponding responses over the time period of the study when compared to s.c. administration. The results are indicative of a probable structural and functional modification of this rH variant after s.c. administration which may be responsible for the altered pharmacokinetics and pharmacodynamics after s.c. dosing.
- Published
- 1993
- Full Text
- View/download PDF
45. Alteration of pharmacokinetics and pharmacodynamics of recombinant hirudin (rHV2-Lys 47) after repeated intravenous administration in dogs.
- Author
-
Iyer L, Shavit J, Koza M, Calabria R, Moran S, and Fareed J
- Subjects
- Animals, Calcium chemistry, Dogs, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Enzyme-Linked Immunosorbent Assay, Half-Life, Hirudins genetics, Partial Thromboplastin Time, Recombinant Proteins pharmacokinetics, Recombinant Proteins pharmacology, Thrombin chemistry, Hirudins pharmacokinetics, Hirudins pharmacology
- Abstract
Native hirudin is a heterogenous polypeptide obtained from the medicinal leech, Hirudo medicinalis. Recent advances in molecular biological techniques have led to the availability of large amounts of hirudin in the recombinant form. Recombinant hirudins (rH) are currently being investigated for potential use in the prophylaxis and treatment of deep venous thrombosis (DVT), in disseminated intravascular coagulation (DIC) and during cardiovascular bypass surgery. In this study, one specific variant of rH with a lysine residue in position 47 (rHV2-Lys 47) was administered in dogs in a multiple dose regimen of 2 mg/kg (i.v. bolus) for three weeks with a dosing interval of one week. After each dose, blood samples were collected at regular time intervals, plasma separated and stored at -4 degrees C. Concentrations of rHV2-Lys 47 in each sample were determined using an enzyme-linked immunosorbent assay (ELISA). Ex vivo antithrombin responses measured included activated partial thromboplastin time (APTT), calcium-thrombin time (Ca++TT-10 NIH units/ml) and a chromogenic anti-IIa assay. It was the purpose of this study to detect any sensitization or desensitization of antithrombin responses when rHV2-Lys 47 is used in a repeated fashion such as would be expected in the prophylaxis of DVT. The results indicated that there was no attenuation in the responses; however, there was a sensitization of response as measured by the Ca++TT (10 NIH units/ml). These findings could have major implications in the clinical use of rH where this drug is expected to be used in a multiple dose regimen.
- Published
- 1993
- Full Text
- View/download PDF
46. Eradication of colonization by methicillin-resistant Staphylococcus aureus by using oral minocycline-rifampin and topical mupirocin.
- Author
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Darouiche R, Wright C, Hamill R, Koza M, Lewis D, and Markowski J
- Subjects
- Administration, Oral, Administration, Topical, Cross Infection microbiology, Cross Infection prevention & control, Drug Therapy, Combination therapeutic use, Humans, Infection Control methods, Methicillin Resistance, Microbial Sensitivity Tests, Plasmids, Staphylococcal Infections prevention & control, Staphylococcal Infections transmission, Anti-Bacterial Agents therapeutic use, Cross Infection drug therapy, Minocycline therapeutic use, Mupirocin therapeutic use, Rifampin therapeutic use, Staphylococcal Infections drug therapy, Staphylococcus aureus drug effects
- Abstract
In an attempt to control the spread of methicillin-resistant Staphylococcus aureus (MRSA) within a spinal cord injury unit, we investigated the mode of transmission and implemented a multidisciplinary approach for control that consisted of grouping of patients into cohorts, contact isolation, and antibiotics. Surveillance cultures of patients and nose and hand cultures of medical personnel were performed. Of 11 colonized patients, 6 had MRSA isolates that shared a similar plasmid profile and antibiogram, raising the possibility of interpatient spread of the organism. Medical personnel had no evident role in transmitting MRSA. All patients' pretherapy MRSA isolates were susceptible to minocycline and, except for one, to rifampin. Time-kill studies showed an indifferent interaction of these two antibiotics. Ten colonized patients received a 2-week oral course of 100 mg of minocycline twice daily and 600 mg of rifampin once daily, while the 11th patient was treated for only 1 week. Patients with colonization of the nares also had twice daily nasal application of 2% mupirocin for 5 days. Colonization with MRSA cleared in 10 of 11 patients (91%) and 20 of 21 sites (95%). When the individual circumstances of a medical facility justify eradication of MRSA colonization, a multidisciplinary approach that includes antibiotic therapy with oral minocycline and rifampin, along with topical mupirocin for those with nasal carriage, may be successful.
- Published
- 1991
- Full Text
- View/download PDF
47. Comparative studies on various assays for the laboratory evaluation of r-hirudin.
- Author
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Walenga JM, Hoppensteadt D, Koza M, Pifarre R, and Fareed J
- Subjects
- Animals, Biomarkers, Enzyme-Linked Immunosorbent Assay, Heparin pharmacology, Hirudins pharmacology, Humans, Species Specificity, Thrombin antagonists & inhibitors, Blood Coagulation Tests, Hirudins analysis, Recombinant Fusion Proteins analysis
- Abstract
Several laboratory methods are available to measure r-hirudin, including clot-based, amidolytic, immunologic, and physicochemical techniques. The global tests, such as the PT, APTT, and Heptest, did not show an adequate response to r-hirudin in the range of 0.5 to 10.0 micrograms/ml, where full anticoagulation is achieved, as determined by animal models of thrombosis. The 10 U/ml thrombin time assay was very sensitive to r-hirudin, whereas the 10 U/ml calcium thrombin time gave a dose-dependent response from 0.15 to 10.0 micrograms/ml. Whole blood clotting assays (ACT, TEG) effectively measured r-hirudin levels up to 25 micrograms/ml. The amidolytic anti-Factor IIa assay, specific for evaluating direct thrombin inhibition, was very effective, particularly when modified to decrease the sample: thrombin ratio for higher r-hirudin concentrations. This assay may be useful in quality control, since it is biochemically defined and reagents are easily standardized. Thrombin generation assays based on synthetic substrates showed limited effect of r-hirudin; however, assays based on TAT complex and prothrombin fragment F1+2 generation showed a dose-dependent response. Immunologic methods (ELISA) are under development. Since these assays measure both complexed and noncomplexed hirudin, and since they are only sensitive to submicrogram levels, they may only be useful for the direct quantitation of absolute levels of r-hirudin but not for monitoring clinical anticoagulation. Thus, thrombin-based clotting, amidolytic, and immunologic assays can be used to evaluate and measure r-hirudin. However, optimization of each assay to respond to high and low concentrations of r-hirudin and their application to clinical monitoring, batch control, and standardization needs to be determined.
- Published
- 1991
- Full Text
- View/download PDF
48. Comparison of recombinant hirudin and heparin as an anticoagulant in a cardiopulmonary bypass model.
- Author
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Walenga JM, Bakhos M, Messmore HL, Koza M, Wallock M, Orfei E, Fareed J, and Pifarre R
- Subjects
- Animals, Bleeding Time, Blood Loss, Surgical, Dogs, Extracorporeal Circulation, Fibrin analysis, Hematocrit, Heparin pharmacology, Hirudins administration & dosage, Hirudins pharmacology, Infusions, Intravenous, Injections, Male, Recombinant Proteins administration & dosage, Recombinant Proteins pharmacology, Recombinant Proteins therapeutic use, Thrombin Time, Thrombosis etiology, Cardiopulmonary Bypass adverse effects, Heparin therapeutic use, Hirudin Therapy, Thrombosis prevention & control
- Abstract
Recombinant (r) hirudin is a potent thrombin-specific inhibitor originally derived from the natural hirudin of the leech (Hirudo medicinalis). We have studied the efficacy of r-hirudin compared to heparin in a dog model of cardiopulmonary bypass (CPB) surgery. Two administration regimens were used for r-hirudin: Group I received 1.0 mg/kg intracardiac (i.c.) bolus then intravenous (i.v.) bolus at 30 min (n = 10); Group II received 1.0 mg/kg (i.c.) bolus with 1.25 +/- 0.04 mg/kg/h (i.v.) infusion (n = 8). Group III was given heparin 1.66 mg/kg (i.c.) bolus (n = 9). Aspiration of blood from the chest cavity revealed no significant difference between the three groups. Measurement of fibrin deposits in the pump line filter revealed higher amounts in the r-hirudin groups (P = 0.02). Decreases in platelets, fibrinogen and haematocrit due primarily to haemodilution were the same in each group. The bleeding time was less prolonged for r-hirudin than for heparin (p less than 0.001). No antagonist for r-hirudin was used; however, due to its short half-life, all coagulation parameters returned to baseline within 30 min after CPB. Since r-hirudin has no effect on platelets, is a poor immunogen, does not require a plasma cofactor, and may not require an antagonist, it may provide an alternative anticoagulant to heparin in CPB. Additional studies are, however, needed to optimize the dose and to evaluate other clinical aspects of r-hirudin.
- Published
- 1991
- Full Text
- View/download PDF
49. Some objective considerations for the neutralization of the anticoagulant actions of recombinant hirudin.
- Author
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Fareed J, Walenga JM, Pifarre R, Hoppensteadt D, and Koza M
- Subjects
- Animals, Blood Loss, Surgical prevention & control, Ear Diseases chemically induced, Ear, External injuries, Factor VIIa pharmacology, Fibrinolytic Agents toxicity, Hemorrhage chemically induced, Heparin pharmacology, Heparin Lyase, Hirudins toxicity, Humans, Platelet Aggregation drug effects, Platelet Factor 4 pharmacology, Polysaccharide-Lyases pharmacology, Protamines pharmacology, Rabbits, Recombinant Proteins antagonists & inhibitors, Recombinant Proteins toxicity, Wounds, Stab complications, Antifibrinolytic Agents pharmacology, Heparin Antagonists pharmacology, Hirudins antagonists & inhibitors
- Abstract
Recombinant hirudin (r-hirudin) is currently under development as an anticoagulant for use in surgery, therapeutic anticoagulation, disseminated intravascular coagulation and other pathologic states involving the generation of thrombin. Circulating levels of r-hirudin as an antithrombotic agent range from 2 to 20 micrograms/ml (0.1-1.0 mg/kg) as determined in an animal model of stasis thrombosis. In order to establish a relationship between the r-hirudin circulating level and bleeding, we utilized a rabbit ear blood loss model. r-Hirudin did not produce any loss of blood at dosages up to 20 micrograms/ml i.v. (1.0 mg/kg). When the circulating levels were maintained at 20 micrograms/ml for periods of up to 3 h, no increase in blood loss was observed. At 50 and 100 micrograms/ml initial circulating levels (2.5 and 5.0 mg/kg) a dose-dependent increase in the blood loss was observed which was equivalent to that observed with 1.25 and 2.5 mg/kg i.v. heparin. Such levels of r-hirudin are not expected in clinical usage. In contrast to heparin, the anticoagulant actions of r-hirudin were not neutralized by protamine sulfate, platelet factor 4, other polycationic agents and heparinase. In our studies, the blood loss induced by greater than 2.0 mg/kg i.v. dosages of r-hirudin in an animal model was neutralized by the administration of an activated prothrombin complex concentrate at 25 U/kg. In a similar experimental setting, r-factor VIIa was also partially effective. These studies suggest that r-hirudin anticoagulation may not require neutralization, since bleeding effects are not observed at effective antithrombotic dosages in individuals with normal hemostatic status.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1991
- Full Text
- View/download PDF
50. Laboratory assays for the evaluation of recombinant hirudin.
- Author
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Walenga JM, Hoppensteadt D, Koza M, Wallock M, Pifarre R, and Fareed J
- Subjects
- Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, Factor Xa Inhibitors, Feedback, Heparin pharmacology, Hirudins analysis, Hirudins genetics, Humans, Partial Thromboplastin Time, Peptide Fragments pharmacology, Protein Engineering, Prothrombin Time, Recombinant Proteins analysis, Recombinant Proteins pharmacology, Blood Coagulation drug effects, Blood Coagulation Tests, Hirudins pharmacology, Prothrombin antagonists & inhibitors
- Abstract
Several laboratory methods are available to measure the anticoagulant activity of recombinant hirudin (r-hirudin), a potent thrombin inhibitor. These assays include clot-based, amidolytic, immunologic and physicochemical techniques. Although r-hirudin, like heparin, is an effective anticoagulant, the mechanism of action of the two agents is different. Thus it is not surprising that the global tests, such as the prothrombin time (PT), partial thromboplastin time (APTT) and the Heptest (Haemachem, Inc., St. Louis, Mo., USA), do not show adequate responses to r-hirudin. In the range of 0.5-10.0 microgram/ml, where full anticoagulation is achieved, as determined by animal models of thrombosis, these assays show little to no prolongation of the time to clot. In order to find a more suitable assay system, modifications of the above assays were evaluated. The diluted APTT and diluted Heptest showed linear concentration-dependent responses to lower levels of r-hirudin with an enhanced sensitivity than that of the classical assays. On the other hand, the diluted thrombin time was too sensitive. Whole-blood clotting assays, ACT and thrombelastograph, effectively measured r-hirudin levels up to 25 micrograms/ml. The amidolytic anti-factor IIa assay, specific for evaluating direct thrombin inhibition, was very effective particularly when modified to decrease the sample:thrombin ratio. This assay may be useful in quality control since it is biochemically defined, and reagents are easily standardized. The relevance of the results of the anti-IIa assay to clinical conditions, however, remains to be determined. Thrombin generation assays have limited value in monitoring the anticoagulant effect of r-hirudin since the effect of thrombin inhibition by r-hirudin on coagulation feedback mechanisms, and thus the effect on thrombin generation, appears to be minimal. Immunologic methods such as ELISA and RIA are under development, but they may only be useful for the direct quantitation of absolute levels of r-hirudin and not for monitoring the clinical anticoagulant action. Furthermore, these assays are only sensitive to sub-microgram/ml levels. Therefore, thrombin-based clotting and amidolytic assays may at present be the best choice for evaluating the functional, clinical antithrombotic effects of r-hirudin.
- Published
- 1991
- Full Text
- View/download PDF
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